Physiological consequences of abnormal connectivity in a developmental epilepsy
Name
nihms-652594.pdf
Size
1.48 MB
Format
Adobe PDF
Checksum (MD5)
07e71af3c1586e8c1fc077bb383bf1ab
Author(s)
Shafi, Mouhsin M.
Vernet, Marine
Klooster, Debby
Chu, Catherine J.
Boric, Katica
Barnard, Mollie E.
Romatoski, Kelsey
Westover, M. Brandon
Christodoulou, Joanna A.
Gabrieli, John D. E.
Date Issued
February 2015
Journal
Annals of Neurology
Publisher
Wiley Blackwell
Citation
Shafi, Mouhsin M. et al. “Physiological Consequences of Abnormal Connectivity in a Developmental Epilepsy.” Annals of Neurology 77, 3 (January 2015): 487–503 © 2015 American Neurological Association
Version
Author's final manuscript
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.
Interpretation
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/ana.24343
