Nocturnal sodium oxybate increases the anterior cingulate cortex magnetic resonance glutamate signal upon awakening

Clinical guidelines recommend sodium oxybate (SXB; the sodium salt of γ-hydroxybutyrate) for the treatment of disturbed sleep and excessive daytime sleepiness in narcolepsy, yet the underlying mode of action is elusive. In a randomised controlled trial in 20 healthy volunteers, we aimed at establishing neurochemical changes in the anterior cingulate cortex (ACC) following SXB-enhanced sleep. The ACC is a core neural hub regulating vigilance in humans. At 2:30 a.m., we administered in a double-blind cross-over manner an oral dose of 50 mg/kg SXB or placebo, to enhance electroencephalography-defined sleep intensity in the second half of nocturnal sleep (11:00 p.m. to 7:00 a.m.). Upon scheduled awakening, we assessed subjective sleepiness, tiredness and mood and measured two-dimensional, J-resolved, point-resolved magnetic resonance spectroscopy (PRESS) localisation at 3-Tesla field strength. Following brain scanning, we used validated tools to quantify psychomotor vigilance test (PVT) performance and executive functioning. We analysed the data with independent t tests, false discovery rate (FDR) corrected for multiple comparisons. The morning glutamate signal (at 8:30 a.m.) in the ACC was specifically increased after SXB-enhanced sleep in all participants in whom good-quality spectroscopy data were available (n = 16; pFDR < 0.002). Further, global vigilance (10th-90th inter-percentile range on the PVT) was improved (pFDR < 0.04) and median PVT response time was shorter (pFDR < 0.04) compared to placebo. The data indicate that elevated glutamate in the ACC could provide a neurochemical mechanism underlying SXB's pro-vigilant efficacy in disorders of hypersomnolence

Lower glutamate and GABA levels in auditory cortex of tinnitus patients: a 2D-JPRESS MR spectroscopy study

We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no hearing loss (n = 16) vs. a matched control group (n = 17) to further elucidate the role of excitatory and inhibitory neurotransmitters in tinnitus. Two-dimensional J-resolved spectroscopy (2D-JPRESS) was applied to disentangle Glutamate (Glu) from Glutamine and to estimate GABA levels in two bilateral voxels in the primary auditory cortex. Results indicated a lower Glu concentration (large effect) in right auditory cortex and lower GABA concentration (medium effect) in the left auditory cortex of the tinnitus group. Within the tinnitus group, Glu levels positively correlated with tinnitus loudness measures. While the GABA difference between groups is in line with former findings and theories about a dysfunctional auditory inhibition system in tinnitus, the novel finding of reduced Glu levels came as a surprise and is discussed in the context of a putative framework of inhibitory mechanisms related to Glu throughout the auditory pathway. Longitudinal or interventional studies could shed more light on interactions and causality of Glu and GABA in tinnitus neurochemistry