Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor
- University Hospital for Psychiatry Zurich, Switzerland
- Yale University School of Medicine, United States
- Yale University, United States
- University of Ljubljana, Slovenia
Figures
Figure 1 with 3 supplements
Effect of drug condition on global brain connectivity and subjective drug effects.
(A) Z-score map for the effect of LSD condition vs. (Ket+LSD)+Pla condition within areas showing a significant main effect of drug (TFCE type I error protected). Red/orange areas indicate regions …
Figure 1—figure supplement 1
Effect of Ket+LSD vs. Pla on global brain connectitiy.
Top panel displays significant (TFCE type I error protected) areas showing increased (red) and decreased (blue) GBC in the Ket+LSD condition compared to Pla, which were trivial. Lower panel shows …
Figure 1—figure supplement 2
Study Design.
The study employed a fully double-blind, randomized, within-subject cross-over design. 25 total participants received either: (1) placebo +placebo (Pla) condition: placebo (179 mg Mannitol and …
Figure 1—figure supplement 3
Quality Control (QC) measures do not correlate with mean global brain connecticity.
We computed the relationship between QC measures and the mean GBC for various conditions across subjects. (A) Signal-to-noise ratio (defined as mean signal over the entire BOLD time series for a …
Figure 2
Effect of drug condition on global brain connectivity without global signal regression.
(A) Z-score map for the effect of LSD condition vs. (Ket+LSD)+Pla condition within areas showing a significant main effect of drug (TFCE type I error protected). Red/orange areas indicate regions …
Figure 3 with 1 supplement
Beta map of the global signal for the LSD>Pla contrast.
(A) The top panel displays significant (TFCE type I error protected) areas showing increased (red) and decreased (blue) covariance with the GS in the LSD condition compared to Pla. The Z map in the …
Figure 3—figure supplement 1
Z-map of change in local voxel-wise variance under LSD vs. Pla.
The effect illustrates a very weak alteration in local variance (min/max Z = -1.54/+2.28). No effects survived whole-brain correction. This result in not consistent with the hypothesis that LSD …
Figure 4 with 3 supplements
Evaluation of influence of global signal regression informed by seed-based thalamus connectivity.
(A) The Z map illustrates the mean thalamus coupling with all grayordinates in the Pla condition. Warm colors indicate positive connections with the thalamus. Cool colors indicate negative …
Figure 4—figure supplement 1
Thalamus seed-based connectivity.
Mean Z-maps for thalamus coupling with all grayordinates in the brain in session 1 of all drug conditions (A-C). Correlation (upper panels) and covariance maps (lower panels) were computed before …
Figure 4—figure supplement 2
Thalamus seed-based connectivity contrast maps.
Contrast Z-maps for thalamus coupling with all grayordinates in the brain in session one comparing drug conditions (A-C). Correlation (upper panels) and covariance maps (lower panels) were computed …
Figure 4—figure supplement 3
Across-subject correlation matrix between top and bottom connections and different analysis methods.
The matrix shows the correlation coefficients (Pearson’s r) between contrasts between drug conditions obtained using thalamic seed connectivity (seed) and GBC with and without GSR and calculated as …
Figure 5 with 1 supplement
Time course of subjective drug effects.
Five Dimension Altered States of Consciousness Questionnaire short version scores assessed at 180, 250, and 300 min after second drug administration for the means across scales, and scale scores for …
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Figure 5—source data 1
Five Dimension Altered States of Consciousness Questionnaire short version
- https://cdn.elifesciences.org/articles/35082/elife-35082-fig5-data1-v2.xlsx
Figure 5—figure supplement 1
Across-subject correlation.
(Pearson’s r) between Five Dimension Altered States of Consciousness Questionnaire short version scores assessed at three time points (T1 = 180 min, T2 = 250 min, and T3 = 300 min) in the LSD …
Figure 6 with 1 supplement
Effect of session on global brain connectivity in the Ketanserin+LSD condition.
(A) Top panel displays significant (TFCE type I error protected) areas showing increased (red) and decreased (blue) GBC in session 1 (75 minutes after second drug administration) compared to session …
Figure 6—figure supplement 1
Effect of session on global brain connectivity.
Animal studies suggest distinct temporal phases of LSD pharmacology, with an early phase mediated by 5-HT2A and a later phase mediated by D2 receptor stimulation (Marona-Lewicka et al., 2005; Marona-…
Figure 7
Effect of drug condition, session, and globals signal regression on global brain connectivity in functional networks (A–G).
Brain maps illustrate lateral, medial, and subcortical view of functional networks. Bar plots show mean connectivity strength (Fz) values for grayordinateswithin functional networks for Pla, LSD, …
Figure 8
Correlation between global crain connectivity and subjective effects.
(A) The brain map illustrates lateral, medial, and subcortical view of the somatomotor network. (B) The scatterplot shows the significant positive correlation between Fz mean connectivity change …
Figure 9 with 1 supplement
Correlation between global brain connectivity and cortical gene expression maps.
(A) The top left panel shows the average GBC Z-score (LSD condition vs. (Ket+LSD)+Pla condition) with and without GSR and mean gene expression value within functional networks. (B) The top right …
Figure 9—figure supplement 1
Schematic illustrating the process of generating cortical gene expression maps from the Allen Human Brain Atlas (AHBA).
Author response image 1
