Resting-state brain activity is not steady but dynamic, with vigilance fluctuations playing a key role. In a randomized, double-blind, placebo-controlled crossover study of 24 healthy young adults, subanesthetic S-ketamine decreased functional connectivity in the medial prefrontal cortex and increased connectivity in intraparietal cortices, measured with simultaneous EEG-fMRI. Ketamine also shifted EEG power toward slow (delta, theta) and fast (gamma) frequencies. Frontal connectivity negatively related to EEG gamma and theta activity, while parietal connectivity positively related to delta power. These results indicate a direct link between ketamine-induced connectivity changes and reduced vigilance, offering potential surrogate endpoints for understanding ketamine's antidepressant effects.
A subanesthetic dose of S-Ketamine, an NMDAR antagonist, alters resting-state brain connectivity in healthy men. In the executive control network, ketamine increased connectivity with the anterior cingulum and superior frontal gyrus, but these changes did not correlate with clinical symptoms. In the salience network, ketamine decreased connectivity with the calcarine fissure, and this decrease correlated with negative symptoms measured by the PANSS (R² > 0.4). The findings suggest that reduced salience network connectivity may serve as a predictive biomarker for ketamine-induced negative symptoms relevant to schizophrenia research.