Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 9, 171
eCollection

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

Affiliations
Review

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

Jesse Wood et al. Front Syst Neurosci.

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.

Keywords: OCD (obsessive-compulsive disorder); OFC; accumbens; amygdala; compulsive behavior; dopamine; network; ventral striatum.

Figures

Figure 1
Figure 1
Organization of corticolimbic-ventral striatal network. Stylized coronal section schematics of the corticolimbic inputs to the ventral striatum (VS) are depicted alongside a schematic of the VS. Input regions are pictured in the left column, and coronal schematics are organized from top to bottom according to relative anterior to posterior locations. (A) Prefrontal section with the two regions comprising the medial OFC and ventromedial OFC–depicted in blue tones. (B) Simplified depiction of the amygdala complex in orange and violet tones. The amygdala contains several nuclei, which follow numerous naming conventions. The left hemisphere contains a more detailed depiction of subregion outlines, and the right hemisphere highlights several nuclei. The lateral, basolateral (also known as basal nucleus), and basomedial (also known as accessory basal nucleus) nuclei collectively form the basolateral complex. The cortical nucleus is not depicted in this schematic. (C) The two largest nuclei of the VTA, the parabrachial and paranigral nuclei, are highlighted in green tones. Some definitions of the VTA also include midline nuclei not depicted, such as the interfascicular, rostral linear, and central linear nuclei. (D) The VS is depicted, with special emphasis on the NAc. The core and shell regions of the NAc are denoted with arrows and bounded by dashed lines. For reference, the dorsal striatum (caudate/putamen) is notated. All schematics adapted from the 3rd edition of The Mouse Brain, by Franklin and Paxinos (1997).
Figure 2
Figure 2
Spiraling striatal-dopamine connections from ventral striatum to dorsal striatum. Some striatal neurons project to dopaminergic regions of the midbrain, and dopamine neurons in turn innervate the striatum; there is a general ventral-to-dorsal topography of these connections. This figure presents a highly simplified schematic, depicting the ultimate flow of information from ventral to dorsal striatum, and from ventral to dorsal dopamine systems–VTA and substantia nigra pars compacta (SNpc). Arrows depicted in darker shades of green denote more dorsal pairs of striatal and dopamine projections. Note that dopamine regions receive input from a given striatal region and in turn, innervate a more dorsal region of the striatum. These connections suggest that there is a general ventral to dorsal flow of information through striatal-dopamine circuits, allowing information processed in VS to influence neuronal activity in the entire striatum, through a poly-synaptic pathway (Haber et al., 2000). This suggests that VS is able to integrate information transmitted by the corticolimbic inputs highlighted in this review into the dorsal striatum. Furthermore, these pathways provide one anatomical mechanism for a complementary relationship between the corticolimbic-ventral striatal model put forth here, and traditional cortico-striatal-thalamo-cortical circuit models of OCD. Dopamine neurons which innervate the same striatal region they receive input from are not depicted, but do exist.
Figure 3
Figure 3
Amygdala projections to ventral striatum. The VS receives a glutamatergic projection from the basolateral amygdala complex. (A) Schematics of VS and amygdala following the same conventions as Figure 1 are presented for clarity. (B) Substantia nigra par compacta (SNpc), which receives input from projection neurons in the patch compartments of the NAc core, sends a large number of dopamine projections to the dorsal striatum. The substantia nigra pars reticulata (SNpr), which is part of the traditional striatal direct pathway and promotes selection of behaviors, is preferentially innervated by projection neurons in the matrix compartments of the NAc core. This compartmental segregation of NAc-SN projections is followed by the basolateral amygdala complex as well. Projections from the basolateral nucleus terminate preferentially in the patch compartments of NAc, while projections from the basomedial nucleus terminate preferentially in the matrix compartments of the NAc. Thus, a basolateral nucleus-NAc core patch- SNpc circuit could regulate dopamine transmission in the striatum. On the other hand, a basomedial-NAc core matrix- SNpr circuit could modulate information transmission in the direct pathway. Thus, these circuits provide a theoretical foundation for amygdala-VS circuits to modulate behavioral selection and striatal processing. Dysregulation of this circuit in OCD could potentially contribute to compulsive behavior.
Figure 4
Figure 4
Theoretical model of how dysregulated information processing in corticolimbic inputs to ventral striatum could underlie compulsive behavior in OCD. Each of the corticolimbic inputs highlighted in this review are depicted in the left column. VS is depicted in the right column for illustrative purposes. Bulleted text highlights information that is processed by each input region, and could theoretically be a source of dysregulated information processing in VS of OCD patients. (A) Value comparisons and decision-making are important functions of mOFC. Aberrant representations of this information could lead individuals with OCD to improperly evaluate behavioral choices. This could, in turn, lead to inflated valuation, and subsequent selection of compulsive behaviors. Alternatively, these aberrant representations could render goal-directed decision making ineffective, and bias behavioral control toward habit-like selection of compulsive behaviors. (B) The amygdala processes threatening/fearful stimuli, rewarding stimuli, and aversive stimuli. Aberrant representations of this information in OCD could lead to improper behavioral selection and compulsive behavior. As summarized in the text, amygdala is often hypoactive in response to rewarding or neutral stimuli, and hyperactive in response to threatening or symptom-provoking stimuli, which could lead to excessive influence of these stimuli over behavior. This is consistent with clinical observations of provocation of compulsive behaviors by environmental stimuli that are perceived as threatening. Amygdala projections to VS are particularly important to Pavlovian instrumental transfer (PIT). Symptom provoking stimuli could theoretically acquire an influence over behavior through PIT, and thus, dysregulation of PIT could also contribute to OCD. Amygdala is also important for processing anxiety, which is associated with the generation and/or maintenance of compulsive behaviors in OCD; this link places special emphasis on amygdala-based information processing in OCD. (C) The VTA is a major source of dopamine input to VS, and processes reinforcement signals which inform behavioral selection. This input is also necessary for sustaining behavioral sequences and effortful behavior. Considerable evidence suggests that OCD is associated with dysregulation of the dopamine system, potentially leading to a hyperdopaminergic state. These disruptions would theoretically impact information processing necessary for selecting and sustaining behavioral sequences, and could promote compulsive behavioral patterns. VTA input to VS is also necessary for PIT, and a hyperdopaminergic state could also contribute to the ability of environmental stimuli to impact behavioral selection in OCD.

