Investigation of anatomical thalamo-cortical connectivity and fMRI activation in schizophrenia

Stefano Marenco; Jason L. Stein; Antonina A. Savostyanova; Fabio Sambataro; Hao Yang Tan; Aaron L. Goldman; Beth A. Verchinski; Alan S. Barnett; Dwight Dickinson; José A. Apud; Joseph H. Callicott; Andreas Meyer-Lindenberg; Daniel R. Weinberger

doi:10.1038/npp.2011.215

Investigation of anatomical thalamo-cortical connectivity and fMRI activation in schizophrenia

Stefano Marenco, Jason L. Stein, Antonina A. Savostyanova, Fabio Sambataro, Hao Yang Tan, Aaron L. Goldman, Beth A. Verchinski, Alan S. Barnett, Dwight Dickinson, José A. Apud, Joseph H. Callicott, Andreas Meyer-Lindenberg, Daniel R. Weinberger

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104 Scopus citations

Abstract

The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age-and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.

Original language	English (US)
Pages (from-to)	499-507
Number of pages	9
Journal	Neuropsychopharmacology
Volume	37
Issue number	2
DOIs	https://doi.org/10.1038/npp.2011.215
State	Published - Jan 2012
Externally published	Yes

Keywords

diffusion tensor imaging (DTI)
medio-dorsal nucleus
prefrontal cortex
probabilistic tractography
reproducibility
working memory

ASJC Scopus subject areas

Pharmacology
Psychiatry and Mental health

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10.1038/npp.2011.215

Cite this

Marenco, S., Stein, J. L., Savostyanova, A. A., Sambataro, F., Tan, H. Y., Goldman, A. L., Verchinski, B. A., Barnett, A. S., Dickinson, D., Apud, J. A., Callicott, J. H., Meyer-Lindenberg, A., & Weinberger, D. R. (2012). Investigation of anatomical thalamo-cortical connectivity and fMRI activation in schizophrenia. Neuropsychopharmacology, 37(2), 499-507. https://doi.org/10.1038/npp.2011.215

Marenco, S, Stein, JL, Savostyanova, AA, Sambataro, F, Tan, HY, Goldman, AL, Verchinski, BA, Barnett, AS, Dickinson, D, Apud, JA, Callicott, JH, Meyer-Lindenberg, A & Weinberger, DR 2012, 'Investigation of anatomical thalamo-cortical connectivity and fMRI activation in schizophrenia', Neuropsychopharmacology, vol. 37, no. 2, pp. 499-507. https://doi.org/10.1038/npp.2011.215

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title = "Investigation of anatomical thalamo-cortical connectivity and fMRI activation in schizophrenia",

abstract = "The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age-and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.",

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author = "Stefano Marenco and Stein, {Jason L.} and Savostyanova, {Antonina A.} and Fabio Sambataro and Tan, {Hao Yang} and Goldman, {Aaron L.} and Verchinski, {Beth A.} and Barnett, {Alan S.} and Dwight Dickinson and Apud, {Jos{\'e} A.} and Callicott, {Joseph H.} and Andreas Meyer-Lindenberg and Weinberger, {Daniel R.}",

note = "Funding Information: This study was entirely funded by the NIMH IRP. The material in this paper was presented in abstract form at the annual meeting of the American College of Neuro-PsychoPharmacology in Boca Raton, FL (9–13 December 2007), at the meeting of the Society for Biological Psychiatry in Washington, DC (1–3 May 2008), and at the meeting of the International Schizophrenia Research Society in Venice, Italy (21–25 June 2008). This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). We thank Fengyu Zhang (NIMH) for statistical advice, Tim Behrens and Saad Jbadi (Oxford) for guidance on probabilistic tractography, and Dharshan Chandramohan for help in the revision process.",

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AU - Sambataro, Fabio

AU - Tan, Hao Yang

AU - Goldman, Aaron L.

AU - Verchinski, Beth A.

AU - Barnett, Alan S.

AU - Dickinson, Dwight

AU - Apud, José A.

AU - Callicott, Joseph H.

AU - Meyer-Lindenberg, Andreas

AU - Weinberger, Daniel R.

N1 - Funding Information: This study was entirely funded by the NIMH IRP. The material in this paper was presented in abstract form at the annual meeting of the American College of Neuro-PsychoPharmacology in Boca Raton, FL (9–13 December 2007), at the meeting of the Society for Biological Psychiatry in Washington, DC (1–3 May 2008), and at the meeting of the International Schizophrenia Research Society in Venice, Italy (21–25 June 2008). This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). We thank Fengyu Zhang (NIMH) for statistical advice, Tim Behrens and Saad Jbadi (Oxford) for guidance on probabilistic tractography, and Dharshan Chandramohan for help in the revision process.

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Investigation of anatomical thalamo-cortical connectivity and fMRI activation in schizophrenia

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Keywords

ASJC Scopus subject areas

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