A synchronized dual-scale platform combining flexible micro-ECoG and skull-screw EEG reveals frequency-dependent cortex-to-skull spectral gain in awake mice

Electroencephalography (EEG) is the most scalable window onto brain dynamics, yet how cortical activity is transformed before reaching extracranial electrodes has largely been inferred from forward models rather than directly measured. We built a dual-scale sensing platform in awake mice that records a 16-channel flexible micro-electrocorticography (micro-ECoG) array and five skull-screw EEG electrodes on a single 30-kHz clock, enabling sample-aligned comparison of cortical and skull-level signals. Across 115 simultaneously recorded ECoG-EEG pairs from three mice, cortex-to-skull spectral gain was not frequency-flat but increased with frequency following a power law, indicating that skull EEG relatively preserves high-frequency cortical activity rather than acting as a simple low-pass copy. This gain was also non-stationary: it shifted across blocks of a fixed-order auditory protocol and was not explained by measured video motion, whereas trial-matched cross-scale coherence depended on the reference transform. With channel number equalized, micro-ECoG retained a larger unique spatial component than skull EEG. These results convert the cortex-to-skull relationship from a static modeling assumption into a measurable, frequency- and state-dependent quantity. For neural sensing, they provide an empirical calibration target for choosing electrode scale, reference, and analysis band and for validating EEG forward models and EEG-to-intracranial translation. More broadly, they indicate that noninvasive biomarkers and brain-computer interface features, particularly in high-frequency bands, should be interpreted through frequency- and state-aware cortex-to-skull mappings.