Integration of gray matter nodules into functional cortical circuits in periventricular heterotopia

Joanna A. Christodoulou, Mollie E. Barnard, Stephanie N. Del Tufo, Tami Katzir, Susan Whitfield-Gabrieli, John D.E. Gabrieli, Bernard S. Chang

Research output: Contribution to journalArticlepeer-review


Alterations in neuronal circuitry are recognized as an important substrate of many neurological disorders, including epilepsy. Patients with the developmental brain malformation of periventricular nodular heterotopia (PNH) often have both seizures and dyslexia, and there is evidence to suggest that aberrant neuronal connectivity underlies both of these clinical features. We used task-based functional MRI (fMRI) to determine whether heterotopic nodules of gray matter in this condition are integrated into functional cortical circuits. Blood oxygenation level-dependent (BOLD) fMRI was acquired in eight participants with PNH during the performance of reading-related tasks. Evidence of neural activation within heterotopic gray matter was identified, and regions of cortical coactivation were then mapped systematically. Findings were correlated with resting-state functional connectivity results and with performance on the fMRI reading-related tasks. Six participants (75%) demonstrated activation within at least one region of gray matter heterotopia. Cortical areas directly overlying the heterotopia were usually coactivated (60%), as were areas known to have functional connectivity to the heterotopia in the task-free resting state (73%). Six of seven (86%) primary task contrasts resulted in heterotopia activation in at least one participant. Activation was most commonly seen during rapid naming of visual stimuli, a characteristic impairment in this patient population. Our findings represent a systematic demonstration that heterotopic gray matter can be metabolically coactivated in a neuronal migration disorder associated with epilepsy and dyslexia. Gray matter nodules were most commonly coactivated with the anatomically overlying cortex and other regions with resting-state connectivity to heterotopia. These results have broader implications for understanding the network pathogenesis of both seizures and reading disabilities.

Original languageEnglish
Pages (from-to)400-406
Number of pages7
JournalEpilepsy and Behavior
Issue number2
StatePublished - Nov 2013

Bibliographical note

Funding Information:
We thank our participants and their families for their participation, without which this study could not have been completed. We thank Tyler Perrachione, Jack Murtagh, and Kelly Halverson for assistance. Scanning was conducted at the Athinoula A. Martinos Imaging Center at McGovern Institute for Brain Research, MIT. BSC was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke ( R01 NS073601 ), the Epilepsy Foundation , and the William F. Milton Fund of Harvard University .


  • Connectivity
  • Dyslexia
  • Epilepsy
  • Malformation
  • Migration

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Behavioral Neuroscience


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