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Association of γ-aminobutyric acid and glutamate/glutamine in the lateral prefrontal cortex with patterns of intrinsic functional connectivity in adults

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Abstract

This study examined how levels of neurotransmitters in the lateral prefrontal cortex (LPFC), a region underlying higher-order cognition, are related to the brain’s intrinsic functional organization. Using magnetic resonance spectroscopy (MRS), GABA+ and Glx (glutamate + glutamine) levels in the left dorsal (DLPFC) and left ventral (VLPFC) lateral prefrontal cortex were obtained in a sample of 64 female adults (mean age = 48.5). We measured intrinsic connectivity via resting-state fMRI in three ways: (a) via seed-based connectivity for each of the two spectroscopy voxels; (b) via the spatial configurations of 17 intrinsic networks defined by a well-known template; and (c) via examination of the temporal inter-relationships between these intrinsic networks. The results showed that different neurotransmitter indexes (Glx-specific, GABA+-specific, Glx-GABA+ average and Glx-GABA+ ratio) were associated with distinct patterns of intrinsic connectivity. Neurotransmitter levels in the left LPFC are mainly associated with connectivity of right hemisphere prefrontal (e.g., DLPFC) or striatal (e.g., putamen) regions, two areas of the brain connected to LPFC via large white matter tracts. While the directions of these associations were mixed, in most cases, higher Glx levels are related to reduced connectivity. Prefrontal neurotransmitter levels are also associated with the degree of connectivity between non-prefrontal regions. These results suggest robust relationships between the brain’s intrinsic functional organization and local neurotransmitters in the LPFC which may be constrained by white matter neuroanatomy.

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Acknowledgements

The research reported in this study was supported by NIMH Grant R01 105501 to MTB and BLK.

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Authors and Affiliations

  1. Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China; School of Psychology, Center for Studies of Psychological Application, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, No. 55 West Zhongshan Avenue, Guangzhou, 510631, Guangdong, China

    Kai Wang

  2. Institute of Cognitive Science, University of Colorado Boulder, 344 UCB, Boulder, CO, 80309-0344, USA

    Kai Wang, Harry R. Smolker & Marie T. Banich

  3. Department of Psychology and Neuroscience, University of Colorado Boulder, E230 Muenzinger Hall, UCB 345, Boulder, CO, 80309-0345, USA

    Harry R. Smolker & Marie T. Banich

  4. Institute for Behavioral Genetics, University of Colorado Boulder, 1480 30th Street, Boulder, CO, 80303, USA

    Harry R. Smolker

  5. Department of Radiology, University of Colorado Anschutz Medical Campus, 12401 E 17th Place, Aurora, CO, 80045, USA

    Mark S. Brown

  6. Department of Psychology, Brandeis University, 415 South Street, Waltham, MA, 02453, USA

    Hannah R. Snyder

  7. Psychology Department, University of Illinois-Urbana Champaign, 603 E. Daniel Street, Champaign, IL, 61820, USA

    Benjamin L. Hankin

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  1. Kai Wang
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Wang, K., Smolker, H.R., Brown, M.S. et al. Association of γ-aminobutyric acid and glutamate/glutamine in the lateral prefrontal cortex with patterns of intrinsic functional connectivity in adults. Brain Struct Funct 225, 1903–1919 (2020). https://doi.org/10.1007/s00429-020-02084-9

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