The trajectory of cortical GABA across the lifespan, an individual participant data meta-analysis of edited MRS studies.

γ-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the human brain and can be measured with magnetic resonance spectroscopy (MRS). Conflicting accounts report decreases and increases in cortical GABA levels across the lifespan. This incompatibility may be an artifact of the size and age range of the samples utilized in these studies. No single study to date has included the entire lifespan. In this study, eight suitable datasets were integrated to generate a model of the trajectory of frontal GABA estimates (as reported through edited MRS; both expressed as ratios and in institutional units) across the lifespan. Data were fit using both a log-normal curve and a nonparametric spline as regression models using a multi-level Bayesian model utilizing the Stan language. Integrated data show that an asymmetric lifespan trajectory of frontal GABA measures involves an early period of increase, followed by a period of stability during early adulthood, with a gradual decrease during adulthood and aging that is described well by both spline and log-normal models. The information gained will provide a general framework to inform expectations of future studies based on the age of the population being studied.

Reductions in GABA following a tDCS-language intervention for primary progressive aphasia.

Transcranial direct current stimulation (tDCS) has shown efficacy in augmenting the effects of language therapy in primary progressive aphasia (PPA). The mechanism of action of tDCS is not understood, but preliminary work in healthy adults suggests it modulates γ-aminobutyric acid (GABA) levels to create an environment optimal for learning. It is unknown if this proposed mechanism translates to aging or neurodegenerative conditions. This study tested the hypothesis that tDCS reduces GABA at the stimulated tissue in PPA. We applied GABA-edited magnetic resonance spectroscopy to quantify GABA levels before and after a sham-controlled tDCS intervention with language therapy in PPA. All participants showed improvements but those receiving active tDCS showed significantly greater language improvements compared to sham both immediately after the intervention and at 2-month follow-up. GABA levels in the targeted tissue decreased from baseline after the intervention and remained decreased 2 months after the intervention. This work supports the hypothesis that tDCS modulates GABAergic inhibition to augment learning and is clinically useful for PPA combined with language therapy.

Suppression and facilitation of human neural responses.

Efficient neural processing depends on regulating responses through suppression and facilitation of neural activity. Utilizing a well-known visual motion paradigm that evokes behavioral suppression and facilitation, and combining five different methodologies (behavioral psychophysics, computational modeling, functional MRI, pharmacology, and magnetic resonance spectroscopy), we provide evidence that challenges commonly held assumptions about the neural processes underlying suppression and facilitation. We show that: (1) both suppression and facilitation can emerge from a single, computational principle - divisive normalization; there is no need to invoke separate neural mechanisms, (2) neural suppression and facilitation in the motion-selective area MT mirror perception, but strong suppression also occurs in earlier visual areas, and (3) suppression is not primarily driven by GABA-mediated inhibition. Thus, while commonly used spatial suppression paradigms may provide insight into neural response magnitudes in visual areas, they should not be used to infer neural inhibition.