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.
Comparable studies
Other observational and cohort studies on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report Patients with a depressive disorder | 2015 | Observational study | |
| The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network Experienced subjects | 2015 | Observational cohort | n = 10 |
| Human Psychopharmacology of Hoasca, A Plant Hallucinogen Used in Ritual Context in Brazil Long-term members of a syncretic church that uses hoasca as a psychoactive sacrament... | 1996 | Observational cohort with matched controls | n = 30 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Personality, Psychopathology, Life Attitudes and Neuropsychological Performance among Ritual Users of Ayahuasca: A Longitudinal Study Regular ayahuasca users and active controls in non-ayahuasca religions | 2012 | Observational cohort | n = 242 |
Citations in the library
Cites 7
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Homological scaffolds of brain functional networks Journal of the Royal Society, Interface October 29, 2014
- Enhanced repertoire of brain dynamical states during the psychedelic experience Human Brain Mapping July 3, 2014
- Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics Journal of Pharmacology and Experimental Therapeutics June 18, 2003
- Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & Therapeutics May 1, 2004
and 2 more in the library