the internal control of action and parkinson's disease: a kinematic analysis of visually-guided...

Exp Brain Res (1995) 105:147-162 �9 Springer-Verlag 1995

S.R. Jackson �9 G.M. Jackson �9 J. Harrison �9 L. Henderson C. Kennard

The internal control of action and Parkinson's disease: a kinematic analysis of visually-guided and memory-guided prehension movements

Received: 17 November 1994 / Accepted: 9 March 1995

Abstract This paper reports two experiments which examined the effects of Parkinson's disease (PD) upon the sensorimotor mechanisms used to control prehension movements. Transport and grasp kinematics for visually-guided and memory-guided prehension movements were examined in healthy control subjects and compared against those of patients with idiopathic PD. Two research questions were addressed: (1) Are patients with PD particularly susceptible to distraction by non-relevant objects? (2) Are patients with PD especially reliant on external feedback when executing goal-directed actions? The results indicated that the patient group were no more susceptible to distraction by non-relevant objects than the control group. In contrast, the patients with PD were shown to be significantly, impaired when executing memory-guided reaches. Furthermore, the deficits exhibited by the PD group on memory-guided reaches were confined solely to those markers associated with the transport component of the prehension movement. That is, while both controls and patients with PD widened their grip aperture on memory-guided trials, the magnitude of this adjustment was comparable across the two groups. The implications of these findings for theories of visuomotor processing in sufferers of PD and the control of prehension movements more generally are discussed.

Key words Prehension �9 Reach to grasp �9 Working memory �9 Visual attention �9 Visual feedback - Human

J. Harrison - L. Henderson �9 C. Kennard Clinical Neuroscience Unit, Charing Cross and Westminster Medical School, Chafing Cross Hospital, London W6 8RF, UK

S.R. Jackson ( ~ ) �9 G.M. Jackson Human Movement Laboratory, School of Psychology, University of Wales, Bangor, Gwynedd LL57 2DG, UK; Fax no.: +44-248-382599; e-mail: [email protected]

Introduction

Parkinson's disease (PD) is characterised by an inability to initiate and control voluntary movement (akinesia and bradykinesia) and rigidity of the musculature, which may be accompanied by limb tremor at rest. These physical symptoms are associated with neural degenera- tion of nigrostriatal dopamine projections within the basal ganglia. The basal ganglia receive neural projections from both motor and sensory cortices and are be- lieved to integrate information originating within different cortical regions to control aspects of voluntary behaviour. Patients with PD exhibit considerable difficulty initiating and controlling voluntary movements, despite being able to perform reflexive movements quite normally (Benecke et al. 1986). Furthermore, such problems are compounded when patients are required to control behaviour in the absence of external feedback. Thus, while patients with PD can accurately track a target moving regularly and predictably, e.g. a saw-tooth pattern on an oscilloscope screen, their performance de- clines when visual feedback is removed, requiring them to make predictive movements (Bloxham et al. 1984). Such findings have led us to suggest that many of the deficits observed in PD can be characterised as a dysfunction in the ability to select between, switch or control actions on the basis of internal forms of representation (Jackson and Houghton 1994; Jackson et al. 1994). More specifically, we have suggested that the basal ganglia provide an important means by which different cortical networks exert control over subcortical structures implicated in visuospatial cognition (e.g. superior col- liculus) and may perform a general computational function concerned with sensorimotor selection (Jackson and Houghton 1994).

Consistent with the view that patients with PD may experience problems in sensorimotor selection, anecdotal accounts from sufferers of PD suggest that movement initiation may become difficult under conditions of visual "clutter", e.g. when reaching for an object placed amongst a number of non-relevant objects (L. Hender-

148

son, October 1994, personal communication). Brown and Marsden (1988) characterise the attentional dysfunction observed in PD as an impairment in the ability to guide behaviour on the basis of internal modes of control. Within this view, distractibility arises as a consequence of an inability to maintain an internally represented behavioural goal "in-mind". This distinction parallels that made by Goldman-Rakic with respect to the visuospatial function of the dorsolateral prefrontal cortex (Goldman- Rakic 1987, 1988, 1992). According to Goldman-Rakic, studies of the effects of prefrontal lesions on the performance by primates on a delayed response task (DRT) suggest that the internal control of voluntary behaviour is dependent on the "central executive" function of the prefrontal cortex, which involves the ability to: select appropriate information; hold that information on-line when the stimulus is no longer present; and; on the basis of the selected information, initiate and execute an appropriate motor response.

Goldman-Rakic and colleagues recently developed an oculomotor version of the DRT. In this taks, a primate trained to maintain fixation was presented with a briefly illuminated visual target and, after a variable delay period, was required to indicate the location of the visual target by making an eye movement to its remembered location (Funahashi et al. 1989). Using this task, Funahashi et al. demonstrated that neurons in the dorsolateral prefrontal cortex coded for the remembered location of a target stimulus. That is, the firing rates of indi- vidual cells were correlated with targets appearing at specific locations. Furthermore, in a subset of these neurons, firing rates increased after the target stimulus had been removed from view, and activity was maintained throughout the delay period (Funahashi et al. 1989, 1990). Finally, these authors also demonstrated that primates with unilateral prefrontal lesions, while not impaired when required to move their eyes to the location of a peripheral target stimulus, were significantly impaired when required to move their eyes to the remembered location of the same target (Funahashi et al. 1986).

A version of the oculomotor delayed response (ODR) task has also been used to investigate visuomotor dysfunction in patients with PD. While they show normal reflex saccades to peripheral targets, patients with PD are frequently impaired when required to make a saccade to the remembered location of a visual target (Crawford et al. 1989; Lueck et al. 1992). Importantly, while frontal lobe lesions have been shown to result in an inability to maintain a spatial memory of the location of the target stimulus, i.e. saccades are generally inaccurate (e.g. increased variable error in the end point of final eye position), the remembered saccades of patients with PD are typically as accurate as those of control subjects, but are frequently hypometric, requiring one or more additional saccades to reach the target location. These results suggest that patients with PD may exhibit a general deficit in executing memory-guided action. Furthermore, the nature of this deficit appears to take the form of a dys-

function in subjects' ability to use memorial information to generate appropriately scaled motor commands.

