P 58 EEG responses from direct cerebellar activation with Transcranial Magnetic Stimulation

Abstract

Introduction: Measuring cortical responses from cerebellar stimulation might provide diagnostic biomarkers for the dentato-thalamo-cortical pathway's integrity. Recent studies have investigated the feasibility of delivering cerebellar stimulation through transcranial magnetic stimulation-electroencephalography (TMS-EEG). TMS-EEG presents several potential advantages and could provide more information than previous methods, which rely on motor output measures. However, past TMS-EEG studies were subject to considerable limitations, including contamination of the TMS-evoked potentials by peripherally-evoked potentials (PEPs). Therefore, we aimed to investigate cortical signatures of cerebellar stimulation, while controlling for confounding factors. Methods: We recruited 23 healthy, right-handed volunteers (13 females, mean ± SD age, 22.4±2.2 years). For each, resting motor threshold was used to titrate the intensity necessary to elicit a detectable cerebellar brain inhibition, which was set as the cerebellar TMS-intensity. A total of 280 single TMS pulses were then delivered to the cerebellum, 140 corresponding to REAL and 140 to SHAM condition. SHAM consisted of TMS to the right shoulder, whereas REAL consisted of both TMS to the right cerebellar hemisphere and to the right shoulder. Two further conditions were tested: TMS to the right occipital cortex and TMS to the right trapezius muscle, with otherwise the same parameters of the REAL condition. These conditions aimed to control for confounding factors, respectively collateral occipital cortex activation and PEPs from cerebellar TMS stimulation. EEG-signals of the different conditions were compared with respect to the evoked responses and changes in the time-frequency response via cluster-based t-tests. Results: Comparison of REAL and SHAM revealed significant differences. While some of these differences were explained by the occipital control stimulation, a left-hemispheric prefrontal early positive deflection at 20-26 ms and a left-hemispheric temporal negative deflection peaking at 45 ms (i.e. both contralateral to the cerebellar stimulation) were specific to the cerebellar stimulation. Furthermore, increased frontal theta power immediately after the TMS pulse was specific to the cerebellar stimulation. Conclusions: The investigation of multiple control conditions allowed for unmasking the cortical response resulting specifically from cerebellar TMS. The observed left-hemispheric prefrontal and subsequent temporal cortex responses were only present in conditions involving cerebellar stimulation and could neither be explained by collateral occipital stimulation, nor by a non-specific somatosensory input. These results are anatomically plausible, as targets of the dentato-thalamo-cortical pathway predominantly involve the contralateral prefrontal cortex and structural connectivity between the cerebellum and the contralateral superior temporal sulcus could be demonstrated in past studies.