State-Dependent Aberrant Gamma-Aminobutyric Acid Reactivity and Downstream Functional Connectivity of Central Autonomic Network Subserve Pathological Intrusive Thinking

Abstract

Abstract Alterations in neurotransmission mediated by gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter, are posited to play a pathophysiological role in stress-related disorders. Evidence, however, comes from the comparisons of pathological and healthy samples at rest and not during specific disease states, making it difficult to understand the processes underlying this assumption. The present study used 3T-proton magnetic resonance spectroscopy to investigate the effects of an experimental induction of intrusive thinking (IT; a transdiagnostic psychiatric symptom) on GABAergic and glutamatergic neurometabolic concentration within the bilateral Anterior Cingulate Cortex (ACC) in individuals with a pathological tendency to engage in IT (n = 29; 11 males) and controls (n = 29; 16 males). To assess physiological and functional concomitants of these neurochemical changes, autonomic measures and resting-state functional magnetic resonance imaging were also acquired before and after induction of IT. While engendering levels of IT amplified ACC GABA and GABA to Glx in the pathological group, an opposite trend emerged for controls. Notably, the pre-to post induction increase in GABAergic neurometabolism in the pathological group was accompanied by a dampened autonomic and resting state functional connectivity within nodes of the Central Autonomic Network. Current results are in line with the view of IT as a “better safe than sorry” strategy, which may be maintained in pathological conditions via a negative reinforcement mechanism through which increased GABAergic neurotransmission fosters avoidance of the transition from a relaxed state to a sudden spike of autonomic activation.