A critical component of the visual processing associated with the control of goal-directed action may be the selection of a behaviourally relevant object from amongst one or more behaviourally non-relevant objects. Jackson et al. (1995), recently examined transport and grasp kinematics for both visually-guided and memory-guided prehension movements. In that study, subjects reached for a wooden block presented either alone or else accompanied by a non-target object (wooden cylinder). Their results indicated that when subjects reached for target objects accompanied by non-target flankers under normal viewing conditions, there were no interference effects on reach kinematics and minimal interference effects on grasp kinematics. In contrast, when subjects made memory-guided reaches (i.e. with their eyes closed), there were large interference effects affecting both transport and grasp kinematics. In the current study we report two experiments which examined the ability of patients with PD to execute visually-guided and memory-guided prehension movements. Transport and grasp kinematics were examined in healthy control subjects and compared with those of patients with idiopathic PD. Two specific research questions were addressed: (1) Are patients with PD particularly susceptible to distraction by non-relevant objects? (2) Are patients with PD especially reliant on on-line visual information (external feedback) when executing goal-directed actions?

Materials and methods

Subjects

Parkinson's disease group

Six non-dementing patients with idiopathic PD were recruited from amongst patients attending the Department of Neurology, Charing Cross Hospital, London. This group consisted of four men and two women who had a mean age of 64.2 years. Demo- graphic details are presented in Table 1. None of these patients had a history of head injury or neurological disorder (other than PD), none were taking psychoactive medication or anti-depressants and none had regularly consumed excessive amounts of alcohol. Patients were not selected on the basis of any behavioural criteria.

Table 1 Details of patients with Parkinson's disease

Patient Age Years WCST Webster Mini- (years) since (cats) score mental

onset of /33 /30 illness

l 70 6 6 7 28 2 71 2 2 6 27 3 69 4 6 10 29 4 49 6 5 7 30 5 64 6 6 13 30 6 62 4 6 6 28

M i d saggi ta l

p l ane

Star t ing pos i t ion of the h a n d

T ~

i 20cm

Midline distractor location

lOcm v ~ /

Target positions

Peripheral distractor location

l A W

Fig. 1 The relationship between target and distractor positions adopted in the current study. Targets were placed either 10 cm to the right or left of the sagittal axis. On trials where a distractor was present, the distractor (a wooden cylinder) was placed either at the midline location or at the more peripheral location. In each case tile distractor was placed 10 cm from the target object

Control subjects

Six age-matched but otherwise healthy subjects were recruited to act as a control group (HCS). None of these subjects had a history of head injury or neurological disorder, none were taking psychoactive medication or anti-depressants and none had regularly consumed excessive amounts of alcohol. All subjects had normal or corrected-to-normal vision, and all were paid the sum of s for their participation.

Apparatus and stimuli

Subjects were seated in front of a table, approximately 100 cm 2 with a matt black surface, and made prehension movements towards target objects presented either alone or in the company of a single flanker object. A red wooden block measuring 2.25 cm• c m x l 0 cm) was used as the target object for subjects' prehension movements, and a yellow wooden block of the same dimensions was used as the distractor object. Targets were placed at one of two locations along a line 25 cm from the starting position of the hand. These locations were on opposite sides and equidistant (10 cm) from the subjects' sagittal axis. Distractor objects were placed at one of three locations, either 10 cm more peripheral than the target object (relative to the subject's sagittal axis), or else at a position on the midline (see Fig. 1). In all cases, distractors were located within the same hemispace (ipsilateral/contralateral) as the target and never occupied either of the two target locations.

Prehension movements were made under two types of viewing condition: visually-guided movements, in which subjects reached

149

for target objects under normal binocular viewing conditions, or memory-guided movements, where subjects reached for target objects with their eyes closed.

Procedure

Visually-guided and memory-guided reaches were blocked, as were reaches with the right and left hands. Thus, each subject par- ticipated in four blocks of trials (30 trials per block), which were carried out in a random order and separated by a short break. Each block of 30 trials consisted of 15 trials where subjects reached for a target presented in their ipsilateral hemispace and 15 trials to targets presented in their contralateral hemispace. These 15 trials consisted of the following types: 5 trials to a target object presented without an accompanying distractor; 5 trials to a target presented with a midline distractor; and 5 trials to a target presented with a peripheral distractor. The order of presentation of trials within each block was randomised for each subject.

At the beginning of each test session subjects were tested for handedness. They were then seated at the testing table and instructed on the prehension task. The starting position was indicated by a T-shaped mark 3 cm tall by 4 cm wide. Subjects were instructed to place their right hand flat (palm down) upon the testing table with their hand oriented along the mid-sagittal plane, their middle finger lying slightly behind the horizontal bar of this T marker and their thumb closed against their index finger. They were informed that, once they had placed their hand in the correct position, they would receive an auditory "start" signal and should reach out and grasp the red (target) block along its longest axis, using their index finger and thumb, returning the target block to the "start" position. Subjects were instructed that the red block would always be the target object and that at no time should they pick up the yellow block, which might accompany the target block on some but not all trials. Finally, subjects were asked to try to make their movements as natural as possible. They were not instructed to reach as quickly as possible.

Before commencing the 30 trials making up the first (eyes- open) block, subjects were allowed to carry out a maximum of five practice reaches to the target object presented at a location on the subject's sagittal axis, 25 cm from the start position (note that this location did not correspond to any of the target or distractor locations used within this study).

After completing the block of 30 eyes-open trials, subjects car- fled out 30 trials in which they reached for the target object with their eyes closed. Each eyes-closed trial commenced with the subject placing their fight hand at the starting position in the manner outlined above. The target object (and accompanying distractor where appropriate) was then placed on the testing table and subjects were given a period of approximately 15 s to study the scene on the table top. Subjects were then instructed to close their eyes and approximately 2 s after doing so received the auditory signal to com- mence their reach. All other details were identical to those described for eyes-open trials. As with the eyes-open trials, subjects were provided with a maximum of five practice trials at the start of the block.

Movement recording and data analysis

Hand movements were recorded at a sampling rate of 50 Hz using a MacReflex 3D infra-red motion-analysis system. Three 5 mmx5 mm reflective markers were placed: on the distal portion of the thumbnail, on the distal portion of the index finger, and on the wrist. Two additional markers were fixed to the target and distractor objects, respectively. The three-dimensional (3D) spatial co-ordinates of these markers were analysed off line. Data were filtered using a fourth-order, zero-lag Butterworth digital filter.

