Abstract
Abstract
Essential tremor (ET), a disorder driven by abnormal neural oscillatory activity, affects approximately 25 million people worldwide and substantially impairs daily activities and quality of life. Here, we identify neurophysiological mechanisms underlying tremor suppression induced by customized, closed-loop sensory peripheral electrical stimulation (PES). Fourteen patients with medication-refractory ET received PES synchronized to tremor activity or sham stimulation. Active PES reduced tremor and was associated with decreased disynaptic group I inhibition between wrist flexor and extensor muscles, alongside reduced oscillatory power of local field potentials recorded from the ventral intermediate nucleus of the thalamus. These effects were significantly attenuated during sham stimulation. A single 20-minute PES session reduced tremor severity by 30.00%, compared to 7.70% after sham. Daily treatment over two weeks produced progressive benefits, with tremor reduction reaching 40.51% from the first to the final day. These findings show that phase-locked PES provides effective, noninvasive tremor suppression without adverse effects, potentially associated with modulation of segmental spinal circuits and central oscillatory dynamics. This approach could offer a practical alternative or complement to current therapies.