Article Figures & Data
Figures
- Figure 1.
Summary of the neural mass model used in the dynamic causal modeling.
- Figure 2.
Ratings of psychometric scale items performed within 15 min of participants exiting the scanner after both sessions. Items were completed using a visual analog scale format, with a bottom anchor of “no, not more than usually” and a top anchor of “yes, much more than usually” for every item, with the exception of “I felt entirely normal,” which had bottom and top anchors of “No, I experienced a different state altogether” and “Yes, I felt just as I normally do,” respectively. Shown are the mean ratings for 15 participants plus the positive SEMs. All items marked with an asterisk were scored significantly higher after psilocybin than placebo infusion at a Bonferroni-corrected significance level of p < 0.0022 (0.5/23 items).
- Figure 3.
Statistical parametric maps showing the locations of significant (p < 0.05, corrected) changes in source oscillatory power. Contrasts of spectral power represent the difference of psilocybin after and before infusion versus placebo after and before infusion. All significant changes are decreases in spectral power after psilocybin infusion in the six frequency bands that span from 1 to 100 Hz. L, Left; R, right.
- Figure 4.
The estimated spatial distribution of seven resting-state networks that were significantly modulated (p < 0.01) by psilocybin. Network structures are superimposed onto the MNI template brain. These independent components were thresholded at 0.2, and the frequency band used to derive each map is indicated by the relevant Greek letter. The right-hand graphs show the SD of the temporal expression of each independent component for both the placebo and psilocybin conditions. This can be interpreted as a measure of activity in the relevant frequency band for the relevant network. The p value reflects the interaction term in a 2 × 2 repeated-measures ANOVA. Pre, Before; Post, after.
- Figure 5.
a, Power spectra for reconstructed source data from the PCC. Data are presented for both psilocybin (Psilo) and placebo (Pla) sessions both before (Pre) and after infusion (Post). The black bars represent areas where 2 × 2 repeated-measures ANOVA revealed an interaction effect in the frequency spectra (p < 0.05, corrected). b, Schematic representation of the neural mass model (the canonical cortical microcircuit) used to predict spectral activity. The model consists of four cell types with 10 connectivity parameters (γ1…10). Four parameters (β1, 2, 3, 4) encoding gain were allowed to vary between presessions and postsessions. These four parameters allow the gain of the four cell types to differ between Pre and Post. Data fitted were the source-modeled spectral response of the PCC. c, The parameter estimates for the four cell types for both psilocybin and placebo. The only parameter that was significantly altered (placebo versus psilocybin) was the β4 parameter (t = 3.23, p = 0.0065), using a paired t test over subjects. Note: the Bonferonni-adjusted significance level of p = 0.0125 (0.05/4) for these tests. The direction of effect indicated that the obtained spectral responses were best modeled by increased excitability of the deep pyramidal cell population. All individual data and model fits can be found in Figure 6. The results for all β parameters were as follows: β1 (t = −1.86, p = 0.085); β2 (t = −2.31, p = 0.03); β3 (t = −1.11, p = 0.028); and β4 (t = −3.23, p = 0.0065). Hence, only β4 survived multiple-comparison correction.
- Figure 6.
Single-participant [participant 1 (P1) to P14] DCM model fits for source-level power spectra for prerecordings and postrecordings following placebo and psilocybin infusion for reconstructed PCC activity. Model-estimated spectra for Pre are in red and Post are in blue, and are overlaid on the data in black. DCM models were fitted from the range 1–100 Hz but are plotted here only up to 50 Hz for better visualization of alpha peaks.
- Figure 7.
a, Grand-averaged source activity for movement-related gamma (60–90 Hz) activity (p < 0.05, corrected) following administration of either placebo or psilocybin. The grand-averaged peak source location for each was located in Brodmann area 4. b, Grand-averaged time–frequency spectrograms showing source-level oscillatory amplitude changes following index finger movement (movement onset at time = 0). Spectrograms are displayed as the percentage change from the prestimulus baseline and were computed for frequencies up to 150 Hz, but are truncated here to 100 Hz for visualization purposes. c, Envelopes of oscillatory amplitude for the gamma (60–90 Hz) and beta (15–30 Hz) bands, respectively. No significant differences were seen between placebo and psilocybin for these envelopes.
- Figure 8.
a, Grand-averaged source activity for visual gamma (35–80 Hz) activity (p < 0.05, corrected) following administration of either placebo or psilocybin. For each, the grand-averaged peak source location for each was located in pericalcarine cortex. b, Grand-averaged time–frequency spectrograms showing source-level oscillatory amplitude changes following visual stimulation with a grating patch (stimulus onset at time = 0) following administration of either placebo or psilocybin. Spectrograms are displayed as the percentage change from the prestimulus baseline and were computed for frequencies up to 150 Hz, but are truncated here to 100 Hz for visualization purposes. c, Envelopes of oscillatory amplitude for the gamma (35–80 Hz) and alpha (8–13 Hz) bands, respectively. Although there was a tendency for slightly reduced alpha desynchronization with psilocybin, this was not statistically significant.
Tables
- Table 1.