Dependent measures

Movement onset was defined as the first frame in which the wrist marker exceeded a velocity (in the direction of movement) of 2.5 crrds. Movement end point was defined as the first frame in which

150

Table 2 Movement time (in milliseconds, with SD in parentheses): reaches with preferred hand (PD Parkinson's disease; HCS healthy controls)

PD group HCS Group

Visually-guided Memory-guided

Ipsilateral Contralateral Ipsilateral Contralateral



No distractor 806.0 862.0 1056.7 970.6 853.6 812.9 (137.6) (131.8) (262.2) (150.0) (165.0) (162.7)

Midline distractor 845.6 884.5 1014.7 1036.9 831.2 802.1 (156.2) (195.1) (199.9) (254.7) (166.9) (133.0)

Peripheral distractor 843.5 917.1 1111.28 1033.6 777.6 875.3 (165.5) (174.6) (227.0) (230.2) (149.4) (191.3)

866.2 879.3 (207.8) (183.8) 882.5 955.5 (201.0) (182.9) 857.6 899.0 (166.1) (208.7)

Table 2A Summary of effects on movement time

Effect F statistic Corrected P value a

Visual availability F1,10=9.2 P<0.01

a dfs were adjusted using the Huynh and Feldt (HF) procedure for epsilon values of 1.0 or less. Where the HF procedure could not be used, the more conservative Greenhouse-Geisser adjustment procedure was adopted

horizontal displacement of the target marker exceeded 0.5 mm. Movement time (MT) was defined as movement end point minus movement onset. The following dependent measures were computed from the 3D co-ordinates for the wrist marker and were used to analyse the kinematics of the transport component of the prehension task: (1) peak velocity in the direction of movement (PV) and (2) deceleration time (DT), i.e. time after PV. The following dependent measures were computed from the 3D co-ordinates for the markers placed on the thumb, index finger and wrist, and were used to analyse the kinematics of the grasp component: (1) peak aperture (PA) between index finger and thumb (measured as the internal angle, in degrees, made by the thumb marker, index finger marker and wrist marker, vertex); (2) time taken to reach PA (TTPA); and (3) time taken to reach PA as a percentage of total movement time (TTPA%).

Results

For each subject, for each dependent variable, mean values were calculated for the five trials in each handxvi- sion availabilityxtype of reachxdistractor position condition. Data were analysed for each hand separately and were entered into a 2x2x3 repeated-measures analysis of variance (ANOVA).

Experiment 1: reaches made using subjects' preferred hand

Movement time

MTs are presented in Table 2. Analysis of these data revealed only one statistically significant effect; this was a main effect of vision availability (F1,1o=9.2, P<0.01). MTs were extended when subjects made memory-guided reaches (visually-guided 842.6-+153.7 ms vs memory- guided 963.7_+209.1 ms).

Transport component

Peak velocity. PVs for each group are presented in Table 3, with a summary table of those factors that bad a significant effect on PV. Mean PVs were considerably reduced when subjects reached to the remembered location of the target object (visually-guided 783.1 mm/s vs memory-guided 687.6 ram/s) and when subjects reached for a target object when an accompanying distractor was present (no distractor 755.1 ram/s; midline distractor 728.0 ram/s; peripheral distractor 723.0 ram/s). Further- more, there were several significant interaction effects. Firstly, in confirmation of our previous finding with young adults (Jackson et al. 1995), there was a significant type of reach_+distractor location interaction (F2,20=23.1, P<0.0001). While PVs for ipsilateral and contralateral reaches did not differ when targets were presented alone (FIA0=2.9, P>-0.1) , PVs were reduced when reaching contralaterally in the presence of a midline distractor compared with ipsilateral reaches accompanied by a midline distractor (F~,~0=33.8, P<0.0001). This effect was reversed, however, for reaches towards targets accompanied by a peripheral distractor. Under these circumstances PVs where substantially reduced on ipsilateral reaches compared with contralateral reaches (F1,10=-14.2, P<0.005).

The type of reachxdistractor location interaction was also found to interact with the visual availability factor (F2,20=6.7, P<0.01). Relevant means are presented in Fig. 2. This interaction effect is accounted for by the fact that, while the difference between ipsilateral and contralateral reaches in the no-distractor condition was statistically significant for visually-guided reaches (Ft,10=4.8, P<0.05), it was not for memory-guided reaches (Fl,10=0.4, P=0.5).

The analyses also revealed a statistically significant groupxvisual availabilityxtype of reach interaction effect (F2,z0=6.4,P<0.05). The simple effects of this interaction were investigated by performing separate analyses of PV for each group. The main finding to arise from these analyses was the following: PVs for the PD group were significantly slowed on memory-guided reaches (F1,5=36.0, P<0.002; visually-guided 773.8_+95.1 mm/s vs memory- guided 639.9_+123.5 ram/s). In contrast, this slowing was not statistically significant for the HCS group (F1,5=2.9,

Table 3 Peak velocity (in millimetres per second): reaches with preferred hand

151

PD group



HCS group

Visually-guided Memory guided

Ipsilateral Contralateral lpsilateral Contralateral

No distractor 810.7 773.0 670.2 665.9 (91.2) (104.6) (143.5) (138.0)

Midline distractor 795.5 739.8 667.4 584.6 (106.2) (80.1) (106.0) (109.1)

Peripheral distractor 750.9 772.8 582.5 669.0 (92.1) (117.1) (88.3) (157.0)

814.1 796.4 762.1 748.2 (115.2) (91.2) (100.4) (68.6) 796.0 780.3 778.8 682.1 (76.1) (48.1) (94.8) (62.0) 762.0 806.3 715.1 725.3 (90.6) (90.3) (70.0) (49.0)

Table 3A Summary of effects on peak velocity


Visual availability F1,10=22.3 P<0.001 Distractor location F2,20=9.3 P<0.005 Groupxvisual availabilityxtype F1,10=6.4 P<0.05 of reach Type of reachxdistractor location F2.20=23.1 P<0.0001 Visual availabilityxtype of reach /72,2o=6.7 P<0.01 xdistractor location


P>0.1; visually-guided 792.5_+83.0mm/s vs memory- guided 735.3_+77.7 ram/s).

D e c e l e r a t i o n time. Table 4 shows mean DTs (expressed as a percentage of total MT) for each group, with a summary table to those factors that had a significant effect on DTs. DTs were extended for ipsilateral reaches (ipsilateral 60.1+7.4% vs contralateral 67.3+7.2%) and also for memory-guided reaches (visually-guided 56.6+6.4% vs memory-guided 60.1+7.8%). Furthermore, the AN- OVA revealed a significant visual availabilityxgroup interaction (FIA0=I 1.7, P<0.01). Analysis of the simple effects of group revealed that, whereas DTs for the patient group were significantly increased for memory-guided reaches (F1,5=21.0, P<0.01), DTs for visually-guided and memory-guided reaches did not differ reliably for the control group (Fl,5=1.1, P=0.3). Relevant means are: PD group, visually-guided 55.6+4.9% vs memory-guided 63.2_+6.9%; HCS group, 57.5+7.5%% vs 58.5_+8.0%.

