Comparing White Matter vs. Subgaleal Reference in Seeg: Frequency-dependent Differences in Neural Signals

Introduction: Stereo-electroencephalography (sEEG) is a common method for clinical epilepsy monitoring and provides unique opportunities for human intracranial research. Optimal selection of reference electrodes is essential for obtaining high-quality data. Electrode contacts localized in white matter (WM) are commonly used for this purpose but present several limitations that could influence the data. First, probe trajectories are planned to maximize gray matter sampling, and thus, there might be a limited number of electrodes in WM. Second, signals in nearby gray matter can influence WM electrodes, thus not representing an ideal neutral reference. Third, a WM contact reference inherently selects a hemisphere, introducing laterality bias. Here, we detail the use of a midline subgaleal electrode as an alternative reference for sEEG recordings.

Methods: The subgaleal reference was used for nine patients with drug-resistant epilepsy undergoing intracranial monitoring. Following sEEG electrodes placement, one 8-contact sEEG electrode (n=2) or a 4-contact strip (n=7) was placed in the subgaleal space at the parietal midline. In two participants, we compared the power spectral density (PSD) of neural signals recorded using subgaleal versus right temporal WM reference during separate 5-minute baseline blocks.

Results: No adverse effect of the subgaleal electrode placement was reported in any participant. Pairwise comparisons of PSD across contacts revealed reference-dependent differences: a shallower PSD slope was found for subgaleal versus WM reference (t-test, p< 0.001). Specifically, the majority of contacts (patient 1: 80%; patient 2: 72%) showed lower power for frequencies below 50 Hz and higher power above 50 Hz with the subgaleal reference.

Conclusion : Our findings demonstrate that the reference choice influences the spectral power distribution of sEEG recordings. In contrast to the standard WM reference, a subgaleal reference yields higher sensitivity to local, high-frequency signal content. Extracranial placement of a subgaleal electrode allows for a more neutral midline reference.