Psilocybin desynchronizes brain networks

Abstract

The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later. Psilocybin disrupted connectivity across cortical networks and subcortical structures, producing more than 3-fold greater acute changes in functional networks than methylphenidate. These changes were driven by desynchronization of brain activity across spatial scales (area, network, whole brain). Psilocybin-driven desynchronization was observed across association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduced psilocybin-induced network changes, suggesting a neurobiological basis forgrounding, connecting with physical reality during psychedelic therapy. The acute brain effects of psilocybin are consistent with distortions of space-time and the self. Psilocybin induced persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after 6 months. Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for pro-plasticity and anti-depressant effects of psilocybin.

Dynamic medial parietal and hippocampal deactivations under DMT relate to sympathetic output and altered sense of time, space, and the self

“…Yet, medial parietal and hippocampal deactivations during peak effects may represent a signature activity pattern common to most psychedelics (Carhart-Harris et al, 2014; Tagliazucchi et al, 2014). Future work repeatedly assessing the same participant (Poldrack et al, 2015; Gratton et al, 2018; Siegel et al, 2023) across different days and dosing protocols may shed light on the inter- and intra-individual neural variability of psychedelic experiences.…”

Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options

“…In this regard, functional Magnetic Resonance Imaging (fMRI) studies have provided valuable information on how psilocybin remodels brain connectivity, identifying distinctive patterns of functional connectivity that suggest increased interaction between brain regions that are not normally so interconnected [ 93 ]. This phenomenon is associated with the so-called default mode network, a system of brain regions that collaborate when the mind is at rest and not engaged in specific external tasks [ 94 ].…”

“…Psilocybin has an impact on this network which is essential for cognition and introspection. fMRI has revealed that psilocybin induces changes in default network activity, generating a decrease in activity in some areas and an increase in others [ 93 , 94 ]. On one hand, the reduction in activity in certain regions such as the Posterior Cingulate Cortex (PCC) and the Medial Prefrontal Cortex (MPFC) during the experience is associated with a temporary disconnection of the ego and dissolution of boundaries between the self and the environment [ 84 ].…”

Psychedelic 5-HT2A receptor agonism: neuronal signatures and altered neurovascular coupling.

“…5c, bottom). This topography potentially corresponds to a main effect of psychedelics in humans, specifically, loss of functional segregation between primary cortical regions (e.g., somatosensory, and visual) and the default mode network assessed in the infraslow band (i.e., frequencies below 0.1 Hz) [14,15,19,100,127,147].…”