Within the framework of its theme 3 “Health, quality of life at work”, the Disability, Employment and Health at Work Research Chair of the UPEC aims to carry out research projects on psychological disabilities, more specifically on Obsessive Compulsive Disorders.

The World Health Organization ranks OCD as one of the ten most disabling mental health disorders (World Health Organization [WHO]. International Classification of Functioning (ICF). Disability and health, WHO library, Geneva (2001)). Although the disability associated with the disorder has been recognized for many years (Markarian Y, Larson MJ, Aldea MA, Baldwin SA, Good D, Berkeljon A, Murphy TK, Storch EA, McKay D. Multiple pathways to functional impairment in obsessive-compulsive disorder. Clin Psychol Rev. 2010 Feb;30(1):78-88.), research focused on its determinants, consequences, and possible compensations remains lacking.
The treatment of severe OCD is based on pharmacological and/or psychotherapeutic treatments, the effectiveness of which is now well established; however, in approximately 30% of cases, they do not sufficiently eliminate the impact of the symptoms on the personal, family and professional functioning of the persons concerned. These realities make it necessary to pursue fundamental and clinical research on this frequent and often highly disabling pathology, particularly in a professional environment.

This is the objective that the psychiatry team of Professors Pelissolo and Mallet has been pursuing for many years at the UPEC and the Henri-Mondor University Hospitals, in collaboration with the Brain Institute. This team has studied technological assistance solutions, in collaboration with professionals, patients and their relatives, to reduce the handicap linked to severe OCD (DOMOTOC and EQUOSMART programs).
Other of their works have shown the impact of the symptoms of compulsive and repeated checking (often several hours a day) on the functioning, notably professional, of the persons concerned. At the same time, this team has conducted numerous neuroscientific explorations of these pathological checking phenomena, in order to understand their neural determinants and the means to fight them. The psychiatry department of the HU Henri-Mondor/Albert-Chenevier is also internationally renowned in the treatment of people suffering from severe and disabling OCD, with the development of numerous innovative treatment techniques (notably deep brain stimulation).

Dr Ghassene BOUKHARI, intern in psychiatry with a double medical and scientific training and leading a research project on the neurobiology of OCD in the framework of a Master 2, under the direction of Prs Mallet and Pelissolo.

The research project to be conducted by Dr. Ghassene BOUKHARI will have two complementary components :

• one focused on the understanding of verification phenomena with an exploration of functional brain imaging
• and the other aimed at establishing, within a group of people suffering from OCD, the impact of the pathology on their professional adaptation (and the determinants of this adaptation) with the aim of facilitating access to, and maintenance in, employment.

These two focuses, based on the previous work of the research team, will make it possible to propose solutions, behavioral and/or technological, to help people suffering from OCD in the workplace.

Brain correlates of obsessive-compulsive disorder:
Study of checking compulsions in functional MRI scan

Obsessive-Compulsive Disorder (OCD) is a severe mental disorder characterized by obsessive thoughts and/or compulsive behaviors of varying degrees. It can sometimes be severe and disabling and can develop in a chronic mode. The pharmacotherapies and psychotherapies indicated for OCD are still often insufficient, which indicates a need for more targeted therapies whose development would require a better understanding of the pathophysiology of this disorder. Checking is one of the most frequent types of compulsions observed in people followed for OCD.
It is not a behavior that is pathological in nature, but it is the repetition and intensity of the anxiety that accompanies it that makes it maladaptive. The checks are therefore not done once but several times, very closely and daily, their retention representing an effort described as insurmountable (anxious struggle, egodystonia) by the patients when they do not benefit from psychotherapeutic support.
The compulsions observed in OCD, often linked to obsessive thoughts, have been the subject of numerous investigations on the semiological, cognitive-behavioral and more recently neurobiological levels. Nevertheless, the genesis of these behaviors and their pathological redundancy, as well as their cortico-subcortical correlates, have not yet been elucidated. Furthermore, it is possible to make progress in the understanding of the mechanisms underlying compulsive behavior by observing, provoking or experimentally reducing OCD symptoms. It is in order to progress in the understanding of the neurobiological processes underlying compulsive behaviors that we propose this work, based on an experimental provocation task of verification behaviors and validated in clinical populations during previous works [1, 2], and already used during neurophysiological investigations [3] and in functional neuroimaging [4].

