Ketamine improves short-term plasticity in depression by enhancing sensitivity to prediction errors.

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Major depressive disorder (MDD) impairs the brain's predictive coding framework.
• Understanding ketamine's neural mechanisms for antidepressant effects is crucial.

Purpose of the Study:

• Investigate ketamine's impact on predictive coding and short-term plasticity in MDD patients.
• Examine neural effects during the period of emerging antidepressant symptom improvement.

Main Methods:

• Electroencephalography (EEG) using an auditory roving mismatch negativity (rMMN) paradigm.
• Administered intravenous ketamine (0.44 mg/kg) or active placebo (remifentanil).
• Assessed depression severity using the Montgomery-Asberg Depression Rating Scale (MADRS).

Main Results:

• Ketamine significantly increased MMN and P3a event-related potentials.
• Dynamic causal modeling revealed greater forward connectivity modulation between auditory and temporal cortices.
• Connectivity changes correlated with 24-hour antidepressant response.

Conclusions:

• Ketamine may increase sensitivity to unexpected stimuli and restore prediction error signaling deficits in depression.
• Short-term effects do not fully restore adaptive internal model calibration deficits, as indicated by lack of repetition suppression.