What determines the cortical location where a given functionally specific region will arise in development? Here we test the hypothesis that functionally specific regions develop in their characteristic locations because of pre-existing differences in the extrinsic connectivity of that region to the rest of the brain. We exploit the Visual Word Form Area (VWFA) as a test case, scanning children with diffusion and functional imaging at age five, before they learned to read, and at age 8, after they learned to read. We find the VWFA develops functionally in this interval and that its location in a particular child at age 8 can be predicted from that child’s connectivity fingerprints (but not functional responses) at age 5. These results suggest that early connectivity instructs the functional development of the VWFA, possibly reflecting a general mechanism of cortical development.

Developmental dyslexia, an unexplained difficulty in learning to read, has been associated with alterations in white matter organization as measured by diffusion-weighted imaging. It is unknown, however, whether these differences in structural connectivity are related to the cause of dyslexia or if they are consequences of reading difficulty (e.g., less reading experience or compensatory brain organization). Here, in 40 kindergartners who had received little or no reading instruction, we examined the relation between behavioral predictors of dyslexia and white matter organization in left arcuate fasciculus, inferior longitudinal fasciculus, and the parietal portion of the superior longitudinal fasciculus using probabilistic tractography. Higher composite phonological awareness scores were significantly and positively correlated with the volume of the arcuate fasciculus, but not with other tracts. Two other behavioral predictors of dyslexia, rapid naming and letter knowledge, did not correlate with volumes or diffusion values in these tracts. The volume and fractional anisotropy of the left arcuate showed a particularly strong positive correlation with a phoneme blending test. Whole-brain regressions of behavioral scores with diffusion measures confirmed the unique relation between phonological awareness and the left arcuate. These findings indicate that the left arcuate fasciculus, which connects anterior and posterior language regions of the human brain and which has been previously associated with reading ability in older individuals, is already smaller and has less integrity in kindergartners who are at risk for dyslexia because of poor phonological awareness. These findings suggest a structural basis of behavioral risk for dyslexia that predates reading instruction.

Dyslexia is one of the most common learning disabilities, yet its brain basis and core causes are not yet fully understood. Neuroimaging methods, including structural and functional magnetic resonance imaging, diffusion tensor imaging, and electrophysiology, have significantly contributed to knowledge about the neurobiology of dyslexia. Recent studies have discovered brain differences prior to formal instruction that likely encourage or discourage learning to read effectively, distinguished between brain differences that likely reflect the etiology of dyslexia versus brain differences that are the consequences of variation in reading experience, and identified distinct neural networks associated with specific psychological factors that are associated with dyslexia.