Finally, the ANOVA also revealed a significant three- way visual availabilityxtype of reachxdistractor position interaction (F2,zo=4.9, P<0.05). Relevant means are presented in Fig. 3. Investigation of this effect was carried out by independently examining the type of reachxdistractor position (TxD) interaction for visually-guided and memory-guided reaches. These analyses revealed that for visually-guided reaches, the TxD interaction was not significant (F2,2o=0.8, P=0.5), whereas for memory-

A Visually-guided

I000

900

E 800

�9 ~- 700

> 600 ~o

500

400

Ipsilateral

No Dist. Midline Peripheral

B Memory-guided

1000 ]

t i 001 .~- 700

600

e. 500

400 No Dist. Midline Peripheral

Fig. 2A, B Peak velocities for ipsilateral and contralateral reaches to targets presented alone or when accompanied by midline or peripheral distractors. A Peak velocities for visually-guided reaches; B peak velocities for memory-guided reaches. Error bars represent the SEM (Dist. distractor)

152

Table 4 Deceleration time (as a percentage of total movement time): reaches with preferred hand

PD group HCS group





No distractor 56.2 55.1 64.1 59.7 59.7 55.2 56.1 57.3 (4.8) (5.7) (8.9) (6.7) (9.5) (5.3) (7.1) (9.9)

Midline distractor 58,4 54.4 63.6 61.8 60.4 55.1 58.9 62.6 (2.4) (3.2) (5.5) (5.8) (8.6) (5.7) (5.2) (7.9)

Peripheral distractor 57.0 52.7 68.4 61.8 58.1 56.5 60.3 56.0 (5.3) (6.8) (7.8) (5.8) (7.3) (9.1) (8.9) (9.2)

Table 4A Summary of effects on deceleration time

Effect F statistic Corrected P value

Visual availability

Groupxvisual availability Type of reach

Visual availabilityxtype of reach xdistractor location

F 1,1o=20.1 P<0.001 Fl,10 =11.7 P<0.01

F1,1o =7.6 P<0.025 F:,2o=4.9 P<0.025

a dfs were adjusted using the Huynh and Feldt (HF) procedure for epsilon values of 1.0 or less. Where the HF procedure could not be used, the more conservative Greenhouse-Geisser adjustment procedure was adopted

Fig. 3A, B Deceleration time (expressed as a percentage of total movement time) for ipsilateral and contralateral reaches to targets presented alone or when accompanied by midline or peripheral distractors. A De- celeration times for visually- guided reaches; B deceleration times for memory-guided reaches. Error bars represent the SEM

A Visually-guided

100

90-

80- i

o

70! O

~, 60 o O o

50

40 No Dist�9

�9 Ipsilateral [] Contralateral

Midline Peripheral

B M e m o r y - g u i d e d

100

90

80 i

= 70 O

- ,~

60 o eD (9

50


Table 5 Peak aperture (degrees): reaches with preferred hand

153

PD group



HCS group



No distractor 33.4 33.2 44.8 43.8 (4.0) (3.1) (5.5) (5.6)

Midline distractor 3l .4 32.7 40.6 38.2 (1.8) (3.1) (5.2) (6.4)


34.1 33.2 43.0 42.5 (4.4) (5.3) (5.1) (5.5) 33.4 32.3 40.0 36.6 (3.9) (3.7) (5.8) (5.0) 31.8 34.2 36.9 39.0 (3.8) (4.1) (6.0) (5.7)

Table 5A Summary of effects on peak aperture


Visual availability Distractor location Visual availabilityxdistractor location Type of reachxdistractor location Visual availabilityxtype of reach • location Group• availabilityxtype of reach• location

F1,10=41.7 P<0.001 F2,20=37.0 P<0.0001 F2,20=16.9 P<0.000I

F2,20=23.8 P<0.0001 F2,20=10.8 P<0.001

F2,20=5.3 P<0.025

a dyes were adjusted using the Huynh and Feldt (HF) procedure for epsilon values of 1.0 or less. Where the HF procedure could not be used, the more conservative Greenhouse-Geisser adjustment procedure was adopted

A

BO {Z}

i

C~

t~ {1)

5O

A ~

No Dist.

�9 Ipsilateral [] Contralateral

Midline Peripheral

guided reaches there was a marginal TxD effect (F2,20=3.0, P=0.07). On memory-guided reaches DTs for ipsilateral and contralateral reaches did not differ when either no accompanying distractor or a midline distractor was present (maximum F~,10=0.8, P=0.4). However, deceleration times for ipsilateral reaches were significantly longer than for contralateral reaches when target objects were presented alongside a peripheral distractor (F1,~0=8.7, P<0.01).

Grasp component

Peak aperture. Table 5 shows mean PAs for each group, with a summary table to those factors that had a significant effect on PA. PAs were significantly greater for memory-guided reaches than for visually-guided reaches (visually-guided 32.9_+3.5 ~ vs memory-guided 40.5+5.8~ but were reduced when subjects reached for targets accompanied by distractor objects (no-distractor trials 38.5_+6.8 ~ midline distractor trials 35.7+5.5~ peripheral distractor trials 36.0_+5.6~ Linear contrasts revealed that trials with midline and peripheral distractors each produced smaller PAs than trials in which the target object was presented alone (minimum Ft,~0=48.6, P<0.0001).

�9 Visually-guided Memory-guided

50

45

"~ 40 t

O3

35

3o

25


Fig. 4A, B Mean peak apertures for ipsilateral and contralateral reaches to targets presented alone or when accompanied by midline or peripheral distractors. A Peak apertures for visually-guided reaches; B peak apertures for memory-guided reaches. Error bars represent the SEM

154

Table 6 Time to peak aperture (as a percentage of total movement time): reaches with preferred hand

PD group HCS group


Ipsilateral Contralateral ipsilateral Contralateral


lpsilateral Contralateral Ipsilateral Contralateral

No distractor 79.8 81.6 69.2 73.4 (10.6) (11.9) (14.4) (10.9)



68.0 70.6 71.5 71.5 (11.1) (7.5) (12.0) (6.3) 70.7 77.6 71.6 75.0 (9.6) (7.4) (7.4) (6.6) 72.0 73.6 69.7 69.3 (11.9) (8.0) (15.1) (11.1)

Table 6A Summary of effects on time aperture

Effect F statistic Corrected P v a l u e a

Distractor location F2,20=3.9 P<0.05 Type of reachxdistractor location F2,z0=4.6 P<0.05


The analysis revealed two significant two-way inter- actions: a type of reachxdistractor position interaction (F2,20=23-8, P<0.0001), and a visual availabilityxdistractor position interaction (F2,20=16,9, P<0.0001). Relevant means are presented in Fig. 4. The type of reachxdistractor position interaction is identical to that observed for PV in the current study and confirms our previous observations with young adult subjects (Jackson et al. 1995). PAs for ipsilateral and contralateral reaches did not differ when targets were presented alone (F1,10=2.9, P<0.1). In contrast, PAs were substantially smaller for contralateral reaches accompanied a midline distractor compared with contralateral reaches made in the presence of a peripheral distractor (Fl,t0=13.6, P<0.005). Moreover, this effect was reversed when reaching into ipsilateral space. Thus, PAs were substantially smaller when making an ipsilateral reach in the presence of a peripheral distractor as compared to a midline distractor (Ft,10=31.1, P<0.0001).

