Combining small animal molecular imaging with next generation neuromodulation to explore novel treatments for Obsessive Compulsive Disorder.

In vivo molecular imaging is a highly sensitive tool to study in vivo neuroreceptor kinetics and to visualize entire brain network dynamics in human patients as well as in small laboratory animals. Obsessive-compulsive disorder (OCD) is a chronic disabling psychiatric disease, characterized by unwanted obsessions and compulsions to temporarily neutralize the anxiety provoked by these obsessions. The prevalence of OCD is reported to be 0.8% to 3.2% and an estimated 60% of patients remain unresponsive to medical intervention. OCD is an extremely complex psychiatric disorder resulting from a pathological interplay of serotonergic (5-HT), dopaminergic (DA) and glutamatergic neurochemical dysfunctions. In this project we have three clear objectives:1. elucidate the pathophysiology in an animal model for OCD;2. modulate glutamate levels for better target selection;3. evaluate novel neuromodulation techniques miniaturized for small animals. To achieve our goals we have defined three work packages with two intermediate milestones to consolidate progress or to fall back to an alternative approach. Our first work package sets up the "compulsive checking" animal model and employs Positron Emission Tomography (PET) to visualize changes in whole brain activity (FDG μPET), serotonin (MDL μPET), dopamine (Raclo μPET) as well as glutamate transmission (by Magnetic Resonance Spectroscopy) and correlates these with symptomatic behaviour. At our first milestone after 15 months we will evaluate our findings versus existing literature and we will then decide on alternative animal models if needed. In a second work package we will challenge the animal model with glutamate-altering drugs, known to aggravate or ameliorate human OCD symptoms, in order to more specifically pinpoint a target region for neuromodulation (second milestone; mid-term). We can always fold back to targeting the nucleus caudatus. The knowledge generated (neurobiology-WP1 and target region-WP2) will then be applied in a third work package to investigate repetitive Transcranial Magnetic Stimulation (rTMS) versus gold standard intra-cortical pharmacological modulation and Deep brain Stimulation (DBS).SUMMARY: we want to exploit multimodal and multiprobe molecular imaging to investigate the neuropathophysiology of OCD in an animal model and to evaluate novel neuromodulation treatments which we miniaturized for use in rodents.

Keywords:OBSESSIVE COMPULSIVE DISORDER, DEEP BRAIN STIMULATION, SMALL ANIMAL IMAGING, TRANSCRANIAL MAGNETIC STIMULATION

Disciplines:Medical imaging and therapy, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing