Decreased Directed Functional Connectivity in the Psychedelic State

Abstract

Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the largescale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.

RETRACTED ARTICLE: A mechanistic model of the neural entropy increase elicited by psychedelic drugs

“…These simplifications do not prevent the model from reproducing statistical features of brain signals under the placebo and 5HT2A-R conditions, but could result in an inability to reproduce finer aspects of the dynamics of the whole-brain activity in these conditions. Extending the model to reproduce other dynamical signatures of psychedelics (like alpha suppression 8 or reduced directed functional connectivity 41 ) constitutes a natural extension of this work, with the recent example of Kringelbach et al 42 , where an extension of the DMF can reproduce dynamical features of the brain in placebo and in the psychedelic state.…”

Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

“…However, the decrease of within-network connectivity is accompanied by increases in between network connectivity (i.e., deviation of functional connections from network pathways). This pattern of reduced-within and increased-between connectivity-coined as disintegration and desegregation (R. L. Carhart- -is documented across resting state networks under psychedelics (Varley et al, 2019) (Barnett et al, 2019) and alters the functional integration of brain regions (Petri et al, 2014), see Figure 6. FPCN desegregated connectivity is highlighted by several studies (Lord et al, 2018(Lord et al, , 2019Tagliazucchi et al, 2016) and speaks to the importance of connectivity in FPCN in psychedelic experiences.…”

“…Decreases of connectivity within FPCN are detected under both LSD and psilocybin (Barnett, Muthukumaraswamy, Carhart-Harris, & Seth, 2019;Lord et al, 2018Lord et al, , 2019. However, the decrease of within-network connectivity is accompanied by increases in between network connectivity (i.e., deviation of functional connections from network pathways).…”

“…Both observations might also relate to the phenomenological richness of psychedelic experience and therapeutic outcomes thought to depend on increased access to (precise) bottom-up prediction errors necessary for the revision of priors. The coinciding disintegration of the FPCN (Barnett et al, 2019;Lord et al, 2018Lord et al, , 2019 and relaxation of priors (R. L. Carhart- Harris & Friston, 2019) would also be mechanistic in this process, however may contribute to cognitive aspects of ego dissolution. Untangling the mechanistic relationship between FPCN changes under psychedelics and their role in ego dissolution needs more research; however, existing evidence points to the potential importance of its role in cognitive aspects of the psychedelic experience.…”

A mechanistic model of the neural entropy increase elicited by psychedelic drugs

“…These simplifications do not prevent the model from reproducing statistical features of brain signals under the placebo and LSD conditions, but could result in an inability to reproduce finer aspects of the dynamics of the whole-brain activity in these conditions. Extending the model to reproduce other dynamical signatures of psychedelics (like alpha suppression 8 or reduced directed functional connectivity 36 ) constitutes a natural extension of this work.…”