Identification of Common Neural Circuit Disruptions in Cognitive Control Across Psychiatric Disorders

Am J Psychiatry. 2017 Jul 1;174(7):676-685. doi: 10.1176/appi.ajp.2017.16040400. Epub 2017 Mar 21.


Objective: Cognitive deficits are a common feature of psychiatric disorders. The authors investigated the nature of disruptions in neural circuitry underlying cognitive control capacities across psychiatric disorders through a transdiagnostic neuroimaging meta-analysis.

Method: A PubMed search was conducted for whole-brain functional neuroimaging articles published through June 2015 that compared activation in patients with axis I disorders and matched healthy control participants during cognitive control tasks. Tasks that probed performance or conflict monitoring, response inhibition or selection, set shifting, verbal fluency, and recognition or working memory were included. Activation likelihood estimation meta-analyses were conducted on peak voxel coordinates.

Results: The 283 experiments submitted to meta-analysis included 5,728 control participants and 5,493 patients with various disorders (schizophrenia, bipolar or unipolar depression, anxiety disorders, and substance use disorders). Transdiagnostically abnormal activation was evident in the left prefrontal cortex as well as the anterior insula, the right ventrolateral prefrontal cortex, the right intraparietal sulcus, and the midcingulate/presupplementary motor area. Disruption was also observed in a more anterior cluster in the dorsal cingulate cortex, which overlapped with a network of structural perturbation that the authors previously reported in a transdiagnostic meta-analysis of gray matter volume.

Conclusions: These findings demonstrate a common pattern of disruption across major psychiatric disorders that parallels the "multiple-demand network" observed in intact cognition. This network interfaces with the anterior-cingulo-insular or "salience network" demonstrated to be transdiagnostically vulnerable to gray matter reduction. Thus, networks intrinsic to adaptive, flexible cognition are vulnerable to broad-spectrum psychopathology. Dysfunction in these networks may reflect an intermediate transdiagnostic phenotype, which could be leveraged to advance therapeutics.

Keywords: Cognition; Cognitive Control; Meta-analysis; RDoC; Transdiagnostic; fMRI.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / physiopathology*
  • Brain Mapping
  • Cognitive Dysfunction / physiopathology*
  • Dominance, Cerebral / physiology
  • Humans
  • Mental Disorders / diagnosis
  • Mental Disorders / physiopathology*
  • Mental Disorders / psychology
  • Nerve Net / physiopathology*
  • Neuropsychological Tests / statistics & numerical data
  • Psychometrics
  • Reference Values