A Mechanistic Link from GABA to Cortical Architecture and Perception

Abstract

SummaryUnderstanding both the organization of the human cortex and its relation to the performance of distinct functions is fundamental in neuroscience. The primary sensory cortices display topographic organization, whereby receptive fields follow a characteristic pattern, from tonotopy to retinotopy to somatotopy [1]. GABAergic signaling is vital to the maintenance of cortical receptive fields [2]; however, it is unclear how this fine-grain inhibition relates to measurable patterns of perception [3, 4]. Based on perceptual changes following perturbation of the GABAergic system, it is conceivable that the resting level of cortical GABAergic tone directly relates to the spatial specificity of activation in response to a given input [5, 6, 7]. The specificity of cortical activation can be considered in terms of cortical tuning: greater cortical tuning yields more localized recruitment of cortical territory in response to a given input. We applied a combination of fMRI, MR spectroscopy, and psychophysics to substantiate the link between the cortical neurochemical milieu, the tuning of cortical activity, and variability in perceptual acuity, using human somatosensory cortex as a model. We provide data that explain human perceptual acuity in terms of both the underlying cellular and metabolic processes. Specifically, higher concentrations of sensorimotor GABA are associated with more selective cortical tuning, which in turn is associated with enhanced perception. These results show anatomical and neurochemical specificity and are replicated in an independent cohort. The mechanistic link from neurochemistry to perception provides a vital step in understanding population variability in sensory behavior, informing metabolic therapeutic interventions to restore perceptual abilities clinically.

CRPS Is Not Associated with Altered Sensorimotor Cortex GABA or Glutamate

“…While in healthy control subjects, one might hypothesize that increased use of the dominant hand would result in better tactile acuity than the nondominant hand, we found no difference in dominant and nondominant tactile acuity in control subjects, a result consistent with findings of previous investigations (Gelber et al, 1995;Ozcan et al, 2004;Pleger et al, 2006;Tustumi et al, 2015). Despite some past studies showing an increased sensorimotor GABA concentration correlating with better tactile acuity performance (Puts et al, 2011;Kolasinski et al, 2017), there is also evidence that lower M1 GABA concentration correlates with better motor learning capabilities in a healthy sample (Stagg et al, 2011b). Our results did not show any correlation between sensorimotor GABA concentration and tactile acuity in either healthy control subjects or CRPS patients.…”

“…Furthermore, since GABA and glutamate work together to maintain excitatory/inhibitory balance, we also investigated sensorimotor glutamate concentration and hypothesized that it would remain at control levels in CRPS. Finally, since greater sensorimotor GABA concentration has been found to predict better tactile acuity performance (Puts et al, 2011;Kolasinski et al, 2017) and individuals with CRPS have poor tactile acuity (Catley et al, 2014), we hypothesized that CRPS subjects would have reduced tactile acuity and that this would be correlated with reduced sensorimotor GABA concentration.…”

Causal explanation of individual differences in human sensorimotor memory formation

“…Due to the size of the voxel, adjacent regions of sensory cortex (S1) were also included in the measure of M1 metabolites. This is a common methodological limitation of MRS studies (Stagg et al 2009;Lunghi et al 2015;Antonenko et al 2017;Ip et al 2017;Kolasinski et al 2017;O'Shea et al 2017). Although we cannot rule out the contribution of S1 to our results, M1 is likely to play a predominant role because of a convergence of studies implicating it in the consolidation of adaptation memory (Wise et al 1998;Li et al 2001;Paz et al 2003;Paz et al 2005;Hadipour-Niktarash et al 2007;Landi et al 2011;Leow et al 2016).…”

Somatomotor cortical representations are predicted by levels of short-interval intracortical inhibition

“…Evidence shows that these somatomotor representations are dynamic, actively maintained, and likely mediated by the inhibitory neurotransmitter GABA [4]. GABAas a mediator of neural communicationplays a pivotal role in neuroplasticity and in shaping the cortical tuning function of sensorimotor representations [5]. Furthermore, altered distribution and concentration of GABA and GABAergic mechanisms can lead to a loss of the spatial specificity of somatomotor cortical representations [6].…”