Neural correlates of the LSD experience revealed by multimodal neuroimaging

Abstract

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Keywords: LSD; brain; consciousness; psychedelic; serotonin.

Fig. 1.

Whole-brain cerebral blood flow maps for the placebo and LSD conditions, plus the difference map (cluster-corrected, P < 0.05; n = 15).

Fig. 2.

Significant between-condition differences (orange = increases) in RSFC between the V1 seed region (purple) and the rest of the brain. Unthresholded maps can be viewed here: neurovault.org/collections/FBVSAVDQ/ (n = 15).

Fig. 3.

Significant between-condition differences in RSFC between the PH seed and the rest of the brain (orange = increases; blue = decreases). Unthresholded maps can be viewed here: neurovault.org/collections/FBVSAVDQ/ (n = 15).

Fig. 4.

(A) Mean percentage differences (+SEM) in CBF (red), integrity (blue), and signal variance (green) in 12 different RSNs under LSD relative to placebo (red asterisks indicate statistical significance, *P < 0.05; **P < 0.01, Bonferroni corrected). (B) Differences in between-RSN RSFC or RSN “segregation” under LSD vs placebo. Each square in the matrix represents the strength of functional connectivity (positive = red, negative = blue) between a pair of different RSNs (parameter estimate values). The matrix on the far right displays the between-condition differences in covariance (t values): red = reduced segregation and blue = increased segregation under LSD. White asterisks represent significant differences (P < 0.05, FDR corrected; n = 15).

Fig. 5.

MEG results. (A) Statistical analysis of planar gradiometer-configured MEG data comparing LSD with placebo in the eyes-closed condition. Blue indicates less power under LSD. Units are t-statistics. Significant sensor clusters are marked such that stars correspond to P < 0.01 and crosses to P < 0.05 (corrected). Source localization results are also displayed. (B) Significant correlations between changes (decreases) in oscillatory power and subjective phenomena. (C) Power spectra for the significant sensor cluster in B (simple hallucinations), with placebo data plotted in blue and LSD in red (n = 14).