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D8 Tms-eeg markers of inhibitory deficits in huntington’s disease
  1. Michael Orth1,
  2. Isabella MS Mayer1,2,
  3. Sarah J Tabrizi3,
  4. John C Rothwell2,
  5. Elias Casula2
  1. 1Department of Neurology, Ulm University, Ulm, Germany
  2. 2Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London, UK
  3. 3Department of Neurodegenerative Disease, University College London, Institute of Neurology, London, UK

Abstract

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.

  • transcranial magnetic stimulation
  • TMS evoked potential
  • time domain
  • oscillation

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