Abstract
BACKGROUND: Animal studies suggest that synchronized electrical activities in the brain are regulated by the primary inhibitory and excitatory neurotransmitters gamma-aminobutyric acid (GABA) and glutamate, respectively. Identifying direct evidence that this same basic chemical-electrical neuroscience principle operates in the human brains is critical for translation of neuroscience to pathological research. OBJECTIVE/HYPOTHESIS: We hypothesize that the background neurochemical concentrations may affect the cortical excitability probed by transcranial magnetic stimulation (TMS). METHODS: We used TMS with simultaneous evoked potential recording to probe the cortical excitability and determined how background frontal cortical GABA and glutamate levels measured using magnetic resonance spectroscopy (MRS) modulate frontal electrical activities. RESULTS: We found that TMS-evoked N100 reflects a balance between GABA-inhibitory and glutamate-excitatory levels. About 46% of individual variances in frontal N100 can be explained by their glutamate/GABA ratio (r = -0.68, p = 0.001). Both glutamate (r = -0.51, p = 0.019) and GABA (r = 0.55, p = 0.01) significantly contributed to this relationship but in opposite directions. CONCLUSION: The current finding encourages additional mechanistic studies to develop TMS evoked N100 as a potential electrophysiological biomarker for translating the known inhibitory GABAergic vs. excitatory glutamatergic chemical-electrical principle from animal brain studies to human brain studies.