REVIEW

The Basics of Brain Development

Joan Stiles & Terry L. Jernigan

Received: 7 August 2010 /Accepted: 11 October 2010 /Published online: 3 November 2010# The Author(s) 2010. This article is published with open access at Springerlink.com

Abstract Over the past several decades, significantadvances have been made in our understanding of thebasic stages and mechanisms of mammalian braindevelopment. Studies elucidating the neurobiology ofbrain development span the levels of neural organizationfrom the macroanatomic, to the cellular, to the molecular.Together this large body of work provides a picture ofbrain development as the product of a complex series ofdynamic and adaptive processes operating within a highlyconstrained, genetically organized but constantly chang-ing context. The view of brain development that hasemerged from the developmental neurobiology literaturepresents both challenges and opportunities to psychologistsseeking to understand the fundamental processes that underliesocial and cognitive development, and the neural systems that

mediate them. This chapter is intended to provide an overviewof some very basic principles of brain development, drawnfrom contemporary developmental neurobiology, thatmay be of use to investigators from a wide range ofdisciplines.

Keywords Brain development; maturation .Magneticresonance imaging . Diffusion weighted imaging . Geneticpatterning of brain . Neurogenesis . Myelination .

Effects of experience on connectivity

Acronym ListCP cortical plateCR Cajal-Retzius cellsCT corticothalamic pathwayDTI diffusion tensor imagingE# embryonic day (number of days post

conception, e.g. E25)FA fractional anisotrophyGW# gestational week (number of weeks post

conception, e.g. GW8)M1 primary motor cortexMR magnetic resonanceMRI magnetic resonance imagingMZ marginal zoneODC ocular dominance columnsOPC oligiodendrocyte progenitor cellsPAC primary auditory cortexPVC primary visual cortexS1 somatosensory cortexSP subplateTC thalamocortical pathwayV1 primary visual cortexVZ ventricular zone

This work was supported by grants to Joan Stiles from the NationalInstitute of Child Health and Human Development: R01-HD25077,R01 HD060595, and to Terry Jernigan from the National Institute ofDrug Abuse: RC2DA029475 and the Lundbeck Foundation: R32-A3161. The authors would also like to acknowledge the support of theUCSD Kavli Institute for Brain and Mind.

J. Stiles : T. L. JerniganDepartment of Cognitive Science, Center for HumanDevelopment, University of California,San Diego, CA, USA

T. L. JerniganDepartments of Psychiatry and Radiology, School of Medicine,University of California,San Diego, CA, USA

T. L. Jernigan (*)UCSD Center Human Development 0115,9500 Gilman Drive,La Jolla, CA 92093, USAe-mail: tjernigan@ucsd.edu

Neuropsychol Rev (2010) 20:327348DOI 10.1007/s11065-010-9148-4

Human brain development is a protracted process thatbegins in the third gestational week (GW) with thedifferentiation of the neural progenitor cells and extendsat least through late adolescence, arguably throughout thelifespan. The processes that contribute to brain develop-ment range from the molecular events of gene expression toenvironmental input. Critically, these very different levelsand kinds of processes interact to support the ongoing series ofevents that define brain development. Both gene expressionand environmental input are essential for normal braindevelopment, and disruption of either can fundamentally alterneural outcomes. But neither genes nor input is prescriptive ordeterminative of outcome. Rather brain development is aptlycharacterized as a complex series of dynamic and adaptiveprocesses that operate throughout the course of developmentto promote the emergence and differentiation of new neuralstructures and functions. These processes operate withinhighly constrained and genetically organized, but constantlychanging contexts that, over time, support the emergence ofthe complex and dynamic structure of the human brain(Waddington 1939; Morange 2001; Stiles 2008).