Similar articles

See all similar articles

Cited by 17 PubMed Central articles

See all "Cited by" articles

References

    1. Aberman J. E., Salamone J. D. (1999). Nucleus accumbens dopamine depletions make rats more sensitive to high ratio requirements but do not impair primary food reinforcement. Neuroscience 92, 545–552. 10.1016/s0306-4522(99)00004-4 - DOI - PubMed
    1. Admon R., Bleich-Cohen M., Weizmant R., Poyurovsky M., Faragian S., Hendler T. (2012). Functional and structural neural indices of risk aversion in obsessive-compulsive disorder (OCD). Psychiatry Res. 203, 207–213. 10.1016/j.pscychresns.2012.02.002 - DOI - PubMed
    1. Ahmari S. E. (2015). Using mice to model obsessive compulsive disorder: from genes to circuits. Neurosci. [Epub ahead of print]. 10.1016/j.neuroscience.2015.11.009 - DOI - PMC - PubMed
    1. Ahmari S. E., Dougherty D. D. (2015). Dissecting ocd circuits: from animal models to targeted treatments. Depress. Anxiety 32, 550–562. 10.1002/da.22367 - DOI - PMC - PubMed
    1. Ahmari S. E., Spellman T., Douglass N. L., Kheirbek M. A., Simpson H. B., Deisseroth K., et al. . (2013). Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science 340, 1234–1239. 10.1126/science.1234733 - DOI - PMC - PubMed
Feedback