Transcutaneous afferent patterned stimulation reduces essential tremor symptoms through modulation of neural activity in the ventral intermediate nucleus of the thalamus

Essential tremor (ET), the most common movement disorder in adults, presents with involuntary shaking of the arms during postural hold and kinetic tasks linked to dysfunction in the cerebello-thalamo-cortical (CTC) network. Recently, transcutaneous afferent patterned stimulation (TAPS), applied through a wrist-worn device, has emerged as a non-invasive therapy for medication refractory ET. However, its mechanism remains unclear. We hypothesize that TAPS reduces tremor through modulation of the VIM thalamus in the CTC network. Employing refractory ET patients seeking VIM deep brain stimulation (DBS), we quantified clinical tremor improvement following TAPS treatment in a pre-operative setting, followed by intra-operative, microelectrode recording of the contralateral thalamus with concurrent TAPS treatment on and off. After one preoperative session, TAPS significantly reduces upper limb tremor, with asymmetric effect favoring the treated limb and greatest improvement tending to kinetic tremor. The magnitude of TAPS-related tremor reduction demonstrates a positive correlation with the modulation of alpha and beta band LFPs in the VIM. TAPS also modulated spiking activity in the VIM, though it was uncorrelated with the degree of tremor reduction. Of note, TAPS related modulation of LFPs and spiking activity was greatest near the optimal placement location for DBS lead in treating ET. In sum, TAPS likely reduces tremor in ET by modulating the VIM and connected nodes in the cerebello-thalamo-cortical pathway.