Multi-unit activity and high-gamma patterns dissociate in the seizure onset zone during focal to bilateral tonic-clonic seizures.

ObjectivesTo track multi-unit activity (MUA) using hybrid Behnke-Fried electrodes continuously throughout human seizures, and to characterize how both neuronal firing and high-gamma (HG) changes over the ictal course, within versus outside the seizure-onset zone (SOZ), and by seizure severity. MethodsWe analyzed 32 seizures - 9 focal preserved consciousness (FPC), 17 focal impaired consciousness (FIC), 6 focal-to-bilateral tonic-clonic (FBTC) - from 8 patients implanted with Behnke-Fried hybrid depth electrodes. Spikes were sorted jointly across a 10-min pre-ictal baseline and ictal period, yielding 895 units trackable through seizures. Macroelectrode contacts within 15 mm of each microelectrode were classified by the SOZ status of the corresponding micro site. Firing rates from MUA, HG power and phase-locked high-gamma (PLHG) were baseline-normalized and compared across seizure types and periods (first/second half; pre/post-generalization). ResultsUnit waveforms were identified throughout seizures. Within the SOZ, firing increased at onset in all types, then attenuated (FPC, FIC) or plateaued (FBTC). PLHG peaked early and declined across all seizure types, including post-generalization in FBTC. In contrast, HG stayed elevated at onset for all seizures, was highest in FBTC, and increased further after generalization. Outside the SOZ, MUA, HG, and PLHG stayed near baseline in FPC, and rose progressively in FIC. In FBTC they showed a temporal dissociation: HG/PLHG rose pre-generalization and remained high, while MUA increased sharply only after generalization. SignificanceWe demonstrated feasibility to track multi-unit activity throughout seizures and revealed seizure-type- and location-specific micro-macro dynamics. Collectively, early rise and later decline in PLHG that mostly aligns with neuronal firing was concordant within SOZ. Moreover, increases in all measures outside the SOZ are a hallmark of seizures with impaired consciousness, and may suggest presence of a third driver. These findings offer testable biomarkers for future larger clinical studies. KEY POINTSO_LIMUA can be tracked continuously during seizures with Behnke-Fried hybrid electrodes. C_LIO_LIIn the SOZ, firing rises at onset, then attenuates in FPC/FIC or plateaus in FBTC; HG rises while PLHG peaks early then declines. C_LIO_LIOutside SOZ, firing, and HG/PLHG progressively increase, specifically after generalization. C_LIO_LICombined MUA/HG/PLHG provide candidate biomarkers for SOZ mapping and impaired consciousness. C_LI