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Abstract

Aims: Low-frequency brain oscillations in NREM sleep provide a reliable estimate of homeostatic sleep need. Brain imaging studies revealed that sleep slow waves (SWA) recruit distinct nodes of the default mode network (DMN). We recently showed that availability of metabotropic glutamate receptors of subtype 5 (mGluR5) in four DMN nodes, is increased after total sleep deprivation (TSD). Here we examined the relationship between regional mGluR5-availability and EEG slow waves in NREM-sleep. Furthermore, to investigate changes in endogenous glutamate, glutamine or GABA, these neurochemicals were determined in prefrontal cortex by MR spectroscopy (MRS). Methods: J-resolved single-voxel proton 3T MRS (n=17) and whole-brain PET measurements with the selective mGluR5 non-competitive antagonist 11C-ABP688 (n=26) were performed in healthy volunteers after 9 and 33 hours awake in randomized cross-over manner. Sleep was polysomnographically recorded before and after TSD. Statistics included mixed-model ANOVAs, Pearson’s correlations, and Fisher’s r-to-z transformation. Results: In baseline and recovery nights, mGluR5 in four fronto-parietal DMN regions explained 40-66 of inter-individual variation of EEG <1 Hz activity in NREM-sleep (rall>0.63, pall<0.002). Moreover, whole-brain mGluR5 levels in both sleep conditions correlated with EEG SWA (r>0.44, p<0.04). Importantly glutamate/glutamine levels were not altered by TSD (p>0.5), yet the SWA to glutamate/GABA ratio changed with sleep deprivation (z=2.12; p<0.05), and was significant only after sleep deprivation (r=0.83; p<0.002). Conclusions: The data suggest that TSD alters mGluR5-dependent signalling and that these changes are linked to markers of sleep need.