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bioRxiv · 10.64898/2026.04.15.718683

Infra-slow brain-heart-gut electrophysiological interactions reveal a coordinated multisystem physiological network in humans

Sitti, G.·Pitti, L.·Candia-Rivera, D.
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Abstract

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. Abstract figure legend O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/718683v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@6600d1org.highwire.dtl.DTLVardef@bfd404org.highwire.dtl.DTLVardef@1f85612org.highwire.dtl.DTLVardef@dac616_HPS_FORMAT_FIGEXP M_FIG C_FIG Simultaneous resting-state electroencephalographic (EEG), electrocardiographic (ECG), and electrogastrographic (EGG) recordings were processed to extract time-resolved physiological markers for each organ: EEG alpha-band power for the brain, cardiac sympathetic and parasympathetic indices (CSI, CPI) for the heart, and EGG power for the gastrointestinal tract. Coupling between time series was then quantified, and statistical significance was assessed using a surrogate-based method. Significant couplings were subsequently integrated to construct a large-scale network representation, summarizing the strength, temporal delays, and directionality of the predominant electrophysiological interactions among the three organs. Key points summaryO_LIFirst in-human, non-invasive investigation of parallel brain-heart-gut electrophysiological interactions in awake, healthy individuals. C_LIO_LIWe 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. C_LIO_LIWe found that brain-heart-gut interactions extend into the infra-slow (0.01 - 0.1 Hz) range, indicating that spontaneous fluctuations in the electrophysiological activity of one organ at rest are typically followed by corresponding changes in the other two. C_LIO_LIWe found a consistent brain-heart-gut network topology across participants, with multidirectional interactions and bodily dynamics converging toward midline central-posterior brain regions. C_LIO_LIThese findings provide one of the first endeavours in understanding the physiology of brain-heart-gut interactions, and a methodology with strong biomarker development potential. C_LI

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Sitti, G., Pitti, L., Candia-Rivera, D.. 2026-04-17. Infra-slow brain-heart-gut electrophysiological interactions reveal a coordinated multisystem physiological network in humans. https://doi.org/10.64898/2026.04.15.718683

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