Deep brain stimulation does not modulate resting-state functional connectivity in essential tremor

Abstract

While the effectiveness of deep brain stimulation in alleviating essential tremor is well-established, the underlying mechanisms of the treatment are unclear. Essential tremor, as characterised by tremor during action, is proposed to be driven by a dysfunction in the cerebello-thalamo-cerebral circuit that is evident not only during motor actions but also during rest. Stimulation effects on resting-state functional connectivity were investigated by functional MRI in 16 essential tremor patients with fully implanted deep brain stimulation in the caudal zona incerta during On and Off therapeutic stimulation, in a counterbalanced design. Functional connectivity was calculated between different constellations of sensorimotor as well as non-sensorimotor regions (as derived from seed-based and data-driven approaches), and compared between On and Off stimulation. We found that deep brain stimulation did not modulate resting-state functional connectivity. The lack of modulation by deep brain stimulation during resting-state, in combination with previously demonstrated effects on the cerebello-thalamo-cerebral circuit during motor tasks, suggest an action-dependent modulation of the stimulation in essential tremor.