Psychedelics relax predictive processing in the post-acute period by remodeling cortico-cortical feedback circuits

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Serotonergic psychedelics show promise for treating psychiatric disorders.
• Therapeutic effects can persist for weeks after a single dose.
• Theories suggest psychedelics alter brain circuit hierarchy, reducing top-down influence.

Purpose of the Study:

• To investigate the lasting effects of psychedelics on predictive processing in the fronto-visual system.
• To test the hypothesis that psychedelics reduce top-down influence on information processing.
• To explore the neural mechanisms underlying these effects in humans and mice.

Main Methods:

• Human participants recently exposed to psychedelics (psilocybin, LSD) underwent EEG and electrooculography during a saccadic prediction task.
• Mouse models were used for direct recordings of primary visual cortex (V1) after psilocybin administration.
• Neural plasticity, including spine growth and top-down modulation, was assessed in mouse brains.

Main Results:

• Recent psychedelic users exhibited disrupted predictive processing, with fewer fast saccades and reduced EEG power suppression.
• These disruptions correlated with time since psychedelic use and were observed with different psychedelics.
• Psilocybin administration in mice led to a loss of predictive suppression in V1 and weakened top-down modulation from the medial prefrontal cortex.

Conclusions:

• Psychedelics induce lasting changes in neural plasticity, reorganizing cortical feedback circuits.
• These changes reduce top-down influence on sensory processing, potentially creating a therapeutic window.
• The findings provide concrete evidence for altered hierarchical brain function following psychedelic exposure.