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Development of functional asymmetries in young infants: A sensory-motor approach

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Development of functional asymmetries in young infants: A sensory-motor approach

Cover design by Johan Backlund Permission to reprint Study I granted by John Wiley & Sons, Inc. March 2006

Copyright © 2006 Erik Domellöf ISBN 91-7264-066-9 Printed by Print & Media, Umeå University, Sweden

ABSTRACT Domellöf, Erik (2006). Development of functional asymmetries in young infants: A sensory-motor approach. Doctoral dissertation from the Department of Psychology, Umeå University, SE-901 87, Umeå, Sweden: ISBN 91-7264-066-9. Human functional laterality, typically involving a right-sided preference in most sensory-motor activities, is still a poorly understood issue. This is perhaps particularly true in terms of what underlying mechanisms that may govern lateral biases, as well as the developmental origins and course of events. The present thesis aims at investigating functional asymmetries in the upper and lower body movements of young human infants. In Study I, the presence of side biases in the stepping and placing responses and head turning in healthy fullterm newborns were explored. No evident lateral bias for the leg responses in terms of the first foot moved or direction of head turning was found. However, a lateral bias was revealed for onset latency in relation to the first foot moved in both stepping and placing. Asymmetries in head turning did not correspond to asymmetries in leg movements. In Study II, functional asymmetries in the stepping response of newborn infants were investigated in more detail by means of 3-D kinematic movement registration. Evident side differences were found in relation to smoother movement trajectories of the right leg by means of less movement segmentation compared to the left leg. Side differences were also found in relation to intralimb coordination in terms of stronger ankle-knee couplings and smaller phase shifts in the right leg than the left. In Study III, using the same movement registration technique, the kinematics of left and right arm movements during goal-directed reaching in infants were prospectively studied over the ages 6, 9, 12, and 36 months. Main findings included side differences and developmental trends related to the segmentation of the reaching movements and the reaching trajectory, as well as the distribution of arm-hand-use frequency. The results from Study I and II are discussed in relation to underlying neural mechanisms for lateral biases in leg movements and the important role of a thorough methodology in investigating newborn responses. Findings from Study III are discussed in terms of what they imply about the developmental origins for hand preference. An emphasis is also put on developmental differences between fullterm and preterm infants. Overall, the studies of the present thesis show that an increased understanding of subtle expressions of early functional asymmetries in the upper and lower body movements of young

infants may be gained by means of refined measurements. Furthermore, such knowledge may provide an insight into the underlying neural mechanisms subserving asymmetries in the movements of young infants. The present studies also add new information to the current understanding of the development of human lateralized functions, in particular the findings derived from the longitudinal data. Apart from theoretical implications, the present thesis also involves a discussion with regard to the clinical relevance of investigating functional asymmetries in the movements of young infants.

Key words: Laterality, development, handedness, human infant, stepping response, placing response, head turning, arm movement, reaching, kinematic parameters, intralimb coordination

ACKNOWLEDGEMENT I am grateful to many people that in different ways have contributed to this thesis being completed. These are the people that I would like to particularly thank.

First of all, Louise Rönnqvist, my scientific advisor, who a long time ago lured me into the infant laboratory in an attempt to get me interested in something called “motor and perception development” and an apparently fascinating phenomenon called “laterality”. It worked! Louise, thank you for your tremendous inspiration and encouragement, sharing your knowledge and guiding me all the way to the finishing line! Much thanks to you, I will always fondly remember my time as a PhD student.

Through Louise I have also had the pleasure and privilege of getting to know and collaborate with Brian Hopkins, whom I would like to particularly thank for advice, inspiration, and much more!

For reading and providing helpful comments on this thesis, I thank Louise Rönnqvist, Patrik Hansson, Steven Nordin, and Claes von Hofsten at the Department of Psychology, Uppsala University.

I would further like to express my gratitude towards all colleagues at the Department of Psychology, Umeå University, for providing a creative and friendly working place, rewarding and often very funny discussions, computers, fruity Tuesdays and other nice things! Special thanks to Bert Jonsson for support in matters concerning departmental duties. My fellow doctoral students deserve a particular acknowledge, I will probably always remember things like up-side-down horses, soccer fever, Beijing clubbing, and the curious incident with the fender in the snowstorm…

I would also like to thank Thomas Rudolfsson for MATLAB programming and more, Rose Eriksson for generously providing a language review of this thesis, Johan Backlund for the nice thesis cover design, and “photo model” Freja Annasdotter Neely (see Figure 2-3).

A very special thank you goes to my parents, Lennart and Gunilla, and all of my family for never failing love and support! I direct a special thanks to my brother Magnus and my sister-in-law Fátima for their “local support” and warm hospitality.

Thanks also to my friends-outside-work (no one mentioned, no one forgotten) for encouragement and happy times!

Finally, Magdalena, this is for us. And for Baby. Umeå, April, 2006 Erik Domellöf

LIST OF PAPERS This doctoral dissertation is based on the following articles: I. Domellöf, E., Hopkins, B., & Rönnqvist, L. (2005). Upper

and lower body functional asymmetries in the newborn: Do they have the same lateral biases? Developmental Psychobiology, 46, 133-140.

II. Domellöf, E., Rönnqvist, L., & Hopkins, B. (2006).

Functional asymmetries in the stepping response of the human newborn: A kinematic approach. Manuscript submitted for publication.

III. Rönnqvist, L., & Domellöf, E. (2006). Quantitative

assessment of right and left reaching movements in infants: A longitudinal study from 6 to 36 months. Manuscript accepted for publication in Developmental Psychobiology.

TABLE OF CONTENTS INTRODUCTION ................................................................................. 1 BACKGROUND ................................................................................... 3

Motor control .................................................................................. 3 Reflex/Hierarchical-oriented theories ................................... 3 Systems-oriented theories ...................................................... 5

Neural setting ................................................................................. 7 The motor system ..................................................................... 8 Development of the motor system ....................................... 9

Infant motor asymmetries......................................................... 12 Head turning ............................................................................. 13 Stepping and placing responses ......................................... 16 Arm and hand movements ................................................... 21

Clinical implications .................................................................... 28 Insult to the developing brain .............................................. 28 Kinematic registration as a potential tool for early diagnosis.................................................................................... 30

RESEARCH OBJECTIVES ............................................................... 32 Main research questions ........................................................... 33

METHODS.......................................................................................... 34 Participants.................................................................................... 34

Study I and II ............................................................................. 34 Study III ...................................................................................... 34

Design ............................................................................................. 35 Apparatus and measurements................................................. 35 Methodological considerations ............................................... 38

Behavioral state ....................................................................... 38 Postural control ........................................................................ 40 Registration technique ........................................................... 42

SUMMARIES OF THE EMPIRICAL STUDIES............................. 45 Study I: Upper and lower body functional asymmetries in the newborn: Do they have the same lateral biases? ........ 45 Study II: Functional asymmetries in the stepping response of the human newborn: A kinematic approach ................... 47 Study III: Quantitative assessment of right and left reaching movements in infants: A longitudinal study from 6 to 36 months.............................................................................. 49

GENERAL DISCUSSION................................................................. 52 Concordances between newborn head turning, stepping and placing responses ............................................................... 52 Onset latency: newborn stepping and placing responses 53 Kinematic parameters: newborn stepping responses ....... 55 Video scoring: infant reaching and grasping ....................... 56 Kinematic parameters: infant reaching and grasping........ 57 Birth condition: infant reaching and grasping ..................... 58

CONCLUSIONS ................................................................................ 60 Future directions .......................................................................... 62

REFERENCES .................................................................................... 65

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INTRODUCTION The human being is characterized by several types of asymmetries, both structural (e.g., cerebral, physical and visceral) and functional (e.g., handedness, speech, perception and emotion). Furthermore, even though animals are lateralized in a similar way as humans (Denenberg, 1988), no other species is as markedly lateralized as we are. Through history, handedness, in terms of the inclination of most people to preferably use one hand over the other in manual activities, has evoked particular interest as right-handedness constitutes one of the strongest expressions of laterality in humans. About 70-90% of humans, depending on cultural background and preference assessment criteria, show a right-handed preference (Porac & Coren, 1981). Narrowing it down to the Western countries, this figure increases to 85-95% (Brackenbridge, 1981). Furthermore, even though right-handedness is the most consistently laterally biased behavior, a majority of human populations also tend to prefer the right foot, right eye and right ear (Porac & Coren, 1981). However, it is still an open question why humans seem to be characterized by right-sidedness as the norm and how this develops. In the ongoing theoretical and empirical debate, both genetic (e.g., Annett, 1985; Corballis, 1997; McManus & Bryden, 1993) and non-genetic (e.g., Hepper, Shahidullah, & White, 1990; Michel, 1981; Previc, 1991; Provins, 1997) models have been proposed. At present, there is no single model that convincingly can explain the phenomenon of human laterality. Although, in the efforts to learn more about the mechanisms that influence the development of functional asymmetries and their origins, as well as deviations from the dextral norm, infant studies have proved to be of high significance (Hopkins & Rönnqvist, 1998).

Humans start showing lateral preferences already during early infancy. In the past, it was generally assumed that the brain of the human newborn was both structurally and functionally symmetrical. Later functional asymmetries were looked upon as an age-dependent phenomenon, emerging as a consequence of hemispheric dominance for language abilities (Hopkins & Rönnqvist, 1998). However, modern research has provided evidence for motor asymmetries as early as in the healthy first (Hepper, McCartney, & Shannon, 1998; McCartney & Hepper, 1999), second (Hepper et al., 1990) and third (Ververs, de Vries, van Geijn, & Hopkins, 1994) trimester fetus, as well as in the newborn in the first few hours after birth (Hopkins, Lems, Janssen, & Butterworth, 1987), challenging the old assumptions. Thus, it is now well known that the

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movement repertoire of the healthy fullterm human newborn is characterized by a number of functional asymmetries. As a consequence, it has been progressively recognized that in the exploration of the nature and developmental characteristics of the earliest lateralized behaviors lies important clues to the puzzling issue of human laterality.

Investigating the development of functional laterality in the sensory-motor performance of human newborn infants involves looking at the emergence of a preference for one side or the other and whether this can be determined as a stable phenomenon or not. As right hand preference is one of the most dominant and reliable human lateralized behaviors, observing young infants’ functional asymmetries in relation to development of handedness has naturally gained most research interest. There are also many different models concerning the origins of handedness and how early neuroanatomical asymmetries are involved in this development (see Hopkins & Rönnqvist, 1998, for a review). The development of foot preference behavior has not been explored to the same extent. Furthermore, what underlying neural mechanisms that seem to govern early functional asymmetries, as well as the relation between asymmetries of the upper and lower body, are still largely unknown areas.

The importance of studying infant functional asymmetries is perhaps best understood when considering the relationship between development of functional laterality and developmental delays in young infants and children born at-risk for deviant developmental outcomes (e.g., preterm infants). Many studies have demonstrated that left-handedness is clearly overrepresented in groups with severe and generalized cognitive deficits, and that there is an association between left-handedness, as well as ambiguous handedness, and different developmental disorders (e.g., Bishop, 1990). An overrepresentation of left- and non-right-handers has also been described in ex-preterm children (e.g., Giménez, Junqué, Narberhaus, et al., 2004; Marlow, Roberts, & Cooke, 1989; O’Callaghan, Burn, Mohay, Rogers, & Tudehope, 1993a; 1993b), as well as various perceptual-motor difficulties and cognitive or behavioral problems at school age (e.g., Jongmans, Mercuri, Dubowitz, & Henderson, 1998). Exploring the nature of early lateral biases and, further on, the link between these biases (or deviations from such biases) to later forms of side preferences could thus be of clinical importance in terms of refining the methods for discovering neurological dysfunctions. For instance, a fuller understanding of lateralized patterns in sensory-motor behavior in the beginning of life could help in the early identification of neurological disorders such as cerebral palsy as expressed by side-related deviations.

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In the present thesis, early functional asymmetries in both the upper and lower body are explored. Beginning with the newborn infant, side differences in the stepping and placing responses are examined in pursuit of an increased understanding with regard to early lateral biases in leg movements. The question whether upper and lower body functional asymmetries share the same lateral biases is also addressed by investigating the relationship between asymmetries in leg responses and head turning preferences. To attain further knowledge about the developmental pattern of arm-hand preference and the origins of handedness, goal-directed arm-hand movements in 6 to 36-month-old children, studied longitudinally, are then examined. In addition, deviations in functional asymmetries as expressed in early movements (arm-hand movements in particular), potentially associated with neurological deficits, are also discussed. Before presenting the research objectives, methods and overviews of the empirical studies in more detail, a full background is given below.

BACKGROUND

Motor control There are several different theories of motor control aiming to explain the complex issue of movement and its relation to the nervous system (and beyond). Some of them stem from over 100 years ago and some are more contemporary, but they all contain elements worth considering when discussing issues involving the generation and control of movement and its development. In the following section, the most influential theories are summarized.

Reflex/Hierarchical-oriented theories In the early 1900s, the famous British neurophysiologist Sir Charles S. Sherrington founded the classic reflex chaining theory. Sherrington, often cited in neuroscience textbooks for his description of “the final common path” (i.e., the final expression of a motor behavior is completed by way of the motor neurons of the spinal cord and the muscles), proposed that movements are triggered by stimuli and based on reflex elements linked together in a chain of activations. Although appealing in its assumptions,

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Sherrington’s reflex theory of motor control contains several limitations. For instance, the model fails to explain both spontaneous and voluntary movements, movements without sensory input and novel movements (Shumway-Cook & Woollacott, 2001).

The hierarchical theory of motor control, initiated by Hughlings Jackson in the early 1900s, suggests that the nervous system is characterized by a strict top-down hierarchical organization. In this model, the brain controls motor function at different levels (higher, middle and lower levels of control, roughly corresponding to the association areas, motor cortex and the spinal cord). Thus, a reflex in this theoretical framework is a primitive lower-level reaction under cortical control, as opposed to Sherrington’s view of the reflex as the fundamental unit of action (Shumway-Cook & Woollacott, 2001).

Advanced scientific observations of infants in relation to motor development evolved strongly as a research area in the 1930s and 1940s. Pioneer scientists such as Arnold L. Gesell and Myrtle B. McGraw initiated the field of thoroughly studying and documenting early motor responses, as well as implemented the use of new and sophisticated techniques and methods to do it, with a lasting impact on current research on infant motor development (Bergenn, Dalton, & Lipsitt, 1992; Thelen & Adolph, 1992). For instance, McGraw conducted elegant studies on infant neuromuscular development in e.g. analyzing the achievement of erect locomotion from stepping response to mature gait (McGraw, 1940). This type of research added evidence to a reflex/hierarchical theory of motor control as correlations could be drawn between stages of motor development and increased maturation of the central nervous system (CNS), with increased higher-level control over lower-level reflexes as a result (e.g., as demonstrated by the successive disappearance of various postnatal “primitive reflexes”). However, more updated modern hierarchical theories suggest a more flexible hierarchical organization in motor control. Depending on task, any level can exert control over another (top-down or bottom-up), with reflexes as one of many processes involved. Thus, lower-level behaviors may not be as immature or primitive as previously thought (Shumway-Cook & Woollacott, 2001).

One example of a more modern approach to the reflex/hierarchical theories is known as the motor programming theory. In this theoretical framework the focus is put on the concept of a central motor pattern (i.e., a patterned motor response generated in the absence of an afferent input). For example, based on experimental findings such as preserved locomotion ability in spinal cats, the hypothesis of a central pattern generator (CPG) in the spinal cord, autonomously generating locomotion

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(although with sensory input recognized as having important modulatory effects), was formed (e.g., Forssberg & Grillner, 1973; Grillner & Wallen, 1985). The CPG has also been suggested as the neural network behind the production of stepping movements in the human infant (Forssberg, 1985). Even though fundamental neural structures producing complex coordinated behavior in the absence of feedback have been proven evident by numerous experiments, the concept of the CPG as central control of motor action such as locomotion (hardwired inside the organism and more or less independent of other contexts) has been criticized (see below).

Systems-oriented theories Parallel in time to Gesell and McGraw, the Russian neurophysiologist Nicolai Bernstein outlined a theory portraying the body as a mechanical system with mass and joints and subjected to both external and internal forces. Thus, Bernstein’s system theory takes into account that movements are dependent on situational and environmental factors (e.g., gravity) as well as the neural control of movements. As a result of this constantly changing contextual influence, the same motor command can produce diverse movements as well as different motor commands can produce the same movement. Furthermore, Bernstein did not regard neural motor control as a strict top-down program. Instead he claimed that movement control is distributed and a function of a number of interacting systems working together at different levels within the body’s mechanical system. Complicating movement coordination and control even more, Bernstein introduced the concept of degrees of freedom (e.g., all body joints can flex, extend or even rotate, causing many independent states for central control to consider in planning and carrying out a movement). Even though Bernstein acknowledged a hierarchical control system, with higher and lower levels, a central executive could never manage to control movement down to each and every muscle by itself. The solution must be that movement control is a shared process and Bernstein suggested that “synergies”, i.e. groups of muscle action units collaborating in effectuating actions of the muscles, existed to help reduce the degrees of freedom and thus simplify for the executive level (Schmidt & Lee, 1999; Shumway-Cook & Woollacott, 2001).

Bernstein’s system theory offers a broader perspective than the other pioneer theories on motor control and has had an important impact on modern thinking in relation to movement coordination and control and

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its development. An example of a modern theoretical approach inspired by Bernstein’s system theory is the dynamical systems model. In line with Bernstein, dynamical systems theorists discard the thought of actions as hard-wired. Actions are viewed as self-organized, resulting from multiple collaborating subsystems, and patterns of movement vary dynamically with the bodily system and context or task (Ulrich, 1989). For instance, Thelen and collaborators have in a series of experiments investigated early motor development from a dynamical systems perspective (e.g., Thelen & Fisher, 1983; Thelen, Fisher, & Ridley-Johnson, 1984; Thelen, Ridley-Johnson, & Griffin, 1982). In contrast to motor control theories with a more structural approach (i.e., focusing on the underlying programs for behaviors), Thelen et al. employ a functional perspective where the actual performance, including changes in physiological and emotional state of the performer as well as the context of the action, plays a vital part. During development, children’s motor performance gets increasingly better, not simply because of neural maturation (as believed by McGraw, see above) but rather as a result of context-tuned control structures progressively becoming integrated with the inborn movement system and thus optimized for action (Thelen, 1985; Thelen, Kelso, & Fogel, 1987). The motor neurophysiologist hypothesis of a CPG controlling locomotion is also discordant with this dynamical systems model. The critique raised by Thelen in relation to the CPG concept is that it effectively overlooks the complexity of postural control and the role of sensory information (Thelen & Smith, 1998). For example, in the dynamical systems perspective an early response such as stepping is not hard-wired to the CNS or the result of a spinal pattern generator gradually coming under cortical control, but an active functional behavior displaying dynamic changes and sensitivity to states of wakefulness. Furthermore, as shown by Thelen and coworkers (1982; 1984) the stepping response does not “disappear” as previously believed, but gets affected by changes in physical growth, body composition and environmental factors. They showed that by facilitating the biodynamical demands the response could actually be restored in infants older than 2-3 months (approximately the age when the response seemingly disappears). Thus, it was concluded that growth-related changes in body segment biodynamic properties can be as important as neural maturation.

Today, the dynamical systems approach to motor control has become widely accepted, at least in a developmental perspective. Brain maturation and concepts such as the CPG are still regarded as important factors, but integrated into the more holistic framework of the dynamical systems model. For example, Vaal, van Soest and Hopkins (1995) present an

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interesting model for the early development of locomotion. In this model, interactions and modulatory feedback loops between different subsystems, including higher centers, a CPG, the musculo-skeletal system and the environment, represent the control and coordination of locomotory movements. During development, changes occur in the dynamical processes at three time-scales: state dynamics (the direct system behavior in real time), parameter dynamics (modulation of the weight of neuronal connections in environmental or task constraint adjustment) and graph dynamics (influential processes in relation to the “system architecture”, e.g. establishment or destruction of connections). Subsequently, changes arise at all levels of the interactional subsystem model (e.g., in the integration of visual, vestibular and proprioceptive information at the higher level and in the growth and differentiation of muscles at the lower level) that will affect the control and coordination of locomotion.

