PHYSIOBS

Obsessive-compulsive disorder (OCD), ranked by the World Health Organization as the tenth most disabling illness, is a neuropsychiatric disease affecting 2.5-3% of the population and characterized by recurrent, persistent thoughts, repetitive compulsive behaviours with chronic evolution with severe complications such as depression, suicide and substance use disorders. Although some forms of OCD can be alleviated with pharmacological and cognitive-behavioural approaches, more than 40% of patients are resistant to these standard treatments and about 10% show severe disability and require institutionalization. Resistant patients may benefit from new surgical therapeutic approaches such as deep brain stimulation (DBS) of specific cerebral regions to modulate neural networks. So far, the number of OCD patients treated with DBS is very limited. Although strict inclusion criteria have been defined based primarily on lesion surgery criteria (e.g. clinical severity, co-morbidity and treatment resistance), DBS outcome varies from excellent to poor between patients for reasons that are still unclear. The goal of PHYSIOBS is to map cortical regions that are modulated by DBS of the subthalamic nucleus (STN) in patients suffering from severe OCD. Brain activation elicited by STN DBS will be compared to that of Parkinson’s disease (PD) patients, in order to identify specific markers of the associative limbic loop as opposed to the motor loop that are the respective DBS targets in those diseases. Neurophysiological activations will be complemented with neuroanatomical measurements and will be correlated to DBS outcome. In particular, we want to provide a neuroimaging approach for the optimisation of stimulation protocols targeting frontal regions. PHYSIOBS methodology will be based upon acquisition and processing of high-density electroencephalography (EEG), high-density functional near infrared optical imaging (fNIRS) and structural magnetic resonance images (MRI, T1 and diffusion tensor imaging – DTI). Those modalities will be used to characterise neuromodulation mechanisms underlying clinical effects of STN DBS. An important concern for therapeutic tuning of DBS parameters in OCD is the delay between the onset of the stimulation procedure and the first detectable positive clinical effects. Therefore, we will specifically search for neurophysiological markers that would predict patients’ outcome and/or that would indicate optimal stimulation parameters. In addition, invasive recordings (multiunit activity, MUA, and local field potentials, LFP) will be recorded during electrodes implantation to relate functional properties of targeted STN subdivisions with modulation of cortical regions by DBS. The expertise gathered in PHYSIOBS is optimal for conducting the proposed research. The coordinating group, Inserm U836 GIN, Grenoble, has been developing for many years electrophysiology and DBS for psychiatric disorders. The consortium also includes the Inserm U1105 GRAMFC, Amiens, for the development of new fNIRS DBS methodology, and the CEA Neurospin, Gif-sur-Yvette, for MRI tractography of stimulated subcortico-cortical tracts.