Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting

Abstract

Objective We conducted intraoperative measurements of tremor during DBS containing short pauses (≤50 ms) to determine if there is a minimum pause duration that preserves tremor suppression. Methods Nine subjects with ET and thalamic DBS participated during IPG replacement surgery. Patterns of DBS included regular 130 Hz stimulation interrupted by 0, 15, 25 or 50 ms pauses. The same patterns were applied to a model of the thalamic network to quantify effects of pauses on activity of model neurons. Results All patterns of DBS decreased tremor relative to ‘off’. Patterns with pauses generated less tremor reduction than regular high frequency DBS. The model revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but pauses in stimulation allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions. Conclusion The temporal pattern of stimulation influences the efficacy of thalamic DBS. Pauses in stimulation resulted in decreased tremor suppression indicating that masking of pathological bursting is a mechanism of thalamic DBS for tremor. Significance Pauses in stimulation decreased the efficacy of open-loop DBS for suppression of tremor.

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“…However, the nature of the intraoperative testing environment precluded assessment of the effect of stimulation pattern of the side effects produced by DBS. Intermittent DBS may be an alternative approach to reduce stimulation energy, but intermittent thalamic stimulation in patients with essential tremor (42, 43) and intermittent STN DBS in patients with PD (19) were less effective than constant stimulation.…”

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