Psilocybin desynchronizes brain networks
Nicol, G. E.
This functional mapping study (n=24) examined brain changes in healthy adults before, during, and up to 3 weeks after taking oral psilocybin (25mg) and methylphenidate (Ritalin), with a follow-up 6+ months later. Psilocybin caused over 3-fold greater acute changes in functional networks than Ritalin, with the most significant disruptions observed in the default mode network (DMN), linked to our sense of self. While a perceptual task reduced these changes, suggesting a way to ground individuals during psychedelic therapy, the acute effects of psilocybin were consistent with distortions of space-time and self. Notably, psilocybin led to a persistent decrease in connectivity between the anterior hippocampus and cortex, especially the DMN, lasting weeks but normalizing after six months, potentially explaining its pro-plasticity and anti-depressant effects.
Abstract
A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials In animal models, psilocybin induces neuroplasticity in cortex and hippocampus. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.