Short latency activation of cortex by clinically effective thalamic brain stimulation for tremor

Abstract

Deep brain stimulation relieves disabling symptoms of neurologic and psychiatric diseases when medical treatments fail, yet its therapeutic mechanism is unknown. We hypothesized that ventral intermediate nucleus stimulation for essential tremor activates cortex at short latencies and that this potential is related to suppression of tremor in the contralateral arm. We measured cortical activity with electroencephalography in 5 subjects (7 brain hemispheres) across a range of stimulator settings, and reversal of the anode and cathode electrode contacts minimized the stimulus artifact, allowing visualization of brain activity. Regression quantified the relationship between stimulation parameters and both the peak of the short latency potential and tremor suppression. Stimulation generated a polyphasic event related potential in ipsilateral sensorimotor cortex with peaks at discrete latencies beginning less than one millisecond after stimulus onset (mean latencies 0.9±0.2, 5.6±0.7, and 13.9±1.4 milliseconds, denoted R1, R2, and R3, respectively). R1 showed more fixed timing than the subsequent peaks in the response (p<0.0001, Levene’s test), and R1 amplitude and frequency were both closely associated with tremor suppression (p<0.0001, respectively). These findings demonstrate that effective ventral intermediate nucleus thalamic stimulation for essential tremor activates cerebral cortex at approximately one millisecond after the stimulus pulse. The association between this short latency potential and tremor suppression suggests that deep brain stimulation may improve tremor by synchronizing the precise timing of discharges in nearby axons, and by extension the distributed motor network, to the stimulation frequency or one of its subharmonics.

Nonlinear interactions in the thalamocortical loop in essential tremor: A model-based frequency domain analysis

“…However, this provides no more specific information as to the subcortical areas participating in this loop. Such degree of delay is clearly beyond the lags inferred by direct white matter tracts connecting thalamus and cortex that are at most in the range of few milliseconds (Walker et al, 2012). The time lags estimated at the resting state are much shorter but again in the range of 20ms implying a multisynaptic, albeit faster or shorter, pathway of functional connectivity between the two structures.…”

A Slow Axon Antidromic Blockade Hypothesis for Tremor Reduction via Deep Brain Stimulation

“…There are a number of hypotheses [5], [6], and numerous experiments have been conducted to test them, but the results have been inconclusive [6]–[9]. There are two main problems: (i) the lack of specific testable experimental predictions associated with the hypotheses, and (ii) the fundamental difficulty in explaining certain basic features of DBS.…”

Network effects of deep brain stimulation

“…Clearly more work is needed to understand these findings. Walker et al (2012a) demonstrated short-latency cortical effects of Vim DBS recorded with scalp EEG that were a part of a complex EP. Effective Vim thalamic stimulation appeared to activate the cortex at ϳ1 ms after the stimulus pulse, leading the authors to suggest that DBS may improve tremor by synchronizing the precise timing of discharges through the thalamocortical network to the stimulation frequency or one of its subharmonics.…”