The functional neuroimaging data currently available are essentially derived from measurements performed either at rest or under conditions of simple exposure to anxiety-provoking stimuli [5], or in behavioral tasks not directly related to compulsions per se [6]. Although fragmented, these data suggest the presence of functional abnormalities in the cortico-striato-thalamo-cortical circuits (CSTC) [7] in these patients.
Moreover, the involvement of subcortical structures has been shown in a population of patients with severe and resistant OCD, by means of this verification task, highlighting especially the role of neurons of the subthalamic nucleus in a decision phase during the execution of the task, underlining the interest in exploring subcortical networks in the pathophysiology of pathological verification [3]. In addition, the only study using a verification task analogous to the one used in the present project suggests a deficit in behavioral adaptation during verification behaviors, which would be mediated by orbitofrontal hyperactivation. To date, we are not aware of any previous publications that have specifically studied compulsions in functional neuroimaging, comparing them to healthy controls, particularly in a situation of retention of these behaviors.

• Presence of cortico-subcortical dysfunctions during the execution and behavioral regulation (retention) of compulsions in patients vs. healthy controls
• Involvement of the basal ganglia and frontal cortical areas in the expression of these compulsions

Based on collected but not yet exploited and published clinical and neuroimaging data, we plan to :

• highlight the neural correlates associated with the expression of checking compulsions in patients with OCD
• compare the expression and inhibition of checking compulsions in patients vs. healthy controls
• identify the cortico-subcortical neural circuits involved in the initiation, maintenance and completion of these checking compulsions according to the behavioral context

(With clinical and neuroimaging data already collected, steps 1-5 of the methodology have been completed to date) 

1. Development and validation of a cognitive task that can represent an experimental model of checking compulsions; this task must be clinically relevant and adaptable in neuroimaging, in order to study the brain activity underlying these compulsions. 
2. Adaptation of the verification task in functional MRI (fMRI). The use of fMRI will allow us to observe the neural networks related to the verification compulsion by focusing on cortical areas and basal ganglia. 
3. Inclusion of 14 patients with OCD according to DSM-5-TR criteria and matching to 14 healthy controls according to age, gender, and education level. 
4. Psychometric assessment (Y-BOCS, Padua Inventory, HAD, STAI-B) 
5. Acquisition of fMRI data, pre-processing of imaging data 
6. Data analysis: 
   1. for the decision to check and the execution of checking compulsions in patients vs. healthy controls 
   2. for brain activity associated with retention of checking behaviors in patients 
   3. for brain activity associated with processing feedback associated with the decision to check or not in patients vs. healthy controls 
   4. to search for correlations between the degree of hyper/hypoactivation of certain brain regions and clinical scores.

NB: Outside the regions of interest previously mentioned, the exploratory research (whole-brain) of potential neuro-functional correlates will be controlled by a measure of the false discovery rate to limit the risk of type 1 (problem of multiple comparisons). 

After analysis of the data and synthesis of the conclusions of our study, we wish to contribute to a better understanding of the neurobiological mechanisms contributing to the expression and inhibition of checking compulsions in OCD, particularly within the cortical-subcortical circuits. We plan to publish our results in an international scientific journal, given the interest of the subject and the novel methodology of our work.

In the medium and long term, by providing a better understanding of the pathophysiology of OCD, our study could contribute to the development of innovative treatments, psychotherapeutic, psychotropic, or by different stimulation techniques specifically targeting the neural circuits and pathways involved in compulsions in these patients.

[1] Rotge JY, Clair AH, Jaafari N, et al. A challenging task for assessment of checking behaviors in obsessive–compulsive disorder. Acta Psychiatr Scand 2008; 117: 465–473.

[2] Clair A-H, N’Diaye K, Baroukh T, et al. Excessive checking for non-anxiogenic stimuli in obsessive-compulsive disorder. Eur Psychiatry 2013; 28: 507–513.

[3] Burbaud P, Clair A-H, Langbour N, et al. Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive–compulsive disorder. Brain 2013; 136: 304–317.

[4] Rotge J-Y, Langbour N, Dilharreguy B, et al. Contextual and behavioral influences on uncertainty in obsessive-compulsive disorder. Cortex 2015; 62: 1–10.

[5] Morgiève M, N’Diaye K, Haynes WIA, et al. Dynamics of psychotherapy-related cerebral haemodynamic changes in obsessive compulsive disorder using a personalized exposure task in functional magnetic resonance imaging. Psychol Med 2014; 44: 1461–1473.

[6] van den Heuvel OA, van Wingen G, Soriano-Mas C, et al. Brain circuitry of compulsivity. Eur Neuropsychopharmacol 2016; 26: 810–827.

[7] Boedhoe PSW, Schmaal L, Abe Y, et al. Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis. Am J Psychiatry 2017; 174: 60–69.