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An exploratory persistent-homology analysis of resting-state fMRI functional connectivity under Ayahuasca

Tales Ramos Monteiro Dos Santos, Draulio B Araujo, Helcio Felippe, José Garcia Vivas Miranda, Fernanda Palhano-Fontes, Raphael Silva Do Rosário, Heloisa Onias, Aline Viol, Gandhimohan M. Viswanathan, Fernando A. N. Santos

Chaos Solitons & Fractals May 30, 2026 DOI: 10.1016/j.chaos.2026.118554 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Placebo-controlled Peer reviewed
Sample size 9
Population Adults before and after ayahuasca ingestion
Intervention Ayahuasca
Topics Ayahuasca
Keywords Functional connectivity Exploratory analysis Resting State FMRI Functional analysis Spectral analysis Cognitive psychology
Key findings Persistent entropy of H2 features showed a nominal pre/post decrease that did not survive correction for multiple comparisons and was not reproduced with signed correlations.

Abstract

Psychedelic states offer a useful setting for studying changes in large-scale brain organization. Here, we applied Topological Data Analysis (TDA) to resting-state fMRI functional connectivity from nine participants scanned before and after Ayahuasca ingestion. Vietoris–Rips filtrations were constructed from correlation-derived dissimilarity matrices, and persistent entropy was used to quantify the distribution of persistence lifetimes across homology dimensions S 0 – S 3 . In the primary absolute-correlation analysis, persistent entropy of H 2 features showed a nominal pre/post decrease ( W = 4 . 0 , p = 0 . 027 , rank-biserial correlation = 0 . 822 ). This effect did not survive correction across the four tested homology dimensions ( q FDR = 0 . 109 ) and was not reproduced when signed correlations were preserved using d ( i , j ) = 1 − r ( i , j ) . Exploratory signal-complexity analyses using Lempel–Ziv complexity and sample entropy showed descriptive but statistically non-significant increases in temporal complexity. These results should therefore be interpreted as preliminary and hypothesis-generating, particularly given the small sample size, lack of placebo control, availability of only GSR-preprocessed connectivity data, and sensitivity to the distance definition. The study suggests that persistent homology may provide a useful framework for studying psychedelic-associated changes in the higher-dimensional topology induced by functional connectivity, but replication in larger placebo-controlled datasets is required.

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