D8 Tms-eeg markers of inhibitory deficits in huntington’s disease

Background Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterised by cortical and striatal pathology. One of the first HD-related alterations is the progressive degeneration of cannabinoid type 1 receptors in basal ganglia, which are highly expressed in GABAergic neurons of the striatum. Aims Given the GABAergic nature of TMS-evoked EEG activity, we investigated whether GABAergic deficits in preHD patients produce any significant change in TMS-EEG measures, compared to healthy volunteers (HV). Methods We stimulated the primary motor cortex (M1) and premotor area (PM) with single-pulse TMS (90% of RMT) while recording EEG in 16 preHD patients and 16 HV. TMS-evoked activity was analysed in time, space and oscillatory domains. Results Time-domain analysis revealed a strong reduction of later M1-TMS-evoked activity (150–250 ms after TMS) in preHD patients, compared to HV. The effect was prominent over the site of stimulation. Oscillatory-domain analysis revealed that this effect was due to a strong desynchronization of TMS-evoked responses of HD patients in the theta and alpha range. Conclusions The observed decrease of GABAb-mediated TEPs may be a consequence of the lower GABAergic inhibition that causes excitotoxicity in HD patients. This interpretation is corroborated by the weak synchronisation in slow (theta and alpha) and late (150–250 ms) post-synaptic potentials evoked by TMS, that are thought to be of GABAb origin.