Acute Modulation of Cortical Glutamate and GABA Content by Physical Activity

Converging evidence demonstrates that physical activity evokes a brain state characterized by distinctive changes in brain metabolism and cortical function. Human studies have shown that physical activity leads to a generalized increase in electroencephalography power across regions and frequencies, and a global increase in brain nonoxidative metabolism of carbohydrate substrates. This nonoxidative consumption of carbohydrate has been hypothesized to include increased de novo synthesis of amino acid neurotransmitters, especially glutamate and GABA. Here, we conducted a series of proton magnetic resonance spectroscopy studies in human volunteers before and after vigorous exercise (≥80% of predicted maximal heart rate). Results showed that the resonance signals of both glutamate and GABA increased significantly in the visual cortex following exercise. We further demonstrated a similar increase in glutamate following exercise in an executive region, the anterior cingulate cortex. The increase in glutamate was similar when using echo times of 30 and 144 ms, indicating that exercise-related T2 relaxation effects across this range of relaxation times did not account for the findings. In addition, we found preliminary evidence that more physical activity during the preceding week predicts higher resting glutamate levels. Overall, the results are consistent with an exercise-induced expansion of the cortical pools of glutamate and GABA, and add to a growing understanding of the distinctive brain state associated with physical activity. A more complete understanding of this brain state may reveal important insights into mechanisms underlying the beneficial effects of physical exercise in neuropsychiatric disorders, neurorehabilitation, aging, and cognition. SIGNIFICANCE STATEMENT Increasing evidence suggests that distinctly different brain states are associated with sedentary behavior compared with physically active behavior. Metabolic studies show that the nonoxidative consumption of carbohydrates by the brain increases greatly during vigorous activity. Prior studies have suggested that one component of this metabolic shift may involve increasing the reserves of neurotransmitters in the brain via de novo synthesis from carbohydrate substrates. The current study reports the results of three experiments that support this hypothesis by showing increased cortical content of glutamate and GABA following physical activity. Understanding how brain metabolism and function differ during sedentary versus active behavioral states may provide important insights into the neurotherapeutic potential of exercise.