Individual Differences in the Balance of GABA to Glutamate in pFC Predict the Ability to Select among Competing Options

Abstract

Individuals vary greatly in their ability to select one item or response when presented with a multitude of options. Here we investigate the neural underpinnings of these individual differences. Using magnetic resonance spectroscopy, we found that the balance of inhibitory versus excitatory neurotransmitters in pFC predicts the ability to select among task-relevant options in two language production tasks. The greater an individual’s concentration of GABA relative to glutamate in the lateral pFC, the more quickly he or she could select a relevant word from among competing options. This outcome is consistent with our computational modeling of this task [Snyder, H. R., Hutchison, N., Nyhus, E., Curran, T., Banich, M. T., O’Reilly, R. C., et al. Neural inhibition enables selection during language processing. Proceedings of the National Academy of Sciences, U.S.A., 107, 16483–16488, 2010], which predicts that greater net inhibition in pFC increases the efficiency of resolving competition among task-relevant options. Moreover, the association with the GABA/glutamate ratio was specific to selection and was not observed for executive function ability in general. These findings are the first to link the balance of excitatory and inhibitory neural transmission in pFC to specific aspects of executive function.

Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: Implications for sex-specific regulation of social play behavior

“…Interestingly, individual variations in the glutamate excitation/GABA inhibition balance in cortical regions affect behavioral performance and executive function in healthy men (Jocham et al 2012; de la Vega et al, 2014). Moreover, alterations in the glutamate/GABA ratio in the cortex may contribute to the pathophysiology of various neurological and psychiatric disorders (Sherwin, 1999; Sanacora et al, 2004; Kugaya & Sanacora, 2005).…”

Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder

“…Furthermore, TE = 70 ms has been reported to successfully acquire GABA signal using MEGA-PRESS in Siemens system (Hattingen et al 2014;Sanaei Nezhad et al 2018;Vega et al 2014). A frequency-selective editing pulse was applied at 1.9 ppm (ON) and 7.5 ppm (OFF) in alternating spectral lines to differently refocus the GABA triplet signal at 3.02 ppm.…”

All Competition Is Not Alike: Neural Mechanisms for Resolving Underdetermined and Prepotent Competition

“…The prediction that inhibition is the key mechanism allowing VLPFC to resolve underdetermined competition has been less extensively tested, but is supported by findings that pharmacological increases in GABA improve inhibition (Snyder et al, 2010), while anxiety, associated with reduced inhibition, impairs selection (Snyder et al, 2010; 2013). Recent evidence also shows that higher levels of GABA (relative to glutamate) in lateral prefrontal cortex predict better selection (de la Vega et al, under review). This prediction could be further tested with future research directly manipulating GABA function (e.g., with TMS).…”