Fig. 4. The control energy needed to transition between brain states is reduced by LSD, psilocybin and the spatial distribution of 5-HT2a receptor maps.

a LSD comparisons (n = 15) (b) Psilocybin comparisons (n = 9). (a, b, left) Comparison of the empirically observed transition probabilities between states, derived from the brain state time series, e.g. Figure 3a. (a, b, center left) Comparison of the transition energies calculated from placebo brain states versus those calculated from LSD or psilocybin brain states using uniformly-weighted whole-brain inputs. LSD and psilocybin brain states both had significantly lower energy required for every transition. (a, b, center right) Weighting the control vector by the 5-HT2a receptor density map³⁵ results in significantly lower energies for the placebo centroids (brain states) compared to uniformly-weighted control vector inputs. (a, b, right) To probe the spatial specificity of the previous result, we repeated the calculations using 10,000 spin-permuted receptor maps⁴⁸. We found that the control vector constructed using the true 5-HT2a receptor map resulted in significantly lower energy required for nearly every transition compared to the control vector constructed using the shuffled receptor maps. (See SI for choice of the time-span T over which the transition energy was computed). Comparisons for i-iii were made with two-sided t-tests. P-values for iv were calculated as the fraction of times that true distribution resulted in higher energies than the spun distribution. P-values were corrected for multiple comparisons (Benjamini-Hochberg) where indicated. *uncorrected p < 0.05, **corrected p < 0.05.