The visual availabilityxdistractor position interaction effect was further investigated by examining the effect of distractor location for visually-guided reaches and memory-guided reaches separately. These analyses consisted of a series of linear contrasts between relevant means. The analyses revealed that for visually-guided reaches PAs were not significantly reduced for trials where either a midline (Fi,10=4.0, P<0.06) or a peripheral distractor was present (F1,10=1.5, P<0.02). In contrast, analysis of the memory-guided trials revealed that PAs were considerably reduced for trials accompanied by a midline or a peripheral distractor (minimum Fl,t0=72.3, P<0.0001). Once again these results confirm our previous findings of substantially increased distractor effects for memory- guided reaches (Jackson et al. 1995).

Finally, the ANOVA also revealed a significant four- way interaction effect involving visual availabilityxtype of reachxdistractor positionxgroup (F2,20=8.9, P<0.025). As this rather complex effect was not predicted, it will not be discussed further in this paper.

Time taken to reach peak aperture. Table 6 shows mean TTPAs (expressed as a percentage of total MT) for each group, with a summary table to those factors that had a significant effect on TTPA. Subjects reached their PA significantly later when reaching for targets accompanied by a midline distractor (no-distractor trials 73.2+11.0%; midline distractor trials 77.0+_9.1%; peripheral distractor trials 74.0+_12.6%).

A similar type of reachxdistractor position interaction effect to that observed in the current study for both PV and PA was found for TTPA (F2,20=4.6, P<0.05). TTPAs for ipsilateral and contralateral reaches carried out without an accompanying distractor, or when accompanied by a peripheral distractor object, did not differ reliably from one another (maximum FL10=2.5, P=0.02). Howev- er, TTPAs for contralateral reaches were significantly increased compared with ipsilateral reaches when accompanied by a midline distractor (ipsilateral 74.2+_12.2% vs contralateral 79.7+_8.9%; F~,5=17.0, P<0.001).

Experiment 2: reaches made using subjects' non-preferred hand

In experiment 1, which described reaches made with subjects' preferred hand, complex interaction effects were described in full, even where these effects did not differ in the patient and control groups. However, in the interests of brevity we will, from this point forward, only report complex interaction effects where these differ across the patient and control groups.

Movement time

Table 7 shows mean MTs for each group, with a summary table of those factors that had a significant effect on MT. Analysis revealed that MTs were extended when subjects made memory-guided reaches (visually-guided

Table 7 Movement time (in milliseconds): reaches with non-preferred hand

155

PD group



HCS group



No distractor 821.8 893.9 1187.9 1143.4 (222.8) (213.8) (222.4) (259.2)



783.7 797.2 898.2 847.8 (145.0) (128.3) (227.0) (165.8) 764.0 758.8 839.3 907.8 (103.1) (145.8) (147.0) (239.6) 778.6 786.3 897.2 912.5 (149.0) (146.3) (297.0) (197.6)

Table 7A Summary of effects on movement time


Group F1,10=3.9 P=0.08 Visual availability F~,10=27.3 P<0.0005 Groupxisual availability F1,10=6.2 P<0.05 Type of reach• position F2,20=6.6 P<0.025 Groupxtype of reachxdistractor F2,20=4.8 P<0.05 position Visual availability• of reach F2,20=9.3 P<0.005 •


839.5+200.5 ms vs memory-guided 1040.6+279.2 ms). Furthermore, this effect interacted with group (F1,10=6.2, P<0.05), Relevant means are presented in Fig. 5B. In- spection of this figure clearly demonstrates that the patient group show a substantially larger increase in MT on memory-guided reaches than the control group.

The ANOVA revealed three further interaction effects: (1) a two-way interaction between type of reach and distractor position (F2,2o=6.6, P<0.025); (2) a three-way type of reachxdistractor positionxgroup interaction (/72,20=4.8, P<0.05); and (3) a three-way visual availabilityxtype of reachxdistractor position interaction (/72,2o=9.3, P<0.005). As this last effect does not differ for the patient and control groups, it will not be discussed further.

The three-way type of reachxdistractor positionxgroup interaction was further investigated by examining the effects of type of reach and distractor position for each group separately. These analyses revealed that while there was a significant type of reach and distractor position interaction for the patient group (F2,10=14.0, P<0.01), this effect was not observed for the control group (F2,1o=0.2, P=0.7). Relevant means are presented in Fig. 6 for the PD group. The form of this interaction was identical to that described earlier for reaches with the preferred hand. MTs for ipsilateral and contralateral reaches did not differ when targets were presented alone

(F1,1o=0.1, P=0.7). In contrast, MTs where substantially increased for contralateral reaches accompanied by a midline distractor when compared with ipsilateral reaches made in the presence of a midline distractor (F1,~0=22.9, P<0.005). Furthermore, this effect was reversed when reaches were accompanied by a peripheral distractor. That is, MTs were extended when making an ipsilateral reach in the presence of a peripheral distractor as compared to a contralateral reach (F1,10=7.1, P<0.05).

Transport component

Peak velocity. PVs for each group are presented in Table 8, with a summary table of those factors that had a significant effect on PV. PV was reduced in the patient group (PD 640.5 mm/s vs HCS 823.9 ram/s). PV was also reduced for all subjects when they carried out memory-guided reaches (visually-guided 776.3+120.0 mm/s vs memory-guided 688.1+202.9 ram/s). However, two interaction effects were worthy of note: (1) a type of reachxdistractor location interaction (F2,20= 10.0, P<0.0025) and (2) a visual availabilityxgroup interaction (Fl,10=10.2, P<0.01).

Investigation of the type of reachxdistractor location interaction revealed this effect to be similar to that reported for reaches with subjects' preferred hand. PVs for contralateral reaches to targets presented alone (i.e. no- distractor condition) were significantly smaller than ipsilateral reaches made under the same circumstances (F~,10=8.2, P<0.01). Furthermore, PVs were also reduced when reaching contralaterally in the presence of a midline distractor compared with ipsilateral reaches for targets accompanied by a midline distractor (F1,1o=11.2, P<0.005). This effect was reversed, however, for reaches towards targets accompanied by a peripheral distractor. Under these circumstances PVs were substantially reduced on ipsilateral reaches compared with contralateral reaches (F1,10=5.6, P<0.05).

