What's the matter? White matter?

Although many children acquire reading skills rapidly with some formal training, for others learning to read is among the most difficult challenges they face in the first few years at school. The reasons for these large individual differences in skill acquisition are still obscure, with the relative contribution of biological and environmental factors vigorously debated. As the social and economic consequences of widespread illiteracy can be profound, better understanding of the brain mechanisms responsible for the acquisition of reading skills has become a national priority (Lyon 1995xLyon, G.R. J. Child Neurol. 1995; 10: 120–126See all ReferencesLyon 1995).The localization of the neural mechanisms responsible for reading has been an area of active investigation for over 100 years. Until relatively recently, most of these studies involved careful observation of disordered reading following focal brain injury, with postmortem anatomical localization of the lesion presumed to be responsible for the behavioral deficit. Perhaps the earliest formal structure/function correlation study in man was published by Starr in 1889. On the basis of examining 50 cases of aphasia, Starr hypothesized that the critical lesion responsible for disordered reading comprehension involved the axonal pathways connecting occipital cortex to the left angular gyrus. In 1892, Dejerine proposed a more detailed model of the reading process based on examination of a patient with pure alexia, that is, isolated inability to read. In this account the reading disability was caused by damage to extrastriate visual cortex and its projections to the left angular gyrus, resulting in a disconnection of the word recognition system from its visual input. This notion of white matter damage causing reading disability was elaborated by Geschwind 1965xGeschwind, N. Brain. 1965; 88: 237–294Crossref | PubMed | Scopus (886)See all ReferencesGeschwind 1965, who further delineated a reading circuit that included posterior temporal cortex (semantic processing), the angular gyrus (phonological processing), and the inferior frontal gyrus (speech). This “disconnection” model predicted that damage to the connections among these regionally specialized processing regions could result in disordered reading.The advent of structural brain imaging techniques allowed reexamination of these issues in living subjects. Damage involving white matter tracts in left extrastriate cortex was detected using X-ray computed tomography in a series of 16 cases of pure alexia (Damasio and Damasio 1983xDamasio, A.R. and Damasio, H.D. Neurology. 1983; 33: 1573–1583Crossref | PubMedSee all ReferencesDamasio and Damasio 1983). The lesions affected both intrahemispheric and interhemispheric pathways, strengthening the case that pure alexia may result from disconnection of phonological and semantic processing centers from their sensory input. More recently, there have been a large number of investigations utilizing structural magnetic resonance imaging that have largely confirmed the major findings of the earlier studies.Against this background of structure/function localization derived from the study of acquired reading disorders (lesion studies) is the question of the localization of the pathophysiology of developmental language disorders, particularly developmental dyslexia. Anatomical studies of postmortem brains of dyslexic individuals have revealed abnormalities in left perisylvian structures (reviewed by Galaburda 1993xGalaburda, A.M. Curr. Opin. Neurobiol. 1993; 3: 237–242Crossref | PubMed | Scopus (33)See all ReferencesGalaburda 1993). More recent studies involving functional neuroimaging and electrophysiology have suggested that the localization of the pathophysiology in developmental dyslexia might be confined to the junction of temporal and parietal cortex (reviewed by Eden and Zeffiro 1998xSee all ReferencesEden and Zeffiro 1998). In addition, one group has interpreted functional imaging results collected in a group of dyslexics and controls as being most consistent with a disconnection of posterior and anterior reading areas (Palesu, 1996). These results, and others, have provided strong circumstantial evidence that the core pathophysiology in developmental dyslexia involves posterior perisylvian cortical areas and their connections.In the context of these previous studies of acquired and developmental reading disorders, it is interesting to note the neuroanatomical localization of the results of a study reported in this issue of Neuron. Klingberg et al. (2000) employed diffusion tensor imaging, a novel, noninvasive, structural neuroimaging technique, to examine the relationship between reading skills and the microstructural integrity of cerebral white matter. Their measure of structural integrity, the white matter diffusion anisotropy, was positively correlated with the subject's reading ability in a spatial distribution confined to left posterior perisylvian regions. These results suggest that developmental reading disorder may be due to damage similar to that occurring in cases of acquired reading disorder, that is, damage to the fiber tracts connecting cortical structures responsible for sensory and phonological processing (see figure).This work is an excellent example of the application of a relatively new technique, diffusion tensor imaging, to the problem of analysis of the pathophysiology of a developmental neurological disorder. As noted by the authors, this is not a functional imaging technique and therefore does not require a high level of subject cooperation (other than remaining still for the duration of the imaging session). As a result, this approach is potentially useful in the study of individuals of widely differing behavioral capacities. This particular application of diffusion tensor imaging represents a significant advance in the study of neurobehavioral disorders. Careful behavioral assessment coupled with noninvasive structural and functional brain imaging is likely to be an effective strategy to explore the complex mechanisms of reading acquisition and its failure.Figure 101The Brain Reading AloudBlood oxygenation changes, including in the angular gyrus bilaterally, related to reading. Two axial slices from a single subject are shown (anatomical left is on image right).View Large Image | View Hi-Res Image | Download PowerPoint Slide