Ketamine effects on default mode network activity and vigilance: A randomized, placebo-controlled crossover...

Area of Science:

• Neuroscience
• Pharmacology
• Psychiatry

Background:

• Resting-state functional connectivity (rsFC) research often assumes a steady state, but vigilance fluctuations significantly impact brain dynamics.
• Drugs like ketamine affect vigilance, necessitating vigilance assessment in rsFC pharmacodynamic studies.
• Previous studies noted ketamine-induced prefrontal connectivity decreases, but the link to vigilance was unclear.

Purpose of the Study:

• To investigate the relationship between ketamine-induced changes in functional connectivity and vigilance.
• To determine if ketamine's effect on prefrontal connectivity is mediated by vigilance changes.
• To explore the neurophysiological underpinnings of ketamine's effects using simultaneous fMRI and EEG.

Main Methods:

• Conducted a randomized, double-blind, placebo-controlled crossover study with 24 healthy subjects.
• Administered subanesthetic S-Ketamine and acquired simultaneous resting-state fMRI and EEG data.
• Performed seed-based default mode network (DMN) functional connectivity and EEG power spectrum analyses.

Main Results:

• Ketamine decreased medial prefrontal cortex connectivity and increased intraparietal cortex connectivity.
• EEG data showed a shift in energy towards slow (delta, theta) and fast (gamma) wave frequencies post-ketamine.
• Frontal connectivity correlated negatively with EEG gamma and theta, while parietal connectivity correlated positively with delta power.

Conclusions:

• Ketamine-induced functional connectivity alterations are directly related to decreased vigilance, as measured by EEG.
• These findings suggest vigilance assessment is crucial in fMRI studies involving vigilance-altering substances.
• Observed neurophysiological changes may serve as surrogate endpoints for ketamine's therapeutic effects, like antidepressant action.