PROJECT: JTC2013: TYMON

Uncertainty monitoring vs. inhibition of action in obsessive-compulsive disorder: role of the subthalamic nucleus and effects of stimulation in humans and rodents

Abstract

Obsessive-Compulsive Disorder (OCD) is an anxiety disorder characterized by intrusive thought (obsession) associated with repetitive behavior, such as compulsive checking. Recently, it has been shown that this dimension of compulsive checking could be reduced with high-frequency electric stimulation of the subthalamic nucleus (STN-HFS) in severe OCD patients. However, the exact psychopathological processes and underlying neural mechanisms through which STN-HFS influence the action of checking remain unknown. TYMON project will investigate the role of the STN on two possible processes: uncertainty reduction (by accumulation/integration of evidence) and control of impulses to check (checking inhibition). We will test these two alternatives in an ambitious translational approach that includes behavioral and physiological experiments in human and animal studies. We will first disambiguate the role of the STN in uncertainty reduction and/or checking inhibition and seek for their potential electrophysiological correlates. Thus, we will address specifically the therapeutic role of STN stimulation in compulsive checking by comparing performance on checking tasks in OCD patients treated with STN-HFS, and in a mouse model of OCD with optogenetic stimulation of the STN circuitry. Altogether, our transdisciplinary project will allow better understanding of OCD mental disorder etiology and promote the development of more targeted and efficient therapies for OCD such as STN-HFS.

Keywords

Optogenetics, Animal models, translational, Electrophisiological approaches, Behavioural methodologies, anxiety disorders, aetiology, ocd, Electrical and magnetic brain stimulation, psychopathology, subthalamic nucleus

Call topic

Mental Disorders

Proposed runtime

2014 - 2018

Project team

Luc Mallet (Coordinator)
France (ANR)
Lars Wojtecki
Germany (BMBF)
Rui Costa
Portugal (FCT)