Seeing with the eyes shut: neural basis of enhanced imagery following Ayahuasca ingestion

Abstract

The hallucinogenic brew Ayahuasca, a rich source of serotonergic agonists and reuptake inhibitors, has been used for ages by Amazonian populations during religious ceremonies. Among all perceptual changes induced by Ayahuasca, the most remarkable are vivid "seeings." During such seeings, users report potent imagery. Using functional magnetic resonance imaging during a closed-eyes imagery task, we found that Ayahuasca produces a robust increase in the activation of several occipital, temporal, and frontal areas. In the primary visual area, the effect was comparable in magnitude to the activation levels of natural image with the eyes open. Importantly, this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales. The activity of cortical areas BA30 and BA37, known to be involved with episodic memory and the processing of contextual associations, was also potentiated by Ayahuasca intake during imagery. Finally, we detected a positive modulation by Ayahuasca of BA 10, a frontal area involved with intentional prospective imagination, working memory and the processing of information from internal sources. Therefore, our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision, memory, and intention. By boosting the intensity of recalled images to the same level of natural image, Ayahuasca lends a status of reality to inner experiences. It is therefore understandable why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature.

Figure 1

Experimental design of one fMRI scanning session. Subjects were submitted to three conditions (natural image, imagery with closed eyes, and scrambled image) in a block design (21 sec per condition; 3 conditions per block, 7 blocks per session). Each subject performed two fMRI sessions. In the first session, subjects were scanned before Ayahuasca intake. Immediately after the first scan, subjects drank Ayahuasca. The second fMRI session began 40 min after intake.

Figure 2

Individual scores reached on the psychiatric scales BPRS and YMRS at 0, 40, 80, and 200 min for all subjects. Ayahuasca intake took place at T = 0 min. The psychological effects with respect to baseline (T = 0 min) reached significance at 40 min (P = 0.05 for BPRS, P < 0.036 for YMRS, Wilcoxon corrected for multiple comparisons), immediately before scanning, and peaked at 80 min (P = 0.036 for BPRS and P = 0.036 for YMRS, Wilcoxon corrected for multiple comparisons). Line connects mean values at different time points. Note that the variability is very low at 0 and 200 min, when most subjects presented identical scores.

Figure 3

Main effect of the imagery task (q(FDR) < 0.05). The contrast corresponds to (imagery after > imagery before)‐(natural image after > natural image before). Retinotopic mapping appears in light blue, blue and purple corresponding to areas V1, V2, and V3, respectively.

Figure 4

Average time courses of BOLD responses before and after Ayahuasca intake (blue for imagery before intake, red for imagery after intake, white for natural image before intake, and green for natural image after intake). Each time point corresponds to an fMRI TR = 3 sec. Note the marked increase in BOLD signal during imagery following Ayahuasca intake. Shaded gray area represents baseline periods (scrambled image condition). Blue line–imagery before intake; red line–imagery after intake; light gray line–natural image before intake; green line–natural image after intake.

Figure 5

Scatter plot and trend lines of the beta values against individual BPRS scores at 40 min, with respect to baseline (T = 0 min). Statistically significance was found only for BA17 (P = 0.037, corrected for multiple comparisons).

Figure 6

BOLD signal correlations between brain areas before and after Ayahuasca intake. The labels correspond to the same Brodmann areas defined in Figure 3. Arrow direction indicates that the source precedes the target by at least 5 TR's (15 sec); undirected links indicate that there is no such temporal delay between the areas. The top row shows the full connectivity for the four conditions. The second, third, and fourth rows from the top correspond to links involving only BA17, BA10, and BA19, respectively.