Abstract
Corticostriatal circuits through the orbitofrontal cortex (OFC) play key roles in complex human behaviors such as evaluation, affect regulation and reward-based decision-making. Importantly, the medial and lateral OFC (mOFC and lOFC) circuits have functionally and anatomically distinct connectivity profiles which differentially contribute to the various aspects of goal-directed behavior. OFC corticostriatal circuits have been consistently implicated across a wide range of psychiatric disorders, including major depressive disorder (MDD), obsessive compulsive disorder (OCD), and substance use disorders (SUDs). Furthermore, psychiatric disorders related to OFC corticostriatal dysfunction can be addressed via conventional and novel neurostimulatory techniques, including deep brain stimulation (DBS), electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Such techniques elicit changes in OFC corticostriatal activity, resulting in changes in clinical symptomatology. Here we review the available literature regarding how disturbances in mOFC and lOFC corticostriatal functioning may lead to psychiatric symptomatology in the aforementioned disorders, and how psychiatric treatments may exert their therapeutic effect by rectifying abnormal OFC corticostriatal activity. First, we review the role of OFC corticostriatal circuits in reward-guided learning, decision-making, affect regulation and reappraisal. Second, we discuss the role of OFC corticostriatal circuit dysfunction across a wide range of psychiatric disorders. Third, we review available evidence that the therapeutic mechanisms of various neuromodulation techniques may directly involve rectifying abnormal activity in mOFC and lOFC corticostriatal circuits. Finally, we examine the potential of future applications of therapeutic brain stimulation targeted at OFC circuitry; specifically, the role of OFC brain stimulation in the growing field of individually-tailored therapies and personalized medicine in psychiatry.
Highlights
The past quarter-century has seen tremendous advances in our understanding of the functions of the frontal lobes of the human brain
We have reviewed a growing body of evidence that dysfunction in these orbitofrontal cortex (OFC)-striatal circuits may be central to the pathophysiology of a variety of psychiatric illnesses
The role of these pathways in Obsessive-compulsive disorder (OCD) has been recognized for decades, OFC-striatal dysfunction appears to play an important role in the pathophysiology of major depressive disorder (MDD), substance use disorders (SUDs), and potentially many other major categories of psychiatric disease
Summary
The past quarter-century has seen tremendous advances in our understanding of the functions of the frontal lobes of the human brain. Weaker functional connectivity between these regions was associated with an increase in illness duration These brain regions have been associated with the subjective experience of agency and language processing, respectively, which has led to the hypothesis that dysfunction of the lateral orbitofrontal ‘‘non-reward’’ circuit may lead to the generation of negative self-thoughts and reduced self-esteem; two important factors in the development and maintenance of MDD (Wegener et al, 2015). Taken together, these findings provide evidence for the notion that disturbances in the functional balance between the mOFC and lOFC, and their associated corticostriatal circuit loops, contribute to specific symptom clusters in MDD. These results suggest that rTMS may be able to effectively and selectively modulate psychiatric symptomatology in which the OFC is implicated
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