Arbitration between habitual and goal-directed behavior in obsessive-compulsive disorder: circuit dynamics and effects of noninvasive neurostimulation

点击翻译按钮获取中文摘要

Abstract (parent award): Dysfunctional decision-making may be a prominent mechanism underlying maladaptive behavior in multiple psychiatric disorders, including obsessive-compulsive disorder (OCD). Debilitating compulsivity and avoidance in OCD are believed to be a direct result of flawed decision-processing. A better understanding of the brain mechanisms of abnormal decision-making in OCD is essential for the development of more effective treatment options. This mentored patient-oriented career development project plans to address this underexplored area. By providing the necessary mentorship and support and building upon the candidate’s solid skillset in basic and clinical neuroscience, the primary goal of this K23 project is to establish the candidate’s career as an independent clinician-scientist with expertise in clinical decision neuroscience. The candidate will benefit from the clinical and academic environments of UCLA and Caltech as well as from a mentorship team with a complementary expertise and exceptional scientific and mentoring records to fill gaps in his knowledge and skills in 3 areas: 1) cognitive neuroscience of decision-making; 2) clinical neuroscience task-based functional magnetic resonance imaging (fMRI) methodology; and 3) noninvasive neurostimulation methodology. Integrated with the above-mentioned training goals, the research project will examine neurobehavioral characteristics of decision-making in OCD. [People utilize two behavioral strategies, goal-directed (GD) and habitual (HB) when engaging in value-based decision-making that involves rewarding or punishing outcomes. Furthermore, an arbitration mechanism has been proposed recently that controls the balance between those two strategies in healthy participants. Arbitration regions (the frontopolar and inferolateral prefrontal cortex (ilPFC)) regulate the goal-directed/habitual decision-making balance by selectively downregulating the activity of the habitual regions (putamen and supplementary motor area). In OCD, an imbalance exists between GD and HB action selection in favor of HB action selection. This project aims to explore the neurobehavioral characteristics of this arbitration mechanism and its relationship with behaviors and clinical phenotypes in OCD by applying cognitive neuroscience, clinical task-based fMRI and transcranial direct current stimulation (tDCS) approaches. Adults with OCD and healthy control participants will perform two tasks while being scanned, and when they receive inhibitory, excitatory, and sham tDCS over the left ilPFC outside of the scanner: I) a decision-making task in which GD and HB strategies compete to control action selection and II) a clinically relevant symptom provocation-avoidance task in which avoidance decisions will be simulated. The project’s research aims are to 1) explore the GD, HB, and arbitration regions’ neural activity and arbitration-habitual circuit connectivity in OCD; 2) examine the association between measures of behavioral performance, arbitration’s neural activity and connectivity, and OCD clinical symptoms; and 3) investigate the behavioral consequences of tDCS over an arbitration region, the left ilPFC, during task performance.]