Cited by 1,435Schizophrenia research and treatmentFunctional Brain Connectivity StudiesMental Health and Psychiatry

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Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia

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Whitfield-Gabrieli, Susan, Thermenos, Heidi W., Milanovic, Snezana, Tsuang, Ming T., Faraone, Stephen V., McCarley, Robert W., Shenton, Martha E., Green, Alan I., Nieto-Castanon, Alfonso, LaViolette, Peter, Wojcik, Joanne, Gabrieli, John D. E., Seidman, Larry J.·2009·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0809141106PMC PMC2633557

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Abstract

We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.

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“This network, especially the midline regions of the MPFC and PCC, overlaps with brain regions activated during self-referential cognitive or emotional tasks (11, 12).”
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Authors: Whitfield-Gabrieli, S., Thermenos, H. W., Milanovic, S., Tsuang, M. T., Faraone, S. V., McCarley, R. W., Shenton, M. E., Green, A. I., Nieto-Castanon, A., LaViolette, P., Wojcik, J., Gabrieli, J. D. E., & Seidman, L. J.
Affiliations: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, and Poitras Center for Affective Disorders Research, Cambridge, MA 02139;
Beth Israel Deaconess Medical Center (US)
Harvard University (US)
SUNY Upstate Medical University (US)
Brigham and Women's Hospital (US)
Dartmouth College (US)
Harvard–MIT Division of Health Sciences and Technology (US)
ORCID: Milanovic, Snezana
Tsuang, Ming T.
Faraone, Stephen V.
McCarley, Robert W.
Shenton, Martha E.
Green, Alan I.
LaViolette, Peter
Gabrieli, John D. E.
Seidman, Larry J.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2009-01-27
Volume: 106
Issue: 4
Pages: 1279-1284
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0809141106
PMC: PMC2633557
OpenAlex: W2115687188
Cited by: 1,435
References: 40
Citations by year: 2026: 31 · 2025: 65 · 2024: 42 · 2023: 60 · 2022: 76 · 2021: 84 · 2020: 68 · 2019: 90 · 2018: 84 · 2017: 93 · 2016: 114 · 2015: 124 · 2014: 109 · 2013: 121 · 2012: 94
FWCI: 55.49
Type: journal article
Language: en
Update notices: correction (2009-03-17)
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders: National Institute of Mental Health (MH 65562, MH62157, MH-50740, R37MH043518, R25 MH60485, MH- 43518, MH40799, R01MH043518, R25MH060485, R01MH050740, R21MH062157, R01MH040799, R01MH063951, R01MH065562, MH-63951)
National Center for Research Resources (P41-RR-14075, P41RR014075)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Keywords: schizophrenia, default mode network, hyperconnectivity, hyperactivation, medial prefrontal cortex, dorsolateral prefrontal cortex, working memory, functional connectivity, psychopathology, resting-state brain activity
MeSH terms: Brain Mapping, Family, Humans, Memory, Nerve Net, Rest, Schizophrenia, Schizophrenic Psychology, Task Performance and Analysis

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Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia

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