Finally, one further concept that is progressively evolving out of the dynamical systems approach should be mentioned, entitled catastrophe theory. Applying the concepts and methods of dynamical systems, catastrophe theory, in relation to e.g. motor development, aims to explain if changes in development constitute nonlinear, discontinuous phase transitions (viz., corresponding to “catastrophes”). For instance, Wimmers, Savelsbergh, van der Kamp and Hartelman (1998) replicated the finding of an increase in reaching without grasping to reaching including grasping in 3 to 5-month-old infants and could further model this finding within the context of catastrophe theory. They found that this particular development could very well emerge from a discontinuous phase transition, indicating an underlying developmental process of structural modification (as opposed to e.g. McGraw’s view of new behaviors as strictly corresponding to the emergence of new underlying fixed structures).

Neural setting It is well known that the body of the human being is represented at the primary motor and somatosensory cortex by different areas for different parts (e.g., head, legs and arms). These areas also vary in size depending on the amount of precise motor control required for a particular body part (e.g., a large area for lips and tongue relating to vocalization movements, as compared to a relatively small area for the trunk). The motor system is best regarded as a network, an ordered system combining hierarchical and parallel models including many shared interconnections. In this network,

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the cortex is the major route through which other structures can reach the spinal cord. The control of movement involves subcortical structures such as the basal ganglia, the thalamus, the red nucleus and the cerebellum; and the widely distributed sensory input serves a monitoring function with regard to the sensory consequences of movement. The following section outlines the human motor system and its development.

The motor system The distal musculature is cortically controlled through the lateral system of the spinal cord. Corticofugal fibers are sent from the cortex to brainstem motor nuclei (corticobulbar fibers) and to the dorsolateral interneurons and motor neurons of the spinal cord (corticospinal fibers). Axons from the cortex can project directly, via the lateral corticospinal tract (pyramidal tract), to the interneurons in the lateral part of the intermediate zone and the lateral motor neurons. The lateral corticospinal tract descends on one side of the brain stem, crosses the midline at the medulla and ends on the opposite side of the spinal cord. Projections through the lateral corticospinal tract control distal muscles of importance for precise movements, e.g., movement of the hand. The corticofugal fibers of the ventromedial system terminate bilaterally on medially located inter- and motor neurons. Projections through the ventral corticospinal tract control proximal movements such as movement of the trunk. The brainstem does also make direct connections to the spinal cord. The rubrospinal tract within the lateral system is involved with limb movement and the reticulospinal, tectospinal and vestibulospinal tracts within the ventromedial system with whole-body movement. The structures in the brainstem do also receive projections from the sensory systems of the spinal cord and are involved in producing movements, as well as regulating motor function and sensory input. The thalamus relays information to the cortex, both sensory input to the primary sensory areas and motor behavior information to the motor areas, and is thus central in both sensation and motor control. The thalamus is also involved in two respective loops through the basal ganglia (involved in motor programs and complex motor sequences) and the cerebellum (involved in coordination and motor learning), transmitting information from these structures to the motor cortex (Kandel, Schwartz, & Jessell, 1991; Kolb & Wishaw, 1996).

Kuypers and colleagues have in a series of studies on the neural structures in rhesus monkeys advanced the knowledge of the motor

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pathways controlling movement (e.g., Brinkman & Kuypers, 1973). In their work they have concluded that three main pathways, corresponding to the tracts described above, are involved in different types of action. Summarizing these pathways, we have (1) the ventromedial brainstem pathways, that are fibers sent from the motor cortex to both sides of the body, involved in the control of whole-body movement, posture and integrated body-limb movement (e.g., walking), (2) the lateral brainstem pathways, that are cells projecting to the contralateral limbs for individual movements (e.g., hand movement or kicking), and (3) the cortico-motor neuronal pathways, containing neurons directly projecting from specific cortical areas (representing the fingers mainly) to the spinal cord and motor neurons serving movements of the digits.

The final expression of the motor behavior is done by way of the motor neurons of the spinal cord and the muscles. The dendrites of a motoneuron extend over most spinal grey matter, receiving both excitatory and inhibitory inputs (mainly from local interneurons). The motor neurons integrate segmental (reflex), proprio and supraspinal inputs and project impulses to the muscles to activate or deactivate. At the muscle level, there is a need for multiple control for postural stability and proximodistal interactions, as well as co-contraction and fractionation (two basic patterns of muscle usage). For instance, when reaching to grasp an object, a given set of motor neurons and muscles act on the hand and fingers, involving different re-combinations of the muscles. To optimally perform the action will require good postural stability, a working proximodistal interaction of shoulder and hand, together with co-contraction (e.g., to prevent other fingers to move when performing a pincer precision grip), and fractionation (e.g., shaping the fingers to grip the object and maintaining grip). Sensory feedback is also involved in the reaching act, as it is essential for guidance of movement. The sensory guidance functions both “externally”, during the actual movement, and “internally”, creating and perfecting models of feed-forward motor control (Lemon, 2002).

Development of the motor system Neurological maturation typically follows a proximal to distal and gross to fine progression, with corticospinal function, as expressed in movements requiring most skill and flexibility (e.g., refined finger movements), being last to develop. Maturation is also generally observed to be progressing in a cephalocaudal (“head to tail”) direction. Thus, during motor skill

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development, the center of the body is controlled before more remote parts, and control of the upper body develops before the lower body. Furthermore, motor experiences together with level of activity in the developing systems seem to play an important part in this developmental progress.

The CNS starts to develop as early as with the formation of the neural tube, approximately 3-4 weeks following conception, and important foundations for the later highly advanced nervous system are progressively built already during the subsequent prenatal period. Of particular interest in relation to the motor system is the neuromuscular development of the fetus. De Vries, Visser and Prechtl (1982; 1984) have by means of ultrasound scanning managed to map the movements of human fetuses at different ages and linked these to changes in the developing neuromuscular system. The first writhing movements of the embryo can be observed at 8 weeks of age, coinciding with the emergence of the spinal cord with motor neurons about to innervate the developing motor system. Increased spontaneous movements at 10 weeks, followed by observations of isolated movements, as well as more general movements of a global character at 11 weeks, appear parallel to the establishment of interconnections between the primary afferent nerves and interneurons of the spinal cord followed by a burst in the number of motor neuron synapses. By 13-15 weeks there is a marked increase in neurons connected to the major body segments and the myelination of nerve fibers also begins. At the same time a range of different, clearly defined movement patterns are observable in the fetus. Taken together, this lends to the suggestion that coinciding changes in fetal behavior and CNS formation seem to exist and that the early movements of the embryo assist the CNS differentiation with important feedback processes.

At birth, the brain stem motor systems are well developed, but the corticospinal system is still in its early stage of maturation (Martin, 2005). The human corticospinal tracts reach the lower levels of the spinal cord (lumbosacral cord) by 29 weeks of gestation (Ten Donkelaar, Lammens, Wesseling et al., 2004). Next, the corticospinal axons progressively innervate the spinal neurons, including motor neurons, and at term age functional corticospinal projections have been established (Eyre, Miller, Clowry, Conway, & Watts, 2000). Transcranial magnetic stimulation (TMS) has been shown to evoke motor responses in term and preterm infants by means of ipsilateral corticospinal responses with shorter onsets compared to contralateral responses (Eyre, Taylor, Villagra, Smith, & Miller, 2001), in keeping with the finding of a shorter ipsilateral pathway in neonates (Eyre, Miller, & Clowry, 2002). Over the first year of life, a

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decrease in the amplitude of these ipsilateral effects, with a parallel increase in the amplitude of contralateral effects can be observed (Eyre et al., 2001). Moreover, central conduction response times in relation to TMS rapidly decline during the first years of life and by approximately two to four years of age they reach adult values. This developmental pattern is consistent with the extended period during which myelination of the pyramidal tract and development of spinal synapses occur (Martin, 2005; Ten Donkelaar et al., 2004).

Thus, a possible cortical involvement in the output of the newborn’s spinal motor centers seems to be present already in the newborn. Corticospinal synapses may even have the capacity to activate spinal targets prenatally (Eyre et al., 2000). Evidence for functional higher level influence on neonatal behavior has been found in terms of inhibition of stretch reflexes at spinal levels, influence on muscle tone and posture, antagonism of the effects of the ventromedial brainstem pathways (i.e., proximal extension and distal flexion), reinforcement of tactile reflexes, early mediating of individual finger movements, and relaying epileptic activity from the cerebral cortex (Sarnat, 2003). In addition, it has also been suggested that behavioral state (i.e., a product of supraspinal regulating centers) asserts a direct influence on the alpha motor neurons as shown by inhibition of muscle activity by a less active state of wakefulness (Casaer, 1979). However, the early corticospinal connections are still immature in terms of e.g. myelination and axonal sprouting at the time of birth. Even though these features already have started to develop prenatally, the corticospinal tracts are not considered to be entirely neuroanatomically developed until 2-3 years of age (Sarnat, 2003).

Evidence from primate studies show that the gradual development of the corticospinal system on a structural level parallels the development of relatively independent finger movements (e.g., Kuypers, 1962; Lawrence & Hopkins, 1976; Olivier, Edgley, Armand, & Lemon, 1997). A similar association between the maturation of corticospinal connections and improvement in finger movement skill is also apparent during human development. As early as 2 to 5 days after birth, human neonates display a variety of fractional finger movements (Rönnqvist & von Hofsten, 1994). In correspondence to the development of the corticospinal system the control of finger movements becomes increasingly advanced, and at about 9 months of age infants start using the pincer grip (von Hofsten & Rönnqvist, 1988). During the subsequent development, further improvements can be observed in terms of e.g. timing of precision grip (Olivier et al., 1997) and coordination of grip and loading forces (Forssberg, Eliasson, Kinoshita, Johansson, & Westling, 1991). Age-

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related changes in cortico-motor neuronal conduction times, as measured by TMS, have also been shown associated with the rate of performance on complex arm-hand movement tasks in children (Müller & Hömberg, 1992).

It has further been suggested that the development of the corticospinal system is critically dependent on motor experiences generated by movements of the limbs already from the very beginning of connectional specificity (Martin, 2005; Martin, Choy, Pullman, & Meng, 2004; Meng, Li, & Martin, 2004). That involvement of motor experience in the shaping of the corticospinal tracts is instigated early in the prenatal life is supported by the observation that most of the movements comprising the newborn repertoire are present already at 14 weeks of gestational age (Nijhuis, 2003). Thus, expressions of adaptive motor behavior reflect the maturation of the corticospinal system and the corticospinal system development is likely to be shaped by activity and motor experience. In a recent study, Erberich and colleagues (Erberich, Panigrahy, Friedlich et al., 2006) used functional magnetic resonance imaging (fMRI) to investigate the independent activation of the left and right hemispheric sensory-motor areas following passive stimulation of the hand in sleeping human neonates. They found an emerging presence of contralateral lateralization of the somatosensory system at around birth, suggesting that there is likely a critical period for the development of the neonatal sensory-motor system involving postnatal pruning and a refinement of the pathways and hemispheric lateralization during the postnatal period. As discussed in the present thesis, early motor asymmetries are possibly involved in this dynamic state (e.g. in terms of lateralized limb movements having an influence on the shaping of corticospinal connections), and the study of early expressions of side differences may contribute to the understanding of development and function of fundamental neural mechanisms from the beginning of life.

Infant motor asymmetries The origins of studying expressions of laterality in infant motor development can, in resemblance to motor control theory (see Motor control), also be traced back to the first half of the 20th century. For instance, Arnold Gesell, known for his detailed observations of infants and children in order to establish developmental norms, also documented expressions of laterality in young infants (e.g., Gesell, 1940). However, it is not until the last decades that early motor asymmetries have been

13

established as a unique phenomenon and a research area in its own right (Hopkins & Rönnqvist, 1998).

Observations of behavioral lateralization have been made as early as during the prenatal development from 10 weeks gestational age and onwards (Hepper et al., 1990; 1998). For instance, McCartney & Hepper (1999) found significantly more right-arm movements than left-arm movements in a longitudinal study of healthy human fetuses from 12-27 weeks’ gestation. These findings suggest that lateralized motor behavior is present in early gestation, initially under spinal or muscular control rather than cortical, thus foregoing later structural brain asymmetries rather than being a consequence of the same (McCartney & Hepper, 1999). Studies of motor asymmetries in newborns and infants cover a wide range of movements. Many of the early expressions of asymmetry studied have also been suggested as developmental precursors of later lateralized functions, especially movements of the upper body in relation to handedness (e.g., Michel & Harkins, 1986; Turkewitz, 1977). Thus, the trend has turned from regarding lateralized motor behavior as a consequence of cerebral specialization for cognitive functions (language mainly) to rather putting the focus on the role of early motor asymmetries in the development of functional cerebral specialization in general (Michel, 1998). In the following section, current knowledge of the relevant infant motor asymmetries is presented.

Head turning In 1947, Gesell and Ames reported the observation of human newborns’ preferential assumption of a right-sided head position when lying supine and with the head released from the body midline (Figure 1), and also related this to the development of right-handedness (Gesell & Ames, 1947). This early finding has continued to attract attention in modern time. The main reason for the common interest in head positioning in newborns is that the propensity for most fullterm newborns to turn their head to the right stands out as the most consistently observed neonatal functional asymmetry (Rönnqvist & Hopkins, 1998; 2000). Where studies of other expressions of motor asymmetries in newborns fail to find consequent lateral biases, the dominant right-sided posture of the head, both in terms of assumption and maintenance, has been repeatedly documented (e.g., Grattan, De Vos, Levy, & McClintock, 1992; Hopkins et al., 1987; Liederman, 1987; Rönnqvist & Hopkins, 1998; 2000; Turkewitz, 1977). Some studies have failed to replicate this finding (e.g.,

14

Saling, 1979; Trehub, Corter, & Shosenberg, 1983) but, as showed by Rönnqvist and Hopkins (1998), assessment procedure and type of scoring method used can possibly explain differences in findings of biased direction.

Figure 1. Newborn right-sided head turning in supine.

The head orientation preference of newborn infants is commonly regarded as included in the general preferential limb-flexed postural organization within the first 10 postpartum days (Casaer, 1979; Jouen, 1992; Michel, 1983). Neonatal limb flexion has been attributed to supraspinal influence (Peiper, 1963), although it is perhaps more likely a result of neuromotor tonus stemming from segmented reflexes partly conditioned by prenatal posture (Michel, 1983). Preferential head orientation has also been theorized as resulting from either supraspinal mechanisms (viz., asymmetrically lateralized activation of neuromotor mechanisms at different levels of the brain) or intrauterine position (Michel, 1981; 1983). However, as head turning movements from a midline position have been observed already in fetuses (Ververs et al., 1994), this would support a view of head orientation preference as neurally governed rather than being the result of intrauterine environment (Michel, 1983). Other explanations include hereditary factors (Liederman & Kinsbourne, 1980) and epigenetic mechanisms (Liederman, 1983; Butterworth & Hopkins, 1993), but there is today a general agreement that newborn head orientation preference reflects asymmetries in the neonatal nervous system (Rönnqvist & Hopkins, 1998).

In defining head turning, the differentiation between assumption (i.e., turning the head after midline release) and maintenance (i.e., keeping the head in the preferred posture) of head position, as described by Turkewitz

15

(1977), is important to consider as there is a discussion about whether they may constitute two separate functional asymmetries with different underlying neural mechanisms (Rönnqvist & Hopkins, 1998). Rönnqvist and Hopkins (1998; 2000) have carried out a series of methodologically advanced studies of healthy newborn head position preference, involving control of biomechanical constraints and the use of both global and specific scoring as well as kinematic measurements. Investigating preferences for both assumption and maintenance, they managed to find support for a neural origin that probably involves ipsilateral innervation and the muscles of the neck (posterior and sternocleidomastoid). They also found that lateral biases of newborn head positioning was strongly associated with behavioral state in that lateralized preference appears to be mediated by the state of the newborn (Rönnqvist & Hopkins, 1998; 2000). Behavioral state, or “level of arousal”, is generally a very important factor to monitor in studies of neonatal movement (Rönnqvist, 1993). Depending on the state of the newborn (ranging from State 1, quiet sleep without REM activity, to State 5, aroused and crying, according to Prechtl’s definition, see Prechtl, 1982, and also Behavioral state below), the motor responses vary in e.g. degree and intensity. Behavioral states thus appear to represent qualitatively different conditions of newborn CNS activity, shown for instance in relation to the Moro response (Rönnqvist, 1995). Furthermore, newborn postural behavior and position in space have also been related to state (Casaer, O’Brien, & Prechtl, 1973), which is a relationship that appears to be possible to further elaborate with regard to preferential head maintenance (Rönnqvist & Hopkins, 2000).

It has been suggested that neonatal right-sided head orientation preference is related to later right handedness, where the former is thought to facilitate the latter (Michel, 1981; Michel & Harkins, 1986). The rationale behind this association lies in the hypothesis that different visual experiences and neuromotor activity of the respective hand following head orientation possibly have a lasting effect on the cortical mechanisms underlying later hand use (Michel, 1983). For example, if the head is oriented preferably to the right in a newborn, she also looks at the right hand and activates the right hand more compared to the left. This, in turn, could result in better visuomotor coordination and consequent preference in favor of the right hand in e.g. later reaching for objects. However, the association between head positioning bias and handedness via experiences in the visual field has been questioned on several accounts. For example, the hypothesis fails to explain effects of biomechanical factors on head position preference and the fact that hand preference in

16

blind children and adults are similar to that in the sighted population. Another reservation concerns why the commonly observed sex difference in strength of lateralized hand-use (viz., females having a stronger right-sided preference than males) is not reflected in newborn head orientation preference (Hopkins & Rönnqvist, 1998; Rönnqvist & Hopkins, 1998).

Stepping and placing responses In studies of newborn infants’ motor asymmetries in leg movements, stepping and placing are two commonly employed responses. The stepping response is elicited by holding the infant upright under the armpits, lowering her towards a flat surface until the soles of both feet touch the surface and tilting her slightly forwards. The infant will then respond by making alternating steplike movements, characterized by a rapid flexion and a prolonged extension of the leg (Figure 2). Even though it may look like the infant is “walking”, the newborn stepping response is not the same as adult gait (in terms of joint movements and muscle activity, see Forssberg 1985). The placing response is elicited by holding the infant the same way as for stepping and lifting her so that the dorsum of the feet touches a vertical edge (e.g., the edge of a table). The response of the infant will be a flexion of one leg, moving it forward and finally placing it on the surface (Figure 3). Thus, this response is also similar to a walking step.

Figure 2. The newborn stepping response.

The neural substrates behind stepping and placing responses are not fully understood, although it is thought that there are different pathways underlying the two respective responses. It has been suggested that stepping occurs through stimulating afferent nerves situated at spinal levels S1 and S2 (by way of the footsole among other things) and by efferent discharges from lumbar-sacral segments (Taft & Cohen, 1967).

17

Placing, in contrast, is triggered by stimulation of the dorsum of the foot and has been claimed to derive from supraspinal mechanisms - initially via midbrain structures and then later in development through cortical mediation (Zapella, 1966). However, as placing can be elicited in hydroencephalic infants and newborns with a lesion of the spinal cord, it is more likely that this response also is primarily rooted at a spinal level (Forssberg, 1981).

Figure 3. The newborn placing response.

