High-frequency oscillations in intraoperative recordings from hybrid arrays with micro- and macrocontacts

Objective. High-frequency oscillations (HFOs) are a potential biomarker of the epileptogenic zone (EZ) in patients with focal epilepsy. Previous research has estimated that HFOs arise from regions as small as a single cortical column (1 mm³), making events difficult to detect with the coarse spatial sampling of clinical-standard electrocorticographic (ECoG) arrays. We tested whether high-resolution micro-ECoG (µECoG) arrays enable improved detection of HFOs compared to clinical-scale ECoG arrays.Approach.We designed a hybrid array with both micro- (200µm diameter, 1 mm spacing) and macrocontacts (2.3 mm diameter, 10 mm spacing). We used the arrays to record neural activity from cortical areas exposed during surgical resections for focal epilepsy (n= 3 subjects). We identified HFOs in the ripple (80-250 Hz) and fast ripple (250-600 Hz) bands using a common energy thresholding criterion. We mapped HFO activity and quantified differences in event count, detection rate, amplitude, signal-to-noise ratio, and spatial extent between contact configurations.Main results.Microcontacts detected 14x as many HFO events as macrocontacts while spanning the same area of cortex. In all three intraoperative recordings, the subregions of highest HFO activity were primarily sampled by microcontacts, suggesting an increased likelihood of detecting focal HFO activity with high-density configurations. 82% of microcontact HFOs spanned multiple contacts, providing an estimate that events typically involved a 1.25 mm radius of cortex. The remaining 18% occurred on only one 200µm diameter contact. In contrast, only 15% of macrocontact HFOs were large enough to span multiple contacts and were estimated to involve a 10.3 mm radius of cortex, a significantly larger region than that of microcontacts (p< 0.0001, Wilcoxon rank sum).Significance.High-resolution microcontacts captured 99% of HFOs, including 93% undetected by clinical-scale macrocontacts, revealing that most events arose from a <1 mm radius of cortex and providing further rationale for the development ofµECoG arrays for EZ localization in patients with drug-resistant epilepsy.