Sitti, G.; Pitti, L.; Candia-Rivera, D.

Growing evidence indicates that brain continuously interacts with other physiological systems through neural and non-neural pathways. The brain-heart and brain-gut axes play a central role in homeostasis, allostasis and behaviour, but also in cognitive aspects including emotion and decision-making. Disruptions in these axes have been linked to a wide range of cardiovascular, neurological, and psychiatric disorders. Despite this evidence, triadic crosstalk between the brain, heart, and gut remains largely unexplored. Brain activity, cardiac autonomic fluctuations, and gastric rhythms all exhibit slow temporal components in resting state, suggesting that brain-heart-gut electrophysiological interactions may occur over timescales from the infra-slow (0.01-0.1 Hz) physiological range. Using non-invasive electrophysiological recordings from 28 healthy participants at rest, we extracted time-varying power dynamics describing the activity of the three organs: brain alpha power, cardiac sympathetic and parasympathetic indices, and the power of the gastric rhythm. Statistical associations among these organs were quantified using the maximal information coefficient across the extended temporal delay range. Physiological interactions were confirmed using surrogate-based testing, which allowed us to construct the network topology of interactions between the three organs. Our findings show that triadic brain-heart-gut interactions form a multi-directional network at infra-slow timescales, shaping resting state activity. This study offers one of the first insights into the physiology of brain-heart-gut interplay, providing a methodological baseline for the development of more comprehensive biomarkers based on network dynamics capable of linking pathological conditions to dysregulation across multiple organ systems.