Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model

Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) is an established therapy for drug-refractory dystonia, yet its precise mechanisms of action remain unclear. This study examines how pallidal DBS influences the spatiotemporal organization of neuronal dynamics in the cerebellar cortex using the dtsz hamster model of dystonia. By employing high-density microelectrode arrays (HD-MEAs), we investigated mean firing rates (MFR), interspike intervals (ISI), spike amplitudes across groups of healthy control hamsters, dystonic dtsz hamsters, and dtsz hamsters subjected to DBS or sham-DBS treatments. A nonlinear data-driven approach was utilized to derive a low-dimensional representation of the neuronal activity patterns from MEA data. The results revealed significantly reduced MFR and spike amplitudes in dtsz hamsters compared to healthy controls, highlighting functional impairments. Pallidal DBS normalized these electrophysiological abnormalities, effectively restoring MFR, spike amplitudes, and ISI to levels observed in healthy controls. This suggests that DBS exerts its therapeutic effects by reestablishing normal neuronal activity patterns within the cerebellar cortex. Long-term DBS treatment demonstrated a network-wide restorative effect, underscoring its potential for modifying dysfunctional cerebellar cortical activity in dystonia.