SAMENTA - Santé Mentale - Addictions

Hyperdirect pathway in Psychiatry: Anatomo-functional characterization of the cortical-subthalamic pathway and its relevance for the treatment of OCD by deep-brain stimulation – HYPSY

Submission summary

The goal of the present project is to analyze the neurocognitive bases of compulsivity, a primary symptom of obsessive compulsive disorder (OCD), and the mechanisms by which deep brain stimulation of the subthalamic nucleus (STN-DBS) has a positive effect on this symptom. For this purpose, our research will be implemented as a translational approach in different species including mice, monkeys and humans. A central hypothesis of our approach being that the limbic cortico-subthalamic projection plays a key role in these processes.
A first series of task will consist of studies of the anatomy of this projection by using the technique of diffusion tensor imaging (DTI) tractography in humans, in macaques, and in mice. Comparative analyses will be done between healthy subjects and OCD patients and between wildtype and SAPAP3-KO mice. Then the histological and electrophysiological characterization of the projection will be investigated by optogenetic manipulation in macaques and mice, and a cross species analysis of the electrophysiological data obtained will be performed. The role that the limbic hyperdirect pathway can play in behavioral flexibility will be studied in the SAPA3-KO model of compulsive disorder while its functional and structural correlates will be studied in healthy humans. Finally, the search for electrophysiological biomarkers of the response to STN-DBS will be continued in human OCD patients as well as for functional connectivity of the hyperdirect pathway in the SAPA3-KO mouse.

Project coordination

Jérôme YELNIK (Institut National de la Sante et de la Recherche Medicale - CRICM)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

INSERM Institut National de la Sante et de la Recherche Medicale - CRICM
ICM Institut du Cerveau et de la Moelle épinière
APHP Assistance Publique - Hôpitaux de Paris
CNRS Centre National de la Recherche Scientifique
INSERM Institut National de la Sante et de la Recherche Medicale - CRICM
CEA Centre de l'Energie Atomique - NeuroSpin

Help of the ANR 496,359 euros
Beginning and duration of the scientific project: March 2014 - 48 Months

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