JOURNAL ARTICLE

A structural basis for reading fluency: white matter defects in a genetic brain malformation

B S Chang, T Katzir, T Liu, K Corriveau, M Barzillai, K A Apse, A Bodell, D Hackney, D Alsop, S T Wong, S Wong, C A Walsh
Neurology 2007 December 4, 69 (23): 2146-54
18056578

BACKGROUND: Multiple lines of evidence have suggested that developmental dyslexia may be associated with abnormalities of neuronal migration or axonal connectivity. In patients with periventricular nodular heterotopia--a rare genetic brain malformation characterized by misplaced nodules of gray matter along the lateral ventricles--a specific and unexpected reading disability is present, despite normal intelligence. We sought to investigate the cognitive and structural brain bases of this phenomenon.

METHODS: Ten adult subjects with heterotopia, 10 with dyslexia, and 10 normal controls were evaluated, using a battery of neuropsychometric measures. White matter integrity and fiber tract organization were examined in six heterotopia subjects, using diffusion tensor imaging methods.

RESULTS: Subjects with heterotopia and those with developmental dyslexia shared a common behavioral profile, with specific deficits in reading fluency. Individuals with dyslexia seemed to have a more prominent phonological impairment than heterotopia subjects. Periventricular nodular heterotopia was associated with specific, focal disruptions in white matter microstructure and organization in the vicinity of gray matter nodules. The degree of white matter integrity correlated with reading fluency in this population.

CONCLUSIONS: We demonstrate that a genetic disorder of gray matter heterotopia shares behavioral characteristics with developmental dyslexia, and that focal white matter defects in this disorder may serve as the structural brain basis of this phenomenon. Our findings represent a potential model for the use of developmental brain malformations in the investigation of abnormal cognitive function.

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