Deep brain stimulation of the ventrointermediate nucleus of the thalamus to treat essential tremor improves motor sequence learning

Abstract

The network of brain structures engaged in motor sequence learning comprises the same structures as those involved in tremor, including basal ganglia, cerebellum, thalamus, and motor cortex. Deep brain stimulation (DBS) of the ventrointermediate nucleus of the thalamus (VIM) reduces tremor, but the effects on motor sequence learning are unknown. We investigated whether VIM stimulation has an impact on motor sequence learning and hypothesized that stimulation effects depend on the laterality of electrode location. Twenty patients (age: 38-81 years; 12 female) with VIM electrodes implanted to treat essential tremor (ET) successfully performed a serial reaction time task, varying whether the stimuli followed a repeating pattern or were selected at random, during which VIM-DBS was either on or off. Analyses of variance were applied to evaluate motor sequence learning performance according to reaction times (RTs) and accuracy. An interaction was observed between whether the sequence was repeated or random and whether VIM-DBS was on or off (F[1,18] = 7.89, p = .012). Motor sequence learning, reflected by reduced RTs for repeated sequences, was greater with DBS on than off (T[19] = 2.34, p = .031). Stimulation location correlated with the degree of motor learning, with greater motor learning when stimulation targeted the lateral VIM (n = 23, ρ = 0.46; p = .027). These results demonstrate the beneficial effects of VIM-DBS on motor sequence learning in ET patients, particularly with lateral VIM electrode location, and provide evidence for a role for the VIM in motor sequence learning.

Keywords: deep brain stimulation; essential tremor; motor sequence learning; serial reaction time task; ventrointermediate nucleus of the thalamus.

FIGURE 1

SRTT paradigm. (a) SRTT: Positions on computer screen corresponded with button locations on one‐handed response pad. (b) Single SRTT session, with two learned and two random runs per block. Each patient participated in two sessions on the same day. One session was performed with the stimulation on throughout and one session was performed with the stimulation off throughout, with the order counterbalanced. L, learned sequences; R, random sequences

FIGURE 2

SRTT performance. (a) Interaction between within‐subject factors Stimulation (on/off) and Sequence type (learned/random) (F[1,18] = 7.89, p = .012). (b) The normalized learning score was greater with the stimulation on than off (T[19] = 2.47, p = .023). (c) The learning score increased over time when the stimulation was on and not off, but neither Time (F[1,14] = 1.83, p = 0.20) nor an interaction between Stimulation and Time (F[1,14] = 2.13, p = 0.17) was significant

FIGURE 3

Electrode location. (a) Stimulated electrode coordinates relative to AC–PC line, color‐coded according to within‐patient mean RT difference with stimulation on. (b) Correlation between RT difference with stimulation on and x‐coordinates of stimulated electrodes (Spearman's ρ = 0.46; p = .027)