High-Frequency Activity for Language Mapping during Stereo-EEG: Comparison with Direct Cortical Stimulation

ObjectiveDirect cortical stimulation (DCS) is the gold standard for language mapping during SEEG but is prone to false negatives and false positives that may contribute to post-operative dysphasia or else overly conservative resections. Task-induced high-frequency activity (HFA, 30-200Hz) is an emerging functional biomarker that may augment DCS, but its clinical utility remains uncertain. We aimed to quantify HFAs diagnostic concordance with DCS, assessing its potential as both a surrogate marker and a screening tool. MethodsIn this single-centre prospective study, 23 adults undergoing SEEG completed language mapping with DCS and HFA. HFA was mapped using auditory and visual naming tasks (ANT/VNT), quantified via Morlet wavelet transforms with baseline-normalised z-scores. DCS-positive channels were those where 50Hz stimulation elicited language disruption. HFA distribution was examined independently of DCS. HFA-DCS concordance was assessed for individual and combined (ANT+VNT; maximal HFA across tasks) conditions at channel and sublobar levels across two thresholds: a specificity-optimized stringent threshold (Z>0.8) to examine HFA as a surrogate for DCS, and a sensitivity-optimized permissive threshold (Z>0.3) to evaluate its potential as a screening tool. ResultsTwelve (52%) participants were female, and 17 (74%) were MRI-negative. HFA patterns differed by task: VNT produced greater HFA magnitude in the dominant frontal lobe (p=0.0498), while ANT produced greater magnitude and activation rate in the non-dominant temporal lobe (p=0.015; p=0.0189), highest in the non-dominant superior temporal gyrus. In the combined condition, concordance with DCS was low at the stringent threshold (channel-wise sensitivity/specificity=0.24/0.88; region-wise=0.43/0.77). Sensitivity improved at the permissive threshold (channel-wise 0.56, NPV=0.96), with region-wise sensitivity of 0.75, specificity=0.45, and NPV=0.94. SignificanceRegion-level HFA at a permissive threshold is useful for identifying language-negative regions and prioritising DCS testing. Poor concordance at a stringent threshold suggests HFA and DCS index distinct functional properties and are not interchangeable. Anatomically plausible HFA localisation supports the need for further multimodal validation to clarify its role in presurgical mapping. Key PointsO_LIHFA and DCS show threshold- and scale-dependent diagnostic concordance for language mapping during SEEG C_LIO_LISensitivity-optimized sublobar HFA shows high negative predictive value and moderate sensitivity for DCS-positive language sites C_LIO_LIThese metrics support sublobar HFA as a screening tool to exclude non-eloquent regions and streamline DCS language mapping C_LIO_LISpecificity-optimized HFA concords poorly with DCS, indicating these markers index distinct properties and are not interchangeable C_LIO_LICombined HFA/DCS profiles may help stratify surgical risk: HFA-/DCS-regions as low risk, while HFA+/DCS+ sites denote high risk C_LI