title: Physiological consequences of abnormal connectivity in a developmental epilepsy.
abstract: OBJECTIVE
  Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities.
  
  
  METHODS
  We employed transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recording in 8 patients with epilepsy from periventricular nodular heterotopia and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions.
  
  
  RESULTS
  Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in 1 subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone.
  
  
  CONCLUSIONS
  Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions.
authors: Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Comprehensive Epilepsy Center, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors: Mouhsin M
authors: MM
authors: Shafi
authors: Marine
authors: M
authors: Vernet
authors: Debby
authors: D
authors: Klooster
authors: Catherine J
authors: CJ
authors: Chu
authors: Katica
authors: K
authors: Boric
authors: Mollie E
authors: ME
authors: Barnard
authors: Kelsey
authors: K
authors: Romatoski
authors: M Brandon
authors: MB
authors: Westover
authors: Joanna A
authors: JA
authors: Christodoulou
authors: John D E
authors: JD
authors: Gabrieli
authors: Susan
authors: S
authors: Whitfield-Gabrieli
authors: Alvaro
authors: A
authors: Pascual-Leone
authors: Bernard S
authors: BS
authors: Chang
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D004569:Electroencephalography / Q000379:methods*; D004827:Epilepsy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology*; D054091:Periventricular Nodular Heterotopia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult