Serotonergic psychedelics temporarily modify information transfer in humans

Abstract

Background: Psychedelics induce intense modifications in the sensorium, the sense of "self," and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects.

Methods: Here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy, a nonlinear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in 2 experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine.

Results: The analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. Transfer entropy analysis showed that frontal sources decreased their influence over central, parietal, and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior transfer entropy decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced.

Conclusions: These results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain.

Keywords: Oscillatory brain dynamics; functional connectivity; human; psychedelics; transfer entropy.

Figure 1.

Results of the statistical test are shown on schematic representations of electrodes on the scalp. Significant changes are shown by connections between the corresponding electrodes. Warm colors indicate significant increases (first row) and cold colors (second row) indicate significant decreases. Thick, dark-colored connections indicate statistically significant changes with P<.01, whereas thick and thin light-colored connections indicate P<.05 and 0.1, respectively. Connections are shown only if their number in the connections map was above the threshold set by the binomial criterion. Otherwise, no connections are depicted, because they are considered a random result not due to drug administration (see text). The connection maps for the time points that are not shown had a lower number of significant connection changes, and they were considered not relevant based on the binomial criterion. The third and fourth rows show the directionality maps depicting the number of outgoing (in green) or incoming (in gray) connections for each electrode, respectively. In each case, a 7-level color scale indicates intensity. Note that the darkest tone indicates 6 or more connections going in or out of the corresponding electrode, and white indicates no connections.

Figure 2.

Time course of the number of significant changes induced by ayahuasca administration detected by transfer entropy (TE; yellow bars). The red and green traces show the N,N-dimethyltryptamine (DMT) concentration and visual analog scale scores, respectively.

Figure 3.

Scatter plots showing the relationship between mean transfer entropy (TE) values for the time period 1.5 to 2.5 hours and Hallucinogen Rating Scale (HRS) scores.

Figure 4.

Reanalysis of functional connectivity at the 2-hour time point using Granger Causality (GC) with model orders of 4, 8, and 16. Significant changes are shown in the first row by lines connecting the corresponding electrodes and indicate increases. Thick, dark lines indicate statistically significant increases with P<.01, whereas thick and thin light-colored lines indicate increases with P<.05 and 0.1, respectively. The second and third rows show the directionality maps showing the number of outgoing (green) or incoming (gray) connections for each electrode, respectively. In each case, a 7-level color scale indicates intensity. Note that the darkest tone indicates 6 or more connections going in or out of the corresponding electrode, and white indicates no activity.