The visual availabilityxgroup interaction was investigated further by examining the effect of visual availability for each group separately. Relevant means are presented in Fig. 7B. The main finding to arise from these analyses was that while PVs for the PD group were significantly slowed on memory-guided reaches (F1,5=18.1,

156

Fig. 5 Mean movement times for visually-guided and memory-guided reaches made by the patients with Parkinson's disease (PD) and their healthy controls (HCS). A Reaches with subjects' preferred hand; B reaches with the non-preferred hand. Error bars represent the SEM

A Movement times for reaches with subjects' preferred hand

i

~D

a.a *.a

~D

O

1400-

1300-

1200-

1100-

1000

900

800-

700.

6OO

t l Visually-guided Memory-guided I

PD i

HCS

B Movement times for reaches with subjects' non-preferred hand

i

o

> 0

1400-

I300 ]

laOO~

1100 [

lOOO ~ 900 2

8oos 700 i 6OO I

PD HCS

1400 ] 1300 ~

120G i

I10G

1000

E 90C > O

80C

70C

�9 Ipsilateral I Contra|ateral

60C No Dist. Midline Peripheral

Fig. 6 Mean movement times for the patients with Parkinson's disease, when making ipsilateral and contralateral reaches to targets presented alone or when accompanied by midline or peripheral distractors. Error bars represent the SEM

P<0.01; visually-guided 730.6+138.7 mm/s vs memory- guided 550.3+114.1 ram/s), PVs for visually-guided and memory-guided reaches did not differ reliably for the HCS group (F1,5=0.01, P<0.9; visually-guided 822.0_+ 75.4 mm/s vs memory-guided 825.8_+177.3 ram/s),

Deceleration time. Table 9 shows mean DTs (expressed as a percentage of total MT) for each group, with a summary of those factors that had a significant effect on DTs. DTs were significantly longer when subjects made memory-guided reaches (visually-guided 56.0+9.0% vs memory-guided 62.0_+8.5%). Furthermore, this effect varied with group, as there was a marginal visual availabilityxgroup interaction (F1jo=4.l , P=0.07). Relevant means are presented in Fig. 8B. Once again these data suggest that the PD group are particularly affected when required to carry out memory-guided reaches.

Grasp component

Peak aperture. Table 10 shows mean PAs for each group, with a summary table of those factors that had a signifi-

Table 8 Peak velocity (in millimetres per second): reaches with non-preferred hand

157

PD group



HCS group



No distractor 769.1 713.1 583.6 563.1 (127.6) (149.2) (128.3) (109.4)



846.5 825.0 971.1 777.9 (86.5) (63.4) (351.7) (78.2) 841.2 798.2 834.9 738.2 (80.8) (62.1) (60.0) (111.3) 805.7 815.1 754.5 878.5 (59.3) (110.3) (71.8) (149.2)

Table 8A Surnlnary of effects on peak velocity


Group F1,10=12.5 P<0.005 Visual availability F1,10=9.4 P<0.01 Groupxvisual availability F1A0=10.2 P<0.01 Type of reach• location F2,20=10.0 P<0.0025 Visual availabilityxtype of reach F2,20=4.5 P<0.05 • location


cant effect on PA. PAs were significantly greater for memory-guided reaches (visually-guided 32.9+3.8 ~ vs memory-guided 41.9+_5.7~ but were reduced when subjects reached for targets accompanied by distractor objects (no-distractor trials 39.2+7.7~ midline distractor trials 36.4+6.2~ peripheral distractor trials 36.4_5.5~ Linear contrasts revealed that trials with midline and peripheral distractors each produced smaller PAs than trials in which the target object was presented alone (minimum F1,10=42.5, P<0.0001).

The analysis revealed two significant two-way inter- actions: a type of reachxdistractor position interaction (F2,20=9.2, P<0.005) and a visual availabilityxdistractor position interaction (F2,20=18.8, P<0.0001). The first of these interaction effects was similar to the effect reported earlier for reaches with subjects' preferred hand, and to that reported previously (Jackson et al. 1995). For this reason it will not be described further. The second effect was also shown to interact significantly with group (F2,20=7.6, P<0.01). Relevant means are presented in Fig. 9.

The visual availabilityxdistractor position (VxD) interaction was examined for each group separately. These analyses revealed that for the HCS group the V• interaction was no t statistically significant (F2,10 = 1.0, P=0.4), although the analysis did reveal significant main effects of both visual availability and distractor position (minimum F280=7.8, P<0.025). In contrast, the analysis of the PD group data revealed not only reliable main effects of

A Peak velocity for reaches using subjects' preferred hand.

1000

900

, 800

700 >

600 ID

500

Iw Visually-guided [

400 PD HCS

B Peak velocity for reaches using subjects' non-preferred hand.

!8oo 1 �9 ~ 700 2 i13 >

.-,e 600 ~D

5O0

400 PD HCS

Fig. 7A, B Mean peak velocities for visually-guided and memory-guided reaches made by the patients with Parkinson's disease (PD) and their healthy controls (HCS). A Reaches with subjects' preferred hand; B reaches with the non-preferred hand. Error bars represent the SEM

158

Table 9 Deceleration time (as a percentage of total movement time): reaches with non-preferred hand

PD group HCS group





No distractor 52.9 52.9 65.4 65.7 (13.1) (10.2) (4.2) (4.8)



57.2 56.0 57.5 58.7 (9.2) (7.2) (11.3) (9.7) 58.2 54.8 57.8 58.3 (6.4) (10.1) (7.8) (11.2) 57.5 57.2 58,2 59.6 (9.1) (11.1) (14.3) (10.3)

Table 9A Summary of effects on deceleration time


Visual availability Fmo=7.6 P<0.025 Group• availability Fro0=4.1 P<0.07


visual availability and distractor position (minimum F2,t0=21.5, P<0.005) but also a significant VxD interaction (Fz,t0=34.1, P<0.0001).

Despite the difference in the statistical significance of the VxD interaction term, it is clear that the general pattern of the data is broadly similar for both groups. Thus, both groups show enlarged PAs when performing memory-guided reaches, but reduced PAs when reaching in the presence of non-target distractor objects. However, two findings are worthy of note: firstly, in our previous studies we found that subjects showed minimal effects of non-target distractors when making visually-guided reaching movements (Jackson et al. 1995). In the current study we find that on visually-guided trials, for the HCS group alone, PAs for reaches to targets presented alone do not differ from those accompanied by distractors (maximum Ft,5=2.2, P<0.2). In contrast, the PD group were shown to be influenced by the presence of midline distractors on visually-guided trials as well as memory- guided trials (F1,5=5.7, P<0.05).

