Broadband Cortical Desynchronization Underlies the Human Psychedelic State

Abstract

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-HT 2A 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-HT 2A receptor-mediated excitation of deep pyramidal cells.

Psychedelics

“…Analyses of EEG sources showed changes in current density in the ACC, but even more so in the PCC. These electrophysiological findings have been replicated in a MEG study of psilocybin use (Muthukumaraswamy et al, 2013).…”

A placebo-controlled investigation of synaesthesia-like experiences under LSD

“…We have previously observed negligible effects of psychedelics on perceptual and physiological responses in other stimulus-response paradigms (Muthukumaraswamy et al, 2013), leading us to infer that the predominant (and indeed quintessential) effect of psychedelics is on spontaneous (i.e. on-going) processes, rather than induced responses.…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…Interestingly, a more recent experiment using intravenous psilocybin (2 mg) indicated reduced blood flow and blood oxygen level signals in the anterior and posterior cingulate cortex and thalamus of psilocybin-experienced healthy volunteers reporting strong subjective acute effects of the drug (Carhart- . This was replicated by a subsequent magnetoencephalography study showing large decreases in spontaneous oscillary power after psilocybin, especially in cortical association areas and default-mode network (Muthukumaraswamy et al, 2013). These changes were of neuronal origin, consistent with excitation of 5-HT 2A receptors on deep layer 5 pyramidal neurons, which results in activation of inhibitory mechanisms in more superficial layers (Andrade, 2011;Bastos et al, 2012).…”