The role of superficial and deep layers in the generation of high frequency oscillations in the human epileptic cortex

Abstract Objective:Describing intracortical laminar organization of high frequency oscillations (HFOs).Methods:We recorded potential gradients with laminar microelectrode arrays (LME) for current source density (CSD) and multi-unit activity (MUA) analysis of interictal discharges (IID) and HFOs in the neocortex and mesial temporal lobe of focal epilepsy patients. Results:Ripples were only observed in 9/29 patients, all within the seizure onset zone (SOZ). Ripples variably (≈50%) coincided with IIDs. CSD analysis revealed slow ripples (<150Hz) to exhibit an alternating sink-source pair in the upper cortical layers. In contrast, fast ripples (>150Hz) were biased to the lower layers, tending to precede the superficial activity (10-30ms).Conclusion: Our findings suggest that cortical slow ripples are generated primarily in upper layers while fast ripples and associated MUA in deeper layers. The dissociation of macro- and microdomains suggests that microelectrode recordings may be more selective for SOZ-linked ripples.Significance:We found a complex interplay between neural activity in the neocortical laminae during ripple formation. We observed a potential leading role of cortical neurons in deeper layers, suggesting a refined utilization of LMEs in SOZ localization.