The relationship between transcranial magnetic stimulation measures of intracortical 1 inhibition and spectroscopy measures of GABA and glutamate + glutamine

31 Transcranial magnetic stimulation (TMS) can provide an index of intracortical 32 excitability/inhibition balance. However, the neurochemical substrate of these measures remains 33 unclear. Pharmacological studies suggest the involvement of GABAA and GABAB receptors in 34 TMS protocols aimed at measuring intracortical inhibition, but this link remains inferential. 35 Proton magnetic resonance spectroscopy (H-MRS) permits measurement of GABA and 36 glutamate + glutamine (Glx) concentrations in the human brain, and might help in the direct 37 empirical assessment of the relationship between TMS inhibitory measures and neurotransmitter 38 concentrations. In the present study, MRS-derived relative concentrations of GABA and Glx 39 measured in the left M1 of healthy participants were correlated with TMS measures of 40 intracortical inhibition. Glx levels were found to correlate positively with TMS-induced silent 41 period duration whereas no correlation was found between GABA concentration and TMS 42 measures. The present data demonstrate that specific TMS measures of intracortical inhibition are 43 linked to shifts in cortical Glx, rather than GABA neurotransmitter levels. Glutamate might 44 specificaly interact with GABAB receptors, where higher levels of MRS-derived Glx 45 concentrations seem to be linked to higher levels of receptor activity. 46 47