While many studies have addressed the issue of neonatal upper body functional asymmetries as potential precursors for later handedness, only a small number of studies have focused on the predictability of functional asymmetries in stepping and/or placing responses in relation to “footedness”. As a right-sided foot preference is an evident lateralized behavior in humans, as well as being strongly correlated with right handedness (Porac & Coren 1981), further investigation of this relation is justified. The studies that have been made of expressions of asymmetry in newborn leg responses to date show a lack of consistent evidence for a lateral bias (Table 1). In terms of stepping and placing, two studies have noted a right foot preference for stepping (Melekian, 1981; Peters & Petrie, 1979), two other studies did not find any lateral bias for stepping (Kamptner, Cornwell, Fitzgerald, & Harris, 1985; Thelen et al., 1982), and one reported no lateral bias for placing (Korczyn, Sage, & Karplus, 1978). Furthermore, in three other studies where both stepping and placing responses in the same newborns were observed, the same discordant pattern appears. A right foot preference for stepping but no preference for placing was found in one (Grattan et al., 1992), no preferred foot for stepping but a right-foot bias for placing in the second (Cioni & Pellegrinetti, 1982), and a left foot preference for stepping together with a right foot preference for placing in the third (Trehub et al., 1983).

18

The inconsistency of reported lateral biases in lower limb responses between these previous studies may partly be explained by differences in methodology and measurement. For instance, the behavioral state of the newborns and the manner by which the responses were elicited differ between the studies (or were not controlled). In Study I and II of this thesis, leg responses of newborn infants are investigated with an effort to refine both the methodology and measurement used. Furthermore, only one previous study has compared lower and upper body functional asymmetries (Grattan et al., 1992). Thus, Study I also includes analysis of stepping and placing responses in relation to head turning.

Tabl

e 1

Stud

ies

of n

ewbo

rn le

g re

spon

ses

with

rega

rd to

exp

ress

ions

of l

ater

ality

. Abb

revi

atio

ns: 2

-D =

two-

dim

ensi

onal

; 3-D

= th

ree-

dim

ensi

onal

; AG

A =

ap

prop

riate

for g

esta

tiona

l age

; F =

fem

ale;

FT

= fu

llter

m; G

A =

ges

tatio

nal a

ge; h

= h

our;

M =

mal

e; N

= n

umbe

r; PT

= p

rete

rm; S

GA

= s

mal

l fo

r ges

tatio

nal a

ge

Auth

or

Part

icipa

nts

Resp

onse

M

etho

d Re

sults

Ko

rczy

n et a

l., 19

78

150 F

T inf

ants,

age r

ange

: 1-3

da

ys

Plac

ing

First

foot

mov

ed (1

trial

) No

pref

eren

ce

Peter

s & P

etrie,

1979

24

infa

nts (

12F;

12M

), me

an

age:

17, 5

1, 82

and 1

05 da

ys

Step

ping

Fi

rst fo

ot m

oved

(3 tr

ials)

4 tes

t ses

sions

Ri

ght-s

ided

pref

eren

ce

Mele

kian

, 198

1 33

7 FT

infan

ts (1

74F;

163M

), ag

e ran

ge: b

irth (

0 h) -

1 we

ek

(5-9

days

)

Step

ping

Fi

rst fo

ot m

oved

(1 or

3 tri

als)

1-2 t

est s

essio

ns

Righ

t-sid

ed pr

efer

ence

Cion

i & P

elleg

rinett

i, 19

82

89 F

T in

fant

s (43

F; 46

M),

age

rang

e: 2-

4 day

s St

eppi

ng

Plac

ing

First

foot

mov

ed (4

trial

s) Fi

rst fo

ot m

oved

(4 tr

ials)

No pr

efer

ence

Ri

ght-s

ided

pref

eren

ce

Thele

n et a

l., 19

82

65 in

fant

s (29

F; 36

M),

mean

ag

e: 43

.2 h

State

: 1-6

(asle

ep-cr

ying)

Step

ping

Fi

rst fo

ot m

oved

(1 or

mor

e tri

als)

No pr

efer

ence

Treh

ub et

al., 1

983

12 F

T inf

ants,

mea

n age

: 3 da

ys

20 P

TAGA

infa

nts,

mean

age:

33, 3

4, 35

and 4

0 wee

ks G

A 20

PTS

GA in

fant

s, me

an ag

e: 33

, 34,

35 an

d 40 w

eeks

GA

State

: 4 (a

ctive

wak

eful

ness

), Pr

echt

l

Step

ping

Pl

acin

g, in

depe

nden

t sti

mulat

ion r

ight

/left

foot

First

foot

mov

ed (1

trial

) 4 t

est s

essio

ns fo

r PT,

1 fo

r FT

Ab

sent

or pr

esen

t res

pons

e (1

trial

) 4 t

est s

essio

ns fo

r PT,

1 fo

r FT

Left-

sided

pref

eren

ce (F

T)

No pr

efer

ence

(PT)

Ri

ght-s

ided

pref

eren

ce (F

T)

No pr

efer

ence

(PT)

Thele

n et a

l., 19

83

8 FT

infan

ts (5

F; 3M

), me

an

age:

2, 4,

6, 8,

10, 1

2, 14

, 16,

18, 2

2, 24

and 2

6 wee

ks

State

: 1-6

(asle

ep-cr

ying)

Spon

taneo

us ki

ckin

g in

supi

ne

Elec

troph

ysio

logi

cal (

EMG)

an

d beh

avio

ral (2

vide

o ca

mera

s) re

cord

ing

11 te

st se

ssio

ns

No pr

efer

ence

Kamp

tner

et al

., 198

5 38

FT

infan

ts (1

6F; 2

2M),

mean

age:

3, 16

, 32,

65 an

d 95

days

Step

ping

Fi

rst fo

ot m

oved

(3 tr

ials)

5 tes

t ses

sions

No

pref

eren

ce

19

Gra

ttan

et a

l., 1

992

36 F

T in

fant

s (18

F; 1

8M),

mea

n ag

e: 5

0 ±

4 h

Stat

e: 4

-6 (a

ctiv

e w

akef

ulne

ss-

cryi

ng),

Braz

elto

n

Step

ping

Pl

acin

g in

supi

ne,

inde

pend

ent s

timul

atio

n rig

ht/le

ft fo

ot

Mea

sure

of b

ehav

iora

l la

tera

lity

(MO

BL);

thre

shol

d,

onse

t lat

ency

, stre

ngth

, co

ordi

natio

n, h

abitu

atio

n (5

-po

int s

cale

for e

ach

para

met

er)

Righ

t-sid

ed p

refe

renc

e (s

treng

th, c

oord

inat

ion)

, no

pref

eren

ce (t

hres

hold

, ons

et

late

ncy,

hab

ituat

ion)

N

o pr

efer

ence

Piek

& G

asso

n, 1

999

7 FT

infa

nts (

2F; 5

M)

7 PT

infa

nts (

2F; 5

M)

mea

n ag

e: 4

, 8, 1

2, 1

6, 2

0 an

d 24

wee

ks

Stat

e: 4

(aw

ake,

ale

rt)

Spon

tane

ous k

icki

ng in

su

pine

2-

D k

inem

atic

mov

emen

t re

gistr

atio

n (M

acRe

flex,

Q

alisy

s); i

ntra

limb

coor

dina

tion,

pha

se la

g 6

test

sess

ions

Righ

t leg

: hig

her d

egre

e of

co

ordi

natio

n (a

nkle

-kne

e,

ankl

e-hi

p) a

nd le

ss p

hase

lag

(ank

le-k

nee)

Dom

ellö

f et a

l., 2

005

43 F

T in

fant

s (23

F; 2

0M),

mea

n ag

e: 6

4.9

h St

ate:

3-5

(qui

et w

akef

ulne

ss-

cryi

ng),

Prec

htl

Step

ping

Pl

acin

g

Firs

t foo

t mov

ed (3

tria

ls),

onse

t lat

ency

(fra

me-

by-

fram

e vi

deo

anal

ysis)

Left-

sided

pre

fere

nce

(sho

rter l

aten

cy),

no

pref

eren

ce (f

irst f

oot m

oved

) Sa

me

as fo

r ste

ppin

g

Dom

ellö

f et a

l., su

bmitt

ed

40 F

T in

fant

s (17

F; 2

3M),

mea

n ag

e: 6

5.7

h St

ate:

3-5

(qui

et w

akef

ulne

ss-

cryi

ng),

Prec

htl

Step

ping

3-

D k

inem

atic

mov

emen

t re

gistr

atio

n (P

roRe

flex,

Q

ualis

ys);

velo

city

, ver

tical

di

spla

cem

ent,

mov

emen

t un

its (M

U),

intra

limb

coor

dina

tion,

pha

se sh

ift

Left

leg:

hig

her p

eak

velo

citie

s, m

ore

MU

s Ri

ght l

eg: h

ighe

r deg

ree

of

coor

dina

tion

(ank

le-k

nee)

an

d le

ss p

hase

shift

(ank

le-

hip,

kne

e-hi

p)

20

21

Arm and hand movements The development of hand preference is an intriguing topic that for decades has been the focus of many developmental studies. Following Gesell and Ames (1947), research on reaching behavior during infancy has provided important contributions to present knowledge of the development of hand preference (see Hopkins & Rönnqvist, 1998, for a review). However, the question of how hand preference develops is still not fully answered. As previously described (see Introduction) many explanations for the origins of human handedness have been suggested, mainly linking early asymmetries and later handedness to either inheritance or early acquired biased perceptual-motor experience.

Perhaps the most well-known genetic model is Annett’s right shift theory. In short, this theory suggests that there is a single right shift gene (RS+) that weakens cortex related to speech in the right hemisphere and promotes a dominant left hemisphere for speech. As a consequence of this, left handedness becomes less occurring on behalf of an increased probability for right handedness. If the right shift gene is absent (RS-), there is an equal chance of left or right hemispherical dominance for speech/handedness (Annett, 1985). The right shift theory is attractive as it fits closely with relative proportions of right- and left-handers in relation to various combinations of parental handedness (also when considering the effects of developmental deviations or brain injuries). Annett’s model and other genetic models (e.g., McManus & Bryden, 1993) thus provide an apparently convincing account for familial handedness in the development of hand preference and relative manual skill. However, a genetic model such as the right shift theory may have a good fit with hand preference traits but still not be the whole explanation, as there might be multiple genes involved as well (Corballis, 1997). Furthermore, the biased gene model assumes that there is a 50% frequency of dominant and recessive alleles in humans which is not a proven fact. Other shortcomings that have been pointed out in relation to the right shift theory are that there is no linking of the model to newborn functional asymmetries (in the role of precursors for later hand preference), and the lack of support for the assumption that handedness has evolved as a consequence of cerebral speech lateralization (Hopkins & Rönnqvist, 1998).

The other main line of explanation suggests that the origins of human lateralization lie in the early expressions of postural and motor asymmetry, and, furthermore, that these early asymmetries are likely to reflect asymmetries in the neonatal nervous system. Michel’s (1981) biased head

22

model (see Head turning) is one example of epigenetic models that relate early postural asymmetries (i.e., newborn lateralized head orientation) to later hand preference. Another way of approaching this issue is to look even deeper and focus on the origins of these postural asymmetries. One theory is that fetal intrauterine and birth position may exert an influence on later posturally based asymmetry. The most common birth position is the so called left vertex position, where the fetus lies with the back to the mother’s left side with the right side of the head facing outwards. An interesting result of this position is that it is likely to facilitate e.g. right arm-hand movement and induce asymmetrical forces (Hopkins & Rönnqvist, 1998). Previc’s (1991) left-otolithic dominance hypothesis suggests that, in the left vertex position, the left otolith gets more stimulation by hair cells as it registers the sharper backward deceleration as compared to forward acceleration when the mother walks (due to the braking effect). This, in turn, leads to more impulses to the brain stem terminating on the vestibulospinal tract (i.e., uncrossed, ending on spinal cord interneurons for ipsilateral control of extensor muscles). As studies of newborn head position preference point to a neural origin, probably involving ipsilateral innervation and the posterior and sternocleidomastoid muscles of the neck (Rönnqvist & Hopkins, 1998; 2000), it may be the case that head turning to the right is driven by the left bilateral sternocleidomastoid as enhanced according to Previc’s left-otolithic dominance hypothesis (Hopkins & Rönnqvist, 1998). Asymmetries in early arm-hand movements have also been suggested as precursors of later hand preference. As previously mentioned (see Infant motor asymmetries), Hepper and colleagues have explored upper body asymmetries in the human fetus in utero, claiming that behavioral lateralization is present as early as from 10 weeks gestational age (Hepper et al., 1990; 1998; McCartney & Hepper, 1999). In a recent follow-up study, it was also found that previously observed prenatal lateralized behavior, in its expression as thumb sucking at 15 weeks, could be related to handedness at 10-12 years of age (Hepper, Wells, & Lynch, 2005). However, it should be noted that others have failed to replicate the findings by Hepper et al. of a stable right-sided preference for arm activity and thumb sucking (e.g., de Vries, Wimmers, Ververs et al. 2001).

Whatever the explanation for the origins of hand preference may be, it is difficult to find any straightforward associations between behavioral asymmetries in the very beginning of life and the direction of hand preference at later ages. In keeping with high variability as a typical characteristic of infant motor output (Piek, 2002; Thelen, 1995), a common result in studies devoted to age-related changes in hand use in

23

infant reaching movements (Figure 4) is that lateral biases are markedly inconsistent and unstable during at least the first two years of life (e.g., Corbetta & Thelen, 1999; Fagard, 1998; Fagard & Lockman, 2005; Gesell & Ames, 1947; Thelen, Corbetta, & Spencer, 1996). These fluctuations concern hand preference as well as the use of one or both hands in reaching and grasping tasks. Also frequently noted is that the reaching strategies of young infants vary both within and between test sessions. At about 3-4 years, hand preference typically begins to stabilize in its adult form, although the strength of handedness (i.e., as determined by hand skill) may increase with time (e.g., McManus, Sik, Cole, Mellong, Wong, & Kloss, 1988). It has been demonstrated that fluctuations in handedness may still be present at this age (e.g., Bryden, Pryde, & Roy, 2000; Fagard & Lockman, 2005), but the age of 3 years seems to mark the beginning of a distinct increase in preferential right-hand use. As judged by questionnaire data, both hand and foot preferences seem to be manifested in 6-year-old children (Domellöf & Rönnqvist, 2004). These preferences were also found positively associated in about 70% of the children, well in keeping with findings of lateralized patterns in adults (see Porac & Coren, 1981).

Figure 4. 3-year-old boy performing a reaching movement.

How can the shifts and fluctuations that seem to characterize hand preference in infant reaching be explained? According to the literature, part of the answer may be found in influencing factors such as developmental changes in organization and control of arm-hand movements, postural control, learning to walk, experiences of carrying out actions in a right-sided world, or even constraints of the reaching task.

24

Accurate reaching and grasping of an object involves two major motor components: transporting the hand to the object and configuring the fingers to a grip that is suitable for picking it up. It has been suggested that these components are associated with two structurally and functionally different sensory-motor systems: one for object approach, mainly related to arm movement and visual properties; and one for object grasping, mainly related to the specialization of the hand and proprioceptive properties (Jeannerod, 1997). Object approach involves encoding the location of the object and adjusting the direction and amplitude of the arm movement for optimal reaching. Object grasping requires coding of the intrinsic properties of an object, i.e. size, shape and orientation, which will influence the shaping of the hand prior to the encounter with the object. In terms of neural organization, both systems imply visuomotor transformation and rely mainly on the dorsal corticocortical system for object-oriented action (Jeannerod, 1997, see also The motor system). Developmentally, the approach system emerges before the grasping system. In the beginning of life, the newborn infant can be observed extending the arms towards a visible object. At about 2 months of age the infant seems to be able to differentiate hand movement from approach (i.e., making a fist as the arm extends). At around 4 months of age, infants start to reach and grasp for objects seen within grasping range, indicating that both differentiation and integration of the approach and grasping systems are at least partially present (von Hofsten & Rönnqvist, 1988).

Developmental studies using the kinematic registration technique have provided an informative insight into the kinematic characteristics of reaching movements during infancy (e.g., Thelen et al., 1996; von Hofsten, 1991). In a series of studies, von Hofsten and colleagues have extensively explored the reaching trajectory, object approach and grasp preparation from a developmental perspective (von Hofsten, 1979; 1980; 1983; 1991; von Hofsten & Fazel-Zandy, 1984; von Hofsten & Lindhagen, 1979; von Hofsten & Rönnqvist, 1988; 1993). In terms of reaching trajectory, the velocity profiles can be used to divide the trajectory formation of arm movements into units. The segmentation of the reaching trajectory by means of spatially defined movement units (MUs) is based on the principle of acceleration and deceleration patterns being linked to the control of movement, supported by findings that curvature peaks typically coincide with speed valleys which mark a change in movement direction. Speed-curvature coupling indicates an ability to calibrate arm movements in reaching space that seems to be present already at birth, possibly originating from isolated fetal arm movements in

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utero (von Hofsten, 1992). Reaching movements in adults when approaching an object consist typically of two MUs, one large unit for transporting the hand to the object, and one smaller unit for adjustment in order to grasp the object (e.g., Jeannerod, 1984). Von Hofsten et al. have been able to demonstrate a distinctive developmental change with regard to this organization during the months after acquired reaching and grasping ability (i.e., at about 4 months of age). The transition that occurs is characterized by a more systematic placement of the transport unit, an increase in duration of the transport unit, and a decreasing number of MUs within the reach with a related straightening of the reaching trajectory. The ability for smooth visually guided grasping preparations, in terms of adjusting the hand to the shape, size and orientation of the target object and anticipatory timing, is also subjected to developmental change. Rudimentary preparatory adjustments of the hand to the orientation of the object can be found in the reaching of 5-month-old infants, with an apparent progressive improvement following after 6 months of age. Even newborns can be observed opening the hand during object approach, although adjustments of the opening to the size of the target are not evident before 9 months of age. A third developmental pattern concerns visually controlled timing of the grasp. Well-timed grasping as expressed in closing of the hand relative to object encounter is present already in 5-6-month-old infants. However, the onset of closing during the approach phase is typically found in close proximity to the object. At 13 months of age, infants display a closing of the hand at a larger distance from the object, implicating a more adult-like integration and synchronization of approach and grasp.

Thus, as early as by 31-36 weeks of age the kinematic properties of infant reaching movements begin to resemble adult reaching in terms of movement segmentation as well as anticipatory planning and initiating of a grasp. As pointed out by von Hofsten (1992), the development of reaching and grasping serves as a good example of phylogenetically given prospective abilities that help assembling and organizing this system through interactions with the environment. Thelen and colleagues have confirmed and expanded these findings in demonstrating the impact of biomechanical constraints on the developing arm control in infants, suggesting that motor constraints play an important part in explaining developmental patterns with regard to reaching and grasping (e.g., Corbetta & Thelen, 1996; Corbetta, Thelen, & Johnson, 2000; Thelen et al., 1996). For instance, the fact that infants by 9 months of age are able to make effective and flexible reaching movements, scaled to the size, shape and orientation of the perceived object, is likely a reflection of the

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greater motor capabilities available at this age allowing a better matching of perception-action (Corbetta et al., 2000). By 2 years of age, the smooth, bell-shaped velocity profiles observed in adult reaching kinematics (i.e., stereotyped reaching) is attained (Konczak & Dichgans, 1997), but “fine-tuning” in terms of e.g. grip aperture and use of visual information during different conditions appears still to be developing in children aged 9-11 years (Pryde, Roy, & Campbell, 1998; Watt, Bradshaw, Clarke, & Elliott, 2003).

Although not as many studies have been devoted to infant reaching with regard to laterality, especially by means of kinematic registrations, there are several interesting parallels between findings from age-related developmental studies and those focusing on lateral biases in infant reaching behavior. The acquisition of increased motor capability and control is intimately related to the development of postural control (see e.g., Thelen & Spencer, 1998, and also Postural control below). Hopkins and Rönnqvist (2002) showed that providing additional postural support for 6-month-old infants who had not yet acquired the ability to sit independently resulted in a facilitation of the control of reaching movements as expressed in kinematic parameters. Corbetta and Thelen (1996) also suggested that changes in interlimb coordination as well as lateral preference in reaching movements during the first year of life could be influenced by changes in postural control. The ability to sit alone has been associated with an increase in one-handed reaching as opposed to reaching more with both hands at younger ages, although hand preference may fluctuate (Rochat, 1992). This finding also pertains to the onset of crawling at about the same age (Corbetta & Thelen, 1999). The onset of walking independently seems to mark a return to bimanual reaching strategies, coinciding with a disappearance of lateral tendencies between 6 and 12 months of age (Corbetta & Thelen, 1999).

