Altered Neurocognitive Functional Connectivity and Activation Patterns Underlie Psychopathology in Preadolescence

Briana Lees, Lindsay M. Squeglia, Lisa M. McTeague, Miriam K. Forbes, Robert F. Krueger, Matthew Sunderland, Andrew J. Baillie, Forrest Koch, Maree Teesson, Louise Mewton

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Background: Neurocognitive deficits are common among youth with mental disorders, and patterns of aberrant brain function generally cross diagnostic boundaries. This study investigated associations between functional neurocircuitry and broad transdiagnostic psychopathology dimensions in the critical preadolescent period when psychopathology is emerging. Methods: Participants were 9- to 10-year-olds from the Adolescent Brain Cognitive Development Study. Factor scores of general psychopathology, externalizing, internalizing, and thought disorder dimensions were calculated from a higher-order model of psychopathology using confirmatory factor analysis (N = 11,721) and entered as explanatory variables into linear mixed models to examine associations with resting-state functional connectivity (n = 9074) and neural activation during the emotional n-back task (n = 6146) when covarying for sex, race/ethnicity, parental education, and cognitive function. Results: All dimensions of psychopathology were commonly characterized by hypoconnectivity within the dorsal attention and retrosplenial-temporal networks, hyperconnectivity between the frontoparietal and ventral attention networks and between the dorsal attention network and amygdala, and hypoactivation of the caudal middle frontal gyrus. Externalizing pathology was uniquely associated with hyperconnectivity between the salience and ventral attention networks and hyperactivation of the cingulate and striatum. Internalizing pathology was uniquely characterized by hypoconnectivity between the default mode and cingulo-opercular networks. Connectivity between the cingulo-opercular network and putamen was uniquely higher for internalizing pathology and lower for thought disorder pathology. Conclusions: These findings provide novel evidence that broad psychopathology dimensions are characterized by common and dissociable patterns, particularly for externalizing pathology, of functional connectivity and task-evoked activation throughout neurocognitive networks in preadolescence.

Original languageEnglish (US)
Pages (from-to)387-398
Number of pages12
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number4
StatePublished - Apr 2021

Bibliographical note

Funding Information:
This work was supported by the Australian National Health and Medical Research Council (Grant No. GNT1169377 [to BL] and Grant Nos. GNT1041756 and GNT1078407 [to MT]), National Institute on Drug Abuse (Grant No. U01 DA041093 [to LMS]), National Institute of Mental Health (Grant No. K23 MH104849 [to LMM]), Macquarie University (Research Fellowship [to MKF]), National Institute of Aging (Grant Nos. R01AG053217 and U19AG051426 [to RFK]), and University of New South Wales (Research Fellowship [to LM]). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Australian National Health and Medical Research Council, National Institute on Drug Abuse, National Institute of Aging, Macquarie University, or University of New South Wales.

Funding Information:
Data used in the preparation of this article were obtained from the ABCD Study ( ), held in the National Institute of Mental Health Data Archive. This is a multisite, longitudinal study designed to recruit more than 10,000 children 9 to 10 years of age and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners (Grant Nos. U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147). A full list of supporters is available at . A list of participating sites and a complete list of the study investigators can be found at . ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this article. This article reflects the views of the authors and may not reflect the opinions or views of the National Institutes of Health or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from the curated annual release 2.0.1.

Publisher Copyright:
© 2020 Society of Biological Psychiatry


  • Functional connectivity
  • Functional magnetic resonance imaging
  • Mental disorder
  • Neural activation
  • Preadolescence
  • Psychopathology


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