Reliability of Neuroimaging and Neurophysiological Tremor Features in Parkinson's Disease

Background: Tremor is one of the cardinal motor symptoms of Parkinson's disease (PD). Its severity can be quantified with clinical rating scales and neurophysiology. The pathophysiology of PD tremor involves activity in the cerebello-thalamo-cortical circuit (CTC), which can be quantified with concurrent accelerometry-functional magnetic resonance imaging (fMRI). This opens possibilities for fMRI-informed precision medicine, but it remains unclear if tremor-related fMRI activity is a reliable biomarker at the individual level. Objectives: To assess the test-retest reliability of three PD tremor outcome measures: clinical rating scales, accelerometry, and combined accelerometry-fMRI. Methods: We studied 26 tremor-dominant PD patients OFF medication on two separate days (2-month interval). On each day, tremor was characterized with clinical rating scales (Fahn-Tolosa-Marin Tremor Rating Scale), accelerometry, and concurrent accelerometry-fMRI. Reliability was assessed using Spearman correlations and intraclass correlation coefficients. Results: Clinical and neurophysiological tremor parameters were reliable across sessions. Resting tremor-related fMRI activity was observed within the CTC across both sessions. The amplitude of tremor-related activity in motor cortex and cerebellum had a significant, but moderate, between-session reliability. Furthermore, the activity-by-voxel distribution of tremor-related activity within motor cortex and cerebellum showed a significant between-session correlation in at least two-thirds of patients, and intra-individual variability was significantly lower than inter-individual variability. Conclusions: Both the amplitude and location of resting tremor-related activity in motor cortex and cerebellum, derived from concurrent accelerometry-fMRI, are replicable between sessions. This suggests that accelerometry-fMRI may be used as an individual biomarker for tremor pathophysiology, to guide intervention studies and assess target engagement of new anti-tremor therapies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.