Subthalamic nucleus deep brain stimulation induces impulsive action when patients with Parkinson’s disease act under speed pressure

Abstract

The subthalamic nucleus (STN) is proposed to modulate response thresholds and speed–accuracy trade-offs. In situations of conflict, the STN is considered to raise response thresholds, allowing time for the accumulation of information to occur before a response is selected. Conversely, speed pressure is thought to reduce the activity of the STN and lower response thresholds, resulting in fast, errorful responses. In Parkinson’s disease (PD), subthalamic nucleus deep brain stimulation (STN-DBS) reduces the activity of the nucleus and improves motor symptoms. We predicted that the combined effects of STN stimulation and speed pressure would lower STN activity and lead to fast, errorful responses, hence resulting in impulsive action. We used the motion discrimination ‘moving-dots’ task to assess speed–accuracy trade-offs, under both speed and accuracy instructions. We assessed 12 patients with PD and bilateral STN-DBS and 12 age-matched healthy controls. Participants completed the task twice, and the patients completed it once with STN-DBS on and once with STN-DBS off, with order counterbalanced. We found that STN stimulation was associated with significantly faster reaction times but more errors under speed instructions. Application of the drift diffusion model showed that stimulation resulted in lower response thresholds when acting under speed pressure. These findings support the involvement of the STN in the modulation of speed–accuracy trade-offs and establish for the first time that speed pressure alone, even in the absence of conflict, can result in STN stimulation inducing impulsive action in PD.

The neuroanatomical and neurochemical basis of apathy and impulsivity in frontotemporal lobar degeneration

“…Such models can parameterize effort, fatigue, reward expectations and behavioral biases, and other latent variables related to apathy and impulsivity [19–22]. Differences in the accumulation of “evidence” for effort, or the variation in decision thresholds according to reward, can be mapped to differences in brain structure and function [23].…”

“…A ‘drift-diffusion’ model describes the binary-choice between action and inhibition in a Go/No-Go paradigm, with neuronal ‘accumulators’ integrating the momentary evidence over-time [20–22]. When this evidence reaches a threshold, the agent is committed to response, or inhibition of a response.…”

“…The neural determinants of impulsivity in FTLD syndromes include: (1) subcortical FTLD-related pathological changes within striatal, thalamic, and sub-thalamic neurons which affect reward processing and dis-inhibition of thalamo-cortical loops, with consequent biases towards contextually inappropriate actions [21,22,32]; and (2) neocortical pathology, especially in PFC networks, which impair decision-making and action selection processes [33]. Lesions at different points across the functional gradients of interlocking PFC-striato-thalamo-cortical circuits affect different modes of impulsivity [31].…”

“…These effects span animal models of impulsive disorders [34], neuroimaging data from individuals with impulsive neurodevelopmental disorders [35] and adult patients (e.g., obsessive-compulsive disorders and PD)[21,22,36]. The prevalence of impulsivity in these diverse conditions highlights the value of translational and trans-diagnostic approaches to elucidate the neural underpinnings of impulsivity [8,30].…”

Subjective estimates of uncertainty during gambling and impulsivity after subthalamic deep brain stimulation for Parkinson’s disease

“…It is possible that by modulating the decision threshold, STN-DBS could alter the bound for evidence accumulation and thus uncertainty in the representation of the reward environment (Herz et al, 2018;Pote et al, 2016). Further work employing drift diffusion modelling to quantify rates of evidence accumulation and decision boundaries after STN-DBS may be illuminating, having previously helped to elucidate the mechanisms underlying hallucinations in Parkinson's disease (O'Callaghan et al, 2017).…”