Objective: To investigate the functional state of motor cortex excitability and the involvement of the cerebello-thalamo-cortical pathway using transcranial magnetic stimulation (TMS) in patients with essential tremor (ET).

Background: ET is primarily expressed as action tremor of the upper limbs that may eventually expand to other body regions such as the head, voice or jaw. The pathophysiology of ET likely comprises an abnormal oscillatory network containing the cerebello-thalamo-cortical loops, but there are still many unknowns about the implication of the different areas related with the cerebello-thalamo-cortical pathway. In this context, paired-pulse TMS protocols of cerebellar inhibition (CBI) and short-interval intracortical inhibition (SICI) have been used to examine the cerebello-cortical connectivity and cortical excitability in ET. However the results generated uncertainties about whether cerebello-cortical connectivity and/or cortical excitability are altered or not in these patients.

Method: To better understand the functional state of the cerebello-thalamo-cortical pathway in ET, we investigated CBI and SICI in patients with ET (n=44, 69.2±11.0 years) and age and gender-matched healthy controls (n=33, 65.8±6.2 years). Most patients also underwent unilateral magnetic resonance-guided focused ultrasound thalamotomy of the ventral intermediate nucleus. We took advantage of the thalamotomy to study possible changes of CBI and SICI before and after the intervention. All analyses were performed with Bayesian statistics.

Results: We found anecdotal evidence for a reduction of CBI and a strong evidence for a reduction of SICI (cortical disinhibition) in ET patients compared to healthy controls. Moreover, CBI was further diminished after thalamotomy, suggesting a causal involvement of cerebellar-thalamo-cortical connectivity in the generation of ET. Conversely, SICI was unaffected and remained at the same level of alteration after thalamotomy, suggesting that cortical disinhibition is not simply a consequence of tremor.

Conclusion: Cerebellar and motor cortex excitability are involved in the pathophysiology of ET.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cortical-and-cerebellar-excitability-in-essential-tremor/