Real-Time Neurofeedback Training to Modulate Glutamate-Glutamine Concentration Using Functional Magnetic Resonance Spectroscopy.

Neurofeedback training is a procedure in which participants learn to modulate brain activity through their own efforts. Here, we designed a real-time neurofeedback training using functional magnetic resonance spectroscopy (fMRS) to modulate the concentration of glutamate, a major excitatory neurotransmitter, and its precursor glutamine (collectively referred to as Glx) in a volume-of-interest (VOI) located in the occipital lobes. During an induction phase participants employed a self-selected strategy to increase or decrease Glx concentration relative to a reference concentration measured prior to neurofeedback training. Participants were informed about their performance after the induction phase by displaying a disk in green for success or red for failure. The disk size indicated the magnitude of success or failure. The procedure was repeated over the course of 30 trials. Participants were randomly assigned to experimental and control groups (15 participants per group). The experimental group received veridical feedback about their success or failure in the induction phase. The control group received random feedback. Glx concentration in the VOI was measured using 2-s-long consecutive Point RESolved Spectroscopy (PRESS) scans in a 3-Tesla MRI scanner. The results showed that depending on group assignment, participants in the experimental group learned to increase or decrease Glx concentration over the course of training. No significant changes in Glx concentration were observed in the control group. These findings suggest that, with the help of veridical performance feedback, participants learned to modulate Glx concentration in the VOI in the desired direction over a relatively short period of time. fMRS-based neurofeedback training may complement existing neurofeedback approaches by targeting neurotransmitter-related processes.