Ketamine, an NMDA antagonist used as a rapid-acting antidepressant, disrupts the functional connectivity between the locus coeruleus (LC) and the thalamus, which is linked to a reduction in behavioral alertness. In a placebo-controlled, cross-over study with 35 healthy male participants (average age 25.1 years), ultra-high field 7T functional MRI revealed that acute disruption of the LC alertness network by ketamine correlates with decreased alertness. These findings highlight ketamine's effects beyond the glutamatergic system, suggesting a new mechanism involving noradrenergic pathways that may contribute to its antidepressant properties.
During sleep, brain dynamics shift from wakefulness through NREM stages N1, N2, and N3, driven partly by decreases in the neuromodulators acetylcholine (ACh) and noradrenaline (NA). Analyzing fMRI data from healthy individuals and using a whole-brain model, the study shows that functional connectivity (FC) changes distinctly: locus coeruleus connectivity with the cortex decreases during N2 and N3, while basal forebrain connectivity with the cortex decreases during N3. Compared to wakefulness, the brain becomes more integrated in N1 and more segregated in N3. Region-specific neurotransmitter effects are key to explaining these FC changes, advancing understanding of how neurochemistry modulates sleep stages and consciousness transitions.