title: Abnormal structural and functional brain connectivity in gray matter heterotopia.
abstract: OBJECTIVE
  Periventricular nodular heterotopia (PNH) is a malformation of cortical development associated with epilepsy and dyslexia. Evidence suggests that heterotopic gray matter can be functional in brain malformations and that connectivity abnormalities may be important in these disorders. We hypothesized that nodular heterotopia develop abnormal connections and systematically investigated the structural and functional connectivity of heterotopia in patients with PNH.
  
  
  METHODS
  Eleven patients were studied using diffusion tensor tractography and resting-state functional connectivity MRI with bold oxygenation level-dependent (BOLD) imaging. Fiber tracks with a terminus within heterotopic nodules were visualized to determine structural connectivity, and brain regions demonstrating resting-state functional correlations to heterotopic nodules were analyzed. Relationships between these connectivity results and measures of clinical epilepsy and cognitive disability were examined.
  
  
  RESULTS
  A majority of heterotopia (69%) showed structural connectivity to discrete regions of overlying cortex, and almost all (96%) showed functional connectivity to these regions (mean peak correlation coefficient 0.61). Heterotopia also demonstrated connectivity to regions of contralateral cortex, other heterotopic nodules, ipsilateral but nonoverlying cortex, and deep gray matter structures or the cerebellum. Patients with the longest durations of epilepsy had a higher degree of abnormal functional connectivity (p = 0.036).
  
  
  CONCLUSIONS
  Most heterotopic nodules in PNH are structurally and functionally connected to overlying cortex, and the strength of abnormal connectivity is higher among patients with the longest duration of epilepsy. Along with prior evidence that cortico-cortical tract defects underlie dyslexia in this disorder, the current findings suggest that altered connectivity is likely a critical substrate for neurologic dysfunction in brain malformations.
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Joanna A
authors.initials: JA
authors.lastname: Christodoulou
authors.forename: Linsey M
authors.initials: LM
authors.lastname: Walker
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Del Tufo
authors.forename: Tami
authors.initials: T
authors.lastname: Katzir
authors.forename: John D E
authors.initials: JD
authors.lastname: Gabrieli
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D054091:Periventricular Nodular Heterotopia / Q000150:complications* / Q000473:pathology*; D055815:Young Adult
chemical_list: D010100:Oxygen