Dissociable Effects of Psychedelics and NonPharmacological Interventions on Brain Entropy: A Multi-Dataset Analysis

This study investigated brain entropy changes during altered states of consciousness (ASCs) using resting-state fMRI data from ten independent research projects (N=349), comparing classical psychedelics, other pharmacological interventions, and nonpharmacological methods. Two complementary entropy measures were analyzed: Temporal BOLD Complexity (LZc) and Path-Length Distribution Entropy, using both Global Signal Regression (GSR) and Component-based Correction (CompCor) preprocessing methods. Classical psychedelics showed significant increases in Temporal BOLD Complexity (d=0.94-1.37, p<0.001), while non-pharmacological interventions consistently decreased it (d=-0.75, p<0.001). Unexpectedly, Path-Length Entropy decreased with classical psychedelics (d=-0.80, p<0.001), revealing a significant negative correlation between the two entropy measures (β=-0.973, p=0.001 for GSR). Preprocessing method significantly influenced results: GSR produced stronger effects on Temporal BOLD...Show moreThis study investigated brain entropy changes during altered states of consciousness (ASCs) using resting-state fMRI data from ten independent research projects (N=349), comparing classical psychedelics, other pharmacological interventions, and nonpharmacological methods. Two complementary entropy measures were analyzed: Temporal BOLD Complexity (LZc) and Path-Length Distribution Entropy, using both Global Signal Regression (GSR) and Component-based Correction (CompCor) preprocessing methods. Classical psychedelics showed significant increases in Temporal BOLD Complexity (d=0.94-1.37, p<0.001), while non-pharmacological interventions consistently decreased it (d=-0.75, p<0.001). Unexpectedly, Path-Length Entropy decreased with classical psychedelics (d=-0.80, p<0.001), revealing a significant negative correlation between the two entropy measures (β=-0.973, p=0.001 for GSR). Preprocessing method significantly influenced results: GSR produced stronger effects on Temporal BOLD Complexity compared to CompCor (Mean difference=0.261±0.736 vs. -0.052±0.863) and systematically reduced whole-brain connectivity (β=-1038.90, p<0.001). These findings challenge the Entropic Brain Hypothesis by demonstrating that different forms of brain entropy respond distinctly to consciousness-altering interventions. The inverse relationship between temporal and spatial entropy measures suggests they capture different aspects of neural dynamics rather than a unitary construct of "brain entropy." Furthermore, the consistent decrease in entropy during non-pharmacological interventions indicates that heightened consciousness states do not universally correspond to increased neural entropy. These results call for a more fine-grained theoretical framework linking neural complexity to consciousness, considering multiple forms of brain entropy and their mechanistic relationships to phenomenological experience.Show less

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Dissociable Effects of Psychedelics and NonPharmacological Interventions on Brain Entropy: A Multi-Dataset Analysis