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Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function.
Am J Psychiatry 2008; 165(8):1006-14AJ

Abstract

OBJECTIVE

Although deficits in cognitive control are thought to contribute to the diverse cognitive and behavioral abnormalities in individuals with schizophrenia, the neural mechanisms underlying these deficits remain unclear. In this event-related functional magnetic resonance imaging (fMRI) study, the authors tested the hypothesis that during cognitive control tasks, impaired activation of the dorsolateral prefrontal cortex in schizophrenia patients is associated with disrupted coordinated activity between this prefrontal region and a distributed brain network that supports cognitive control.

METHOD

Through the use of an event-related design, 25 patients with first-episode schizophrenia and 24 healthy comparison subjects, matched on demographic characteristics, were assessed while performing a version of the AX continuous performance task. Functional neuroimaging data were analyzed using 1) univariate (region-of-interest blood-oxygen-level-dependent [BOLD] time series and whole brain voxel-wise regression) analysis to confirm the presence of dorsolateral prefrontal cortex dysfunction and 2) multivariate analysis to examine dorsolateral prefrontal cortex functional connectivity. In addition, correlations between dorsolateral prefrontal cortex functional connectivity and the following variables were investigated: clinical symptoms, task performance, and coordinated brain activity associated with cognitive control.

RESULTS

Schizophrenia patients exhibited a specific deficit in cognitive control, with significantly reduced accuracy in the BX condition relative to any other condition. Univariate fMRI revealed dorsolateral prefrontal cortex dysfunction during the high cognitive control condition. Multivariate analysis revealed significant impairment in functional connectivity between the dorsolateral prefrontal cortex and task-relevant brain regions. Significant correlations were also found between dorsolateral prefrontal cortex functional connectivity and cognitive performance, behavioral disorganization, and global functioning.

CONCLUSIONS

These findings suggest that there is an association between decreased dorsolateral prefrontal cortex activity and connectivity and a task-related neural network. This deficit in coordinated brain activity may result in the disabling disorganization symptoms related to impaired cognition in individuals with schizophrenia.

Authors+Show Affiliations

Department of Psychiatry and Imaging Research Center, University of California, Davis, Sacramento, Calif. 95817, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18519527

Citation

Yoon, Jong H., et al. "Association of Dorsolateral Prefrontal Cortex Dysfunction With Disrupted Coordinated Brain Activity in Schizophrenia: Relationship With Impaired Cognition, Behavioral Disorganization, and Global Function." The American Journal of Psychiatry, vol. 165, no. 8, 2008, pp. 1006-14.
Yoon JH, Minzenberg MJ, Ursu S, et al. Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. Am J Psychiatry. 2008;165(8):1006-14.
Yoon, J. H., Minzenberg, M. J., Ursu, S., Ryan Walter, B. S., Walters, R., Wendelken, C., ... Carter, C. S. (2008). Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. The American Journal of Psychiatry, 165(8), pp. 1006-14. doi:10.1176/appi.ajp.2008.07060945.
Yoon JH, et al. Association of Dorsolateral Prefrontal Cortex Dysfunction With Disrupted Coordinated Brain Activity in Schizophrenia: Relationship With Impaired Cognition, Behavioral Disorganization, and Global Function. Am J Psychiatry. 2008;165(8):1006-14. PubMed PMID: 18519527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. AU - Yoon,Jong H, AU - Minzenberg,Michael J, AU - Ursu,Stefan, AU - Ryan Walter,B S, AU - Walters,Ryan, AU - Wendelken,Carter, AU - Ragland,J Daniel, AU - Carter,Cameron S, Y1 - 2008/06/02/ PY - 2008/6/4/pubmed PY - 2008/9/5/medline PY - 2008/6/4/entrez SP - 1006 EP - 14 JF - The American journal of psychiatry JO - Am J Psychiatry VL - 165 IS - 8 N2 - OBJECTIVE: Although deficits in cognitive control are thought to contribute to the diverse cognitive and behavioral abnormalities in individuals with schizophrenia, the neural mechanisms underlying these deficits remain unclear. In this event-related functional magnetic resonance imaging (fMRI) study, the authors tested the hypothesis that during cognitive control tasks, impaired activation of the dorsolateral prefrontal cortex in schizophrenia patients is associated with disrupted coordinated activity between this prefrontal region and a distributed brain network that supports cognitive control. METHOD: Through the use of an event-related design, 25 patients with first-episode schizophrenia and 24 healthy comparison subjects, matched on demographic characteristics, were assessed while performing a version of the AX continuous performance task. Functional neuroimaging data were analyzed using 1) univariate (region-of-interest blood-oxygen-level-dependent [BOLD] time series and whole brain voxel-wise regression) analysis to confirm the presence of dorsolateral prefrontal cortex dysfunction and 2) multivariate analysis to examine dorsolateral prefrontal cortex functional connectivity. In addition, correlations between dorsolateral prefrontal cortex functional connectivity and the following variables were investigated: clinical symptoms, task performance, and coordinated brain activity associated with cognitive control. RESULTS: Schizophrenia patients exhibited a specific deficit in cognitive control, with significantly reduced accuracy in the BX condition relative to any other condition. Univariate fMRI revealed dorsolateral prefrontal cortex dysfunction during the high cognitive control condition. Multivariate analysis revealed significant impairment in functional connectivity between the dorsolateral prefrontal cortex and task-relevant brain regions. Significant correlations were also found between dorsolateral prefrontal cortex functional connectivity and cognitive performance, behavioral disorganization, and global functioning. CONCLUSIONS: These findings suggest that there is an association between decreased dorsolateral prefrontal cortex activity and connectivity and a task-related neural network. This deficit in coordinated brain activity may result in the disabling disorganization symptoms related to impaired cognition in individuals with schizophrenia. SN - 1535-7228 UR - https://www.unboundmedicine.com/medline/citation/18519527/Association_of_dorsolateral_prefrontal_cortex_dysfunction_with_disrupted_coordinated_brain_activity_in_schizophrenia:_relationship_with_impaired_cognition_behavioral_disorganization_and_global_function_ L2 - https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2008.07060945?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -