Abstract

The complexity of the brain architecture is accompanied by the dynamics of neuronal activity while performing a task or at rest. Even though brain activity constantly fluctuates over time, it exhibits certain repeatability, what allows to identify characteristic global patterns in activity, so called brain states. While dynamic switches between brain states have been well characterised in resting state, it is still unknown how brain activity is modulated by pharmacological drugs. Psychedelics are considered to be one of the most mind‐altering substances affecting brain activity by acting on serotonergic receptors. Their hallucinogenic potential, as well as their ability to induce higher states of consciousness and ego dissolution are well known﴾Johnson et al. 2019﴿. Yet, the specific mechanisms underlying the appearance of these events are poorly understood.

To determine the influence of psychedelics on time‐varying brain activity, we identified and characterised brain states based on functional MRI data acquired from fifteen volunteers in the lysergic acid diethylamide ﴾LSD﴿ and placebo sessions. Brain stateswere identified using unsupervised machine learning method ‐ KMeans clustering algorithm ﴾MacQueen, 1967﴿. Each state was described as a characteristic pattern of activity within seven large‐scale functional brain network systems. Focusing on the temporal aspect of the analysis, brain states’ characteristics were defined using transition and persistence measures, dwell time and fractional occupancy.

Here, we show that LSD‐dependent brain activity showed more frequent transitions to the state associated with reduced activity of the default mode network ﴾DMN﴿ than the activity during the placebo session. In addition, the state itself lasted longer in the LSDcompared to placebo sessions. These results provide evidence supporting the notion of reduced default mode network activity and increased network integration as key mechanisms in inducing psychedelic states. These results reveal that time‐varying brain activity influenced by LSD may play a crucial role in brain‐mind relationship, underlying the occurrence of the phenomenological content. References:[1] Johnson, M. W., Hendricks, P. S., Barrett, F. S., & Griffiths, R. R. ﴾2019﴿. Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & therapeutics, 197, 83‐102.[2] MacQueen, J. ﴾1967, June﴿. Some methods for classification and analysis of multivariate observations. In Proceedings of the fifth Berkeley symposium on mathematical statistics and probability ﴾Vol. 1, No. 14, pp. 281‐297﴿.