Discussion
MRS
The present study aimed at investigating the neuropsychopharmacological effects of a nocturnal dose of 50 mg/kg GHB p.o. on next mornings’ rsFC and its relationship to GABA and Glu alterations in the ACC. First, we observed a newly induced rCEN-SN coupling after a night with GHB, which was not present in the placebo condition; second, we found that this rsFC alteration was significantly associated with GABA changes in the ACC.In previous studies, GHB was found to acutely modulate rsFC patterns. In particular, GHB administration (35 mg/kg p.o.) in wake healthy individuals acutely increased rsFC between the DMN and the SN (at 34 min after GHB-intake) compared with placebo, without significantly affecting the spatial rsFC distribution of all major large-scale networks (These findings are particularly intriguing when considering the detailed functional meaning of the SN and the unique psychopharmacological and behavioral profile of GHB. The SN has been proposed as a detector of saliency to guide adaptive behavior (Now, translating these findings to GHB neuropsychopharmacology, one may expect to observe different network patterns coherently to the different behavioral effects of GHB in the acute and post-acute phase. In the acute phase, 35 mg/kg oral GHB-induced mixed sedative/stimulant behavioral effects, which were accompanied by increased SN-DMN connectivity (As a note, the increase of rsFC between the SN and the rCEN, but not the lCEN, is coherent with previous findings showing asymmetric effects of GHB on RSNs. Increased cerebral blood flow in the right anterior insula and increased rSN-rCEN coupling via the dorsal nexus have been reported after acute GHB challenge (Bosch et al. To investigate how the reported modulation of rsFC alterations relate to the neurochemical brain homeostasis, we analyzed previously published data of MRS from an ACC-seed assessed in the same individuals and from the same experiment (Our study bears several limitations. The final sample size of In conclusion, the present study provided evidence of persisting internetwork connectivity changes in the morning following a nocturnal therapeutic dose of GHB in humans. The observed alteration in connectivity pattern seem to indicate a modulation of the balancing function of the SN between the DMN and the CEN, toward a more externally oriented brain state, which is in line with GHB’s ability to improve next-day waking functions. We also described a GHB-induced positive interaction of GABA/Glu balance in the ACC with whole-brain connectivity changes. Thus, our findings support the idea of an excitatory/inhibitory equilibrium in the ACC to be actively involved in the modulation of rsFC on a large-scale level. Future research should clarify the generalizability of these findings to other stimulant and/or sedative drugs affecting GABA and Glu homeostasis and further assess correlations with cognitive and behavioral effects in clinical populations.