Broadband cortical desynchronization underlies the human psychedelic state.
Psychedelic drugs produce profound changes in consciousness, but the underlying neurobiological mechanisms for this remain unclear. Spontaneous and induced oscillatory activity was recorded in healthy human participants with magnetoencephalography after intravenous infusion of psilocybin--prodrug of the nonselective serotonin 2A receptor agonist and classic psychedelic psilocin. Psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 Hz in posterior association cortices, and from 8 to 100 Hz in frontal association cortices. Large decreases in oscillatory power were seen in areas of the default-mode network. Independent component analysis was used to identify a number of resting-state networks, and activity in these was similarly decreased after psilocybin. Psilocybin had no effect on low-level visually induced and motor-induced gamma-band oscillations, suggesting that some basic elements of oscillatory brain activity are relatively preserved during the psychedelic experience. Dynamic causal modeling revealed that posterior cingulate cortex desynchronization can be explained by increased excitability of deep-layer pyramidal neurons, which are known to be rich in 5-HT2A receptors. These findings suggest that the subjective effects of psychedelics result from a desynchronization of ongoing oscillatory rhythms in the cortex, likely triggered by 5-HT2A receptor-mediated excitation of deep pyramidal cells.
Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff CF119BJ, United Kingdom, Imperial College London, Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, London W12 ONN, United Kingdom, Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom, Sir Peter Mansfield Magnetic Resonance Centre, Nottingham University, Nottingham NG7 2RD, United Kingdom, Academic Unit of Psychiatry, University of Bristol, Bristol BS8 2BN, United Kingdom, The Beckley Foundation, Beckley Park, Oxford OX3 9SY, United Kingdom, and Virginia Tech Carilion Research Institute, and Bradley Department of Electrical & Computer Engineering, Virginia Polytechnic Institute and State University, Roanoke, Virginia 24016.
Suresh D
SD
Muthukumaraswamy
Robin L
RL
Carhart-Harris
Rosalyn J
RJ
Moran
Matthew J
MJ
Brookes
Tim M
TM
Williams
David
D
Errtizoe
Ben
B
Sessa
Andreas
A
Papadopoulos
Mark
M
Bolstridge
Krish D
KD
Singh
Amanda
A
Feilding
Karl J
KJ
Friston
David J
DJ
Nutt
D000328:Adult; D000704:Analysis of Variance; D002540:Cerebral Cortex / Q000187:drug effects*; D003344:Cortical Synchronization / Q000187:drug effects*; D004562:Electrocardiography; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D015225:Magnetoencephalography; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000187:drug effects; D017711:Nonlinear Dynamics; D010775:Photic Stimulation; D011562:Psilocybin / Q000494:pharmacology*; D012146:Rest
D006213:Hallucinogens; D011562:Psilocybin