Trends in Neurosciences
ReviewWhite matter in learning, cognition and psychiatric disorders
Introduction
New findings together with experiments spanning 40 years are forcing a pivotal shift in views of white matter in the brain. White matter comprises over half the human brain, a far greater proportion than in other animals [1]. Only vertebrates have myelin (Figure 1), which greatly increases the speed and power of nervous system function [2]. Recently, unanticipated changes in myelin genes and alterations in white matter structure have been observed in a wide range of psychiatric disorders. Together with new data showing that white matter structure is dynamic and myelin can be regulated by impulse activity, these new findings implicate myelin in cognitive function beyond pathology, and illuminate an underappreciated role of myelin in information processing and learning.
This article considers evidence that white matter is involved in learning, information-processing, neurological and psychological disorders. It examines historical evidence and information from new techniques indicating that white matter changes with functional experience, and it explores the molecular mechanisms. It presents possible mechanisms for white matter effects on synaptic function and cognition, and it outlines unanswered questions and directions for future research.
Section snippets
White matter in cognition and mental illness
A surprisingly diverse range of psychiatric and nervous system disorders are accompanied by changes in white matter structure or abnormalities in myelin genes (see Box 1). Polymorphisms for several myelin genes have emerged as unexpected risk factors for schizophrenia 3, 4, depression [4] and obsessive-compulsive disorder [5]. Post mortem examination of brain tissue from patients suffering schizophrenia 4, 6, major depression [7] and bipolar disorder [4] reveals reduced abundance of several
Experience changes white matter
Myelination is a developmental process, but it has been known for decades that myelination of the human brain continues into the third decade of life [11], and this can now be tracked by noninvasive brain imaging [17]. However, the significance of this was not fully appreciated. If myelin is simply insulation, why is the process not completed by birth?
Myelination is nearly completed by birth in animals, such as horses [28] or wild mice (Acomys) [29], which are precocial and can walk and feed
Myelin in information processing
White matter plasticity in response to environmental experience is puzzling when viewed from the older perspective of myelin. Why should insulation on transmission lines change after neural computation that is carried out in gray matter? The emerging answer is that myelin controls the speed of impulse conduction through axons, and the synchrony of impulse traffic between distant cortical regions is critical for optimal mental performance and learning.
A central concept in synaptic plasticity
Activity-dependent myelination: cellular and molecular mechanisms
Evidence that impulse activity can affect myelination has been in the literature since the 1960s, from experiments rearing mice in the dark [81] or opening the eye of neonatal rabbits prematurely [82]. Rearing animals in the dark reduces the number of myelinated axons in optic nerve, and premature eye opening increases myelin protein expression. Electrical activity also promotes proliferation of oligodendrocyte progenitor cells in optic nerve [83] and, in cell culture, stimulating firing of
Future directions
The signals mediating activity-dependent communication between axons and oligodendrocytes, the developmental time course of activity-dependent effects and the cellular mechanisms that would regulate myelin to optimize conduction velocity are only beginning to be explored.
Is myelin plasticity strictly a change in the number of axons that become myelinated, or a change in the myelin sheath that would regulate impulse conduction speed? Current evidence best supports changes in the number of
Conclusions
Research from new techniques and recent insights into neuron–glial interactions [103] are providing a new perspective on studies of myelin plasticity that have been in the literature for decades. Myelin is not simply a developmental process; it continues for decades in humans; it is modifiable, and it is an important contributor to psychiatric disorders and other diseases affecting cognition.
White matter changes are associated with learning in people, but the extent to which these changes
Acknowledgements
Supported by funds for intramural research, NIH, NICHD.
References (108)
Evolution of myelin sheaths: both lamprey and hagfish lack myelin
Neurosci. Lett.
(1984)Oligodendrocyte dysfunction in schizophrenia and bipolar disorder
Lancet
(2003)Extensive and divergent effects of sleep and wakefulness on brain gene expression
Neuron
(2004)White matter growth as a mechanism of cognitive development in children
Neuroimage
(2006)Hemispheric asymmetries during six- to eight-year-olds performance of Piagetian conservation and reading tasks
Neuropsychologia
(1980)Structural and functional brain development and its relation to cognitive development
Biol. Psychol.
(2000)- et al.
White matter volume predicts reaction time instability
Neuropsychologia
(2007) Intelligence and brain myelination: a hypothesis
Pers. Indiv. Differ.
(1994)Speed of lexical decision correlates with diffusion anisotropy in left parietal and frontal white matter: evidence from diffusion tensor imaging
Neuropsychologia
(2007)- et al.
Left lateralized white matter microstructure accounts for individual differences in reading ability and disability
Neuropsychologia
(2006)
Microstructure of temporo-parietal white matter as a basis for reading ability: evidence from diffusion tensor magnetic resonance imaging
Neuron
Episodic memory and neuroimaging of hippocampus and fornix in chronic schizophrenia
Psychiatry Res.
A comparative study of myelination in precocial and altricial murid rodents
Brain Res.
Long day lengths enhance myelination of midbrain and hindbrain regions of developing meadow voles
Brain Res. Dev. Brain Res.
Differential rearing effects on rat visual cortex synapses. III. Neuronal and glial nuclei, boutons, dendrites, and capillaries
Brain Res.
Sex and environmental influences on the size and ultrastructure of the rat corpus callosum
Brain Res.
Childhood neglect is associated with reduced corpus callosum area
Biol. Psychiatry
P0 mRNA expression increases during gradual nerve elongation in adult rats
Exp. Neurol.
Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth
Neuron
The development of myelin in the spinal cord of the North American opossum and its possible role in loss of rubrospinal plasticity
Brain Res. Dev. Brain Res.
Schizophrenia and Nogo; elevated mRNA in cortex, and high prevalence of a homozygous CAA insert
Brain Res. Mol. Brain Res.
Myelination in rabbit optic nerves is accelerated by artificial eye opening
Neurosci. Lett.
Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials
Neuron
Astrocytes promote myelination in response to electrical impulses
Neuron
Regional differentiation of the axon: a review with special reference to the concept of the multiplex neuron
Brain Res.
White matter matters
Sci. Am.
Genome-wide expression analysis reveals dysregulation of myelinatin-related genes in chronic schizophrenia
Proc. Natl. Acad. Sci. U. S. A.
A genetic family-based association study of OLIG2 in obsessive-compulsive disorder
Arch. Gen. Psychiatry
Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia
Proc. Natl. Acad. Sci. U. S. A.
Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder
Mol. Psychiatry
The progress of cognitive decline in multiple sclerosis. A controlled 3-year follow-up
Brain
Regional distribution of white matter hyperintensities in vascular dementia, Alzheimer's disease and healthy aging
Dement. Geriatr. Cogn. Disord.
The myelogenetic cycles of regional maturation of the brain
Maturation of white matter is associated with the development of cognitive functions during childhood
J. Cogn. Neurosci.
Myelination of language-related areas in the developing brain
Neurology
Frontostriatal microstructure modulates efficient recruitment of cognitive control
Cereb. Cortex
Structural magnetic resonance imaging of the adolescent brain
Ann. N. Y. Acad. Sci.
Cognitive functions correlate with white matter architecture in normal pediatric population: a diffusion tensor MRI study
Hum. Brain Mapp.
Extensive piano practicing has regionally specific effects on white matter development
Nat. Neurosci.
Morphometry of the amusic brain: a two-site study
Brain
Development of the equine brain motor system
Neurobiology (Bp.)
Restraint stress during late pregnancy in rats elicits early hypermyelination in the offspring
Metab. Brain Dis.
Chemical and anatomical plasticity brain
Science
Response of the three main types of glial cells of cortex and corpus callosum in rats handled during suckling or exposed to enriched, control and impoverished environments following weaning
J. Comp. Neurol.
Experience-driven brain plasticity: beyond the synapse
Neuron Glia Biol.
Oligodendroglia regulate the regional expansion of axon caliber and local accumulation of neurofilaments during development independently of myelin formation
J. Neurosci.
Early experience alters brain function and structure
Pediatrics
Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins
Mol. Psychiatry
Uniform olivocerebellar conduction time underlies Purkinje cell complex spike synchronicity in the rat cerebellum
J. Physiol.
Comparative physiology: electric organs
Annu. Rev. Physiol.
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