Secondly, while the increase in peak aperture on memory-guided trials is greater in the no-distractor condition than in both the midline and the peripheral distractor conditions for the HCS group (and thus the interference effect of neighbouring distractors becomes appar- ent), this effect is clearly magnified in the PD group, suggesting that the patients may be particularly influenced by accompanying non-target objects on memory- guided reaches.

Time taken to reach peak aperture. While there were several effects which approached statistical significance, only one effect reached conventional levels of statistical

A Deceleration time for reaches using subjects' preferred hand

i00

90

80 i O

"= 70 �9

6O

<9

50

m Visually-guided Memory-guided

40 PD HCS

B Deceleration time for reaches using subjects' non-preferred hand

100

b-,

J

<9

O

~o <9 r

90

80

70

PD HCS

Fig. 8A, B Mean deceleration times for visually-guided and memory-guided reaches made by the patients with Parkinson's disease (PD) and their healthy controls (HCS). A Reaches with subjects' preferred hand; B reaches with the non-preferred hand. Error bars represent the SEM

Table 10 Peak aperture (degrees): reaches with non-preferred hand

159

PD group



HCS group



No distractor 34.3 33.6 46.7 48.9 (4.2) (6.3) (8.3) (3.3)



32.8 33.6 42.2 41.8 (3.4) (3.5) (4.4) (4.8)

31.7 32.0 40.5 38.5 (3.5) (4.1) (5.7) (7.2) 30.8 33.2 37.6 40.9 (3.3) (2.8) (4.0) (5.6)

Table IOA Summary of effects on peak aperture


Visual availability

Distractor location Visual availabilityxdistractor Groupxvisual availabilityx distractor location Type of reachxdistractor location

F1,1o=116.4 P<0.0001

F2,2o=28.4 P<0.0001 F2,2o=18.8 P<0.0001 F2,zo=7.6 P<0.01

F2,20=9.2 P<0.005


significance. This was a main effect of type of reach (F1,10=9.7, P<0.01). Subjects reached peak aperture slightly earlier when reaching for ipsilateral targets than contralateral targets (ipsilateral 69.1+12.4% vs contralateral 75.0+_13.1%).

Coordination of transport and grasp

One question raised by the current study is whether the relative timing between transport and grasp is preserved in patients with PD executing memory-guided reaches. 1 Furthermore, it can be hypothesised that if the deficit observed in our PD group were to stem from an underesti- mation of distance, then the co-ordination of transport and grasp ought to be preserved. To test this prediction we carried out a series of correlation analyses between the temporal markers for transport (time to peak velocity) and grasp (time to PA) components. Data from trials where distractors were presented were excluded from these analyses. Data were initially analysed for each hand separately. These analyses revealed that for both groups, transport and grasp temporal markers were significantly correlated for both right- and left-handed reaches, under both visually-guided and memory-guided conditions. Accordingly, we report here the correlations

I We are grateful to an anonymous reviewer for drawing this issue to our attention

A HCS group

60-

55 2

502

g 45: ; 40:

35

.-~ 30

25

20

m Visually-guided [] Memory-guided

No Dist. i

Midline Peri ~heral

B PD group

r

~D

601 55

50

45

4(1

35

3(?

25

2C No Dist. Midline Peripheral

Fig. 9A, B Mean peak apertures for visually-guided and memory- guided reaches made to targets presented alone or else alongside midline or peripheral distractors. A Reaches made by the control group (HCS); B reaches made by the PD group. Error bars represent the SEM

160

between transport and grasp temporal markers, for visually-guided and memory-guided reaches made with either hand. These were as follows: HCS- visually- guided, P<0.025, R=0.5; PD-visually-guided, P<0.005, R=0.6; HCS - memory-guided, P<0.0001, R=0.7; PD- memory-guided, P<0.0001, R=0.7.

Discussion

The results of this study indicated the following: firstly, prehension movements for all subjects were clearly affected when carried out without visual guidance; moreover, both transport and grasp movement components were affected by this manipulation. Thus, on memory- guided trials: MTs were lengthened, deceleration phases extended, PVs reduced and PAs widened. These results confirm previously reported findings for memory-guided reaches (e.g. Wing et al. 1986; Jackson et al. 1995). Sec- ondly, prehension movements were affected when reaches were carried out in the presence of non-relevant distractor objects. These effects were again observed for both transport and grasp movement components. When subjects reached for targets accompanied by distractor objects both PVs (transport) and PAs (grasp) were reduced in magnitude. Moreover, consistent with previous reports (Jackson et al. 1995), these effects were found to interact with the kind of reaching movement being executed, so that contralateral reaches were primarily affected by midline distractor objects, whereas ipsilateral reaches were primarily affected by peripheral distractors. Finally, and more importantly, the results indicated that while placing distractor objects in the vicinity of prehension targets produced comparable effects in both the patient and control groups (i.e. there was little evidence to support the view that patients with PD were any more distractible than control subjects), execution of memory- guided reaches was especially difficult for the patient group. Moreover, and of special relevance, the results indicated that the deficits exhibited by the PD group on memory-guided reaches were confined to those markers associated with the transport component alone. That is, a group by visual availability effect was consistently observed for MT, 2 PV, and time spent in the deceleration phase, but was not observed for PA or for time taken to reach PA. In the final section of this paper we consider the implications of these results for theories regarding the nature of the visuomotor deficit associated with PD, and the control of prehension movements more generally.

Independence of transport and grasp components

One important question raised by the current study is why the deficit observed in the PD group on memory-

2 As the end of the prehension movement was defined in this study as that point when horizontal displacement of the target exceeded 0.5 mm, MT can be viewed as a marker for the transport component of the movement

guided trials was confined to kinematic markers for the transport component of the prehension movement alone. It has been suggested that reaching for an object consists of two components: a transportation movement, in which the limb is transferred to the region of the target object, and a grasp component, in which the hand is preshaped and oriented so as to facilitate the act of grasping the object (Jeannerod 1984). Jeannerod proposed that these two components were based upon separate visuomotor chan- nels which provided quite different sources of information about the perceptual properties of objects located in the environment. While the transport component is thought to depend upon an egocentric representation of the external world where objects are represented in terms of their spatial position relative to the body, the grasp component is thought to depend upon an object-centred representation in which intrinsic properties including an objects size, its shape, and the orientation of its major axis are coded. Furthermore, physiological and anatomi- cal demonstrations of independent neural regions concerned with the programming of distal and proximal movements appear to support this distinction (Gentilucci et al. 1988; Rizzolatti and Gentilucci 1988; Rizzolatti et al. 1988). We believe that the results of the current study, which clearly demonstrate that the bradykinesia observed in the PD group on memory-guided trials was confined to kinematic markers for the transport component alone, contribute further evidence for the independent computation of transport and grasp components.

