Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis


in BF Scientific Publications,BF Scientific Publications - Intro,Psilocybin,Research

Robin L. Carhart-Harris , Amanda Feilding, David J. Nutt et al. 2012

A new analysis of the original psilocybin fMRI data has recently been published in a new paper in Schizophrenia Bulletin. The study analysed the effects of psilocybin on functional connectivity within the default mode network (DMN) and found alterations similar as demonstrated in early psychosis.

This similarity is based upon the interplay between two networks. The DMN is a set of highly structurally connected brain regions that are functionally correlated in the resting brain. The network has been linked to internally oriented and self-related cognition, like e.g. the recollection of autobiographical memories, theory of mind, self-reflection and mind-wandering. The task positive network (TPN) is a generic set of brain regions that is in contrast to the DMN activated in the course of a particular externally oriented cognitive task.

The DMN and TPN usually have an antagonistic/orthogonal relationship – when the DMN is active, TPN is not and vice versa. This results in  a competitive relationship between modes of cognition that is illustrated in the familiar fact that during normal waking consciousness explorative inner thought and focused attention do not occur simultaneously.

Interestingly, this study demonstrated that after psilocybin the DMN and TPN become less anti-correlated, and more functionally coupled.

Other states are known to be associated with increased functional connectivity of DMN and TPN:

  • Early psychosis: Linked to development of delusions/hallucinations via inability to tell internal cognition from external cognition. This explains certain similarities in phenomenology between the psychedelic state and psychotic state, and also supports utility of psilocybin as model for early psychosis.
  • Sedation: Also find decreased orthogonality of DMN and TPN when transferring from awake to asleep.

Sedation and psychedelic states are however very different subjective states, therefore the similar physiological basis is interesting. The key neurophysiological difference is that in sedation thalamo-cortical functional connectivity also decreases (so the whole brain is effectively out of phase). Under psilocybin however, functional connectivity between DMN and thalamus is preserved and is even increased between thalamus and TPN. This same pattern is seen in meditation -another state where inner thought and external focus become blurred.

The authors hypothesise that thalamo-cortical functional connectivity may be related to arousal, whereas DMN-TPN functional connectivity is related to the separateness of internally and externally focused states.

Another interesting theoretical implication of these findings is that they allow us to characterize psychedelic and early psychotic states as states of relative disorganisation yet heightened plasticity (i.e. increased capacity for change).

This may enable us to explain a range of phenomena:

  • Psychedelics promote suggestibility, spiritual and religious revelations, delusional thoughts, and can potentially be applied as treatments for addiction.
  • Psychosis is marked by the rapid adoption of strong delusional beliefs, and powerful hallucinations that are adopted immediately into the individual’s model of reality – this is what is referred to by the classic description of psychosis as a ‘loss of reality-testing’.
The work is also covered by the popular neuroscience blog neuroskeptic here:



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