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Disturbed Functional Connectivity of Cortical Activation during Semantic Discrimination in Patients with Schizophrenia and Subjects at Genetic High-risk

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Abstract

Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca’s area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca’s area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca’s area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.

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Acknowledgements

The authors gratefully acknowledge Dr. Hilary Bertisch from New York University Medical School, for her role in recruiting and evaluating subjects. This project was partially supported by a grant from NIMH, R21 MH071720.

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Authors and Affiliations

  1. Department of Radiology, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Avenue, Gruss 204, Bronx, NY, 10461, USA

    Xiaobo Li & Craig A. Branch

  2. Center for Advanced Brain Imaging, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA

    Craig A. Branch & Jay Nierenberg

  3. Harvard Medical School, VA Boston Healthcare System, Brockton, MA, USA

    Lynn E. DeLisi

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  1. Xiaobo Li
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  2. Craig A. Branch
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  3. Jay Nierenberg
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  4. Lynn E. DeLisi
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Correspondence to Xiaobo Li.

Appendix

Appendix

The entire stimuli used in the 5 “A” blocks of the fMRI task:

  1. Block 1:

    PHONE, THIPE, BEACH, FROAR, BROAL, CLEEP, WORLD, FERSE, GLOBE, COACH

  2. Block 2:

    BORZE, SHAWL, PLANT, SALAD, SHONG, LOAST, SHUNG, PIANO, OLIVE, PRORE

  3. Block 3:

    FERRY, DRALE, SAUCE, DRESS, SWAIT, SPAIL, CLANE, DITCH, BLAIN, CLOCK

  4. Block 4:

    PEDAL, GREEL, TROUT, TREAL, BROOM, BRATE, WEECH, APRON, STRAW, FLEEK

  5. Block 5:

    NIGHT, TURGE, OCEAN, BALCE, TAIGE, SHELL, LIVER, BRICK, BLAIE, RUTCH

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Li, X., Branch, C.A., Nierenberg, J. et al. Disturbed Functional Connectivity of Cortical Activation during Semantic Discrimination in Patients with Schizophrenia and Subjects at Genetic High-risk. Brain Imaging and Behavior 4, 109–120 (2010). https://doi.org/10.1007/s11682-010-9090-3

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