It thus seems as the process of acquiring a new postural skill may influence or even disrupt stability of hand preference. This suggestion has been further elaborated in terms of taking task constraints such as object size, manipulation, the precision required for grasping, and task difficulty into consideration. Grasping for large objects has been associated with more bimanual behavior than grasping for small objects in infants aged 7-13 months (Fagard & Jacquet, 1996). At about 9-10 months of age, there is an improvement in asymmetrical bimanual manipulation skill. It has also been demonstrated that patterns of hand preference seem to be more clearly expressed in bimanual manipulation compared to simple grasping tasks, particularly at ages when bimanual manipulation still is challenging for the infant (Fagard & Lockman, 2005; Fagard & Marks, 2000). In

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addition, variability in hand preference for grasping has been shown to decrease when the grasping requires precision, favoring a more consistent use of the right hand compared to the left, but increasing when the object encourages exploratory behavior (Fagard & Lockman, 2005). These findings suggest that variability in infant handedness may reflect general variability in motor behavior, effects of postural maturation, and competition from developing motor skills; but degree of variability also seems to be dependent on level of task constraint.

Independent of the possible factors affecting lateral tendencies such as those mentioned above, early lateral biases that are congruent with later hand preference are still found in studies of early infant arm-hand movements, particularly those involving more refined registration techniques. For instance, Corbetta and Thelen (1999) found that during the first year, infants went through periods where predominant rightward biases persisted in both hand preference in reaching and lateral biases in the velocity profiles of spontaneous nonreaching arm movements consistent with a right-handed preference in the same children at the age of 3 years. In the study by Hopkins and Rönnqvist (2002), it was demonstrated that, unrelated to degree of postural support, there was a lateral bias in terms of movements of the right arm containing fewer MUs than movements of the left arm. As there is a developmental progression from pronounced segmented arm movements early in life toward increased smoothness and straightness during reaching (von Hofsten, 1991; von Hofsten & Rönnqvist, 1993), fewer MUs are an indication of refined control and maturity of arm movements. However, Hopkins and Rönnqvist (2002) could not find any preferential bias in terms of hand contacting the object. Early manifestations of lateral biases in reaching movements could thus mainly be associated with an arm preference, rather than a hand preference. This would also be in keeping with the development of the ventromedial pathways, involving ipsilateral control of the proximal arm muscles, emerging before the development of the direct corticospinal connections, contralaterally controlling the fingers (see Development of the motor system). Although, as concluded by Hopkins and Rönnqvist (2002), it is difficult to tell how a functional lateral bias in the ventromedial system can bring about a lateral bias in the functioning of the corticospinal system, partly due to the lack of a full understanding of the development of the motor systems.

Clearly, the fluctuating lateral biases in infant reaching movements is a puzzling issue. In the continuing exploration of this phenomenon, the use of kinematic measurement technique seems to be promising as it stands out as a sensitive tool for detecting symmetries expressed in kinematic

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parameters of arm and hand movements. More longitudinal studies, enabling observations of developmental changes or stability in lateral patterns, would also be rewarding. To date, longitudinal studies involving quantitative assessment of reaching movements in infants with a focus on patterns of laterality are rare. This may, at least in part, be explained by the many challenges involved in such endeavors. Study III constitutes one new addition to this research effort. In this study, the existence of lateral biases in the kinematics of infant reaching movements is investigated longitudinally from 6-36 months, contributing to the understanding of asymmetries in the arm-hand movements of developing infants.

Clinical implications As stated in the Introduction, apart from the theoretical interest in learning more of the developing sensory and motor pathways in relation to functional asymmetries in young infants, this type of knowledge is also of clinical relevance. The following section aims to explain this statement in more detail.

Insult to the developing brain The formation and development of the CNS is very complex and there are several vulnerable periods when disruptions in terms of malformations, injury or trauma may occur. Such disorders could cause deviations in the functional state of the sensory and motor systems and consequently have an impact on the acquisition of motor skills. The corticospinal tract is a main central motor pathway that develops over a comparatively long time period. During the course of this development, the corticospinal system is susceptible to a wide range of malformations such as disorders of neurogenesis, neuronal migration of the cerebral cortex, axon guidance mechanisms, and white matter injury (Ten Donkelaar et al., 2004). Given the suggested activity-dependent nature of the system’s development, this process may also be vulnerable to functional deviations in terms of activity blockade and limb disuse (Martin, 2005).

Cerebral palsy (CP) is a common result of insult to the developing brain causing mild to severe disturbances in the voluntary control and coordination of movements. Clinically, the term CP refers to a group of neurological disorders of three principal forms (viz., spasticity, dyskinesia, and ataxia), corresponding to a variety of abnormal motor patterns

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affecting different parts of the body. In addition, children with CP also may have associated problems such as mental retardation, epilepsy, visual impairment, hearing or language problems, and perceptual-motor dysfunctions (Hopkins, 2002). Thus, CP is a very general term and the neurodevelopmental outcome is difficult to predict. In terms of motor functioning, CP-related brain damage implicates a modulation of functional neural connections during CNS maturation resulting in motor incoordination. Repeated uncorrelated movements may then reinforce these disordered or inappropriate neural connections later in development. The diagnosis of CP is not made until a child displays movement difficulties that seem unlikely to be resolved (e.g., failure to achieve developmental milestones). Despite modern advances in brain imaging methods, it is not always possible to reveal or define early damage to the brain. Prenatal or perinatal insults to the CNS may therefore not be exposed until confirmation of functional deviations in motor performance during the first years of life. Furthermore, even if an injury is evident, it is difficult to accurately predict delays or deviations in motor skill development (Myklebust & Gottlieb, 1997). Thus, there is a general agreement across disciplines with regard to the significance of finding methods for early measurement and identification of potential risk factors for neurologically based motor impairments such as CP. This would, in turn, facilitate strategies for early therapeutic interventions, of major importance to reduce the effects of impaired motor performance and functional deficits in the developing child.

A specific population at-risk for developing CP and other various motor and/or cognitive problems is preterm children. Preterm birth (especially extreme preterm birth, i.e. < 26 weeks gestational age) is associated with an increased likelihood of injury to the developing brain and subsequent neurodevelopmental problems later in life. The brain tissue found to be most vulnerable to injury includes the fragile area surrounding the ventricles (e.g., Peterson, Anderson, Ehrenkranz et al., 2003; Roelants-van Rijn, Groenendaal, Beek et al., 2001) and related white-matter (Kuban, Allred, Dammann et al., 2001). This is a region where the motor fibers through which the brain communicates with the arms and the legs pass, and, accordingly, movement difficulties affecting the upper and/or the lower extremities is a frequent consequence of brain injury in the preterm infant (see Cioni, 2003, for a review). Two of the more common forms of brain disorders underlying neurodevelopmental handicaps in surviving preterm infants are periventricular leukomalacia (PVL) and bleeding into the ventricles (i.e., intraventricular hemorrhage, IVH) (Haynes, Borenstein, Desilva et al., 2005; Kuban et al., 2001). PVL

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is a specific condition which refers to cell death of the white matter behind and to the side of the lateral ventricles, primarily affecting afferent motor pathways (Hoon, Lawrie, Melhem et al., 2002). The condition is strongly associated with impaired movement, especially of the legs, and is frequently seen with severe IVH. Severe IVH (with or without leukomalacia) is associated with increased risk of later movement problems and deviations as well as other developmental problems. Both conditions are considered to be strong predictors of CP, although, as pointed out above, even in the case of severe PVL or IVH it is complicated to predict the extent of motor impairment with accuracy.

Kinematic registration as a potential tool for early diagnosis In the present thesis, two contributions to improvements in the early detection, diagnosis and understanding of the emergence of neurological dysfunctions such as CP are suggested. The first is related to the main measurement technique used. 3-D optoelectronic registration provides a detailed picture of the spatial and temporal character of early limb movements, as well as their timing and sequential partition. Qualitative abnormalities of spontaneous motor activity (as revealed by a poor movement repertoire) seem to be among the best early predictive markers for neurological deficits resulting from perinatal brain lesions (e.g., Ferrari, Cioni, Einspieler et al., 2002; Prechtl, Einspieler, Cioni et al., 1997), as well as for predicting later dyskinetic movement patterns related to cerebral palsy (e.g., Cioni, 2003; Einspieler, Cioni, Paolicelli et al., 2002; Hadders-Algra, 2004). Quantitative measurements of the quality and repertoire of early movements have further been shown as a promising refinement in terms of detecting infants at-risk of disabilities (see Piek, 2001, for a review). Kinematic recordings of movement patterns (e.g., reaching and grasping) in newborns and young infants generate very precise information in relation to movement performance and how it changes over age (e.g., von Hofsten & Rönnqvist, 1988; 1993). However, kinematic measurements for investigation of how early movement impairments and delays emerge in children are still rare. Study III includes kinematic analyses of goal-directed arm and hand movements in 6 to 36 months old infants born both term and preterm. The findings suggest that a quantitative approach may be useful in detecting developmental deviations or delays, and kinematic movement registration could prove to be an important method in the continued investigations of early brain function and deviations. As it is not uncommon that children with no

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apparent insult to the brain develop motor problems such as CP at later ages, this type of refined measurement is highly advantageous in providing a means to learn more about the salient features that might be causing deviant motor behavior for proper diagnosis and treatment at an early stage.

The second contribution is the focus on development of functional asymmetries in sensory-motor performance. Adhering to the arrogation that kinematic measurement is a sensitive tool for tapping into the processes underlying typical as well as deviant motor outcomes in children at different ages, it would also be a valuable instrument for investigating the same processes in terms of movement-based asymmetries. Indeed, kinematic registration has proved rewarding for detailed quantitative investigations of movements in infants and young children in relation to subtle expressions of functional asymmetries (e.g., Hopkins & Rönnqvist, 2002; Rönnqvist, 1995; Rönnqvist & Hopkins, 2000). Study II of the present thesis is devoted to exploration of functional asymmetries in the kinematics of leg responses in the healthy newborn, important for a better understanding of the early development of underlying mechanisms involved in movements of the leg. Such increased knowledge could, in turn, prove to be of great clinical value in the early diagnosis and treatment of developmental disorders. For instance, one hypothesis about how PVL relates to spastic diplegia (a subtype of CP) is that the lesion, usually bilateral, damages the medial fibers, thus affecting the pathways from the motor cortex to the lower extremities (Hopkins, 2002). As the course of early activity-dependent development in the corticospinal system may be susceptible to functional divergence, this may also apply to deviations in side-related behavior. Complications following preterm birth may impair the functional state of the corticospinal system, which could be reflected in deviant expressions of functional asymmetries. Support for such a suggestion can be gained from the consistent finding that left- and non-right-handers are overrepresented in ex-preterm children (e.g., Marlow et al., 1989; O’Callaghan et al., 1993a; 1993b). Normative kinematic studies will aid in informing us about the nature of typical functional asymmetries and their neural origins in young infants, which is important in order to be able to recognize deviations that may be related to later impairments. Kinematic measurements for investigation of how early movement impairments and delays emerge in children are still rare. However, kinematic analysis has proved to be promising for investigating e.g. reaching in children with neurological dysfunctions (e.g., Chang, Wu, Wu, & Su, 2005; van der Heide, Fock, Otten, Stremmelaar, & Hadders-Algra, 2005), or born at-risk for such dysfunctions (e.g., Fallang,

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Saugstad, Grøgaard, & Hadders-Algra, 2003; Vaal, van Soest, Hopkins, Sie & van der Knaap, 2000). Thus, involving both term and preterm infants in longitudinal studies of lateralized differences in early movement patterns, as done in Study III, is likely to generate further knowledge in providing information about stability and differences in patterns of laterality depending on birth condition.

RESEARCH OBJECTIVES Even though much has been achieved in investigating early expressions of laterality in newborn infants’ motor responses, it is still a comparatively young research area. Thus, a lot of questions remain to be answered with regard to the developmental origins of laterality and what neural mechanisms that subserve early functional asymmetries. These questions are theoretically important, but may also be of great clinical relevance in terms of early diagnosing and management of neurodevelopmental deviations (see Clinical implications). The rationale for the present thesis is to address these questions with regard to functional asymmetries in the upper and lower body of neonates and young infants.

In the first study presented in this thesis, the function of the nervous system in healthy fullterm newborns with regard to asymmetries in the lower body in relation to head turning was explored, while at the same time including a focus on effects of methodological factors in this type of research. In the second study, 3-D optoelectronic movement registration technique was employed to detect kinematic side differences in newborn stepping responses. Picking up the thread from the first study, the aim was to investigate whether such a refined methodology would allow a greater insight into the underlying control mechanisms subserving asymmetries in newborn leg movements. In the third study, focus was turned to side differences in upper limb movements of young infants. The same measurement technique as in the second study was used to longitudinally explore the kinematic characteristics of right and left reaching movements in infants over the ages 6, 9, 12, and 36 months (including four preterm infants), with the aim to add further to the understanding of the developmental origins of lateralized arm-hand function.

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Main research questions

• Is there a right-sided preference for the assumption of a head position after release from midline? (Study I)

• Do stepping and placing both manifest a preferential asymmetry in terms of the first foot moved? (Study I)

• Are lateral biases in head turning, stepping and placing congruent or discordant with each other? (Study I)

• Are left-right asymmetries in stepping and placing manifested by differences in onset latency times? (Study I)

• Are preferential asymmetries in head turning, stepping and placing associated with an active or inactive condition? (Study I)

• Are there left-right differences in leg mass and, if so, do they relate to asymmetries in stepping and placing such that the less heavy leg is not only the first one to move, but also has the shorter latency? (Study I)

• Do newborn stepping responses manifest side differences in terms of spatio-temporal parameters as attained by means of the tangential velocity profiles and/or movement trajectories of the legs? (Study II)

• Are there side differences related to the movement segmentation of stepping responses as captured by the number of movement units (MUs)? (Study II)

• Does the stepping response manifest a lateral bias in terms of intralimb coordination as measured by cross-correlations between the velocity profiles of the three joints of each leg? (Study II)

• Are asymmetries in stepping kinematics associated with an active or inactive state? (Study II)

• Does a lateral preference exist in terms of the frequency of arm/hand-use during successful reaching-grasping in young infants? (Study III)

• How do young infants’ right and left reaching movements differ in terms of spatio-temporal organization and structuring? (Study III)

• If a side difference exists already at 6 months of age in terms of less segmented and smoother reaches by the right arm, how consistent is this side difference over the second half of the first year? (Study III)

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• How are the kinematic characteristics of right-left reaching movements related to the infants’ actual choice and frequency of arm/hand-use? (Study III)

• How is hand preference for different arm/hand activities at 36 months of age related to the kinematic characteristics of right and left reaches during the second half of the first year? (Study III)

• Do kinematic characteristics and side differences in reaching movements diverge depending on birth condition? (Study III)

METHODS

Participants

Study I and II Study I and II were carried out at the nursery ward of the Umeå University Hospital. Forty-three healthy fullterm newborns (23 females and 20 males), of 37-42 weeks gestational age (M = 39.6) participated in Study I, tested at the postpartum age of 48-96 hours (M = 64.9). The participants of Study II consisted of forty healthy fullterm newborns (17 females and 23 males), with gestational ages ranging from 37-41 weeks (M = 39.6), and tested between the postpartum ages of 48-96 hours (M = 65.7). The criteria for selection of all newborn participants were: singleton pregnancy, no medical complications during pregnancy, vaginally delivered, a 5-minute Apgar score of 8 or more, and no evidence of fetal growth restriction. Both studies involved informed consent from the parents and were approved by the local medical ethical committee at the Faculty of Medicine, Umeå University.

Study III Study III was executed in a laboratory room at the Department of Psychology, Umeå University. Seventeen healthy infants (3 females and 14 males), with no known sensory, motor or neurological impairments, participated in the study. Thirteen infants were fullterm of 38-42 weeks gestational age (M = 40.2), and four were prematurely born of 33-36

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weeks gestational age (M = 35.1). The children were brought to the laboratory room by their parents at the ages of 6 (M = 6.2), 9 (M = 8.9), 12 (M = 12.1), and 36 months (M = 35.2). For the last testing session (36 months), the number of returning participants was reduced to sixteen as one family had moved out of town. Study III was approved by the Ethical Review Board of the Swedish Council for Research in Humanities and Social Sciences, and all parents gave their informed consent.

Design Study I and II are cross-sectional (between-subject) studies, aimed to study typical expressions of functional asymmetries in healthy fullterm newborn infants. Study III is of a longitudinal (within-subject and between ages) design, following the same children over four points in time to observe developmental changes in patterns of laterality. As four of the children participating in Study III were prematurely born, comparisons in side-related kinematic behavior could also be made depending on birth condition (fullterm vs. preterm birth). All studies were carried out in controlled experimental laboratory settings.

Apparatus and measurements The testing sessions of Study I and II took place in a warm (25 ± 2˚C), quiet and dimly-lit room. Additional care was taken to optimize clear-cut observations by using e.g. a surrounding screen blocking unwanted sources of lateral stimulation, and a non-slip cloth for the stepping surface (Figure 5).

In Study I, a T-shaped bar had also been designed for precise eliciting of the placing response (Figure 5). In addition, a specially-made boxlike screen was used for optimal testing of head turning. Furthermore, in order to control for behavioral state and leg mass being associated with expressed asymmetries, we also monitored the infants’ state during testing and conducted anthropometic measurements for calculation of the volume of the respective leg of each newborn. Elicitation of the responses were done according to the standard procedure for each response (see Background), with care taken to avoid confounding of expressed asymmetries (e.g., no diapers, postural support during head turning, both feet touching surface or bar at the same time). All sessions were video recorded, allowing later

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verification of on-line notations of leading foot, as well as coding for behavioral state and latency times of the stepping and placing responses.

Figure 5. Set-up for eliciting stepping and placing in Study I. The same set-up was used for eliciting stepping in Study II, although with an additional six cameras for kinematic registration (three on each side of the table).

A six-camera (240 Hz) optoelectronic registration system (ProReflex, Qualisys Inc., Gothenburg, Sweden) was used to capture three-dimensional (3-D) kinematics in Study II and III. ProReflex is an advanced system for highly accurate motion measurement. Each camera of the system is equipped with a bank of diodes emitting infrared light which is returned by passive, reflective, low-weight markers. This process allows the cameras to collect very precise 2-D marker position data in real-time that is subsequently combined and transformed into 3-D coordinates by the system software.

In Study II, the data were sampled at a frequency of 120 Hz (frames per second). The cameras, rigidly mounted on tripods, were situated on the left and right side of the infant, three on each side of the table. Six

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spherical reflective markers (12 mm3), each glued to a soft rubber plate (2 cm3), were mounted bilaterally on the newborn’s left and right leg. The following anatomical sites were used (Figure 6): the greater tronchanter (hip), lateral condyle (knee), and about 5 cm above the malleolus (ankle). 3-D data were generated by a MacReflex 3.3 system software, smoothed by means of a second-order 12 Hz dual pass Butterworth filter, and analyzed in MATLAB (The MathWorks Inc., Natick, MA, USA). Additional video recordings were made of all sessions for comparisons with the kinematic recordings, as well as coding of behavioral state and leading leg at the start of the response.

Figure 6. The anatomical sites for marker attachment in Study II, denoting the three joints of the leg (from the top: ankle, knee, and hip).

In Study III, data were sampled at a frequency of 240 Hz. Two cameras were mounted on a rail structure rigidly attached to the ceiling above the testing area, and four were arranged on tripods in a half circular fashion in front of the infant. Two soft rubber bracelets, each with a spherical reflective marker (10 mm3) fixated to it, attached to the respective wrist, were used to measure right and left reaching movements. Reflective tape (width = 1 cm) was fastened on the base-construction of every object used to obtain an exact time indication for hand-object touch. The infants were seated in an age-appropriate chair, at an

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individually adjusted comfortable reaching distance from the object. At 6, 9, and 12 months, a displayer allowing presentation of an easily graspable spherical object (diameter = 4 cm) in a right, left, or midline position was used. At 36 months, the objects consisted of a selection of pegs (height = 10 cm; diameter = 1.2 cm), each with a reflective half-spherical marker (1 cm3) fastened to the top, and placed in a pegboard at right, left, or midline position. A MacReflex 3.2 system software was used for transformation of 2-D to 3-D data, and derived parameters were filtered with a second-order 10 Hz dual pass Butterworth filter prior to MATLAB analysis. Supplementary video recordings were made of all sessions. These recordings were used for comparisons with the kinematic recordings, most importantly in supporting identification of the precise onset of reaching movements and first hand to contact the object. From the video it was also possible to tell successful from non-successful reaches.

Methodological considerations When setting out to explore early motor behavior, e.g. in relation to functional asymmetries, it is vital to consider the observation techniques and methodology used. In order to get reliable results, there are factors affecting the performance of infants, perhaps neonates in particular, which need to be controlled. In addition, as discussed in the present thesis, the use of optoelectronic technique when exploring early functional asymmetries is likely to generate data of great relevance to the posed research questions. However, there are several problems associated with applying this type of measurement technique to infant studies that are important to accentuate.

Behavioral state As mentioned above (see Head turning), one factor of critical importance to the outcome of infant studies is behavioral state, or “level of arousal”. The term behavioral state refers to the human patterns of rest and activity that seems to be of a particular nature during the first weeks after birth. According to one common definition (also the one followed in Study I-III), neonatal behavioral state can be divided into five conditions (Prechtl, 1977): State 1, eyes closed, regular respiration, no movements; State 2, eyes closed, irregular respiration, no active movements; State 3, eyes open, regular respiration, no active movements, relaxed; State 4, eyes open,

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active movements, fully cooperative, anticipating, not crying; State 5, eyes open or closed, irregular respiration, gross movements, crying. This and other taxonomies of states are based on both behavioral observations (e.g., respiration, movement) and observations by means of electrophysiology (e.g., electroencephalogram, EEG, electrocardiogram, EKG, and electromusculogram, EMG). Thus, state has been demonstrated as manifestly rooted in the nervous system and should not be regarded as merely a convenient categorization of degree of wakefulness. One consequence of this is that early motor activity varies in relation to behavioral state. Levels of arousal have repeatedly been proved having an effect on the quality of newborn movements (e.g., Hadders-Algra, Nakae, van Eykern, Klip van den Nieuwendijk, & Prechtl, 1993; Rönnqvist, 1995; Rönnqvist & Hopkins, 1998; 2000), and state is also regarded as an important factor to consider when studying older infants. In newborn studies, a careful monitoring of arousal level is required as neonates display a rapid change between different states. Differences in behavioral state have also been demonstrated depending on whether the neonate is born fullterm or preterm (e.g., Prechtl, 1974). As changes and differences in behavioral state are associated with different expressions of motor activity, having catered for the effect of arousal level is important when comparing the outcome results between different studies, and especially in relation to evaluation of sensory-motor deviations in clinical practice.

Changes in neonatal behavioral state may, in part, be explained by factors related to feeding. For example, it has been reported that breast-fed newborns are more irritable than their bottle-fed counterparts (DiPietro, Larson & Porges, 1987), and that this difference persists beyond the neonatal period (Lucas & St James-Roberts, 1998). Such a difference could have an impact on whether or not lateral biases are observed in the behavior of newborns. In support of this contention, crying has been shown to be associated with a lack of a lateralized head position preference in one study (Cornwell, Fitzgerald & Harris, 1985) and with a left-sided bias in another one (Rönnqvist & Hopkins, 2000). Furthermore, a consistent finding is that saccharides have a calming influence and facilitate pain reduction in newborn infants (e.g., Blass & Smith, 1992; Blass & Watt, 1999). For instance, the intake of a carbohydrate feed with lactose (a milk sugar yielding glucose on hydrolysis) by newborns has been observed resulting in a change from an “aroused” to a “non-aroused” index of state (Oberlander, Barr, Young, & Brian, 1992). In addition, sweet-tasting substances have been related to the function of both newborn upper and lower body movements by means of e.g. sucrose promoting increased mouthing and hand-to-mouth contacting (Barr,

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Pantel, Young, Wright, Hendricks, & Gravel, 1999), and glucose being associated with less pronounced stepping responses (Domellöf, Hopkins, & Rönnqvist, 2003). As saccharides such as glucose are a part of the handling procedure of newborns (in e.g. screening for phenylketonuria, PKU), these results point to the fact that it may be important to monitor the administration of glucose or other sweet-tasting substances when studying newborn motor behavior. For example, if sugar-based solutions on newborn responses are state dependent, qualitatively different responses (e.g., in terms of vigor) may be elicited in glucose-fed infants depending on whether or not they are crying.

To obtain the most accurate results with regard to neonatal functional behavior, observations should preferably be made when the newborn is in an awake and alert state (i.e., State 4 according to Prechtl, 1977). In Study I and II, the testing sessions began when the newborn had completed feeding and judged by the mother as being in an appropriate state (i.e., awake, not crying or drowsy). No testing was carried out if the infant was judged to be asleep. Attempts were also made to soothe crying infants prior to each test in order to induce a change to a more relaxed condition. This was partly done by administering small doses of glucose, a procedure that was later statistically confirmed not having any effect on any of the parameters studied. The participating newborns were coded for behavioral state (State 3-5) from the video recordings. However, as the majority of the infants persisted in crying during many of the trials, as well as exhibiting changes of state both within and between trials, a three-way classification could not be accounted for. This necessitated the less ideal use of “behavioral condition” as a between-subject factor in the analyses, with States 4 and 5 combined to form an active condition, and State 3 labeled as (relatively) inactive. Study III involved older infants, implicating fewer transitions in behavioral state. In this study, all participants, at all ages, were confirmed to be in an alert and optimal state for testing prior to each trial. In addition, attempts were continuously made to keep the infants’ mood and interest up in order to obtain as many trials as possible.

Postural control Another important factor to consider is postural control. Human postural reactions can be described as programmed sequences, triggered by visual, vestibular and proprioceptive cues about body imbalance, aiming to maintain body equilibrium (Brooks, 1986). Posture also functions as an important reference frame for our perception and actions in the external

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world (Massion, 1998). Thus, posture can be said to be in charge of the coordination of stability as well as for body orientation in space, and is an essential function for motor activity and control. Attempts to achieve and hold a stable posture against the influence of gravity begin in early infancy. Several studies have shown that already in newborns, when held in a more stable posture movements seem to become more functional and mature (Amiel-Tison & Grenier, 1983; Rönnqvist & Hopkins, 1998; Rönnqvist & von Hofsten, 1994). The developmental process of postural control follows a cranial-caudal and proximal-distal progression. Before an infant gains control over her trunk, posture is primarily focused on head and arm control. At around 6 months, the sitting balance improves and infants are able to sit independently with a straight back. The head is kept in an upright position and the infants develop the ability to control spontaneous sway and respond to postural perturbations (Mattiello & Woollacott, 1997). Independent sitting can be regarded as a milestone in postural control achievement. Furthermore, this ability is well associated with reaching movements in terms of spatio-temporal organization and lateral biases, and changes in postural support can be related to improvements in the control of reaching movements (Hopkins & Rönnqvist, 2002). From a dynamic systems viewpoint, this coordinated development of postural and reaching systems reflects the constant interaction between the nervous system, the body and the environment (Thelen & Spencer, 1998). Thus, early movements are dependent on both postural and environmental contexts, with clear implications for infant sensory-motor performance.

In Study I and II, the eliciting procedures of the leg responses involved holding the neonates upright under the armpits, with the head secured in midline, ensuring an equal postural support for all infants. All newborns were tested without diapers in order to promote as natural movements as possible. For the testing of head turning in Study I, all infants were placed supine in a rolled-up towel that served to prevent rotation to either side. In terms of environmental context, care was also taken in Study I and II to remove unwanted sources of stimulation that could have an impact on the outcome (see Apparatus and measurements). Moreover, in terms of bodily aspects, the relative masses of the right and left leg of the newborns were estimated to control for a potential effect of asymmetries in volume on the leg responses studied.

In Study III, the laboratory room used was similarly prepared to minimize irrelevant sources of stimulation by means of e.g. black roller blinds covering the windows and screens hiding the cameras. Of particular importance for this study was to make sure that the infants

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received sufficient postural support from the seating condition. Thus, three different, specially designed, infant chairs were used at the ages 6 and 9 months, 12 months, and 36 months. In addition, the infant’s position relative to the placement of object to be reached was individually adjusted.

Registration technique A large number of studies have demonstrated that kinematic measurement is a sensitive tool for detailed quantitative investigations of many different infant sensory-motor behaviors. This includes investigations of both upper body movements, such as age-related changes in reaching and grasping (e.g., Corbetta & Thelen, 1995; Fetters & Todd, 1987; Forssberg et al., 1991; Jeannerod, 1984; von Hofsten, 1979; von Hofsten & Rönnqvist, 1988), and lower body movements, such as relations between leg joints with regard to infant spontaneous kicking (see Piek, 2001, for a review) and the development of human gait (e.g., Forssberg, 1985; Thelen & Cooke, 1987). Kinematic measurement has also proved to be valuable for investigating movements in children with, or born at-risk for, neurological dysfunctions (see Kinematic registration as a promising tool for early diagnosis). Although kinematic registration seems to generate precise and reliable measurements, there are a number of considerations to bring attention to in relation to applying this technique in infant studies. In order to increase the validity and facilitate comparisons between the outcome results of different kinematic studies, it is important to take factors such as marker size and weight, whether the markers are passive or active, anatomical sites used, calibration procedure, acceptable level of measurement error, actual resolution, and sampling frequency into account as this may have an impact on the derived parameters. This issue is further accentuated when considering the rapidly growing number of studies using kinematic measurement technique, and the increased implementation of kinematics in clinical settings for evaluation of sensory-motor function at different ages.

As previously mentioned (see Apparatus and measurements), the six-camera ProReflex system used in Study II and III works according to the basic principle of motion capture units (MCUs) detecting infrared light reflected by the exposed markers. The infrared flash is formed by the light emitting diodes (LEDs), at the front of the MCU. These LEDs are divided into three groups with respect to their positions relative to the lens, and it is of importance that a proper selection of LED group is done

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relative to the distance between camera and markers. In Study II and III, the inner and intermediate LED groups were selected, appropriate for the distances involved. Care was also taken to optimize the focus and aperture settings of each camera relative to marker size and distance. All cameras were steadily mounted, ensuring that they were not subjected to vibrations of any sort. Positioning of the cameras was done in order to optimize the separation of optical axes (i.e., the angle of incidence between any two cameras exceeded sixty degrees, allowing accurate measurements to be made in all three dimensions), and to minimize unwanted reflections (e.g., from structures in the surrounding or the flash from another camera). Calibration of the system software (MacReflex) was done by means of a CAB 500 calibration reference frame (360 X 560 X 450 mm), with a six-marker configuration suitable for medium size measurement volumes (i.e., about 1 X 1 X 1 m). Initial calibration was always performed prior to start of each measurement session. The passive, wireless markers used are suitable for studying neonates and young infants as they allow full freedom and flexibility to move within the calibrated space.

Despite a careful implementation of the recording system, there are many challenges to overcome when studying these young participants with this technique. Firstly, as witnessed in Study II and III, there can be problems caused by the cameras not being able to see each marker during the motion capture. For instance, many of the newborns in Study II bent or crossed their legs quite extensively, causing one or more markers to be occluded. This prevented data from being collected from these markers and consequently they could not be included in later analysis. A similar problem occurred in relation to the older infants in Study III in terms of some of the infants (mainly at their younger ages) rotating the hand during the reaching movement in such a way that the cameras could not see the wrist marker.

Secondly, a prerequisite for data to be collected is that the specified time intervals for kinematic recordings coincide with the movements studied. This is not always the case when studying infants. A pretrigger mode allows the cameras to continuously fill their buffer memory with data until the recording is triggered. The specified number of preframes is then added to the captured frames for the measurement. This function is very accommodating with regard to infant studies, and was also used in Study II and III. However, it happened that a recording was triggered when it seemed as though a movement was about to begin, when in reality the infant did not start to move until later. In such cases, the recordings were useless and the trial had to be discarded. In Study II, some of the newborns also displayed much prolonged stepping responses (i.e., not

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finished within the specified time interval), resulting in recordings that only succeeded in capturing parts of the movement.

Thirdly, the application of markers to infant participants can be very challenging. The sensitive and often fatty skin of neonates creates difficulties in attaching the markers so that they will not fall off during the measurement. In Study II, it was relatively common that one or more markers of either leg was detached during a trial, sometimes even being re-attached by chance to an irrelevant anatomical point (e.g., when the leg was extensively bent). In Study III, problems could be caused for instance by infants at the younger ages lifting a wrist to the mouth and trying to chew on the marker. The infants also became increasingly aware of the markers being attached to them, especially evident when 36 months old. Thus, an experimenter needs to be resourceful in order to persuade young children to agree to wear markers, and also be aware of the potential effect the infants’ awareness of the markers may have on the outcome variables. The latter recommendation is supported by recent findings with regard to the effect of finger markers on the kinematic properties of reaching movements, suggesting that markers attached to the thumb and index finger have an impact on the spatio-temporal adjustment of the hand in 3-year-old children in terms of prolonged deceleration, increased time to establish a grip, and more movement units (Domellöf & Rönnqvist, 2006).

Fourthly, even when markers are successfully attached to a participant, there is a shortcoming with this method in that the markers are subjected to skin movement artifacts (i.e., the skin slides over underlying bone structures during motion). This may introduce errors in marker position data that correlate with movement and have an impact on subsequent analysis (Chiari, Della Croce, Leardini, & Cappozzo, 2005). There may also be a problem with incorrect location of palpable anatomical landmarks affecting the kinematic outcome (Della Croce, Leardini, Chiari, & Cappozzo, 2005). However, the degree to which these and similar sources of inaccuracy affects kinematic measurements is still unknown, particularly with regard to infant studies.

As there is a risk that challenges such as the ones described above may cause disturbances in the kinematic measurements, it is of critical importance that they are carefully managed. As was the case in Study II and III, additional video recordings of all trials can be helpful in this matter by providing a possibility for on-line explanations of irregularities in the kinematic data.

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SUMMARIES OF THE EMPIRICAL STUDIES

Study I: Upper and lower body functional asymmetries in the newborn: Do they have the same lateral biases? As previously described, a large number of studies have confirmed the finding of a right-sided preference for head positioning in human newborns but much fewer studies have been devoted to investigating functional asymmetries in the lower limbs and also with a lack of consistent findings. Thus, little is known of whether expressions of neonatal functional asymmetries share the same lateral biases across different parts of the body. The aim of the present study was to explore neonatal functional movement asymmetries in the upper body (head turning preference) and lower body (first foot moved in stepping and placing) in terms of concordance. Apparently, only one study has previously addressed this question. Grattan and collaborators (1992) studied the directional biases in upper and lower body movements in a sample of 36 fullterm newborns, not finding a clear-cut association for any of the expressed asymmetries. Accordingly, they concluded that functional asymmetries evident in the upper and lower body of the newborn are governed by different neural subsystems rather than a single system for lateralization. Moreover, Grattan et al. did not find a concordance between lateral biases in stepping and placing in terms of the first foot moved, in line with previous research in relation to asymmetries in these particular responses. Thus, it may be that the underlying neural mechanisms for stepping and placing are different as well. One plausible explanation for the lack of consistency in previous studies of newborn functional asymmetries (head positioning possibly excepted) is differences in methodologies used. Therefore, we also included an enhanced control of variables that could possibly affect expressions of laterality in the responses included in Study I. To date, this type of refinement has not figured to an adequate extent in the relevant studies. Apart from carefully reassuring that the stepping, placing and head turning were elicited in an unbiased manner, we also controlled for the infants’ behavioral state and leg mass. Furthermore, latency time for newborn stepping and placing responses by means of frame-by-frame video analysis was introduced as an alternative measurement variable to frequency of first foot moved.

The participating newborns were given three trials for the respective behavior studied. During each testing session, preference in first foot

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moved and head turning direction was noted. A majority of the newborns in Study I showed a rightward bias for head turning (60.5% right, 39.5% left), though this difference did not reach significance. No preference for stepping or placing in terms of first foot moved was found (Table 2). The newborns displayed wide intra- and inter-individual variability in relation to preferred direction and first foot moved during head turning, stepping and placing. Thus, no significant associations could be found between any of the three respective responses studied. These results lend support to the claim by Grattan et al. (1992) that newborn upper and lower body functional asymmetries are controlled by multiple neural subsystems, likely residing at different levels of the neuroaxis. Table 2 Group data for side preference (stepping, placing and head turning) and onset latency (stepping and placing). Abbreviations: N = number, s = seconds, R = right, L = left, No = excluded infants, SD = standard deviation _________________________________________________________ Preference (N) Latency (s) Range Variable R L No Mean (SD) Min - Max _________________________________________________________ Stepping 23 17 3 1.60 (1.08) 0.14 - 3.95 Placing 19 20 4 0.74 (0.71)* 0.04 - 2.69 Head turn 26 17 0 - - - - _________________________________________________________ Stepping R 1.85 (1.38) 0.66 - 3.95 Stepping L 1.18 (1.32)* 0.14 - 3.58 Placing R 1.04 (1.32) 0.04 - 2.69 Placing L 0.45 (0.62)* 0.04 - 1.47 _________________________________________________________ * = p < .05

With regard to latency times, significant effects were found in relation to the onset foot during stepping and placing, characterized by a shorter onset latency for the response trials when infants started with the left foot

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(Table 2). As judged by a significant correlation between the onset latencies for stepping and placing, the two responses also seem to share a common timing mechanism for initiation, although the newborns had faster onset times for placing than stepping (Table 2). Behavioral state did not account for any effect on side preferences in terms of head turning direction or first foot moved during stepping and placing. However, a significant main effect of state on latency time for stepping was found in that an active state was related to a shorter onset latency, but not for placing. The compatibility in latency times suggests that stepping and placing responses could be propagated by a common neural subsystem, with differences in biomechanical constraints during elicitation of the two responses explaining the divergence in terms of swiftness and effect of state. Leg mass as biomechanical constraint, however, turned out to have no effect on preferred foot or latency time for either stepping or placing.

Study II: Functional asymmetries in the stepping response of the human newborn: A kinematic approach One conclusion derived from the findings in relation to latency times in Study I was that further expressions of asymmetries in newborn leg movements could possibly be captured by means of an improved methodology such as 3-D optoelectronic movement registrations. Thus, focusing on the newborn stepping response, the aim of Study II was to employ kinematic registration in order to add a dimension to previous research by means of informing us about the consequences of differences in the spatio-temporal organization of the leg movements during the response, allowing a greater insight into the nature of lateral biases in the control mechanisms for these movements. To our knowledge, this is the first study made applying a kinematic approach to the study of side differences in newborn stepping responses. Kinematic parameters related to duration of movement, peak velocity, maximum vertical displacement, and segmentation of movement in terms of number of movement units (MUs) were investigated. In addition, to gain insight into side differences related to the intralimb coordination between the ankle-knee, ankle-hip, and knee-hip joints of each leg, the maximum value of the cross-correlation function and the corresponding zero-lags were determined from the velocity profiles.

In terms of kinematic parameters, it was found that the left leg tended to generate higher peak velocities for all joints compared to the right. This result is in keeping with the finding of a shorter latency for the left foot

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compared to the right in Study I, and further points to a more briskly generated response of the left leg.

A significant side difference in terms of MUs was also revealed, characterized by the movements of the left leg containing a larger amount of MUs than right leg movements (Figure 7). Findings related to newborn arm movements and later reaching behavior (von Hofsten, 1991) have suggested that fewer MUs are associated with a smoother control of reaching movements. In keeping with this, the present outcome suggests a less mature left leg movement control.

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LEG JOINTS Figure 7. Mean number of movement units (MUs) of the right and left leg as a function of the leg joints.

