Increased BOLD resting-state fluctuation amplitude following upregulation of inhibitory activity with the GABA agonist alprazolam

Neural activity reflects a complex interplay between excitatory and inhibitory signaling. Yet, the BOLD signal is typically interpreted as related to excitatory activity. However, GABAergic neurotransmission also requires metabolism and BOLD may be sensitive to this inhibitory activity that can promote coordinated activity across networks. Here, we evaluated the changes in BOLD rsfMRI and rsCBF metrics (amplitude of low frequency fluctuations (ALFF), intrinsic connectivity (IC) and local correlations (LC)) after oral administration of alprazolam, a GABA agonist, in healthy volunteers. We observed a highly significant increase of BOLD ALFF across the cortex that suggests increasing inhibition can increase BOLD signals.