This paper will review some of the major events thatcontribute to the development of the human brain from itsearly embryonic state through adolescence. It begins byexamining the foundational changes that occur during theembryonic period, which in humans extends through theeighth week post conception (gestational week eight, orGW8). By the end of the embryonic period the rudimentarystructures of the brain and central nervous system areestablished and the major compartments of the central andperipheral nervous systems are defined (see Fig. 1). Theensuing period of fetal development extends through theend of gestation. During this time there is rapid growth andelaboration of both cortical and subcortical structures,including the rudiments of the major fiber pathways(Kostovic and Jovanov-Milosevic 2006); (Kostovic andJovanov-Milosevic 2006). Changes in the gross morphol-

ogy of the prenatal neural system are underpinned bychanges occurring at the cellular level. Neuron productionin humans begins on embryonic day 42. E42, i.e. 42 dayspost conception (Bystron et al. 2008; Stiles 2008) and islargely complete by midgestation. As they are producedneurons migrate to different brain areas where they begin tomake connections with other neurons establishing rudimentaryneural networks. By the end of the prenatal period majorfiber pathways, including the thalamocortical pathway,are complete.

Brain development continues for an extended periodpostnatally. The brain increases in size by four-fold duringthe preschool period, reaching approximately 90% of adultvolume by age 6 (Reiss et al. 1996; Iwasaki et al. 1997;Courchesne et al. 2000; Kennedy and Dehay 2001; Paus etal. 2001; Kennedy et al. 2002; Lenroot and Giedd 2006).But structural changes in both the major gray and whitematter compartments continue through childhood andadolescence, and these changes in structure parallel changesin functional organization that are also reflected inbehavior. During the early postnatal period, level ofconnectivity throughout the developing brain far exceedsthat of adults (Innocenti and Price 2005). This exuberantconnectivity is gradually pruned back via competitiveprocesses that are influenced by the experience of theorganism. These early experience dependent processesunderlie the well-documented plasticity and capacity foradaptation that is the hallmark of early brain development.

By way of background, this chapter begins with aconsideration of two important concepts that are essentialfor understanding how brains develop. The first involvesgene expression: what genes are and how they play animportant role in brain development. The second is theoutcome of brain development, the mature brain: what arethe major structures and what are the basic principles ofbrain organization. The chapter then considers some ofthe major milestones of brain development with the aimof illustrating the dynamic, interactive nature of braindevelopment.

Genes and Gene Products Genes are the material substancethat is passed intergenerationally from parent to offspring.Genes are contained in the nucleotide sequences of DNAthat are found in the nucleus of every cell in the body. Theexpression of a gene has one result: the production of aprotein molecule. These molecular products of geneexpression are essential for all aspects of development.Genes provide a template for making proteins and it is theproteins that are the active agents in biological development.Thus, while genes contain information that is essential for thedevelopment and functioning of the biological organism,genes are basically inert molecules. Genes cannot participatedirectly in biological processes. They do not directly create

Fig. 1 Human embryo at Carnegie Stage 23, the end of the embryonicperiod (GW8). It is 30 mm long. Image from the Kyoto Collectionreproduced with permission of Prof Kohei Shiota, Graduate School ofMedicine, Kyoto University, and obtained with permission of Dr.Mark Hill, University of New South Wales, http://embryology.med.unsw.edu.au/embryo.htm

328 Neuropsychol Rev (2010) 20:327348

http://embryology.med.unsw.edu.au/embryo.htmhttp://embryology.med.unsw.edu.au/embryo.htm

blue eyes, disease proclivity, intelligence or behavior. Rather,there is an indirect relationship between the information in agene and a developmental outcome. The information in thegene sequences must be extracted, recoded and translated intoproteins. It is the proteins that enter into the complex,interactive signaling cascades that usually involve many geneproducts as well as influences from the environment. Aparticular gene product is thus one of many essential elementsthat interact to support and guide the complex process of braindevelopment.

The Organization of the Mature Brain The human brain isarguably the most complex of all biological systems. Themature brain is composed of more than 100 billion neurons(Pakkenberg and Gundersen 1997). Neurons are theinformation processing cells in the brain (see Fig. 2). Thereare many different kinds of neurons that vary in their sizeand shape as well as in their function. Neurons makeconnections with other neurons to form the informationprocessing networks that are responsible for all of our

thoughts, sensations, feelings and actions. Since eachneuron can make connections with more than 1,000 otherneurons, the adult brain is estimated to have more than 60trillion neuronal connections. The point of connectionbetween two neurons is called a synapse.

The mature human brain has a characteristic pattern offolds (the sulci) and ridges (the gyri). The enfolding of themature brain is thought to be an adaptation to the dramaticgrowth in the size of the brain during the course ofevolution. The folding of brain tissue al