A circuit dissection of perception-action decoupling in S-ketamine-induced hallucination-like states.

Summary

This multimodal mouse study separated perceptual false alarms from disorganized behavioral expression during S-ketamine exposure. The basolateral amygdala-to-caudal striatum pathway promoted salience-weighted false auditory threat responses, whereas the medial prefrontal cortex-to-caudal striatum pathway shaped disorganized actions. Dexmedetomidine restored pathway-level temporal dynamics and reorganized striatal network coupling without merely suppressing neuronal activity.

Key Findings

• The basolateral amygdala-to-caudal striatum pathway promoted S-ketamine-induced false auditory threat responses.
• The medial prefrontal cortex-to-caudal striatum pathway primarily generated disorganized action patterns.
• Dexmedetomidine restored striatal pathway timing and network coupling without simply suppressing overall activity.

Clinical Implications

The findings support further translational studies of dexmedetomidine for managing ketamine-related hallucination-like or behavioral disturbances, particularly in anesthetic and procedural settings. Direct clinical application remains premature because the evidence derives from mice and an experimental S-ketamine paradigm.

Limitations

• The study used a mouse model, so the relationship to human hallucinations and perioperative symptoms remains uncertain.
• The abstract does not provide the number of animals, and the experimental S-ketamine paradigm may not capture the full clinical variability of ketamine exposure.

Future Directions

Future work should validate these pathway mechanisms in human neuroimaging or translational models, define dose- and state-dependent effects of dexmedetomidine, and test whether the circuit signatures predict emergence delirium or ketamine-related perceptual disturbances.