Converging metabolic and functional networks for tremor expression and deep brain stimulation-mediated control

Emerging evidence indicates that movement disorders arise from symptom-specific rather than disease-specific brain network dysfunctions that can be influenced through targeted neuromodulation. Such networks are widely mapped using normative connectome analyses from lesion and stimulation sites. Here, we used [¹⁸F]-fluorodeoxyglucose (FDG)-PET in 14 essential tremor patients undergoing thalamic deep brain stimulation (DBS) to identify stimulation-induced and tremor related regional metabolic changes in a within-subject design and combined this with normative connectome results. Stimulation increased metabolism in motor cortical and cerebellar regions - key hubs of the previously proposed tremor treatment network as derived from normative functional connectivity. Importantly, individual alignment with this network predicted clinical tremor improvement (R² = 0.593, p = 0.007). These same regions showed higher metabolism during tremor expression in the untreated condition, suggesting overlap between the circuits involved in symptom generation and therapeutic response. These findings support indirect connectome-based models by linking them to brain glucose metabolism changes and suggest that DBS relieves tremor by modulating the same circuit that underlies symptom expression.