Side differences were also found in relation to intrajoint coordination, characterized by stronger ankle-knee couplings and smaller phase shifts in the right leg compared to the left. This result is in keeping with previous findings of right-sided biases in intralimb couplings during spontaneous kicking (Piek & Gasson, 1999).

In sum, Study II demonstrates new evidence for side differences in the newborn stepping response in that, as early as 2-3 days postnatally, the movements of the left leg tended to have faster velocities, while at the same time being characterized by more segmentations, compared to those of the right leg. The study also provides evidence for right-sided biases in intralimb coordination during the stepping response. At birth, early

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functional corticospinal projections have already been established (Eyre et al. 2000; Martin, 2005) and spinal pattern-generating circuits for locomotion appear to be well developed (Yang, Stephens, & Vishram, 1998; Yang, Lamont, & Pang, 2005). Thus, in terms of the amplified activity in the left leg, the present findings could be related to a generation of newborn stepping along an ipsilateral pathway that is shorter on the left than on the right side of the body. There may also be early lateral differences in the developing corticospinal projections that are expressed in subtle movement asymmetries such as the ones observed in the present study. For example, the finding of smoother stepping movements of the right leg in terms of fewer MUs could indicate a developmental lead in the ipsilateral pathway subserving the right leg pattern generator.

Study III: Quantitative assessment of right and left reaching movements in infants: A longitudinal study from 6 to 36 months In this study, the issue of hand preference development was addressed by means of a longitudinal exploration of the kinematic characteristics of right- and left-sided reaching movements in infants over the ages 6, 9, 12, and 36 months. The main method in previous studies of hand preference in infants during the first year of life has been observations of the frequency or pattern of hand-use, resulting in a complex and often contradictory collection of outcomes. The few longitudinal studies made add to this complexity in describing frequently occurring lateral fluctuations in hand preference or manual strategies (i.e., uni- or bimanual) between and within the study periods (e.g., Corbetta & Thelen, 1999; Fagard, 1998; see also Arm and hand movements). Studies of side differences in early arm-hand movements based on kinematic registrations have been able to generate more clues to the nature of these inconsistencies and fluctuations. Hopkins and Rönnqvist (2002) compared the 3-D kinematics of both arms during reaching in 6-month-old infants and found fewer MUs in the reaching movements of the right arm (i.e., less segmentation) compared to the left. They suggested that this expression of a lateral bias in reaching could be interpreted as a preference of the arm foregoing hand preference during the course of the early development of handedness. Two previous studies have involved kinematics in longitudinal studies of asymmetries in infant reaching. Corbetta and Thelen (1996; 1999) studied reaching and non-reaching movements in four infants throughout their first year by means of hand

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activity and kinematic analysis of average speed. A marked fluctuation in lateral biases was found in all infants and for all movements. However, periods of temporary right-sided biases were evident, matching a confirmed later right handedness of the infants at 3 years of age. Morange-Majoux and colleagues (Morange-Majoux, Peze, & Bloch, 2000) studied reaching movements in eight infants from 20 to 32 weeks. By means of 2-D video scorings, they found a shorter movement time, a more direct hand trajectory, and fewer corrections of the right hand compared to the left. Thus, the aim of Study III was to further explore side differences in the kinematics of right and left reaching movements during the first year of life, their relation to hand-use preference, and how they comply with expressions of laterality during reaching at the later age of 3 years. In addition, as four of the participants were moderately prematurely born, the effect of birth condition (fullterm vs. preterm) was also investigated.

In terms of side differences associated with the kinematic outcome parameters at 6, 9, and 12 months, the most evident effect concerned the segmentation of the reaching movements. At all ages, a main effect of side was found for number of MUs, characterized by fewer MUs in right reaching movements compared to left. This right-left difference in terms of number of MUs pertained when the infants reached 36 months of age, and was also highly consistent over the time points involved in the study. A majority of the infants (11 of 16 at 36 months) showed a stable pattern of fewer MUs in right reaching movements at three or four out of the four ages tested, five infants showed no stable pattern, and none of the infants had consistently fewer MUs in left reaching movements. In keeping with this finding, an effect of straightness of the reach was also revealed by means of a straighter reaching trajectory in right arm-hand movements than those of the left arm-hand. Moreover, over the second half of the first year, the reaching trajectory became progressively both straighter and smoother (less segmented), a finding that also was confirmed at 36 months of age.

Focusing on the distribution of successful reaching and grasping, as derived from video scoring of the infants’ performances from 6 to 12 months, a main effect of testing age was revealed. Compared to the youngest age, all infants reached and grasped more successfully when they were tested at 9 and 12 months of age. Furthermore, the majority of infants generally displayed an increasing number of one-handed (unimanual) right reaching movements together with a decreasing number of two-handed (bimanual) strategies. At 6 months, more unimanual left than unimanual right and bimanual strategies were showed. At 9 months, they showed significantly more unimanual than bimanual reaching-

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grasping, and, at 12 months, both significantly more unimanual right than left and unimanual than bimanual reaching-grasping (Figure 8).

The effect of object positioning in relation to use of arm-hand was also investigated, showing a developmental trend towards more right reaching-grasping of an object placed to the right compared to left reaching-grasping of an object to the left, as well as the right arm-hand more frequently crossing the midline to grasp an object to the left than vice versa, at 12 months. More right-sided reaching and grasping for an object placed in midline at 12 months was also found compared to the younger ages. This pattern of increased right arm-hand preference also matched the consistent right-sided preferences for throwing, drawing, and hammering, that was found for all infants at 36 months of age. (%)

AGE Figure 8. Distribution of the relative frequencies of successful arm-hand use (unimanual right, unimanual left, bimanual) over the first three testing ages.

When comparing the preterm and the fullterm infants, there were no differences in terms of number of successful reaches and grasps or the use of right or left arm-hand. With regard to the outcomes from the kinematic measurements, the preterm infants generally displayed less consistency, within individual outcomes as well as between ages, compared to their fullterm peers, especially at 6-9-months. In terms of side differences, more MUs in right arm-hand movements were found for the preterm infants than fullterm at 12 months. Overall, the preterm infants also had more MUs at 6, 9, and 12 months, implicating that the arm-hand movements of fullterm infants were smoother at these ages. The

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preterm infants also displayed less straight reaching trajectories and tended to have longer reaching durations than the fullterm infants. However, at 36 months, there were no significant differences between fullterm and preterm infants for any of the analyzed parameters.

GENERAL DISCUSSION The main aim of this thesis was to investigate the prevalence and development of functional asymmetries in the upper and lower body movements of newborns and young infants. This was done by means of comparing asymmetries in newborn head turning, stepping and placing responses (Study I), investigating asymmetries in the kinematics of newborn stepping responses (Study II), and longitudinally investigating side differences in the kinematics of infant reaching movements (Study III). Only Study III provides longitudinal data, enabling a powerful exploration of developmental changes and consistency within the same infants over age, as well as between age groups, in terms of arm-hand preference. However, the cross-sectional efforts of Study I and II also contribute to the developmental picture in providing up-to-date knowledge of potential origins for later lateralized behavior, especially with regard to the understanding of lateral biases in early leg movements. In the following section, the implications of the empirical findings are further discussed.

Concordances between newborn head turning, stepping and placing responses As previously discussed, newborn dominant right-sided preference for head turning in supine is a well-documented finding in most previous studies (e.g., Rönnqvist & Hopkins, 2000; Rönnqvist, Hopkins, van Emmerik, & de Groot, 1998). Although not statistically significant, a rightward bias in head turning was also found in Study I, approximating a 2:1 (right:left) ratio that can be expected for motor asymmetries in general (Previc, 1991). Stepping and placing responses did not manifest any consistent bias in terms of frequency of first foot moved in Study I, adding to the variety of inconsistent outcomes of previous studies with regard to foot preference for newborn stepping and placing responses (see Infant motor asymmetries). Thus, in contrast to the suggestion that asymmetry

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in first foot to move during stepping (and by implication placing) should constitute a more reliable indicator of functional lateralization in the newborn than asymmetry in head position preference (Melekian, 1981; Peters, 1988), these findings support that a lateral bias in head turning is a more robust eventuality than for stepping and placing in the neonate.

One possible explanation as to why this might be the case is the long-standing evidence that muscle spindles as well as joint and skin receptors develop in a cephalocaudal direction in the human (Humphrey, 1964). Even older evidence points to the fact that the number of muscle spindles in the neck musculature is much higher than in other muscles at birth (Voss, 1937). Unfortunately, there is no neuroanatomical evidence indicating whether muscle spindles and other afferent organs develop in an asymmetrical fashion during prenatal life in the human. What is known, however, is that a spontaneous (or induced) asymmetrical tonic neck posture is hardly ever accompanied by a lateral bias in the legs of the human newborn (Touwen, 1976). Such a difference between the upper and lower body is indicative of asymmetrical muscle stretch activity being more pronounced in the neck than the legs.

In terms of head turning, stepping and placing sharing concordant functional asymmetries during the newborn period, an association between directional biases in leg responses and head turning could not be found in Study I. This finding also supports the claim by Grattan et al. (1992) that the control of motor asymmetries in upper and lower body movements of the newborn is mediated by multiple neural subsystems rather than a single lateralized system. Considering the sources of stimulation and control of head turning, stepping and placing responses, suggested originating from different levels of the neuroaxis (see Infant motor asymmetries), there is thus a possibility that there are divergent asymmetrical neural subsystems at these levels in control of the three respective behaviors. However, as described below, this speculation is subject to qualification when considering the onset latencies for stepping and placing responses.

Onset latency: newborn stepping and placing responses By means of the frame-by-frame video analysis used in Study I, the onset latency for both stepping and placing responses was found to be lateralized in terms of a shorter latency for the left foot. Overall, the onset times were faster for placing than for stepping. In addition, there was a significant relationship between the onset latencies for the two responses, suggesting

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that they may share a common timing mechanism for their initiation despite the fact that their sites of elicitation are different. As previously described (see Development of the motor system), TMS in newborns has been shown to evoke shorter ipsilateral motor response latencies, consistent with the finding of a shorter ipsilateral pathway in neonates. Thus, newborn stepping and placing responses could be propagated by a shared neural subsystem, e.g. a descending ipsilateral pathway that is shorter on the left side of the body than on the right. Another possibility may be that the pathways to the left and right leg are at different stages of myelination, with increased myelination of the right pathway resulting in a more inhibited right limb facilitating the differences in latencies between the limbs.

However, two additional findings remain to be explained. The first concerns the infant’s behavioral state (condition) during the elicitation procedure for both responses. Regardless of the first foot moved, the onset latencies for stepping, but not placing, were dependent on infant condition. Thelen et al. (1982) reported that an aroused (i.e., more active) condition results in an increased rate of stepping. Adding to this finding, an active condition may thus also give rise to the stepping response setting off more quickly relative to when the infants are in an inactive disposition. The fact that placing latency times were unaffected by the infants being in an active or inactive condition is puzzling. When considering the neural pathways believed to be mediating the respective responses, behavioral state having an effect on stepping latency but not placing latency suggests an influence of supraspinal levels on the stepping response that challenges the claim that stepping is exclusively spinally mediated. Placing on the other hand, suggested deriving from supraspinal mechanisms, had a significantly shorter onset latency than stepping and was unaffected by behavioral state, indicating a predominant spinal mediation. Taken together, this complex pattern in relation to onset latencies for stepping and placing responses could, at least in part, be explained by differences in biomechanical constraints (e.g., in different starting positions for elicitation and greater mechanical delay time for stepping compared to placing) or dissimilarities in the receptors involved (foot sole stimulation for stepping elicitation vs. dorsum of foot for placing). Nevertheless, a more refined measurement of onset latencies in Study I revealed a hitherto unreported lateral bias in newborn lower-limb responses. Following this intimation, proceeding with identifying the spatial and temporal characteristics of newborn leg movements by means of 3-D movement registration was the next step in generating further evidence for such subtle expressions of laterality.

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Kinematic parameters: newborn stepping responses The analysis of kinematic parameters with regard to side differences in newborn stepping responses in Study II resulted in new evidence for lateralization in early leg movements. The finding of a tendency for the left leg to reach a higher peak velocity than the right, together with such findings as the left ankle tending to be lifted higher in the vertical dimension, are in accordance with the finding of a shorter onset latency for the left foot compared to the right in Study I. Taken together, these findings could be related to a difference in hyperactivity in the flexor-extensor activation for the muscles of the respective legs (i.e., augmented activity for the muscles of the left leg). Another possibility is that left leg movements are subjected to grosser activation than those of the right leg due to differences in capacity to restrain excess muscle activity. This latter suggestion indicates that the development of the control of leg movements may progress along a right-to-left gradient. Support for such an early gradient can be found in a recent finding by Sun and colleagues (Sun, Patoine, Abu-Khalil et al., 2005), suggesting that levels of gene expression in 12-19 week old fetal brains appear to indicate an advance in right hemisphere cortical development.

Support can also be gained from the findings concerning movement segmentation. According to these, left leg movements have more MUs compared to the smoother right leg movements, which is a result that could be due to left-right differences in muscle activation. Although no evident effect of the newborns’ behavioral state on any of the kinematic outcomes was found in Study II, two interactions were found. The first was related to left leg steps of infants in an active but not a relatively inactive state having a shorter duration than right leg steps, in keeping with a brisker left leg response in terms of onset latency and peak velocity. The second was related to left leg movements of infants in a relatively inactive state containing more MUs than right leg movements of infants in either state, implicating that the lower efficiency in activation and organization of left leg movements compared to the right may be even more evident when the newborn is in an inactive state. Taken together, these findings suggest that different behavioral states in newborns may exert contrasting mediating influences on functional asymmetries in lower-limb responses.

In keeping with the side differences found for onset latency in Study I, the findings of asymmetries in Study II are also possible to relate to a

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generation of newborn stepping along an ipsilateral pathway that is shorter on the left than on the right side of the body. The pathways controlling the right leg could also be interpreted as being more inhibitory (i.e., differences in the myelination of the corticospinal tracts). Furthermore, given that early motor experiences generated by limb movements are critical for the optimal development of the corticospinal system, even during the prenatal period (see Development of the motor system), it is possible that they are exerted in a lateralized fashion. Thus, there could be lateral differences in the activity-dependent shaping of corticospinal connections (e.g., axonal withdrawal) that are expressed in subtle movement asymmetries such as the ones observed in the present study. At present, nothing is known about whether leg movements that first appear at 9 weeks gestation (de Vries, Visser, & Prechtl, 1982) assume a lateral preference during prenatal development, e.g. with one leg moving more frequently than the other. Such information would be interesting to be able to relate to the present discussion, as well as to why there seems to be a discrepancy between neonatal “headedness” and lack of “footedness” as was the case in Study I. Of further relevance to include in this context of fetal upper and lower body lateralization would be that, according to Hepper and colleagues (e.g., Hepper et al., 1990; 1998), asymmetries in activity and frequency of prenatal arm movements are present from 10 weeks gestation (see Arm and hand movements). To begin with, whether such early lateral preferences in the movements of the arms seem to correspond to functional asymmetries in infant reaching movements was of interest for Study III.

Video scoring: infant reaching and grasping Previous studies of side preference in the frequency of infant reaching and grasping with the right or left side have failed to find a consistent lateral bias during the infants’ first year of life (Fagard, 1998; Thelen et al., 1996). However, a relatively more consistent right-sided preference has been observed beyond the first year (e.g., Archer, Campbell, & Segalowitz, 1988), and a stable hand preference at around 3 years (Corbetta & Thelen, 1999). In Study III, these findings were confirmed with regard to an unstable hand preference in terms of frequency of successful right- and left-sided reaching and grasping at the ages 6 and 9 months, a rather evident right-sided preference at 12 months, and a clear-cut right-sided bias for the three arm/hand performance tasks used at 36 months.

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The present study also confirmed the consistent finding of young infants’ preference for reaching and grasping with the hand at the same side as the placement of a stationary object. However, reaching across the midline was present already at 6 and 9 months of age, challenging the suggestion that spontaneous midline crossing does not occur until after 1 year of age due to its association with corpus callosum maturation (Bishop, 1990). Furthermore, at 12 months the infants displayed relatively frequent midline crossing with the right arm, but less frequent and later crossing with the left, suggesting that reaching across the midline may be a more sensitive indicator of early side preference than frequency of reaching and grasping.

Kinematic parameters: infant reaching and grasping In terms of the kinematic parameters derived in Study III, side differences by means of less segmented (fewer MUs) and straighter right-sided reaching trajectories in comparison to left-sided were revealed for all ages tested. The finding of such side differences in reaching movements at 6 months of age verifies the findings by Hopkins and Rönnqvist (2002), and is in keeping with those by Morange-Majoux et al. (2000). Study III adds further to this outcome that such side differences are also evident when infants are tested at 9, 12, and 36 months of age, and seem to be consistent over time in most of the investigated infants on an individual basis. Some infants, the preterm mainly, displayed both intra- and inter-individual inconsistency, although none of the participating infants showed a consistent pattern of fewer MUs and/or a straighter reaching trajectory for left-sided reaches over the ages tested.

No evident right-left differences related to other kinematic parameters were found in Study III. In terms of velocity, a similar fluctuating and inconsistent profile in infant reaching movements as previously reported (Corbetta & Thelen, 1996; 1999) was found during the first three ages investigated. The incoherent velocity profiles could be related to the segmentation of the movement. In mature reaching profiles, the first (transport) movement unit is always the largest, containing the highest peak velocity and transporting the hand the longest distance (e.g., Jeannerod, 1984). This pattern of MU size and peak velocity profile within reaches was more variable during reaching at the younger ages, in particular at 6 and 9 months, although apparently without affecting the amount of MUs.

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The evidence for a relatively constant and consistent pattern of smoother and straighter right arm movements compared to left during reaching-grasping in young infants presented in Study III are in agreement with functional asymmetries in early movements of the upper limbs being associated with a biologically based developmental process. In terms of developmental origins for handedness and based on the present findings, it is suggested that human hand preference originates from an early dominant arm advantage (mainly involving bilateral projections) rather than hand (mainly involving contralateral projections), as it is not until later in development that the infant gains increased precision and accuracy of the hand. Such a suggestion is also in agreement with the proposed proximodistal developmental course of motor control functions of the corticospinal system (Martin, 2005), as well as with the proximal to distal development of a control strategy for arm movements in human infants (Berthier, Clifton, McCall, & Robin, 1999).

However, even if the early development of human hand preference is biologically rooted, the developmental process of structural-functional motor asymmetries is still susceptible to change due to external factors. In particular during the early establishment of neural connections, alterations may occur as a result of even minor interruptions (e.g., influences of intrauterine exposure to teratogens and preterm birth). Thus, the development of handedness is by no means “hard-wired” and an epigenetic perspective, including environmental effects on early neural development, is likely the most rewarding.

Birth condition: infant reaching and grasping Four preterm infants (reduced to three when tested at 36 months) may seem like a very limited number of participants to involve in a study of differences between birth conditions. However, previous longitudinal studies by means of kinematic measurements of reaching movements in the same restricted number of infants have been able to generate trustworthy and interesting data (Corbetta & Thelen, 1996; 1999; Thelen et al., 1996). Thus, although based on a less than ideal sample size, this additional focus of Study III is justified. However, the findings should be interpreted with caution.

The reaching trajectories of the preterm infants involved more MUs at 6, 9, and 12 months than those of the fullterm. As previously discussed (see Arm and hand movements) there is an association between a decrease in number of MUs and more smoothly controlled and mature reaching

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movements. Thus, this finding implies that the arm-hand movements of the preterm infants were less smooth during the second half of the first year. The preterm infants also displayed more curved reaching trajectories and tended to have longer reaching durations than the fullterm infants. It is noteworthy that these findings were especially pronounced at 6-9-months. Apart from the finding that side differences were mainly restricted to a larger amount of MUs in the right arm-hand movements of preterm compared to fullterm infants at 12 months, differences were less evident at 12 months. At 36 months, no differences between fullterm and preterm infants could be found. However, a general impression was that the preterm infants displayed less consistency, within individual outcomes as well as between ages, compared to the fullterm infants. All in all, the preterm infants in Study III displayed a developmental delay in terms of reaching kinematics, together with an alternative developmental pattern with regard to expressions of hand preference (e.g., the finding of fewer MUs in left arm-hand movements at 12 months could suggest a temporary advanced maturation of reaching movements with the left arm-hand). However, at 36 months both the fullterm and preterm children showed a dominant right-sided arm-hand preference and there were no significant differences in terms of reaching kinematics.

