Infra-slow brain-heart-gut electrophysiological interactions reveal a co-ordinated multisystem physiological network...

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 homoeostasis, 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 time scales from the infra-slow (0.01-0.1 Hz) physiological range. Using open-access electrophysiological recordings from 28 healthy subjects 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 multidirectional network primarily at infra-slow time scales during resting state. 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. KEY POINTS: First in-human, non-invasive investigation of parallel brain-heart-gut electrophysiological interactions in awake, healthy subjects. We analysed simultaneous electroencephalographic (EEG), electrocardiographic (ECG) and electrogastrographic (EGG) recordings and quantified strength and temporal scale of the derived time series associations to construct a large-scale network of interactions. We found that brain-heart-gut interactions extend into the infra-slow range (0.01-0.1 Hz), indicating that spontaneous fluctuations in the electrophysiological activity of one organ at rest are typically followed by corresponding changes in the other two. We consistently found a robust brain-heart-gut network topology across subjects, with multidirectional interactions and bodily dynamics converging towards midline central-posterior EEG regions. These findings provide one of the first endeavours in characterizing the physiology of brain-heart-gut interactions and a methodology with strong biomarker development potential.