DMT ENHANCES VISUAL–MIRROR NEURON–MENTALIZING NETWORK CONNECTIVITY ACROSS ORAL, NASAL AND INTRAVENOUS ADMINISTRATION ROUTES

Social cognition relies on the integration of visual cues with higher-order cognitive processes to decode others' intentions and mental states. This integration depends on specialized neural networks connecting visual areas with mirror neuron and theory of mind systems. Psychedelics like N,N-dimethyltryptamine (DMT) are known to enhance cross-network functional connectivity, yet their specific effects on social cognition networks remain poorly characterized. In this study, we examined functional connectivity across the third visual pathway (TVP), theory of mind (ToM), and mirror neuron system (MNS) networks using resting-state fMRI from three DMT studies employing different administration routes (intravenous, inhaled, and oral ayahuasca, N=43 healthy participants).
Functional connectivity analyses revealed that DMT consistently enhanced connectivity between TVP, ToM and MNS regions across all administration routes. Specifically, DMT reversed anticorrelation patterns between visual and supplementary motor areas and multiple ToM subregions, with the posterior superior temporal sulcus (pSTS) showing consistent connectivity increases across all routes. These findings suggest that enhanced integration between visual processing in the third visual pathway, mirror neuron systems, and higher-order social cognitive networks represents a key neurobiological mechanism underlying DMT's effects on social brain. This mechanism may inform therapeutic approaches for conditions involving social cognitive impairments.