Wearable peripheral nerve stimulator reduces essential tremor symptoms through targeted brain modulation

Essential tremor (ET), the most common movement disorder in adults, presents with involuntary shaking of the upper extremities during postural hold and kinetic tasks linked to dysfunction in the cerebello-thalamo-cortical network. Recently, transcutaneous afferent patterned stimulation (TAPS), applied through a wrist-worn device, has emerged as a non-invasive treatment for medication-refractory ET. However, its mechanism remains unclear.

We hypothesize that TAPS reduces tremors through modulation of the VIM thalamus in the cerebello-thalamo-cortical network.

Employing refractory pure 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 average (0.61, p = 0.002), with an asymmetric effect favoring the treated limb (p = 0.047) and the greatest improvement tending to kinetic tremor (R2 = 0.943, p = 0.002). The magnitude of TAPS-related tremor reduction demonstrates a positive correlation with the modulation of alpha (R2 = 0.213, p < 0.001) and beta band LFPs (R2 = 0.255, p < 0.001) in the VIM. TAPS also suppressed spiking activity in the VIM (R2 = 0.104, p = 0.029), 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 the DBS lead in treating ET (R2 = 0.122, p = 0.006).

In sum, TAPS likely reduces tremor in ET by modulating the VIM and connected nodes in the cerebello-thalamo-cortical pathway.