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We conducted a pharmacoimaging study to examine ayahuasca\u2019s effects on a key theory of mind region, at the core of the third visual pathway (TVP)\u2014the posterior superior temporal sulcus (pSTS), which is involved in facial emotion recognition and social perception. Twelve healthy participants (mean age: 40\u2009\u00b1\u20096.6\u2009years; four females) completed a crossover design with three conditions: 0.5\u2009mg\/kg N, N-dimethyltryptamine (DMT), 0.8\u2009mg\/kg DMT, and placebo, with 1\u20132\u2009months washout intervals. Resting-state functional magnetic resonance imaging (fMRI) was used to assess pSTS functional and effective connectivity. The highest dose significantly increased right pSTS connectivity and directed modulation from visual (primary and extrastriate cortices) and mirror neuron regions (supplementary motor cortex; SMC). Subjectively, this enhanced social cognitive states, with a strong positive correlation between pSTS\u2013SMC connectivity and perspective-taking experiences. Additionally, ayahuasca produced positive psychological effects, including improved perceived social relationships, at 1-week follow-up despite minimal acute effects. Our findings reveal a novel mechanism of action of psychedelics at early stages of social information processing, with enhanced integration of the TVP and mirror neuron systems. The pSTS emerged as a critical hub supported by top-down and bottom-up evidence, providing a basis for understanding ayahuasca\u2019s prosocial therapeutic effects.<\/jats:p>","DOI":"10.1093\/scan\/nsag004","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T10:15:48Z","timestamp":1769422548000},"source":"Crossref","is-referenced-by-count":0,"title":["Ayahuasca enhances functional connectivity in the third visual pathway and mirror neuron networks: a crossover, multiple-dose functional MRI study"],"prefix":"10.1093","volume":"21","author":[{"given":"Carla","family":"Soares","sequence":"first","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra , Coimbra 3000-548,","place":["Portugal"]},{"name":"University of Coimbra Institute of Nuclear Sciences Applied to Health (ICNAS), , Coimbra 3000-548,","place":["Portugal"]},{"name":"Faculty of Medicine (FMUC), University of Coimbra , Coimbra 3000-548,","place":["Portugal"]}]},{"given":"Gisela","family":"Lima","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra , Coimbra 3000-548,","place":["Portugal"]},{"name":"University of Coimbra Institute of Nuclear Sciences Applied to Health (ICNAS), , Coimbra 3000-548,","place":["Portugal"]},{"name":"Faculty of Medicine (FMUC), University of Coimbra , Coimbra 3000-548,","place":["Portugal"]}]},{"given":"Marta","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra , Coimbra 3000-548,","place":["Portugal"]},{"name":"University of Coimbra Institute of Nuclear Sciences Applied to Health (ICNAS), , Coimbra 3000-548,","place":["Portugal"]}]},{"given":"Rebeca","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Lus\u00f3fona University Research Center for Biosciences & Health Technologies (CBIOS), , Lisboa 1749-024,","place":["Portugal"]},{"name":"iMed.ULisboa, Faculty of Pharmacy, University of Lisbon , Lisboa 1649-003,","place":["Portugal"]}]},{"given":"Patr\u00edcia","family":"Rijo","sequence":"additional","affiliation":[{"name":"Lus\u00f3fona University Research Center for Biosciences & Health Technologies (CBIOS), , Lisboa 1749-024,","place":["Portugal"]},{"name":"iMed.ULisboa, Faculty of Pharmacy, University of Lisbon , Lisboa 1649-003,","place":["Portugal"]}]},{"given":"C\u00e9lia","family":"Cabral","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, University of Coimbra , Coimbra\u00a03000-548,","place":["Portugal"]},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra , Coimbra 3000-548,","place":["Portugal"]},{"name":"Department of Life Sciences, Centre for Functional Ecology, 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