Frontal Lobe γ-Aminobutyric Acid Levels During Adolescence: Associations with Impulsivity and Response Inhibition

Abstract

Background The brain undergoes major remodeling during adolescence, resulting in improved cognitive control and decision-making, and reduced impulsivity, components of behavior mediated in part by the maturing frontal lobe. Gamma-amino butyric acid (GABA), the main inhibitory neurotransmitter system, also matures during adolescence, with frontal lobe GABA receptors reaching adult levels late in adolescence. Thus, the objective of this study was to characterize in vivo developmental differences in brain GABA levels. Methods Proton magnetic resonance spectroscopy (MRS) was employed at 4 Tesla to acquire metabolite data from the anterior cingulate cortex (ACC) and the parieto-occipital (POC) cortex in adolescents (n=30) and emerging adults (n=20). Results ACC GABA/Cr levels were significantly lower in adolescents relative to emerging adults, whereas no age differences were observed in the POC. Lower ACC GABA/Cr levels were significantly associated with greater impulsivity and worse response inhibition, with relationships being most pronounced for ACC GABA/Cr and No-Go response inhibition in adolescent males. Conclusions These data provide the first human developmental in vivo evidence confirming frontal lobe GABA maturation, which was linked to impulsiveness and cognitive control. These findings suggest that reduced GABA may be an important neurobiological mechanism in the immature adolescent brain, contributing to the reduced, yet rapidly developing, ability to inhibit risky behaviors and to make decisions, which could compromise adolescent health and safety.

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

“…Whilst GABA measured this way is predominantly metabolic in origin (Myers et al 2014; Myers et al 2016b), it is interesting that a lowered magnetic resonance spectroscopy GABA signal ([GABA+]) in HV has in some studies been associated with higher levels of impulsivity. For instance, it has been shown that [GABA+] levels in dorsolateral prefrontal regions negatively correlate with urgency impulsivity (Boy et al 2011); low [GABA+] in perigenual anterior cingulate cortex was associated with greater delay aversion on Cambridge gambling task (Fujihara et al 2015) and higher scores on self‐report Barratt Impulsiveness Scale‐11 in one study (Silveri et al 2013) but not another (Janes et al 2013). Lower [GABA+] in the striatum is associated with poorer impulse control in Go‐NoGo task (Quetscher et al 2015).…”

Recent Insights into the Neurobiology of Impulsivity

“…GABAergic projections have been less well investigated in the context of addiction although GABAergic mechanisms influence function of the mesolimbic pathway [58]. While GABAergic manipulation was successful in modulating response impulsivity in rodents, in humans, GABAergic function has been arguably linked more closely to self-report impulsivity and impulsive choice [59–61] than to response impulsivity (although see [62]). Within the mesolimbic pathway, dopamine and serotonin have been the two most heavily studied neurotransmitters with regard to impulsivity.…”

Impulsivity and Aggression in Female BPD and ADHD Patients: Association with ACC Glutamate and GABA Concentrations

“…In a study of children with ADHD, lower GABA levels in a region including parts of the primary somatosensory and motor cortices have been reported (Edden et al, 2012). In healthy adolescents and adults, two recent studies showed a negative association of GABA levels in the dorsolateral prefrontal cortex with impulsivity (Boy et al, 2011;Silveri et al, 2013). Despite these studies, Hayes argues that there is still a lack of research on GABA in the general context of impulsivity (Hayes et al, 2014).…”