DCM parameter priors including the observation model, neuronal model, and experimental effects
Parameters Prior Interpretation Mean (π) Variance (σ) Observation model αu 0 1/16 Exogenous white input αs 0 1/16 Channel white noise βu 0 1/16 Exogenous pink input βs 0 1/16 Channel pink noise ϴ 1 1 Lead-field gain [Deep, super, stellate] [0.2, 0.8, 0.2] [1/16] [Subpopulation contributions] Neuronal sources 1/κ1 2 ms 1/16 Time constant (s.s.) 1/κ2 2 ms 1/16 Time constant (s.p.) 1/κ3 16 ms 1/16 Time constant (i.i.) 1/κ4 28 ms 1/16 Time constant (d.p.) γ1 4 1/16 Intrinsic connection (s.s. to >s.s.) γ2 4 1/16 Intrinsic connection (s.p. to >s.s.) γ3 4 1/16 Intrinsic connection (i.i. to >s.s.) γ4 4 1/16 Intrinsic connection (i.i. to >i.i.) γ5 4 1/16 Intrinsic connection (s.s. to >i.i.) γ6 2 1/16 Intrinsic connection (d.p. to >i.i.) γ7 4 1/16 Intrinsic connection (s.p. to >s.p.) γ8 4 1/16 Intrinsic connection (s.s. to >s.p.) γ9 2 1/16 Intrinsic connection (i.i. to >d.p.) γ10 1 1/16 Intrinsic connection (d.p. to >d.p.) D 1 ms 1/16 Laminar delay Experimental design β1 0 1/8 Modulation of γ1 β2 0 1/8 Modulation of γ7 β3 0 1/8 Modulation of γ4 β4 0 1/8 Modulation of γ10 s.s., Spiny stellate; s.p., superficial pyramidal; i.i., inhibitory interneuron; d.p., deep pyramidal.
- Table 2.
Local maxima of source power changes (Talairach coordinates) corresponding to the images in Figure 1
Talairach coordinates t x y z Delta Precuneus (R) 25 −63 31 −8.14 Posterior cingulate gyrus (L) −23 −45 37 −7.55 Insula (L) −55 −33 19 −6.88 Precentral gyrus (L) −39 −19 35 −6.38 Postcentral gyrus (R) 55 −11 53 −5.08 Anterior cingulate gyrus (L) −19 25 33 −4.74 Postcentral gyrus (R) 51 −17 25 −4.60 Superior frontal gyrus (L) −15 11 53 −4.50 Theta Superior parietal lobule (R) 29 −57 61 −6.24 Postcentral gyrus (L) −27 −37 51 −5.42 Superior temporal gyrus (L) −49 −55 15 −5.35 Superior parietal lobule (L) −15 −67 65 −5.11 Precuneus (L) −5 −47 53 −4.98 Paracentral lobule (L) −5 −41 77 −4.83 Precentral gyrus (R) 39 −15 69 −4.30 Supramarginal gyrus (R) 53 −47 31 −4.19 Alpha Superior parietal lobule (L) −13 −53 61 −8.95 Precuneus (L) −7 −61 33 −8.94 Supramarginal gyrus (R) 59 −43 29 −8.65 Transverse temporal gyrus (L) −55 −19 11 −8.11 Superior temporal gyrus (R) 63 −27 7 −7.18 Insula (R) 33 −11 9 −7.16 Supramarginal gyrus (L) −51 −51 25 −6.68 Anterior cingulate gyrus (R) 5 35 11 −5.48 Inferior frontal gyrus (L) −55 21 21 −5.33 Middle frontal gyrus (L) −55 5 47 −5.28 Cingulate gyrus (L) −1 3 31 −5.15 Middle frontal gyrus (L) −21 −1 45 −5.07 Medial frontal gyrus (L) −5 −3 51 −5.06 Middle frontal gyrus (R) 29 9 57 −4.70 Beta Precuneus (R) 25 −53 33 −9.15 Insula (L) −43 −19 15 −7.73 Superior temporal gyrus (L) −35 −51 17 −7.71 Medial frontal gyrus (L) −21 27 23 −6.87 Superior frontal gyrus (R) 19 65 5 −6.69 Superior Frontal gyrus (R) 5 59 27 −6.50 Superior parietal lobule (L) −21 −69 63 −6.31 Inferior frontal gyrus (L) −57 13 35 −6.26 Postcentral gyrus (L) −59 −33 53 −5.74 Superior frontal gyrus (R) 17 17 65 −4.83 Low gamma Precentral gyrus (R) 37 −25 71 −5.28 Superior parietal lobule (L) −19 −61 65 −5.17 Precentral gyrus (L) 35 −7 69 −5.04 Middle frontal gyrus (L) −47 33 31 −4.91 Superior frontal gyrus (L) −43 15 55 −4.91 Postcentral gyrus (R) 15 −59 69 −4.72 Middle frontal gyrus (L) −23 15 57 −4.71 Middle frontal gyrus (R) 43 23 49 −4.55 Superior parietal lobule (R) 41 −59 57 −4.29 Precentral gyrus (L) −55 −19 37 −4.28 High gamma Middle frontal gyrus (L) −43 15 57 −3.22 Middle frontal gyrus (R) 31 23 59 −3.18 Superior frontal gyrus (R) 23 −1 71 −2.89 Precentral gyrus (L) −63 −15 41 −2.84 L, Left; R, right.
