Dysfluent reading in disorganized brains

Bernard Chang and colleagues, who study a rare genetic disorder called periventricular nodular heterotopia (PNH), have found evidence that points to a specific relationship between certain brain structures and dysfluent reading. People with PNH have difficulty reading fluently and their genetic disorder causes a known aberration in neural structure. Their fluency in reading is correlated with the degree of disorganization in their brains.

During normal development, gray matter (nerve cells) migrates toward the surface and white matter (mostly the nerve fibers that connect gray matter areas) are deeper in the brain. However, in brains affected by PNH some gray matter stays deeper in the brain as nodules. In 10 patients with PNH, Walsh and Chang found that white matter fibers were not organized efficiently, taking circuitous routes around the un-migrated gray matter; they found that patients with greater degree of disorganization had greater reading fluency problems.

This image, created by a specialized form of MRI called diffusion tensor imaging, shows white matter tracts (colored lines), in one corner of the brain. White matter tracts connect brain regions so they can communicate. Tracts appear in this image only if they are organized. In a normal brain (left), tracts run in an organized, uninterrupted fashion between points in the brain (tracts in white box). In patients with periventricular nodular heterotopia (right), tracts are disrupted by nodules of gray matter (red arrow), leaving areas without organized fiber tracts (lack of tracts in white box), which might lead to poor connections between parts of the brain. Image courtesy of Bernard Chang, MD, Beth Israel Deaconess Medical Center

These results do not mean that all individuals with reading fluency problems have PNH nor that they necessarily have genetic disorders. It does help explain why people who do have PNH have fluency problems. Because we know that at least some individuals with dyslexia have disorganized white matter, this study helps understand the potential contribution of white-matter integrity and organization to reading fluency.

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

B. S. Chang, MD, T. Katzir, PhD, T. Liu, PhD, K. Corriveau, MEd, M. Barzillai, MEd, K. A. Apse, ScM, A. Bodell, MS, D. Hackney, MD, D. Alsop, PhD, S. Wong, PhD and C. A. Walsh, MD, PhD

NEUROLOGY 2007;69:2146-2154

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.

Abbreviations: DTI = diffusion tensor imaging; FA = fractional anisotropy; PNH = periventricular nodular heterotopia; ROI = region of interest.

Findings appear in the journal Neurology today. Read the press release from Children’s Hosptial Boston.