A Framework for Understanding the Emerging Role of Corticolimbic-Ventral Striatal Networks in OCD-Associated Repetitive Behaviors

Abstract

Significant interest in the mechanistic underpinnings of obsessive-compulsive disorder (OCD) has fueled research on the neural origins of compulsive behaviors. Converging clinical and preclinical evidence suggests that abnormal repetitive behaviors are driven by dysfunction in cortico-striatal-thalamic-cortical (CSTC) circuits. These findings suggest that compulsive behaviors arise, in part, from aberrant communication between lateral orbitofrontal cortex (OFC) and dorsal striatum. An important body of work focused on the role of this network in OCD has been instrumental to progress in the field. Disease models focused primarily on these regions, however, fail to capture an important aspect of the disorder: affective dysregulation. High levels of anxiety are extremely prevalent in OCD, as is comorbidity with major depressive disorder. Furthermore, deficits in processing rewards and abnormalities in processing emotional stimuli are suggestive of aberrant encoding of affective information. Accordingly, OCD can be partially characterized as a disease in which behavioral selection is corrupted by exaggerated or dysregulated emotional states. This suggests that the networks producing OCD symptoms likely expand beyond traditional lateral OFC and dorsal striatum circuit models, and highlights the need to cast a wider net in our investigation of the circuits involved in generating and sustaining OCD symptoms. Here, we address the emerging role of medial OFC, amygdala, and ventral tegmental area projections to the ventral striatum (VS) in OCD pathophysiology. The VS receives strong innervation from these affect and reward processing regions, and is therefore poised to integrate information crucial to the generation of compulsive behaviors. Though it complements functions of dorsal striatum and lateral OFC, this corticolimbic-VS network is less commonly explored as a potential source of the pathology underlying OCD. In this review, we discuss this network’s potential role as a locus of OCD pathology and effective treatment.

Altered frontal interhemispheric and fronto‐limbic structural connectivity in unmedicated adults with obsessive‐compulsive disorder

“…FMRI findings from OCD participants indeed suggest altered limbic responses to rewarding (Figee et al, ; Marsh et al, ) and threatening stimuli (Admon et al, ), consistent with their altered processing of rewards and heightened tendency to overestimate threat. Altered fronto‐limbic connectivity is also consistent with the purported role of the amygdala on this circuit in the pathophysiology of OCD (Wood & Ahmari, ). Specifically, amygdala dysregulation may contribute to compulsive behaviors by allowing undue affective influence over behavioral selection.…”

Addressing reverse inference in psychiatric neuroimaging: Meta‐analyses of task‐related brain activation in common mental disorders

“…Rather, it indicates the relative importance of the nucleus accumbens in OCD compared to other disorders, which is congruent with current neurocognitive theories of OCD that focus on cortico-striatal-thalamic loops [Graybiel and Rauch, 2000;Milad and Rauch, 2012]. The role of the nucleus accumbens in this framework lies in the integration of affective information with motor selection [Fineberg et al, 2010;Wood and Ahmari, 2015]. However, given the difficulty of imaging a small structure like the nucleus accumbens with high confidence, studies that specifically focus on nucleus accumbens anatomy and…”

Basal ganglia and autism – a translational perspective

“…Similarly, altered reward processing in the VTA likely plays a critical role in restricted and repetitive behaviors that are observed in obsessive-compulsive disorder (OCD) and in addiction [Rothwell, 2016;Sesack & Grace, 2010;Wood & Ahmari, 2015]. Taken together with the compelling evidence from imaging studies (See Section A), animal models (See Section C), and the overlap with circuits in OCD and addiction [Rothwell, 2016;Wood & Ahmari, 2015] the NAC-VTA pathway in the BG is known to play a vital role in restricted and repetitive behaviors in autism. The internal organization of the BG provides some clues to its possible involvement in both motor and non-motor behaviors like social and communication challenges in autism.…”

“…Various clinically observed autism behaviors (see Section B), could be described with specificity by examining the autism BG in detail. Similarly, altered reward processing in the VTA likely plays a critical role in restricted and repetitive behaviors that are observed in obsessive‐compulsive disorder (OCD) and in addiction [Rothwell, ; Sesack & Grace, ; Wood & Ahmari, ]. Taken together with the compelling evidence from imaging studies (See Section A), animal models (See Section C), and the overlap with circuits in OCD and addiction [Rothwell, ; Wood & Ahmari, ] the NAC‐VTA pathway in the BG is known to play a vital role in restricted and repetitive behaviors in autism.…”