Visuomotor deficits associated with Parkinson's disease

Studying the effects of PD on motor function offers per- haps the best means of investigating the role played by the basal ganglia in the control of movement in humans (Stelmach 1991). Brooks (1986) has suggested that basal ganglia may serve to scale the amplitude of movements, and that basal ganglia dysfunction leads to inappropriate scaling of intended motor acts. Likewise, Berardelli et al. (1986) proposed that patients with PD underestimate the muscle activity needed to produce movements of a specific amplitude and suggested that this resulted from a deficit in the mechanisms required to translate perceptual estimates of task requirements (e.g. distance) into appropriately scaled muscle commands. Behavioural evidence that patients with PD produce movements of reduced amplitude include reports of reduced stride length and micrographia (Stelmach 1991), as well as hypometric eye movements for memory-guided saccades (Lueck et al. 1992). Such observations are also supported by studies of electromyographic (EMG) activity during goal-directed movements executed by patients with PD.

In healthy subjects, upper limb movements are characterised by a tri-phasic pattern of activity on the agonist and antagonist muscles (Jeannerod 1988). Movement of the limb is initiated by a burst of activity in the agonist muscle and followed by a burst of activity on the antagonist muscle, which acts to decelerate the limb. In many

cases this is then followed by a final (smaller) burst of activity on the agonist muscle. In contrast, several reports indicate that the EMG activity may be abnormal in patients with PD (e.g. Hallett and Khosbin 1980; Teas- dale et al. 1990). Hallett and Khosbin (1980) examined elbow flexion movements and reported reduced EMGs associated with the initial agonist burst. Furthermore, these authors also reported that patients produced many more cycles of agonist-antagonist activity to execute the movement. Similar results have more recently been ob- tained by Teasdale et al. (1990), who studied movements of different durations.

Hallett (1985) suggested that the underscaling of EMG activity in patients with PD arises as a consequence of a disease-related limitation in the amount of EMG activation which could be used to energise the agonist muscle. However, more recent studies of EMG activity have largely discounted this idea (Berardelli et al. 1986; Teasdale etal. 1990). This idea als0 appears broadly inconsistent with the behavioural evidence ob- tained in the current study and by Lueck et al. (1992). Lueck et al. (1992) reported that the kinematic properties of saccadic eye movements of patients with PD were normal for visually-guided saccades, but hypometric for memory-guided saccades. Likewise, in the current study we demonstrated that the kinematic properties of goal- directed prehension movements of patients with PD only differed from those of their age-matched control group on memory-guided trials. This result is therefore consistent with previous reports that patients with PD may be especially dependent upon visual feedback to guide movements.

Are patients with Parkinson's disease especially reliant on external feedback?

Finally, while it is tempting to interpret the results of the current study as support for the view that patients with PD are especially reliant upon the use of external feedback when carrying out goal-directed action, it must be acknowledged that the current study does not rule out other potential explanations. Goodale and Milner proposed a distinction between a ventral stream of visual processing which mediates visual perception and object recognition and a dorsal stream of visual processing which mediates the visual guidance of a range of motor activities, including prehension movements (Goodale and Milner 1992; Goodale 1993). Within this view it is explicitly assumed that the visuomotor mechanisms making up the dorsal action system operate in real time and, as a consequence, do not include mechanisms capa- ble of storing visual information beyond a few milliseconds. For this reason, memory-guided prehension movements are thought not to depend upon the dorsal action system, but, instead, upon the ventral perceptual system which mediates object recognition (Goodale et al. 1994).

Occluding vision at movement onset (open-loop reaches) deprives subjects of vision of their limb relative

161

to the target object during movement execution. Such procedures have been viewed as depriving the subject of visual feedback and interpreted as demonstrating that such feedback is not necessary for the successful execution of prehension movements (e.g. Jeannerod 1984; Ja- kobson and Goodale 1991). In the current study, however, vision was occluded approximately 2 s prior to the auditory cue instructing subjects to begin the movement. In these circumstances, in addition to removing access to visual feedback, a memory load is imposed on the subject which is not present for visually-guided or open- loop reaches (e.g. Wing et al. 1986; Castiello et al. 1993; Jackson et al. 1995). Furthermore, according to the theo- ry proposed by Goodale and Milner, the visual information held in memory differs from that normally used in the visual guidance of movement (Goodale and Milner 1992; Goodale 1993). Consequently it cannot be deter- mined from the results of the current study whether the deficits observed for memory-guided reaches reflect a deficit in the patients ability to utilise visuospatial working memory or arose as a result of the absence of visual feedback.

We recently attempted to clarify this question in a study which compared visually-guided and open-loop reaches executed by an early onset Parkinson's disease patient (49 years old) (S.R. Jackson, D.L. Morris, J. Har- rison, L. Henderson and C. Kennard, unpublished work). In the first experiment we manipulated transport kinematics by having our subject (and her matched control subject) reach for a target object placed at three different distances from the subject (20, 25, 30 cm). In the second experiment we manipulated grasp kinematics by having our subjects reach to target objects which varied in width (15, 30, 50 ram).

The results of this study were entirely clear. Our patient exhibited a constant underscaling of PV an open- loop reaches, despite being able to appropriately recalibrate the velocity of her reaches for each of the three movement amplitudes (experiment 1). In contrast, the programming of her grip was entirely normal. Both subjects re-scaled their grip on open-loop reaches, and their grip aperture was unaffected by reaching for objects presented at different distances (experiment 1). Further- more, our patient demonstrated that, for both visually- guided and open-loop reaches, she was able to appropriately recalibrate her grip to the width of the target to be grasped, and that the magnitude of this recalibration was of the same magnitude as that shown by the control subject (Experiment 2).

These findings confirm that the deficit observed in patients with PD executing memory-guided prehension movements in the current study extend to movements executed under open-loop conditions. As such, they strong- ly suggest that this deficit is unlikely to result from an impairment in visuo-spatial working memory, as open- loop reaches are not thought to depend upon this system (Goodale etal. 1994). Instead they suggest that, for whatever reason, patients with PD may be especially dependent upon visual feedback to guide movements.

162

Acknowledgements This research was supported by a grant from the Nuffield Foundation to S.R.J. and by a grant from the Well- come Trust to C.K. We are grateful to Llewelyn Morris, Martin Edwards and Katie Stewart for their help in collecting and condi- tioning some of the data presented here. We would also like to thank Melvyn A. Goodale and an anonymous reviewer for their helpful comments on an earlier version of this paper.

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