Inhibitory Control of the Mind : Neural Bases and Impact for Obsessive-compulsive Disorders

Mental-health conditions affect million people worldwide. The economic burden of mental illness is enormous and the economic health of both developing and developed nations will depend on controlling the staggering growth in costs from mental disorders. Obsessive-compulsive disorder (OCD) is a relatively common and frequent form of anxiety that affects approximately 2-3% of the population. OCD is characterized by anxiety, obsessions (persistent intrusive thoughts and images with highly distressing contents) and compulsions (repetitive activity), and severely impairs the lives of those affected. Despite their interest as effective and affordable care and rehabilitation, cognitive therapeutic profits too little from the increasing accumulation of knowledge in neuroscience, and neuroscientists pay too little attention to the challenges faced by clinical psychologists and psychiatrists. To reduce this cultural gap, two teams specialized in the study and multimodal imaging of healthy participants and clinical patients with mental health disorders, the UMR-S INSERM-EPHE-UNICAEN U1077 unit led by Francis Eustache, and ISTS team (UMR-S 6301 CNRS-CEA-UCBN) led by Sonia Dollfus, will joint their efforts to develop an integrated approach of the neural mechanisms at stake from basic neuroscience using state-of-art neuroimaging techniques, to novel and ground breaking psychological intervention. Both teams evolve at the brain imaging Cyceron center in Caen in connection with the Mental Health and Addictology Center, offering unique opportunities for such translational research. This project will capitalize on recent evidence showing that healthy participants can prevent unwanted images from entering consciousness using inhibitory control and memory suppression techniques, disrupting traces of the memories in sensory areas of the brain, and weakening their vividness and later reentrance. OCD is characterized by aberrant and excessive visual intrusions, usually extremely vivid, detailed, and unpleasant. These distressing images are particularly uncontrollable and may frequently initiate compulsive rituals. In a first phase of this proposal will use functional magnetic resonance imaging (fMRI) to develop a neurobiological model of the cognitive computations achieved by inhibition network to suppress memory. To achieve this goal we will develop an attentional model of healthy memory inhibition functioning, simulating the deployment of attentional resources and the different mental processes at stake during suppression. Using sophisticated analyzing tools of fMRI data, we will use this model to decode and infer the representational content of the brain inhibition network, and further refine the connectivity pathways which underlie such control. The lack of a strong neurobiological model prevents the development of therapies which would increase functionality of this network and optimize intervention aiming to disrupt mental intrusions and obsessions. In a second phase, we will assess whether memory suppression may be transferred and trained in OCD patients using images depicting their own obsessions, as a promising avenue to reduce their symptoms on the long run. In addition, fMRI and other brain structural acquisitions will be collected before and after cognitive training to memory suppression, offering a unique opportunity to observe the online dysfunction of intrusion control in OCD patients and to identify neurobiological markers predictive of training outcome and network reconfiguration with training. A fundamental goal of motivated forgetting involves not only to exclude unwelcome content from consciousness but also to reduce their later emotional impact by doing so. In parallel of these two main phases, we will thus also measure physiological markers of autonomic nervous system activity changes in response to suppressed images to better identify the consequences of memory suppression on emotional states, anxiety, and mental health in general.