The anatomy of obsessive-compulsive disorder

OCD has been characterized by recent data as a disorder of cognition. Recent data also show pathology in prefrontal-subcortical networks. We leveraged cross-species prefrontal-subcortical cytoarchitectonic homologies in order to parse anatomical abnormalities in people with OCD into higher resolution areas and neuronal networks. We established that the anatomical abnormalities associated with OCD predominantly reside in a neuronal network associated with emotional processing. We further provide evidence that current tests do not accurately dissociate emotion from cognition and so relying on them risks mis-stating the role of prefrontal-subcortical networks. Taken together, these findings reveal the neglect of the role of emotion in the pathophysiology of OCD. Background Recent advances in the cytoarchitectonic parcellation of the human brain have significant implications for major psychiatric conditions such as obsessive-compulsive disorder (OCD). Brodmann’s areas have remained in use as the histological map of the human brain, framing its functional correlates in health and disease. However, cytological research has continued to refine these divisions in some cases substantially. For instance, the 16 areas in Brodmann’s prefrontal cortex have expanded to 63, delivering a four-fold increase in granular resolution. These contemporary cytoarchitectonic areas have been parcellated into distinct prefrontal-striatal networks responsible for (i) the control of emotions and visceral organs, (ii) mental representation and classification of external objects, and (iii) the control of visual attention. Interacting pathology across prefrontal-striatal circuits makes OCD a paradigmatic condition upon which to apply these advances. The enhanced granular and network resolution this provides could transform human brain imaging from the original divisions of 1909 to higher resolution delineations, for example, providing precise mediolateral partitioning of the orbitofrontal cortex, thereby distilling the substrates of obsessions and compulsions. Advances Here we provide a meta-review of existing reports of thousands of people with OCD to reveal impairments spanning sensory integration, affective arousal, cognitive control, and motor action selection. Behavioral data previously interpreted as implicating only cognitive abnormalities have failed to detect cognitive impairment in children and adolescents with OCD casting doubt on the sensitivity of conventional tests and the temporal relationship between apparent pathology in adults and OCD symptoms. Therefore, by relying on that behavioral evidence alone we risk mis-characterizing OCD solely as a disorder of cognition. Moreover, the presence of sensorimotor and neuroimaging abnormalities in young people with OCD indicate the chronological primacy of undifferentiated abnormalities in neuronal structure and function. Neuronal correlates of OCD symptoms were found to map evenly into emotional-visceral and object assessment networks; within the visual attention network only the premotor cortex had substantive abnormality. Tasks reported as measuring cognition also distributed equally across networks further calling into question the physiological fidelity of these tasks. In contrast, tasks reported as measuring emotion mapped faithfully onto the emotional-visceral network. Volumetric changes in people with OCD also implicated the emotional-visceral network, in which the number of abnormalities were double those in the object assessment network. Outlook Although conventional behavioral tasks characterize OCD as a cognitive disorder, associated anatomical abnormalities are, in fact, distributed across two distinct neuronal networks responsible for (i) the control of emotions and visceral organs and (ii) the representation of external objects. The predominance of abnormalities in an emotional-visceral neuronal network contrasts with the paucity of research on emotional processing in OCD relative to tasks reported to test cognition, showing an inflated attribution of cognitive relative to emotional dysfunction in the pathophysiology of OCD. The histologically derived orbital and medial prefrontal cortex subregions, shown here as selectively affected in people with OCD, provide higher resolution candidate treatment targets for neurostimulation and other therapeutics. Extending our current work to other conditions could identify transdiagnostic neural signatures of psychiatric symptoms. One-Sentence Summary Structural brain changes in people with OCD reside predominantly in a neuronal network responsible for emotional control. ![Figure][1] OCD as a pathology of cytoarchitecture Neuronal networks derived from cross-species studies of cell structure, projections, and function transform the granular resolution of human brain imaging analysis to reveal the role of an emotional-visceral network in the pathophysiology of OCD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement All authors were employed by their affiliated institutions. IEP was also supported by a medical postgraduate scholarship from the National Health and Medical Research Council (NHMRC) of Australia (#1134268). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. 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