Intrinsic Functional Connectivity Associated with γ‑Aminobutyric Acid and Glutamate/Glutamine in the Lateral Prefrontal Cortex and Internalizing Psychopathology in Adolescents
Kai Wang1,2,3 · Harry R. Smolker3,5 · Mark S. Brown6 · Hannah R. Snyder7 · Yu Cheng1,2 · Benjamin L. Hankin8 · Marie T. Banich3,41 Philosophy and Social Science Laboratory of Reading and Development in Children and Adolescents (South China Normal University), Ministry of Education, Guangzhou, China
2 School of Psychology, South China Normal University, Guangzhou 510631, China
3 Institute of Cognitive Science, University of Colorado Boulder, Boulder, CO 80309-0344, USA
4 Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0345, USA
5 Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO 80303, USA
6 Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
7 Department of Psychology, Brandeis University, Waltham, MA 02453, USA
8 Psychology Department, University of Illinois-Urbana Champaign, Champaign, IL 61820, USA
Abstract
In this study, we systematically tested the hypothesis that during the critical developmental period of adolescence, on a macro scale, the concentrations of major excitatory and inhibitory neurotransmitters (glutamate/glutamine and γ‑aminobutyric acid [GABA]) in the dorsal and ventral lateral prefrontal cortex are associated with the brain’s functional connectivity and an individual’s psychopathology. Neurotransmitters were measured via magnetic resonance spectroscopy while functional connectivity was measured with resting-state fMRI (n = 121). Seed-based and network-based analyses revealed associations of neurotransmitter concentrations and functional connectivities between regions/networks that are connected to prefrontal cortices via structural connections that are thought to be under dynamic development during adolescence. These regions tend to be boundary areas between functional networks. Furthermore, several connectivities were found to be associated with individual’s levels of internalizing psychopathology. These findings provide insights into specific neurochemical mechanisms underlying the brain’s macroscale functional organization, its development during adolescence, and its potential associations with symptoms associated with internalizing psychopathology.
Keywords
Functional connectivity; Glutamate; GABA; MR spectroscopy; Resting state fMRI; Psychopathology
