The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network

This open-label within-subjects study (n=10) investigated the effects of ayahuasca (154 mL/70kg; containing 123.2mg/70kg DMT and 32.34mg/70kg harmine) on brain activity during resting state using fMRI. Results indicated that ayahuasca decreases activation and functional connectivity throughout most parts of the Default Mode Network (DMN), similar to the activation profile of altered states related to psilocybin, meditation, and sleep.

Abstract

“Introduction: The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task.

Methods: Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN).

Results: Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality.

Discussion: Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.“

Authors: Fernanda Palhano-Fontes, Katia C. Andrade, Luis F. Tofoli, Antonio C. Santos, Jose Alexandre S. Crippa, Jaime E. C. Hallak, Sidarta Ribeiro & Draulio B. de Araujo

Summary

Research Article

Ayahuasca causes a significant decrease in activity and connectivity of the Default Mode Network (DMN) and the task-positive network (TPN) in ten experienced subjects, which is consistent with the notion that the altered state of consciousness induced by Ayahuasca is linked to the modulation of the activity and the connectivity of the DMN.

Introduction

Psychedelics such as LSD, psilocybin, mescaline and DMT induce complex mystical experiences, modulating the sensory, perceptual, cognitive and autonomic systems, as well as emotional processes.

We used functional Magnetic Resonance Imaging to investigate the effects of Ayahuasca, a powerful psychedelic traditionally used by Amazonian Amerindians and spread to Western countries. Ayahuasca modulates frontal, temporal and occipital brain networks associated with intention, memory and vision.

Ayahuasca induces sedation, gastrointestinal distress, dissociation, sense of well-being, insights, feelings of apprehension, and increased introspection. The Default Mode Network (DMN) is associated with mind-wandering, a private, continuous and often unnoticed phenomenon.

The activity of the DMN is sensitive to a number of tasks, states of consciousness and psychiatric conditions, including schizophrenia, depression, Parkinson’s disease, social phobia, and psilocybin intake.

Resting state fMRI has allowed researchers to study how the default mode network interacts with each other, and has suggested that the default mode network exhibits an intrinsic competitive behavior with the task-positive network.

Ayahuasca intake increases introspection, but also reduces DMN activity. Using rs-fMRI, we investigated how Ayahuasca experience interferes with functional connectivity between different DMN regions, and how Ayahuasca impacts TPN-DMN orthogonality.

Subjects

Ten healthy volunteers with at least 5 years of regular Ayahuasca use were recruited from Santo Daime church to participate in this study. They all presented limited motion artifact in the DMN, which was not significantly different from the control group.

Experimental Design

Subjects underwent two fMRI sessions, before and 40 min after Ayahuasca intake. They performed two protocols, a verbal fluency task and a conventional rs-fMRI acquisition, and were evaluated using the Brief Psychiatric Rating Scale and the Young Mania Rating Scale.

Image Acquisition

For the verbal fluency task, 66 volumes were acquired with 16 slices per volume, and for the resting state protocol, 150 volumes were acquired with the same parameters except for the TR, which was set to 1700 ms and a matrix of 64 x 64.

fMRI Pre-processing

Preprocessing included slice-timing correction, head motion correction, and spatial smoothing. EPI were registered to the anatomical images using a rigid body transformation.

DMN ROI Definition

Statistical analysis was conducted in SPM5 using the General Linear Model (GLM) and a canonical hemodynamic response function (HRF). A contrast was applied between the groups of subjects using t-test, and then entered into a second level random effect analysis.

The DMN mask was created by intersecting nine brain areas with statistically significant voxels: ACC, PC, mPFC, LMFG, LMTG, RMTG, and LIPL.

Effects of Ayahuasca over the DMN

Experimental group maps were compared between conditions, and paired comparisons of the two instants were performed. Mean individual -values were extracted for each ROI, both before and after Ayahuasca intake, and a correlation was computed between these two variables.

fMRI Functional Connectivity (fc-fMRI)

Images from the resting state paradigm were used to evaluate seed-based functional connectivity (fc-fMRI). The results were expressed in terms of voxel-wise Pearson coefficients, z-Fisher transformed, and statistical differences were assessed considering the z-maps of each seed separately.

DMN x TPN Orthogonality

Herein we used a classical approach to define the TPN, where three seed regions were selected, one centered at the IPS, one at the FEF and one at the MT. We then calculated Pearson’s correlation coefficients between the TPN and the DMN for both conditions (before and after Ayahuasca intake).

Results

The signal of the DMN changed significantly when comparing rest with task periods, both before and after Ayahuasca intake. This signal decrease was observed in the ACC, PCC, MPFC, PC and bilateral IPL.

Ayahuasca ingestion resulted in significant negative correlations between YMRS scores 80 minutes after Ayahuasca ingestion only at ACC, and no significant difference in DMN-TPN orthogonality was observed when comparing before and after Ayahuasca ingestion.

We re-analyzed this dataset without global signal regression, and found that the DMN-TPN connectivity pattern presented a positive correlation, both before and after Ayahuasca intake.

Discussion

The data demonstrate that the activity of core DMN structures decreases after Ayahuasca intake. The decrease may be explained by the level of concentration and mind effort demanded during the Ayahuasca experience.

The second hypothesis stems from the consistent evidence that DMN activity is reduced during meditative states, and that psychedelics and meditation share many psychological features. DMN activity is also reduced during periods of mind-wandering, but increases with the awareness that the mind has wandered.

Although there are similarities, each experience has its own particularities, and fc-fMRI results reflect this. For instance, a decrease in connectivity of the PCC with the rest of the DMN is observed during transition from wakefulness to the N1 stage of sleep.

Although Ayahuasca and psilocybin have much in common, their experiences are very different. Ayahuasca usually involves much stronger somatic and sedation effects, while psilocybin acts almost exclusively on the serotonergic system.

The DMN signal reduction in the ACC was associated with individual YMRS scores, and was mainly influenced by mood, affect, speech, and content of thoughts.

When the global signal was regressed out, the DMN was anti-correlated to the TPN, as expected. However, the anti-correlation pattern did not change significantly after Ayahuasca intake, suggesting that the intrinsic DMN-TPN anti-correlation may result from artifacts introduced by regression against global signal.

The present study concludes that the acute effects of Ayahuasca are associated with diminished DMN activation and decreased functional connectivity of the PCC/Precuneus.

Limitations

This study has some caveats and limitations, such as limiting the study to experienced users and not including a control group treated with a placebo. However, previous studies have shown that the effects observed are not explained by a typical placebo effect. Fixed effects analysis was used, the acquisition of fMRI signal was not controlled for order effects, and the two sessions were both in the same day, only two hours apart.