Identification of Common Neural Circuit Disruptions in Emotional Processing Across Psychiatric Disorders

Objective: Disrupted emotional processing is a common feature of many psychiatric disorders. The authors investigated functional disruptions in neural circuitry underlying emotional processing across a range of tasks and across psychiatric disorders through a transdiagnostic quantitative meta-analysis of published neuroimaging data. Methods: A PubMed search was conducted for whole-brain functional neuroimaging findings published through May 2018 that compared activation during emotional processing tasks in patients with psychiatric disorders (including schizophrenia, bipolar or unipotar depression, anxiety, and substance use) to matched healthy control participants. Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates to identify spatial convergence. Results: The 298 experiments submitted to meta-analysis included 5,427 patients and 5,491 control participants. ALE across diagnoses and patterns of patient hyper- and hyporeactivity demonstrated abnormal activation in the amygdala, the hippocampal/parahippocampal gyri, the dorsomedial/pulvinar nuclei of the thalamus, and the fusiform gyri, as well as the medial and lateral dorsal and ventral prefrontal regions. ALE across disorders but considering directionality demonstrated patient hyperactivation in the amygdala and the hippocampal/parahippocampal gyri. Hypoactivation was found in the medial and lateral prefrontal regions, most pronounced during processing of unpleasant stimuli. More refined disorder-specific analyses suggested that these overall patterns were shared to varying degrees, with notable differences in patterns of hyper- and hypoactivation. Conclusions: These findings demonstrate a pattern of neurocircuit disruption across major psychiatric disorders in regions and networks key to adaptive emotional reactivity and regulation. More specifically, disruption corresponded prominently to the salience network, the ventral striatal/ventromedial prefrontal reward network, and the lateral orbitofrontal nonreward network. Consistent with the Research Domain Criteria initiative, these findings suggest that psychiatric illness may be productively formulated as dysfunction in transdiagnostic neurobehavioral phenotypes such as neurocircuit activation.