Jimmy C Yang1, Angelique C Paulk2, Pariya Salami2, Sang Heon Lee3, Mehran Ganji3, Daniel J Soper2, Daniel Cleary4, Mirela Simon2, Douglas Maus2, Jong Woo Lee5, Brian V Nahed6, Pamela S Jones6, Daniel P Cahill6, Garth Rees Cosgrove7, Catherine J Chu2, Ziv Williams6, Eric Halgren8, Shadi Dayeh3, Sydney S Cash9. 1. Department of Neurosurgery, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA. 2. Department of Neurology, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA. 3. Department of Electrical and Computer Engineering, University of California, San Diego; 9500 Gilman Dr., La Jolla, CA 92093, USA. 4. Department of Neurosurgery, University of California, San Diego; 9500 Gilman Dr., La Jolla, CA 92093, USA. 5. Department of Neurology, Brigham and Women's Hospital, 60 Fenwood Rd., Boston, MA 02115, USA. 6. Department of Neurosurgery, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA. 7. Department of Neurosurgery, Brigham and Women's Hospital, 60 Fenwood Rd., Boston, MA 02115, USA. 8. Department of Radiology, University of California, San Diego; 9500 Gilman Dr.; La Jolla, CA 92093, USA. 9. Department of Neurology, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA. Electronic address: scash@partners.org.
Abstract
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-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand these markers' microscale spatial dynamics. METHODS: Electrodes with spatial resolution down to 50 µm 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 µm. 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.
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-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand these markers' microscale spatial dynamics. METHODS: Electrodes with spatial resolution down to 50 µm 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 µm. 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.
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