As discussed previously (see Clinical implications), the course of early activity-dependent development in the corticospinal system (not completed until 2-3 years of age) has been suggested susceptible to functional deviations that also may apply to deviations in side-related behavior. This may also have implications with regard to the present findings. For example, complications following preterm birth may impair the functional state of the corticospinal system, which could be reflected in deviant expressions of functional asymmetries. In terms of motor functioning, brain damage associated with preterm birth implicates a modulation of functional neural connections during CNS maturation that may result in irregularities in motor output. Repeated uncorrelated movements may then reinforce these disordered or inappropriate neural connections later in development (Myklebust & Gottlieb, 1997). One explanation for the temporary deviation from the typical developmental pattern at 6-12 months found in the present study could thus be that preterm birth (in our study, 33-36 weeks of gestational age) may only result in very mild complications that, following increased activity and motor experiences in a dextrally biased world, progressively are compensated for. However, it could also be an expression of a general developmental delay (i.e., not necessarily associated with an underlying neural deviation).

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CONCLUSIONS The aim of the present thesis was to explore functional asymmetries in the upper and lower body of neonates and young infants in order to add to current knowledge of the developmental origins of laterality and what neural mechanisms that subserve early lateral biases. Based on the presented empirical studies, some general conclusions may be drawn. Firstly, refined measurements such as frame-by-frame video analysis of onset latency during newborn leg responses and 3-D movement registrations of newborn stepping responses as well as infant reaching movements seem to enable the possibility to tap into the more subtle expressions of early functional asymmetries in the upper and lower body movements of young infants. Secondly, detailed analyses of the kinematics involved in the leg movements during newborn stepping and arm-hand movements during reaching and grasping in infants over the ages 6-36 months seem to cater for a relatively coherent set of lateral biases. Thirdly, such findings may contribute to the understanding of underlying control mechanisms subserving asymmetries in the movements of young infants and, especially in terms of longitudinal data, to the developmental characteristics of lateralized functions.

In Study I, the introduction of a more strict methodology than what seems to have been the case in previous studies resulted in difficulties to find clear-cut preferences in terms of assumption of a head position after release from midline and frequency of first foot to move during stepping and placing responses. This alerts us to the fact that findings extracted from this type of usually employed measurement method in newborn studies devoted to functional asymmetries may be dependent on the methodology used, which may also explain the differences in outcomes between previous studies. Still, a right-sided head turning preference was found in the majority of newborns, compared to no evident preference in leg responses, in support of neural development along a cephalocaudal direction that also may involve more readily observable expressions of lateral biases.

Analyses of onset latencies during stepping and placing responses (Study I) and kinematics of stepping responses (Study II) revealed an intriguing lateral bias in terms of movements of the left leg being seemingly more “vigorous” than those of the right leg. However, the interpretation of the side differences in kinematic parameters, together with the finding of more segmentation of left leg movements by means of

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number of MUs, suggests that movements of the right leg may be more efficient (in terms of muscle activity) and organized already in the newborn infant. In keeping with this finding for the lower body, a similar difference in number of MUs between left and right reaching movements in infants over the ages 6 to 36 months was also evident in Study III. Thus, accepting that the segmentation of movements into units is a sensitive parameter for the smoothness and organizational maturity of movements, a shared right-sided advantage between the upper and lower body in terms of less movement segmentation seems to exist. This lateral bias could possibly be present from the newborn period onwards and, moreover, actively involved in the developmental progress of the underlying motor pathways. In order not to go too far beyond the scope of the empirical data, however, such speculations need to be supported by further research (see Future directions below).

An additional aim of this thesis was to put an emphasis on deviations in functional asymmetries as expressed in infant upper and lower body movements that may be related to deficits later in development. Study I and II contributes to a better understanding of functional asymmetries in the leg responses of healthy fullterm infants, as well as of possible neural origins for these asymmetries. Such information is important in order to advance the early diagnosis of deviations in infants born at-risk for developmental disorders. Preterm infants is a particularly vulnerable population at increased risk for a range of negative neurodevelopmental outcomes. Following progresses in obstetric and neonatal care there has also been an increase in survival of infants born before term that has led to a growing concern about these children. In terms of functional asymmetries, an overrepresentation of left and non-right-handedness in ex-preterm children seems to be present. Thus, complications following preterm birth that may impair the functional state of the motor pathways likely include side-related behavior as well. In many cases of preterm birth, PVL can be associated with motor deficits such as spastic diplegia in the lower extremities. The present findings related to newborn leg movements may thus aid in the detection and treatment of this disorder early in life.

Study III included four moderately preterm infants that allowed for longitudinal exploration of deviations in patterns of development and laterality in terms of reaching kinematics as compared to fullterm infants. As judged by this study, kinematic measurements are sensitive for capturing various subtle differences in the spatial and temporal organization of arm-hand movements depending on birth condition. Many preterm children in the range of the gestational ages included in Study III are considered “low-risk” and show no obvious

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neurodevelopmental impairments in the beginning of life. However, at school age many of them may begin to show overt abnormalities. Thus, although originating from a limited sample, the contribution to the understanding of the development of arm-hand movements and hand preference gained from Study III may also be of clinical importance with regard to the characteristics of upper body movements in the developing preterm infant.

When carrying out studies with experimental designs on neonates and young infants a number of difficulties have to be dealt with, including such as relatively few participants, methodological complications, problems with collecting an adequate number of trials, and a large variability in the extracted data set. Moreover, comparatively few studies are devoted to functional asymmetries in infant movements, in particular as investigated by means of kinematic measurement, which can be challenging when relating new empirical findings to previous ones. In addition, interpreting findings based on behavioral expressions in relation to underlying neural mechanism requires tactfulness, as it will by necessity be reduced to speculations about possible influences of neural pathways and muscle activity on the observed movements. As proposed in the present thesis, a coherent methodology and a sophisticated measurement technique can still allow for the collection of data that add to the understanding of the origins and mechanisms for functional asymmetries. However, as discussed in the following final section, more research is needed to support the present findings and the interpretations stemming from them.

Future directions The final conclusion of this thesis is that there is a need for more studies to continue bringing together the understanding of functional asymmetries in developing infants, typical as well as atypical. On the basis of the results of the present thesis, several issues of importance for future research to address can be suggested:

• Studies including kinematic recordings as well as EMG and EEG are needed to verify findings such as lateral biases in onset latency and peak velocity during newborn leg responses and their suggested implications (i.e., in terms of differences in underlying muscle activity and a development of leg movement control along a right-to-left gradient).

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• In addition, exploring the kinematics of leg movements in healthy preterm infants (i.e., with no neurological pathologies) could provide a possibility to examine if expressions of laterality are present already in the “prenatal” lower body motor behavior.

• In terms of newborn leg responses, there is also a need for longitudinal studies to learn whether the revealed patterns of laterality are persistent or change from the neonatal period up to the achievement of independent walking.

• Broadening the scope to the development of functional asymmetries across the body, such studies could be encouraged to explore how upper and lower body motor asymmetries co-develop beyond the newborn period.

• It would also be of importance to more rigorously investigate state-related effects on different newborn functional asymmetries in order to separate between asymmetries that are susceptible to supraspinal modulation and those that are not.

• Continued longitudinal kinematic studies of functional asymmetries in arm-hand movements are further needed to confirm the findings of developmental patterns in goal-directed reaching and their implications for the developmental origins of handedness. Such studies should also preferably involve a larger sample; including infants developing both right and left hand preferences.

• Studies examining reaching-grasping in adults have been able to show differences in joint coordination patterns between the dominant and non-dominant arm (Sainburg & Kalakanis, 2000), but not in the pre-shaping of the right and left hand (Grosskopf & Kuhtz-Buschbeck, 2006). Thus, incorporating analyses of intra-joint dynamics also in infant reaching studies would be interesting with regard to further exploration of the relationship between asymmetries in the movements of the shoulder, arm and hand from a developmental perspective.

• Moreover, there is a also a need for additional longitudinal studies involving a larger sample of preterm infants, representing a variety of gestational ages, to more fully pursue the developmental patterns associated with preterm birth.

• Adding structural brain imaging technique such as magnetic resonance imaging (MRI) to these investigations could further provide the means to identify structural brain abnormalities contributing to deviations in movement and movement-based

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asymmetries in the preterm children (i.e., by means of comparing various outcome parameters gathered from those with and without structural deviations, as well as relating brain structure parameters to kinematic parameters).

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REFERENCES Amiel-Tison, C. & Grenier, A. (1983). Neurological evaluation of the

newborn and the infant. New York: Masson. Archer, L.A., Campbell, D., & Segalowitz, S.J. (1988). A prospective

study of hand preference and language development in 18-month-olds to 30-month-olds. 1. Hand preference. Developmental Neuropsychology, 4, 85-92.

Barr, R.G., Pantel, M.S., Young, S.N., Wright, J.H., Hendricks, L.A., & Gravel, R. (1999). The response of crying newborns to sucrose: Is it a “sweetness” effect? Physiological Behavior, 66, 409-417.

Bergenn, V.W., Dalton, T.C., & Lipsitt, L.P. (1992). Myrtle B. McGraw: a growth scientist. Developmental Psychology, 3, 381-395.

Berthier, N.E., Clifton, R.K., McCall, D.D., & Robin, D.J. (1999). Proximodistal structure of early reaching in human infants. Experimental Brain Research, 127, 259-269.

Bishop, D.V.M. (1990). Handedness and developmental disorder. Clinics in Developmental Medicine No. 110. London: Mac Keith Press.

Blass, E.M., & Smith, B.A. (1992). Differential effects of sucrose, fructose, glucose and lactose on crying in 1- to 3-day-old human infants: qualitative and quantitative considerations. Developmental Psychology, 28, 804-810.

Blass, E.M., & Watt, L.B. (1999). Suckling- and sucrose-induced analgesia in human newborns. Pain, 83, 611-623

Brackenbridge, C.J. (1981). Secular variation handedness over ninety years. Neuropsychologia, 19, 459-462.

Brinkman, J., & Kuypers, H.G.J.M. (1973). Cerebral control of contralateral and ipsilateral arm, hand and finger movements in the split-brain rhesus monkey. Brain, 96, 653-674.

Brooks, V.B. (1986). The Neural Basis of Motor Control. New York: Oxford University Press.

Butterworth, G., & Hopkins, B. (1993). Origins of handedness in human infants. Developmental Medicine and Child Neurology, 35, 177-184.

Casaer, P. (1979). Postural behaviour in newborn infants. Clinics in Developmental Medicine No. 72. London: William Heinemann Medical Books.

Casaer, P., O’Brien, M.J., & Prechtl, H.F.R. (1973). Postural behaviour in human newborns. Aggressologie, 14B, 49-56.

,

66

Chang, J.-J., Wu, T.-I., Wu, W.-L., & Su, F.-C. (2005). Kinematical measure for spastic reaching in children with cerebral palsy. Clinical Biomechanics, 20, 381-388.

Chiari, L., Della Croce, U., Leardini, A., & Cappozzo, A. (2005). Human movement analysis using stereophotogrammetry Part 2: Instrumental errors. Gait and Posture, 21, 197-211.

Cioni, G. (2003). Observation of general movements in newborns and young infants: Prognostic and diagnostic value. Revista De Neurologia, 37, 30-35.

Cioni, G., & Pellegrinetti, G. (1982). Lateralization of sensory and motor functions in human neonates. Perceptual and Motor Skills, 45, 1151-1158.

Corballis, M.C. (1997). The genetics and evolution of handedness. Psychological Review, 4, 714-727.

Corbetta, D., & Thelen, E. (1995). A method for identifying the initiation of reaching movements in natural prehension. Journal of Motor Behavior, 27, 285-293.

Corbetta, D., & Thelen, E. (1996). The developmental origins of bimanual coordination: A dynamic perspective. Journal of Experimental Psychology, 22, 502-522.

Corbetta, D., & Thelen, E. (1999). Lateral biases and fluctuations in infants’ spontaneous arm movements and reaching. Developmental Psychobiology, 34, 237-255.

Corbetta, D., Thelen, E., & Johnson, K. (2000). Motor constraints on the development of perception-action matching in infant reaching. Infant Behavior & Development, 23, 351-374.

Cornwell, K., Fitzgerald, H.E., & Harris, L.J. (1985). Neurobehavioral reorganization in early infancy: Patterns of head orientation following lateral and midline holds. Infant Mental Health Journal, 6, 126-136.

Denenberg, V.H. (1988). Laterality in animals: Brain and behavioural asymmetries and the role of early experiences. In: D.L. Molfese, & S.J. Segalowitz (Eds.), Brain lateralization in children. Developmental implications (pp. 59-71). New York: The Guilford Press.

Della Croce, U., Leardini, A., Chiari, L., & Cappozzo, A. (2005). Human movement analysis using stereophotogrammetry Part 4: assessment of anatomical landmark misplacement and its effects on joint kinematics. Gait and Posture, 21, 226-237.

DiPietro, J.A., Larson, S.K., & Porges, S.W. (1987). Behavioral and heart rate pattern differences between breast-fed and bottle-fed neonates. Developmental Psychology, 23, 467-474.

67

Domellöf, E., & Rönnqvist, L. (2004). Handedness and footedness in Swedish 6-year-old children. International Journal of Psychology, 39(Suppl. S), 205-205.

Domellöf, E., & Rönnqvist, L. (2006). Effects of finger markers on the kinematics of reaching movements in young children and adults. Manuscript submitted for publication.

Domellöf, E., Hopkins, B., & Rönnqvist, L. (2003). Glucose effects on stepping and placing responses in newborn infants. European Journal of Pediatrics, 162, 545-547.

Einspieler, C., Cioni, G., Paolicelli, P.B., Bos, A.F., Dressler, A., Ferrari, F., Roversi, M.F., & Prechtl, H.F.R. (2002). The early markers for later dyskinetic cerebral palsy are different from those for spastic cerebral palsy. Neuropediatrics, 33, 73-78.

Erberich, S.G., Panigrahy, A., Friedlich, P., Seri, I., Nelson, M.D., & Gilles, F. (2006). Somatosensory lateralization in the newborn brain. Neuroimage, 29, 155-161.

Eyre, J.A., Miller, S., Clowry, G.J., Conway, E.A., & Watts, C. (2000). Functional corticospinal projections are established prenatally in the human foetus permitting involvement in the development of spinal motor centres. Brain, 123, 51-64.

Eyre, J.A., Miller, S., & Clowry, G.J. (2002). The development of the corticospinal tract in humans. In: A. Pascual-Leone, N.J. Davey, J. Rothwell, E.M. Wasserman, & B.K. Puri (Eds.), Handbook of transcranial magnetic stimulation (pp. 235-249). London: Arnold.

Eyre, J.A., Taylor, J.P., Villagra, F., Smith, M., & Miller, S. (2001). Evidence of activity-dependent withdrawal of corticospinal projections during human development. Neurology, 57, 1543-1554.

Fagard, J. (1998). Changes in grasping skills and the emergence of bimanual coordination during the first year of life. Clinics in Developmental Medicine, 147, 123-143.

Fagard, J., & Jacquet, A.Y. (1996). Changes in reaching and grasping objects of different sizes between 7 and 13 months of age. British Journal of Developmental Psychology, 14, 65-78.

Fagard, J., & Lockman, J.J. (2005). The effect of task constraints on infants’ (bi)manual strategy for grasping and exploring objects. Infant Behavior & Development, 28, 305-315.

Fagard, J., & Marks, A. (2000). Unimanual and bimanual tasks and the assessment of handedness in toddlers. Developmental Science, 3, 137-147.

68

Fagard, J., & Pezé, A. (1997). Age changes in interlimb coupling and the development of bimanual coordination. Journal of Motor Behavior, 29, 199-208.

Fallang, B., Saugstad, O.G., Grøgaard, J., & Hadders-Algra, M. (2003). Kinematic quality of reaching movements in preterm infants. Pediatric Research, 53, 836-842.

Ferrari, F., Cioni, G., Einspieler, C., Roversi, M.F., Bos, A.F., Paolicelli, P.B., Ranzi, A., & Prechtl, H.F.R. (2002). Cramped synchronized general movements in preterm infants as an early marker for cerebral palsy. Archives of Pediatrics & Adolescent Medicine, 156, 460-467.

Fetters, L., & Todd, J. (1987). Quantitative assessment of infant reaching movements. Journal of Motor Behavior, 19, 147-166.

Forssberg, H. (1981). Något om utvecklingsreflexernas centralnervösa styrning [About the neural control of developmental reflexes]. Utveckling av centralnervösa reglermekanismer för människans motorik [Development of neural regulatory mechanisms for human motor functioning] (pp. 105-117). Skövde: RBU-Folksam.

Forssberg, H. (1985). Ontogeny of human locomotor control I. Infant stepping, supported locomotion and transition to independent locomotion. Experimental Brain Research, 57, 480-493.

Forssberg, H., & Grillner, S. (1973). The locomotion of the acute spinal cat injected with clonidine iv. Brain Research, 50, 184-186.

Forssberg, H., Eliasson, A.C., Kinoshita, H., Johansson, R.S., & Westling, G. (1991). Development of human precision grip I: basic coordination of force. Experimental Brain Research, 85, 451-457.

Gesell, A. (1940). The first five years of life. A guide to the study of the preschool child. New York: Harper & Row.

Gesell, A., & Ames, L.B. (1947). The development of handedness. Journal of Genetic Psychology, 70, 155-175.

Giménez, M., Junqué, C., Narberhaus, A., Caldú, X, Salgado-Pineda, S., Bargalló, N., Segarra, D., & Botet, F. (2004). Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity. Neuroimage, 23, 869-877.

Grattan, M. P., Vos, E. de, Levy, J., & McClintock, M. K. (1992). Asymmetric action in the human newborn: Sex differences in patterns of organization. Child Development, 63, 273-289.

Grillner, S., & Wallen, P. (1985). Central pattern generators for locomotion, with special reference to vertebrates. Annual Review of Neuroscience, 8, 233-261.

69

Grosskopf, A., & Kuhtz-Buschbeck, J.P. (2006). Grasping with the left and right hand: A kinematic study. Experimental Brain Research, 168, 230-240.

Hadders-Algra, M. (2004). General movements: A window for early identification of children at high risk for developmental disorders. Journal of Pediatrics, 145, S12-S18.

Hadders-Algra, M., Nakae, Y., Eykern, L.A. van, Klip van den Nieuwendijk, A.W.J., & Prechtl, H.F.R. (1993). The effect of behavioral state on general movements in healthy full-term newborns: A polymyographic study. Early Human Development, 35, 63-79.

Haynes, R.L., Borenstein, N.S., Desilva, T.M., Folkerth, R.D., Liu, L.G., Volpe, J.J., & Kinney, H.C. (2005). Axonal development in the cerebral white matter of the human fetus and infant. The Journal of Comparative Neurology, 484, 156-167.

Heide, J.C. van der, Fock, J.M., Otten, B., Stremmelaar, E., & Hadders-Algra, M. (2005). Kinematic characteristics of reaching movements in preterm children with cerebral palsy. Pediatric Research, 57, 883-889.

Hepper, P.G., McCartney, G.R., & Shannon, E.A. (1998). Lateralised behavior in first trimester human fetuses. Neuropsychologia, 6, 531-534.

Hepper, P.G., Shahidullah, S., & White, R. (1990). Origins of fetal handedness. Nature, 347, 431.

Hepper, P.G., Wells, D.L., & Lynch, C. (2005). Prenatal thumb sucking is related to postnatal handedness. Neuropsychologia, 43, 313-315.

Hofsten, C. von (1979). Development of visually guided reaching: the approach phase. Journal of Human Movement Studies, 5, 160-178.

