Thalamo-cortical evoked potentials during stimulation of the dentato-rubro-thalamic tract demonstrate synaptic filtering

Abstract

Essential tremor DBS targeting the ventral intermediate nucleus (Vim) of the thalamus and its input, the dentato-rubro-thalamic tract (DRTt), has proven to be an effective treatment strategy. We examined thalamo-cortical evoked potentials (TCEPs) and cortical dynamics during stimulation of the DRTt. We recorded TCEPs in primary motor cortex during clinical and supra-clinical stimulation of the DRTt in ten essential tremor patients. Stimulation was varied over pulse amplitude (2–10 ​mA) and pulse width (30–250 ​μs) to allow for strength-duration testing. Testing at clinical levels (3 ​mA, 60 ​μs) for stimulation frequencies of 1–160 ​Hz was performed and phase amplitude coupling (PAC) of beta phase and gamma power was calculated. Primary motor cortex TCEPs displayed two responses: early and all-or-none (<20 ​ms) or delayed and charge-dependent (>50 ​ms). Strength-duration curve approximation indicates that the chronaxie of the neural elements related to the TCEPs is <200 ​μs. At the range of clinical stimulation (amplitude 2–5 ​mA, pulse width 30–60 ​μs), TCEPs were not noted over primary motor cortex. Decreased pathophysiological phase-amplitude coupling was seen above 70 ​Hz stimulation without changes in power spectra and below the threshold of TCEPs. Our findings demonstrate that DRTt stimulation within normal clinical bounds does not excite fibers directly connected with primary motor cortex but that supra-clinical stimulation can excite a direct axonal tract. Both clinical efficacy and phase-amplitude coupling were frequency-dependent, favoring a synaptic filtering model as a possible mechanism of action.