Macromolecule-suppressed GABA measurements correlate more strongly with behavior than macromolecule-contaminated GABA+ measurements

Abstract

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is known to be fundamental to the neuronal processes underlying visual orientation and vibrotactile frequency and amplitude discrimination. Previous studies have demonstrated that performance on visual and vibrotactile psychophysics tasks is associated with in vivo measurements of "GABA+" levels - a measure of GABA substantially contaminated by a macromolecular (MM) signal. Here, we establish that these prior findings are indeed driven by the GABA fraction of that signal. Edited magnetic resonance spectroscopy (MRS) was used to measure GABA with and without MM suppression in the sensorimotor (SM1) and occipital cortices in 14 healthy male adults. Volunteers also underwent psychophysical experiments to assess their performance on visual orientation discrimination and vibrotactile amplitude and frequency discrimination. We show that MM-suppressed GABA levels correlate more strongly with individual differences in vibrotactile (in the case of SM1 GABA; amplitude: r = -0.63, p = 0.03; frequency: r = -0.62, p = 0.02) and visual orientation (in the case of occipital GABA; r = -0.59, p = 0.05) discrimination thresholds than GABA levels contaminated by MM (vibrotactile amplitude: r = -0.36, p = 0.30; vibrotactile frequency: r = -0.53, p = 0.09; visual orientation: r = 0.21, p = 0.55). These findings further support the view that measurements of endogenous GABA acquired with edited MRS can usefully probe neurochemical-behavioral relationships in humans. Moreover, the more specific measurement of GABA used in this study provides increased statistical power to observe these regionally specific relationships.

Reproducibility of flutter-range vibrotactile detection and discrimination thresholds

“…The reproducibility of the remaining measures (detection thresholds, amplitude discrimination, frequency discrimination, and TOJ) is less well-documented; this study presents some of the first evidence that these measures are reproducible to a variable extent. Moreover, the intersubject variability of the various thresholds falls in line with previous findings in adults 13,[27][28][29] , with reaction times having around 20-30% variation, detection and frequency discrimination thresholds having 20-40% variation, and amplitude discrimination thresholds having 40-60% variation. The intrasubject variability of detection thresholds has been shown to be around ~25-30% 55,56 , which also falls in line with the present findings.…”

“…permits interrogation of the somatosensory and higher-level systems in healthy and pathological neurobiology. This battery and its variants have been used to investigate tactile (dys)function in autism spectrum disorder [17][18][19][20][21][22] , Tourette syndrome 23 , and attention-deficit hyperactivity disorder 24 ; in ageing 25,26 ; in multimodal studies involving magnetic resonance spectroscopic measures of GABA [27][28][29] ; in concussion 30,31 ; and in conjunction with neurostimulation 32 . Dynamic detection thresholds, for example, are thought to reflect local feed-forward inhibitory mechanisms [33][34][35] .…”

The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes

“…However, since it is a mixed signal of Glutamine and Glutamate we opted to also analyze the later through PRESS data. Also, the macromolecule contributions to GABA signal should be accounted by using new MRS approaches with MM-suppression [ 52 ].…”

No Effect of Anodal tDCS on Verbal Episodic Memory Performance and Neurotransmitter Levels in Young and Elderly Participants

“…Furthermore, the use of 7T-MRS is promising as it allows not only the disentanglement of glutamate and glutamine peaks in the spectrum [ 104 ] but also the subtraction of the macromolecular baseline from the GABA signal [ 105 ]. The latter is of particular interest since suppressing the macromolecular spectral components increased the correlation of GABA levels with individual discrimination thresholds for vibrotactile and visual stimuli [ 106 ] and may thus contribute to a better understanding of the relationship between neurometabolites and behaviour. Further, functional MRS as opposed to the current resting state assessment of MRS spectra could help to identify more immediate effects of the stimulation, which may be obscured by the long acquisition times over several minutes [ 107 ].…”