Milad & Rauch88. Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012;16:43-51. |
These authors extended previous CSTC models and the view that OCD could be considered a disorder of self-regulation and inhibition to highlight the role of the amygdala and the production and regulation of fear in obsessive-compulsive symptomatology. The model linked neurocognitive mechanisms to dysfunctions in three neurocircuits: 1) the “affective circuit,” which comprised the ACC/vmPFC, NAcc), and thalamus and was proposed to be involved in processing affect and reward; 2) the “ventral cognitive circuit,” which consisted of the anterolateral OFC, putamen and thalamus and was suggested to be involved in motor and response inhibition; 3) the “dorsal cognitive circuit,” which included the dlPFC, dorsal caudate, and thalamus and was proposed to mediate working memory and executive function. The authors also discussed the role of interactions between the amygdala and the affective and dorsal cognitive circuits in impaired fear extinction in OCD. Finally, the authors discussed the possibility of targeting these neurocircuits with deep brain stimulation and/or measuring their function as therapeutic markers to improve treatment for OCD. |
Van den Heuvel et al.99. van den Heuvel OA, van Wingend G, Soriano-Mas C, Alonso P, Chamberlain SR, Nakamae T, et al. Brain circuitry of compulsivity.Eur Neuropsychopharmacol.2016;26:810-27. |
These authors further elaborated and expanded on Milad and Rauch’s88. Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012;16:43-51. model to consider five neurocircuits and associated neurocognitive functions involved in OCD and other disorders characterized by compulsivity. These were: 1) the “sensorimotor CSTC circuit,” which includes the SMA, posterior putamen, and thalamus and is involved in stimulus-response based habit behavior; 2) the “dorsal cognitive CSTC circuit,” which connects the pre-SMA, dlPFC, dmPFC, dorsal caudate, and thalamus and mediates executive control functions such as working memory, planning and emotion regulation; 3) the “ventral cognitive CSTC circuit,” which includes the IFG, vlPFC, ventral caudate, and thalamus and is involved in response inhibition; 4) the “affective CSTC circuit,” which connects the OFC, NAcc and thalamus and is involved in stimulus-response based motivational and affective behaviors; 5) the “fronto-limbic circuit,” which includes the vmPFC and amygdala, involved in the learning and extinction of fear responses. The model highlights the importance of interactions between the circuits, for example with the dorsal and ventral cognitive control circuits exerting top-down regulation of emotion mediated by the fronto-limbic and affective circuits. The authors also considered neural mechanisms involved in treatments for OCD, including CBT, SSRIs, deep brain stimulation, and non-invasive neuromodulatory techniques (rTMS, tDCS). |
Shephard et al.1010. Shephard E, Stern ER, van den Heuvel OA, Costa DL, Batistuzzo MC, Godoy PB, et al. Toward a neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder. Mol Psychiatry. 2021 Jan 7. doi: http://10.1038/s41380-020-01007-8. Online ahead of print. http://10.1038/s41380-020-01007-8...
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We recently expanded on van den Heuvel et al.’s99. van den Heuvel OA, van Wingend G, Soriano-Mas C, Alonso P, Chamberlain SR, Nakamae T, et al. Brain circuitry of compulsivity.Eur Neuropsychopharmacol.2016;26:810-27. model to propose several “clinical profiles” that reflect different phenotypic expressions of OCD, which we derived from patients’ reports of their subjective experiences of OCD symptoms. We linked each clinical profile with underlying neurocognitive alterations related to dysfunctions in the five neurocircuits proposed by van den Heuvel et al.,99. van den Heuvel OA, van Wingend G, Soriano-Mas C, Alonso P, Chamberlain SR, Nakamae T, et al. Brain circuitry of compulsivity.Eur Neuropsychopharmacol.2016;26:810-27. and suggested specific treatment approaches targeting the clinical profiles and neurocircuit dysfunctions that could be tested in future research (illustrated in Figure 1). These clinical profiles were: 1) “dysregulated fear,” characterized by excessive and/or inappropriate and poorly controlled physiological fear responses that are associated with obsessions and drive compulsive behaviors, mediated by hyperactive fronto-limbic (amygdala, vmPFC) activity and hypoactive dorsal cognitive circuit top-down control of fear responses; 2) “intolerance of uncertainty,” reflecting an inability to cope with uncertainty that contributes to obsessions and repetitive behaviors (e.g., repetitive behaviors to attenuate uncertainty preoccupations), underpinned by hyperactive fronto-limbic circuit activity; 3) “sensory phenomena,” i.e., aversive or uncomfortable perceptions or sensations (e.g., the feeling that things are “not just right”; the sensation of feeling dirty) that drive compulsive behaviors, associated with hyperactivity in the sensorimotor circuit as well as the insula; 4) “excessive habit-formation,” reflecting long-standing compulsive behaviors, which were initially associated with recurrent and distressful thoughts, ideas or images, but after multiple repetitions, over time, became more automatic, mediated by hyperactivity in the sensorimotor circuit; 5) “impaired response inhibition,” i.e., difficulties in preventing inappropriate thoughts or behaviors, linked to hypoactivity in the ventral cognitive circuit; 6) “altered reward responsiveness,” reflecting a reduced sensitivity to rewards coupled with exaggerated anticipation of punishments in some patients which leads to feelings of relief/reward obtained by completing compulsive and/or avoidance behaviors, mediated by atypicalities in regional activity and functional connectivity within the ventral affective circuit; 7) “executive dysfunction,” including difficulties with planning, working memory, and top-down emotion regulation due to hypoactivity in the dorsal cognitive circuit. In terms of treatment strategies, we proposed that the “dysregulated fear” and “intolerance of uncertainty” profiles may be best treated using therapies that aim to reduce hyperactivity in the fronto-limbic circuit (CBT, SSRIs, amygdala/vmPFC, fMRI neurofeedback, deep brain stimulation targeting the ALIC) and increase hypoactive dorsal cognitive circuit top-down control of the fronto-limbic circuit (CBT, dlPFC rTMS, medial PFC deep-TMS). We suggested that the “sensory phenomena” and “excessive habit-formation” profiles could be addressed by treatments aiming to reduce excessive sensorimotor circuit activity (habit-reversal training, SMA rTMS) and for sensory phenomena only, regulate insula activity (H-coil insula TMS, ondansetron). For the “impaired response inhibition” profile, we proposed treatments aiming to increase ventral cognitive circuit hypoactivity (deep brain stimulation targeting the subthalamic nucleus and ventral capsule/ventral striatum, fMRI neurofeedback of the IFG). For the “altered reward responsiveness” profile, we suggested therapies targeting reward mechanisms of the ventral affective circuit (SSRIs, dopamine-acting medications such as methylphenidate, fMRI neurofeedback of the NAcc, deep brain stimulation targeting the NAcc). Finally, we suggested that treatment approaches for the “executive dysfunction” profile would involve increasing hypoactivity in the dorsal cognitive circuit (CBT, methylphenidate, dlPFC, and pre-SMA rTMS or tDCS). Evidence for and against each of these neurocircuit-based treatments is discussed in detail in the publication presenting the model.1010. Shephard E, Stern ER, van den Heuvel OA, Costa DL, Batistuzzo MC, Godoy PB, et al. Toward a neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder. Mol Psychiatry. 2021 Jan 7. doi: http://10.1038/s41380-020-01007-8. Online ahead of print. http://10.1038/s41380-020-01007-8...
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