4.6 Article

Microscale dynamics of electrophysiological markers of epilepsy

Journal

CLINICAL NEUROPHYSIOLOGY
Volume 132, Issue 11, Pages 2916-2931

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.clinph.2021.06.024

Keywords

Microelectrode; Interictal Discharges; High Frequency Oscillations

Funding

  1. U.S. Army Research Office [W911NF-14-2-0045]
  2. Defense Advanced Research Projects Agency [W911NF-14-2-0045]
  3. ECOR
  4. NSF-CAREER award [1351980]
  5. NSF CMMI award [1728497]
  6. NIH [DP2-EB029757]
  7. [K24-NS088568]

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This study investigated the microscale spatial dynamics of neurophysiologic biomarkers of epilepsy using custom microelectrodes, revealing the spread and pathways of IIDs and the repeated patterns of HFOs. Microseizure events spanning 50-100 mm were identified, and the relationship between HFOs and MUA was established, but not with IIDs. These findings suggest the importance of microscale approaches in developing novel seizure control therapies.
Objective: Interictal discharges (IIDs) and high frequency oscillations (HFOs) are established neurophysiologic biomarkers of epilepsy, while microseizures are less well studied. We used custom poly(3,4-ethy lenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand these markers' microscale spatial dynamics. Methods: Electrodes with spatial resolution down to 50 mm were used to record intraoperatively in 30 subjects. IIDs' degree of spread and spatiotemporal paths were generated by peak-tracking followed by clustering. Repeating HFO patterns were delineated by clustering similar time windows. Multi-unit activity (MUA) was analyzed in relation to IID and HFO timing. Results: We detected IIDs encompassing the entire array in 93% of subjects, while localized IIDs, observed across < 50% of channels, were seen in 53%. IIDs traveled along specific paths. HFOs appeared in small, repeated spatiotemporal patterns. Finally, we identified microseizure events that spanned 50-100 mm. HFOs covaried with MUA, but not with IIDs. Conclusions: Overall, these data suggest that irritable cortex micro-domains may form part of an underlying pathologic architecture which could contribute to the seizure network. Significance: These results, supporting the possibility that epileptogenic cortex comprises a mosaic of irritable domains, suggests that microscale approaches might be an important perspective in devising novel seizure control therapies. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

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