White matter: organization and functional relevance.

Norman Geschwind's landmark paper in 1965, "Disconnexion Syndromes in Animals and Man," inspired a generation of investigators to consider the effects of focal brain lesions disrupting higher brain functions. Although Geschwind viewed disconnection as resulting from either white or gray matter lesions, his signature article drew upon the insights of 19th century neurologists and firmly established white matter within the vocabulary of behavioral neurology, neuropsychology, and cognitive neuroscience. This influence, and the advent of sensitive neuroimaging techniques later in the 20th century, led to white matter gradually gaining more attention as an essential component of distributed neural networks subserving cognition and emotion. Today, whereas focal white matter lesions remain central to the pathogenesis of classic neurobehavioral syndromes, diffuse white matter involvement is regarded as increasingly relevant to a wide variety of dementia syndromes and a host of neuropsychiatric disorders as well. In parallel, better understanding of the neurobiology of brain white matter at all ages has been achieved. While much remains to be explored, a general conceptual formulation is that white matter supports information transfer to complement the information processing carried out by gray matter. As knowledge of the organization and functional relevance of white matter continues to advance, improved understanding of the role of myelinated tracts in higher function can be anticipated, and with it many clinical benefits.