Real-time VIM thalamus recordings during peripheral nerve stimulation treatment for essential tremor: DBS intraoperative dataset

Background: 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 cerebellothalamo-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.

Objective: We hypothesize that TAPS reduces tremors through modulation of the VIM thalamus in the cerebellothalamo-cortical network.

Methods: 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.

Results: 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).

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