Hofsten, C. von (1980). Predictive reaching for moving objects by human infants. Journal of Experimental Child Psychology, 30, 369-382.

Hofsten, C. von (1983). Catching skills in infancy. Journal of Experimental Child Psychology, 9, 75-85.

Hofsten, C. von (1991). Structuring of early reaching movements: a longitudinal study. Journal of Motor Behavior, 23, 280-292.

Hofsten, C. von (1992). The gearing of early reaching to the environment. In G.E. Stelmach & J. Requin (Eds.), Tutorials in motor behavior II (pp. 287-305). Amsterdam: North Holland.

Hofsten, C. von, & Fazel-Zandy, S. (1984). Development of visually guided hand orientation in reaching. Journal of Experimental Child Psychology, 38, 208-219.

Hofsten, C. von, & Lindhagen, K. (1979). Observations on the development of reaching for moving objects. Journal of Experimental Child Psychology, 28, 158-173.

70

Hofsten, C. von, & Rönnqvist, L. (1988). Preparation for grasping an object: a developmental study. Journal of Experimental Psychology, 14, 610-621.

Hofsten, C. von, & Rönnqvist, L. (1993). The structuring of neonatal arm movements. Child Development, 64, 1046-1057.

Hoon, A.H., Lawrie, W.T., Melhem, E.R., Reinhardt, E.M., Zijl, P.C.M. van, Solaiyappan, M., Jiang, H., Johnston, M.V., & Mori, S. (2002). Diffusion tensor imaging of periventricular leukomalacia shows affected sensory cortex white matter pathways. Neurology, 59, 752-756.

Hopkins, B. (2002). Developmental disorders: an action-based account. In J. Valsiner & K.J. Connolly (Eds.), Handbook of Developmental Psychology. London: Sage.

Hopkins, B., Lems, W., Janssen, B., & Butterworth, G. (1987). Postural and motor asymmetries in newlyborns. Human Neurobiology, 6, 153-156.

Hopkins, B., & Rönnqvist, L. (1998). Human handedness: Developmental and evolutionary perspectives. In F. Simion & G. Butterworth (Eds.), The development of sensory, motor and cognitive capacities in early infancy: From perception to cognition (pp. 191-236). East Sussex: Psychology Press.

Hopkins, B., & Rönnqvist, L. (2002). Facilitating postural control: Effects on the reaching behavior of 6-month-old infants. Developmental Psychobiology, 40, 168-182.

Humphrey, T. (1964). Some correlations between the appearance of human fetal reflexes and the development of the nervous system. Progress in Brain Research, 4, 93-135.

Jeannerod, M. (1984). The timing of natural prehension movements. Journal of Motor Behavior, 16, 235-254.

Jongmans, M.J., Mercuri, E., Dubowitz, L.M.S., & Henderson, S.E. (1998) Perceptual-motor difficulties and their concomitants in six-year-old children born prematurely. Human Movement Science, 17, 629-653.

Jouen, F. (1992). Head position and posture in newborn infants. In A. Berthoz, W. Graf, & P.P. Vidal (Eds.), The Head-Neck Sensory Motor System (pp. 118-120). Oxford: Oxford University Press.

Kamptner, L. N., Cornwell, K. S., Fitzgerald, H. E., & Harris, L. J. (1985). Motor asymmetries in the human infant: Stepping movements. Infant Mental Health Journal, 6, 145-157.

Kandel, E.R., Schwartz, J.H., & Jessell, T.M. (1991). Principles of neural science (3rd ed.). New York: Elsevier Science Publishing Co, Inc.

71

Kolb, B., & Wishaw, I.Q. (1996). Fundamentals of human neuropsychology (4th ed.). New York: W.H. Freeman and Company.

Korczyn, A. D., Sage, J. I., & Karplus, M. (1978). Lack of limb motor asymmetry in the neonate. Journal of Neurobiology, 9, 483-488.

Kuban, K.C.K., Allred, E.N., Dammann, O., Pagano, M., Leviton, A., Share, J., Abiri, M., Di Salvo, D., Doubilet, P., Kairam, R., Kazam, E., Kirpekar, M., Rosenfeld, D.L., Sanocka, U.M., & Schonfeld, S.M. (2001). Topography of cerebral white-matter disease of prematurity studied prospectively in 1607 very-low-birthweight infants. Journal of Child Neurology, 16, 401-408.

Kuypers, H.G.J.M. (1962). Corticospinal connections: Postnatal development in the rhesus monkey. Science, 138, 678-680.

Lawrence, D.G., & Hopkins, D.A. (1976). The development of motor control in the rhesus monkey: Evidence concerning the role of corticomotoneuronal connections. Brain, 99, 235-254.

Lemon, R.N. (2002, January). Historical review and overview of brain circuitry in limb motor control. Paper presented at the meeting of the National Network in Neuroscience on Neural control of motor behavior, Umeå, Sweden.

Liederman, J., & Kinsbourne, M. (1980). Rightward bias in neonates depends upon parental right handedness. Neuropsychologia, 18, 579-584.

Liederman, J. (1987). Neonates show an asymmetric degree of head rotation but lack an asymmetric tonic neck reflex asymmetry: Neuropsychological implications. Developmental Neuropsychology, 3, 101-112.

Liederman, J. (1983). Mechanisms underlying instability in the development of hand preference. In G. Young, S. Segalowitz, C. Corter, & S. Trehub (Eds.), Manual specialization and the developing brain (pp. 71-92). New York: Academic Press.

Lucas, A., & St James-Roberts, I. (1998). Crying, fussing and colic behaviour in breast- and bottle-fed infants. Early Human Development, 53, 9-18.

Marlow, N., Roberts, B.L., & Cooke, R.W.I. (1989). Laterality and prematurity. Archives of Disease in Childhood, 64, 1713-1716.

Martin, J.H. (2005). The corticospinal system: From development to motor control. Neuroscientist, 2, 161-173.

Martin, J.H., Choy, M., Pullman, S., & Meng, Z. (2004). Corticospinal system development depends on motor experience. Journal of Neuroscience, 24, 2122-2132.

72

Massion, J. (1998). Postural control systems in developmental perspective. Neuroscience and Biobehavioral Reviews, 22, 465-472.

Matiello, D. & Woollacott, M. (1997). Postural control in children: development in typical populations and in children with cerebral palsy and Down syndrome. In: K. J. Connolly & H. Forssberg (Eds.), Neurophysiology & Neuropsychology of Motor Development (pp. 54-77). London, UK: Mac Keith Press.

McCartney, G., & Hepper, P. (1999). Development of lateralized behaviour in the human fetus from 12 to 27 weeks’ gestation. Developmental Medicine & Child Neurology, 41, 83-86.

McGraw, M.B. (1940). Neuromuscular development of the human infant as exemplified in the achievement of erect locomotion. Journal of Pediatrics, 17, 747-777.

McManus, I.C., & Bryden, M.P. (1993). The neurobiology of handedness, language, and cerebral dominance: A model for the molecular genetics of behavior. In: M.H. Johnson (Ed.), Brain development and cognition (pp. 679-702). Oxford: Blackwell.

Melekian, B. (1981). Lateralization in the human newborn at birth: Asymmetry of the stepping reflex. Neuropsychologia, 19, 707-711.

Meng, Z., Li, Q., & Martin, J.H. (2004). The transition from development to motor control function in the corticospinal system. Journal of Neuroscience, 24, 605-614.

Michel, G.F. (1981). Right-handedness: A consequence of infant supine head-orientation prefererence? Science, 212, 685-687.

Michel, G.F. (1983). Development of hand-use preference during infancy. In G. Young, S. Segalowitz, C. Corter, & S. Trehub (Eds.), Manual specialization and the developing brain (pp. 33-70). New York: Academic Press.

Michel, G.F., & Harkins, D.A. (1986). Postural and lateral asymmetries in the ontogeny of handedness during infancy. Developmental Psychobiology, 19, 247-258.

Morange-Majoux, F., Peze, A., & Bloch, H. (2000). Organisation of left and right hand movement in a prehension task: A longitudinal study from 20 to 32 weeks. Laterality, 5, 351-362.

Müller, K., & Hömberg, V. (1992). Development of speed of repetitive movements in children is determined by structural changes in corticospinal efferents. Neuroscience Letters, 144, 57-60.

Myklebust, B.M., & Gottlieb, G.L. (1997). Spinal reflex organization in early development: electrophysiological measures and proposed motor pathways. Mental Retardation and Developmental Disabilities Research Reviews, 3, 175-183.

,

73

Nijhuis, J.G. (2003). Fetal behavior. Neurobiology of Aging, 24, S41-S46. O’Callaghan, M.J., Burn, Y.R., Mohay, H.A., Rogers, Y., & Tudehope,

D.I. (1993a). The prevalence and origins of left hand preference in high-risk infants, and its implications for intellectual, motor and behavioral performance at 4 and 6 years. Cortex, 29, 617-627.

O’Callaghan, M.J., Burn, Y.R., Mohay, H.A., Rogers, Y., & Tudehope, D.I. (1993b). Handedness in extremely low birth weight infants: Aetiology and relationship to intellectual abilities, motor performance and behavior at 4 and 6 years. Cortex, 29, 629-637.

Oberlander, T.F., Barr, R.G., Young, S.N., & Brian, J.A. (1992). Short-term effects of feed composition on sleeping and crying in newborns. Pediatrics, 90, 733-740.

Olivier, E., Edgley, S.A., Armand, J., & Lemon, R.N. (1997). An electrophysiological study of the postnatal development of the corticospinal system in the Macaque monkey. Journal of Neuroscience, 1, 267-276.

Peiper, A. (1963). Cerebral Function in Infants and Early Childhood. New York: Consultants Bureau.

Peters, M., & Petrie, B. F. (1979). Functional asymmetries in the stepping reflex of human neonates. Canadian Journal of Psychology, 33, 198-200.

Peterson, B.S., Anderson, A.W., Ehrenkranz, R., Staib, L.H., Tageldin, M., Colson, E., Gore, J.C., Duncan, C.C., Makuch, R., & Ment, L.R. (2003). Regional brain volumes and their later neurodevelopmental correlates in term and preterm infants. Pediatrics, 111, 939-948.

Piek, J.P. (2001). Is a quantitative approach useful in the comparison of spontaneous movements in fullterm and preterm infants? Human Movement Science, 20, 717-736.

Piek, J.P. (2002). The role of variability in early motor development. Infant Behavior and Development, 25, 452-465.

Porac, C., & Coren, S. (1981). Lateral preferences and human behavior. New York: Springer-Verlag.

Prechtl, H.F.R. (1974). The behavioural states of the newborn infant (a review). Brain Research, 76, 185-212.

Prechtl, H.F.R. (1977). The neurological examination of the full term newborn infant. Clinics in Developmental Medicine No. 63 (2nd ed.). London: Willjam Heinemann Medical Books.

Prechtl, H.F.R., & O’Brien, M.J. (1982). Behavioural states of the full-term newborn. The emergence of a concept. In P. Stratton (Ed.), Psychobiology of the Human Newborn (pp. 53-73). West Sussex: John Wiley & Sons, Ltd.

74

Prechtl, H.F.R., Einspieler, C., Cioni, G., Bos, A.F., Ferrari, F., & Sontheimer, D. (1997). An early marker for neurological deficits after perinatal brain lesions. Lancet, 349, 1361-1363.

Previc, F.H. (1991). A general theory concerning the prenatal origins of cerebral lateralization in humans. Psychological Review, 98, 299-334.

Provins, K.A. (1997). Handedness and speech: A critical reappraisal of the role of genetic and environmental factors in the cerebral lateralization of function. Psychological Review, 104, 554-571.

Pryde, K.M., Roy, E.A., & Campbell, K. (1998). Prehension in children and adults: the effects of object size. Human Movement Science, 17, 743-752.

Rochat, P. (1992). Self-sitting and reaching in 5- to 8-month-old infants: The impact of posture and its development on early eye-hand coordination. Journal of Motor Behavior, 24, 210-220.

Roelants-van Rijn, A.M., Groenendaal, F., Beek, F.J.A., Eken, P., van Haastert, I.C., & Vries, L.S. de (2001). Parenchymal brain injury in the preterm infant: Comparison of cranial ultrasound, MRI and neurodevelopmental outcome. Neuropediatrics, 32, 80-89.

Rönnqvist, L. (1993). Arm and hand movements in neonates and young infants. Doctoral dissertation, Umeå University, Umeå, Sweden.

Rönnqvist, L. (1995). A critical examination of the Moro response in newborn infants – symmetry, state relation, underlying mechanisms. Neuropsychologia, 33, 713-726.

Rönnqvist, L. & Hofsten, C. von (1994). Neonatal finger and arm movements as determined by a social and an object context. Early Development and Parenting, 3, 81-94.

Rönnqvist, L., & Hopkins, B. (1998). Head position preference in the human newborn: a new look. Child Development, 69, 13-23.

Rönnqvist, L., Hopkins, B., Emmerik, R. van, & Groot, L. de (1998). Lateral biases in head turning and the Moro response in the human newborn: Are they both vestibular in origin? Developmental Psychobiology, 33, 339-349.

Rönnqvist, L., & Hopkins, B. (2000). Motor asymmetries in the human newborn are state dependent, but independent of position in space. Experimental Brain Research, 134, 378-384.

Sainburg, R.L., & Kalakanis, D. (2000). Differences in control of limb dynamics during dominant and nondominant arm reaching. Journal of Neurophysiology, 83, 2661-2675.

Saling, M. (1979). Lateral differentiation of the neonatal head turning response: A replication. Journal of Genetic Psychology, 135, 307-308.

,

75

Sarnat, H.B. (2003). Functions of the corticospinal and corticobulbar tracts in the human newborn. Journal of Pediatric Neurology, 1, 3-8.

Schmidt, R.A., & Lee, T.D. (1999). Motor control and learning. A behavioral emphasis. Champaign: Human Kinetics.

Shumway-Cook, A., & Woollacott, M.H. (2001). Motor control. Theory and practical applications (2nd ed.). Baltimore: Lippincott Williams & Wilkins.

Sun, T., Patoine, C., Abu-Khalil, A., Visvader, J., Sum, E., Cherry, T.J., Orkin, S.H., Geschwind, D.H., & Walsh, C.A. (2005). Early asymmetry of gene transcription in embryonic human left and right cerebral cortex. Science, 308, 1794-1798.

Taft, L.T., & Cohen, H.J. (1967). Neonatal and infant reflexology. In J. Helmuth (Ed.), Exceptional infant (Vol. 1, pp. 81-120). Seattle: Special Child Publications.

Ten Donkelaar, H.J., Lammens, M., Wesseling, P., Hori, A., Keyser, A., & Rotteveel, J. (2004). Development and malformations of the human pyramidal tract. Journal of Neurology, 251, 1429-1442.

Thelen, E. (1985). Developmental origins of motor coordination: Leg movements in human infants. Developmental Psychobiology, 18, 1-22.

Thelen, E. (1995). Motor development: A new synthesis. American Psychologist, 50, 79-95.

Thelen, E., & Adolph, K.E. (1992). Arnold L. Gesell: the paradox of nature and nurture. Developmental Psychology, 3, 368-380.

Thelen, E., & Cooke, D.W. (1987). Relationship between newborn stepping and later walking – A new interpretation. Developmental Medicine and Child Neurology, 29, 380-393.

Thelen, E., & Fisher, D.M. (1982). Newborn stepping: An explanation for a “disappearing reflex”. Developmental Psychology, 18, 760-775.

Thelen, E., & Fisher, D.M. (1983). The organization of spontaneous leg movements in newborn infants. Journal of Motor Behavior, 15, 353-377.

Thelen, E., & Smith, L.B. (1994). A dynamic systems approach to the development of cognition and action. Cambridge, MA: MIT Press.

Thelen, E., & Spencer, J.P. (1998). Postural control during reaching in young infants: A dynamic systems approach. Neuroscience and Biobehavioral Reviews, 22, 507-514.

Thelen, E., Corbetta D., & Spencer, J.P. (1996). Development of reaching during the first year: Role of movement speed. Journal of Experimental Psychology, 22, 1059-1076.

76

Thelen, E., Fisher, D.M., Ridley-Johnson, R., & Griffin, N. (1982). The effects of body build and arousal on newborn infant stepping. Developmental Psychobiology, 15, 447-453.

Thelen, E., Fisher, D.M., & Ridley-Johnson, R. (1984). The relationship between physical growth and a newborn reflex. Infant Behavior and Development, 7, 479-493.

Thelen, E., Kelso, J.A.S., & Fogel, A. (1987). Self-organizing systems and infant motor development. Developmental Review, 7, 39-65.

Touwen, B.C.L. (1976). Neurological development in infancy. London: Heinemann.

Trehub, S.E., Corter, C.M., & Shosenberg, N. (1983). Neonatal reflexes: A search for lateral asymmetries. In G. Young, S. Segalowitz, C. Corter, & S. Trehub (Eds.), Manual specialization and the developing brain (pp. 257-274). New York: Academic Press.

Turkewitz, G. (1977). The development of lateral differences in the human infant. In S.R. Harnad, R.W. Doty, L. Goldstein, J. Jaynes, & G. Krauthamer (Eds.), Lateralization in the nervous system (pp. 251-259). San Diego, CA: Academic Press.

Ulrich, B.D. (1989). Development of stepping patterns in human infants: A dynamical systems perspective. Journal of Motor Behavior, 21, 392-408.

Vaal, J., Soest, A.J. van, & Hopkins, B. (1995). Modelling the early development of bipedal locomotion: A multidisciplinary approach. Human Movement Science, 14, 609-636.

Vaal, J., Soest, A.J. van, Hopkins, B., Sie, L.T.L., & Knaap, M.S. van der (2000). Development of spontaneous leg movements in infants with and without periventricular leukomalacia. Experimental Brain Research, 135, 94-105.

Ververs, I.A.P., Vries, J.I.P. de, Geijn, H.P. van, & Hopkins, B. (1994). Prenatal head position from 12-38 weeks: I. Developmental aspects. Early Human Development, 39, 83-91.

Voss, H. (1937). Untersuchungen über Zahl, Anordung und Lange der Muskelspindeln in den Lumbralmuskeln des Menschen und einiger Tiere [Investigations of number, organization and length of lumbral muscle spindles in humans and animals]. Zeitschrift für Mikroscopisch Anatomisch Forschung, 42, 509-524.

Vries, J.I.P. de, Visser, G.H.A., & Prechtl, H.F.R. (1982). The emergence of fetal behaviour. I. Quantitative aspects. Early Human Development, 7, 301-322.

Vries, J.I.P. de, Visser, G.H.A., & Prechtl, H.F.R. (1984). Fetal motility in the first half of pregnancy. In H.F.R. Prechtl (Ed.), Continuity of

77

neural function from prenatal to postnatal life. London: Spastics International Medical Publications.

Vries, J.I.P. de, Wimmers, R.H., Ververs, I.A.P., Hopkins, B., Savelsbergh, G.J.P., & Geijn, H.P. van (2001). Fetal handedness and head position preference: A developmental study. Developmental Psychobiology, 39, 171-178.

Watt, S.J., Bradshaw, M.F., Clarke, T.J., & Elliott, K.M. (2003). Binocular vision and prehension in middle childhood. Neuropsychologia, 41, 415-420.

Wimmers, R.H., Savelsbergh, G.J.P., Kamp, J. van der, & Hartelman, P. (1998). A developmental transition in prehension modeled as a cusp catastrophe. Developmental Psychobiology, 32, 23-35.

Yang, J.F., Lamont, E.V., & Pang, M.Y.C. (2005). Split-belt treadmill stepping in infants suggests autonomous pattern generators for the left and right leg in humans. Journal of Neuroscience, 25, 6869-6876.

Yang, J.F., Stephens, M.J., & Vishram, R. (1998). Infant stepping: a method to study the sensory control of human walking. Journal of Physiology, 507, 927-937.

Zappella, M. (1966). The placing reaction in the first year of life. Developmental Medicine Child Neurology, 8, 393-401.