Neurochemistry of response inhibition and interference in gambling disorder: a preliminary study of γ-aminobutyric acid (GABA+) and glutamate–glutamine (Glx)

Abstract

Objective. Neurobehavioural research on the role of impulsivity in gambling disorder (GD) has produced heterogeneous findings. Impulsivity is, however, a multifaceted construct, with different experimental tasks measuring different sub-processes, such as response inhibition and distractor interference. Little is known about the neurochemistry of inhibition and interference in GD.Methods. We investigated response inhibition with the Stop Signal Task (SST) and distractor interference with the Eriksen Flanker Task, and related task performance to metabolite levels in individuals with and without GD. We employed magnetic resonance spectroscopy (MRS) to record glutamate-glutamine (Glx/Cr) and inhibitory, γ-aminobutyric acid (GABA+/Cr) levels in the dorsal ACC (dACC), right dorsolateral prefrontal cortex (dlPFC), and an occipital control voxel.Results. We found slower processing of complex stimuli in the Flanker task in GD (p < .001, η 2 p = .78), while no group differences were identified in SST performance. Levels of dACC Glx/Cr and frequency of incongruent errors were correlated positively in GD only (r = .92, p = .001). Similarly, larger positive correlations were found for those with GD rather than non-GD between dACC GABA+/Cr and SST Go error response times (z = 2.83, p = .004) as well as between dACC Glx/Cr and frequency of Go errors (z = 2.23, p = .03), hinting towards a general Glx-related error processing deficit in GD across impulsivity tasks. Further, both groups expressed equivalent positive correlations between post-error slowing and Glx/Cr in the right dlPFC (GD: r = .74, p = .02; non-GD: r = .71, p = .01). Conclusion.Distractor interference and response inhibition impairments in GD are reflected in dACC baseline metabolite levels and error processing deficits in GD.

To Play or Not to Play: An Investigation Into The Effect of Video Game Use on Executive Functions

“…Put simply, the role of Glx, glutamate in particular, is to trigger neurons to release neurotransmitters and is a major excitatory transmitter in the brain (Zhou & Danbolt, 2014). Weidacker et al (2022) found no correlation between the ACC GABA or Glx in the ability to stop on a stop-signal task. However, they found that ACC Glx positively correlated with errors in Go conditions in a stop-signal task.…”

“…Response inhibition and interference task performance are assumed to depend on optimally balancing excitatory and inhibitory neurometabolites (Krause et al, 2013;Weidacker et al, 2022). γ-aminobutyric acid (GABA) is a well-known neuro-metabolite and is involved in maintaining optimal behavioural performance.…”

“…Numerous studies have linked magnetic resonance spectroscopy (MRS) assessed GABA levels at rest, referred to as baseline GABA levels, to performance on various task types (Boy et al, 2010;Dyke et al, 2017;Hermans et al, 2018;Li et al, 2022;Prena et al, 2020;Silveri et al, 2013;Weidacker et al, 2020;Weidacker et al, 2022;Yoon et al, 2016).…”

“…This technique has traditionally been used in a clinical setting (Barker et al, 1994;Weinberg et al, 2021;Yurista et al, 2022), but there has been an increase in research applications of MRS to understand the neurochemical determinants of behaviour, including the neurometabolites GABA and glutamate due to their antagonistic roles in inhibition and excitation. However, it is of note that due to the similarity of the molecular structure of Glutamate and Glutamine and the resulting similarity in spectral profile, Glutamate is often reported pooled together with glutamine as 'Glx' (Grent-'t-Jong et al, 97 2022;Ramadan et al, 2013;Weidacker et al, 2020;Weidacker et al, 2022). Improvements, including higher magnetic field strength scanners and acquisition techniques, have allowed for investigations of neurometabolites that formally constituted a unitary pool due to structural similarity within the human brain and resultant spectra similarity, such as GABA and Glx (Ramadan et al, 2013;Steel et al, 2020).…”

“…Therefore, recruiting only right-handed participants controlled for this potential confound and was in line with sampling practices in recent comparable studies (Bell et al, 2021;Prena et al, 2020;Weidacker et al, 2020;Weidacker et al, 2022). Any potential contraindications that precluded entering a highly magnetic environment were determined by a completed MR…”