Figure 1.

Psilocybin acts by altering the activity and connectivity across DMN-associated brain regions: (a) psilocybin increases and diversifies functional connectivity (=positively correlated neural activity) patterns throughout the brain. Nodes represent neuronal clusters, shades of grey delineate communities obtained by modularity, node size proportionate to degree of connectedness and edges are direct links between functionally connected areas. Figure was adapted with permission from Petri et al. (2014). (b) According to the ‘REBUS and the anarchic brain’ theory Carhart-Harris and Friston (2019), the top–down inhibitory control by which the PFC and PCC maintain prior beliefs (top) is decreased by psychedelics, enabling incoming inputs from HC, amygdala and sensory cortices to have a larger effect on the subsequent activation patterns (bottom). Thus, under normal circumstances, memory-, emotion- and sensation-related inputs have a more limited impact on the contents of consciousness. In contrast, psychedelics enhance bottom-up information flow by decreasing top–down inhibition, which leads to enriched experience, potentially enabling the emergence of novel insights with therapeutic benefits.

PFC: prefrontal cortex; PCC: posterior cingulate cortex; HC: hippocampus; A: amygdala; V1/2: primary and secondary visual areas.

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