OBJECTIVE Advances in understanding the neurobiological basis of psychiatric disorders will improve the ability to refine neuromodulatory procedures for treatment-refractory patients. One of the core dysfunctions in obsessive-compulsive disorder (OCD) is a deficit in cognitive control, especially involving the dorsal anterior cingulate cortex (dACC). The authors' aim was to derive a neurobiological understanding of the successful treatment of refractory OCD with psychiatric neurosurgical procedures targeting the dACC. METHODS First, the authors systematically conducted a review of the literature on the role of the dACC in OCD by using the search terms "obsessive compulsive disorder" and "anterior cingulate." The neuroscience literature on cognitive control mechanisms in the dACC was then combined with the literature on psychiatric neurosurgical procedures targeting the dACC for the treatment of refractory OCD. RESULTS The authors reviewed 89 studies covering topics that included structural and functional neuroimaging and electrophysiology. The majority of resting-state functional neuroimaging studies demonstrated dACC hyperactivity in patients with OCD relative to that in controls, while task-based studies were more variable. Electrophysiological studies showed altered dACC-related biomarkers of cognitive control, such as error-related negativity in OCD patients. These studies were combined with the cognitive control neurophysiology literature, including the recently elaborated expected value of control theory of dACC function. The authors suggest that a central feature of OCD pathophysiology involves the generation of mis-specified cognitive control signals by the dACC, and they elaborate on this theory and provide suggestions for further study. CONCLUSIONS Although abnormalities in brain structure and function in OCD are distributed across a wide network, the dACC plays a central role. The authors propose a theory of cognitive control dysfunction in OCD that attempts to explain the therapeutic efficacy of dACC neuromodulation. This theoretical framework should help to guide further research into targeted treatments of OCD and other disorders of cognitive control.
Keywords: ALIC = anterior limb of internal capsule; CS = conditioned stimulus; CSTC = cortico-striato-thalamo-cortical; DBS = deep brain stimulation; EEG = electroencephalography; ERN = error-related negativity; ERP = exposure-response prevention; EVC = expected value of control; NIMH = National Institute of Mental Health; OCD = obsessive-compulsive disorder; OFC = orbitofrontal cortex; RCT = randomized controlled trial; RDoC = Research Domain Criteria; US = unconditioned stimulus; VC = ventral ALIC; VS = ventral striatum; YBOCS = Yale-Brown Obsessive-Compulsive Scale; cingulotomy; cognitive control; dACC = dorsal anterior cingulate cortex; dlPFC = dorsolateral prefrontal cortex; dorsal anterior cingulate cortex; expected value of control; fMRI = functional MRI; functional neurosurgery; lPFC = lateral prefrontal cortex; obsessive-compulsive disorder; psychiatric neurosurgery; vmPFC = ventro-mesial prefrontal cortex.