Decisional impulsivity and the associative-limbic subthalamic nucleus in obsessive-compulsive disorder: stimulation and connectivity.


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Authors
Droux, Fabien 
Morris, Laurel 
Chabardes, Stephan 
Bougerol, Thierry 
Abstract

Why do we make hasty decisions for short-term gain? Rapid decision-making with limited accumulation of evidence and delay discounting are forms of decisional impulsivity. The subthalamic nucleus is implicated in inhibitory function but its role in decisional impulsivity is less well-understood. Here we assess decisional impulsivity in subjects with obsessive compulsive disorder who have undergone deep brain stimulation of the limbic and associative subthalamic nucleus. We show that stimulation of the subthalamic nucleus is causally implicated in increasing decisional impulsivity with less accumulation of evidence during probabilistic uncertainty and in enhancing delay discounting. Subthalamic stimulation shifts evidence accumulation in subjects with obsessive-compulsive disorder towards a functional less cautious style closer to that of healthy controls emphasizing its adaptive nature. Thus, subjects with obsessive compulsive disorder on subthalamic stimulation may be less likely to check for evidence (e.g. checking that the stove is on) with no difference in subjective confidence (or doubt). In a separate study, we replicate in humans (154 healthy controls) using resting state functional connectivity, tracing studies conducted in non-human primates dissociating limbic, associative and motor frontal hyper-direct connectivity with anterior and posterior subregions of the subthalamic nucleus. We show lateralization of functional connectivity of bilateral ventral striatum to right anterior ventromedial subthalamic nucleus consistent with previous observations of lateralization of emotionally evoked activity to right ventral subthalamic nucleus. We use a multi-echo sequence with independent components analysis, which has been shown to have enhanced signal-to-noise ratio, thus optimizing visualization of small subcortical structures. These findings in healthy controls converge with the effective contacts in obsessive compulsive disorder patients localized within the anterior and ventral subthalamic nucleus. We further show that evidence accumulation is associated with anterior associative-limbic subthalamic nucleus and right dorsolateral prefrontal functional connectivity in healthy controls, a region implicated in decision-making under uncertainty. Together, our findings highlight specificity of the anterior associative-limbic subthalamic nucleus in decisional impulsivity. Given increasing interest in the potential for subthalamic stimulation in psychiatric disorders and the neuropsychiatric symptoms of Parkinson's disease, these findings have clinical implications for behavioural symptoms and cognitive effects as a function of localization of subthalamic stimulation.

Description
Keywords
deep brain stimulation, impulsivity, obsessive-compulsive disorder, subthalamic nucleus, uncertainty, Adult, Decision Making, Deep Brain Stimulation, Double-Blind Method, Female, Humans, Imaging, Three-Dimensional, Impulsive Behavior, Limbic System, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Obsessive-Compulsive Disorder, Psychomotor Performance, Statistics, Nonparametric, Subthalamic Nucleus, Surveys and Questionnaires, Visual Analog Scale
Journal Title
Brain
Conference Name
Journal ISSN
0006-8950
1460-2156
Volume Title
140
Publisher
Oxford University Press (OUP)
Sponsorship
Medical Research Council (MR/P008747/1)
This work was supported by Agence Nationale de la Recherche (grant number ANR-14-CE13-0030-01 Physiobs); and University Hospital of Grenoble (Direction de la Recherche Clinique et de l’Innovation). This work was supported by a Wellcome Trust Fellowship grant to V.V. (983705/Z/10/Z).