Default mode network connectivity change corresponds to ketamine's delayed glutamatergic effects

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Ketamine shows rapid antidepressant effects, linked to default mode network (DMN) functional connectivity (FC) and glutamate changes.
• Understanding the timing and interplay of these brain changes is crucial for developing new antidepressant therapies.

Purpose of the Study:

• To investigate the relationship between delayed glutamatergic alterations and DMN functional connectivity changes after ketamine infusion.
• To examine the predictive role of acute brain activity markers (fALFF) for these delayed functional changes.

Main Methods:

• A double-blind, randomized, placebo-controlled study involving 61 healthy subjects.
• Subanesthetic ketamine infusion (0.5 mg/kg) with resting-state fMRI and MR-Spectroscopy at 7T.
• Measurements taken 1 hour and 24 hours post-infusion.

Main Results:

• A significant decrease in FC between the posterior cingulate cortex (PCC) and dorsomedial prefrontal cortex (dmPFC) was observed 24 hours post-ketamine, correlating with pgACC glutamatergic changes.
• An acute increase in fractional amplitude of low-frequency fluctuations (fALFF) in the ventral PCC at 1 hour was inversely correlated with the later PCC-dmPFC FC decrease.
• These functional and metabolic changes were specific to the 24-hour time point.

Conclusions:

• The findings suggest a potential mechanistic link between ketamine-induced glutamatergic modulation and the delayed reconfiguration of DMN circuitry.
• Metabolic and functional brain changes following ketamine are time-point specific, offering insights into its antidepressant mechanisms.