Pathophysiological Role of Primary Motor Cortex in Essential Tremor

Background: Essential tremor (ET) is one of the most prevalent movement disorders. However, the complete understanding of ET pathophysiology remains elusive. Objective: To explore the pathophysiological role of primary motor cortex (M1) in ET, specifically exploring its neurophysiological changes and their correlation with voluntary motor abnormalities. Methods: We recruited 30 ET patients and 18 healthy controls (HC). Evaluations were conducted on patients using clinical scales. Transcranial magnetic stimulation (TMS) was used to assess M1 excitability, including motor thresholds and motor evoked potentials (MEPs) input/output curve, together with intracortical excitability measures. Long-term potentiation (LTP)-like plasticity of M1 was tested using intermittent theta-burst stimulation (iTBS). Objective assessments of tremor and voluntary movement execution during finger-tapping were conducted through kinematic analysis. Finally, we explored the potential relationship between TMS, clinical, and kinematic data. Results: Compared with HC, ET patients had lower excitability, intracortical inhibition, and lower LTP-like plasticity of M1. ET patients also exhibited slower finger-tapping performance compared with HC. Among ET patients, the degree of movement slowing during finger-tapping correlated with alterations in corticospinal excitability. Specifically, reduced M1 excitability was associated with lower finger-tapping velocity. No other correlations were found. Conclusions: The study findings reveal neurophysiological alterations of M1 in ET and demonstrate correlations between excitability measures and voluntary motor performance. These results provide novel insight into the pathophysiology of ET, emphasizing the role of M1 changes in this condition. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.