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Variations in interoceptive signals from the baroreceptors (BRs) across the cardiac and respiratory cycle can modulate cortical excitability and so affect awareness. It remains debated at what stages of processing they affect awareness-related event-related potentials (ERPs) in different sensory modalities. We investigated the influence of the cardiac (systole/diastole) and the respiratory (inhalation/exhalation) phase on awareness-related ERPs. Subjects discriminated visual threshold stimuli while their electroencephalogram, electrocardiogram, and respiration were simultaneously recorded. We compared ERPs and their intracranial generators for stimuli classified correctly with and without awareness as a function of the cardiac and respiratory phase. Cyclic variations of interoceptive signals from the BRs modulated both the earliest electrophysiological markers and the trajectory of brain activity when subjects became aware of the stimuli: an early sensory component (P1) was the earliest marker of awareness for low (diastole/inhalation) and a perceptual component (visual awareness negativity) for high (systole/exhalation) BR activity, indicating that BR signals interfere with the sensory processing of the visual input. Likewise, activity spread from the primary visceral cortex (posterior insula) to posterior parietal cortices during high and from associative interoceptive centers (anterior insula) to the prefrontal cortex during low BR activity. Consciousness is thereby resolved in cognitive/associative regions when BR is low and in perceptual centers when it is high. Our results suggest that cyclic fluctuations of BR signaling affect both the earliest markers of awareness and the brain processes underlying conscious awareness.

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MRI-related anxiety in healthy participants is often characterized by a dominant breathing frequency at around 0.32 Hz (19 breaths per minute, bpm) at the beginning but in a few cases also at the end of scanning. Breathing waves at 19 bpm are also observed in patients with anxiety independently of the scanned body part. In patients with medically intractable epilepsy and intracranial electroencephalography (iEEG), spontaneous breathing through the nose varied between 0.24 and 0.37 Hz (~19 bpm). Remarkable is the similarity of the observed breathing rates at around 0.32 Hz during different types of anxiety states (e.g., epilepsy, cancer, claustrophobia) with the preferred breathing frequency of 0.32 Hz (19 bpm), which is predicted by the binary hierarchy model of Klimesch. This elevated breathing frequency most likely reflects an emotional processing state, in which energy demands are minimized due to a harmonic coupling ratio with other brain-body oscillations.

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Narratives can synchronize neural and physiological signals between individuals, but the relationship between these signals, and the underlying mechanism, is unclear. We hypothesized a top-down effect of cognition on arousal and predicted that auditory narratives will drive not only brain signals but also peripheral physiological signals. We find that auditory narratives entrained gaze variation, saccade initiation, pupil size, and heart rate. This is consistent with a top-down effect of cognition on autonomic function. We also hypothesized a bottom-up effect, whereby autonomic physiology affects arousal. Controlled breathing affected pupil size, and heart rate was entrained by controlled saccades. Additionally, fluctuations in heart rate preceded fluctuations of pupil size and brain signals. Gaze variation, pupil size, and heart rate were all associated with anterior-central brain signals. Together, these results suggest bidirectional causal effects between peripheral autonomic function and central brain circuits involved in the control of arousal.

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This Opinion piece discusses several key research questions in health neuroscience, a new interdisciplinary field that investigates how the brain and body interact to affect our health behavior such as health mindsets, decision-making, actions, and health outcomes across the lifespan. To achieve physical, mental, and cognitive health, and promote health behavior change, we propose that the prevention and treatment of diseases should target the root causes-the dysfunction and imbalance of brain-body biomarkers, through evidence-based body-mind interventions such as mindfulness meditation and Tai Chi, rather than dealing with each symptom or disorder in isolation through various treatment approaches.

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Sympathetic innervation plays a crucial role in maintaining energy balance and contributes to metabolic pathophysiology. Recent evidence has begun to uncover the innervation landscape of sympathetic projections and sheds light on their important functions in metabolic activities. Additionally, the immune system has long been studied for its essential roles in metabolic health and diseases. In this review, the aim is to provide an overview of the current research progress on the sympathetic regulation of key metabolic organs, including the pancreas, liver, intestine, and adipose tissues. In particular, efforts are made to highlight the critical roles of the peripheral nervous system and its potential interplay with immune components. Overall, it is hoped to underscore the importance of studying metabolic organs from a comprehensive and interconnected perspective, which will provide valuable insights into the complex mechanisms underlying metabolic regulation and may lead to novel therapeutic strategies for metabolic diseases.

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Initially believed to be specific to humans emerging from life-threatening events, Post-traumatic stress disorder (PTSD) has been found to occur in wild animals and can also be experimentally induced in laboratory rodents. This article aims to highlight and discuss the evolution and relevance of animal models in PTSD research. Studies by LeDoux, Davis, and McGaugh have made significant contributions to our understanding of PTSD. By focusing on fear responses in rodents and aversive Pavlovian conditioning, they suggested that PTSD could result from excessively efficient aversive learning processes, with a significant role played by amygdala. However, numerous studies have shown that this explanation fails to account for the complexity of processes involved in PTSD. Current hypotheses focus on deficits in extinction retention, perception of safety signals, or emotional regulation. This review will specifically address the animal models that closely resemble human PTSD and explore reasons for their limited utilization, as a majority of animal studies continues to employ classical Pavlovian conditioning protocols. Furthermore, this review will present cutting-edge experimental studies that tackle previously challenging questions in animal research. Specifically, we will examine the relationship between respiration and the maintenance of fear states, offering a potential explanation for the efficacy of meditation and breath control techniques in emotion regulation. We will also shed light on recent findings on decoding neural activity related to internal representations in animals, thus enabling now the exploration of rumination, a characteristic symptom of PTSD previously inaccessible to animal studies.

Title: Les modèles animaux du traumatisme et du trouble de stress post-traumatique. Abstract: Le trouble de stress post-traumatique (TSPT) est généralement associé à menace vitale et est parfois considéré comme une condition spécifiquement humaine. Cependant de nombreuses études ont montré qu'il pouvait être observé chez des animaux en milieu sauvage et pouvait être induit en laboratoire chez des rongeurs. Cet article vise à présenter et discuter l'évolution et la pertinence des modèles animaux dans l'étude du TSPT. Les études de LeDoux, Davis et McGaugh sur la peur et le conditionnement aversif pavlovien chez le rongeur ont apporté une immense contribution à la compréhension du TSPT. Initialement, il a été proposé que le TSPT résulterait d'un apprentissage aversif trop efficace, impliquant en particulier l'amygdale. Néanmoins, de nombreuses études ont révélé que cette hypothèse n'était pas suffisante pour expliquer la complexité des processus mis en jeu dans le TSPT. Les théories actuelles suggèrent plutôt des déficits dans la capacité à maintenir l'extinction, la perception des signaux de sécurité ou la régulation émotionnelle. Nous examinerons plus précisément les modèles animaux qui se rapprochent le plus du TSPT humain et nous discuterons des raisons pour lesquelles leur utilisation reste limitée. En effet, la plupart des études chez l'animal continuent de s'appuyer majoritairement sur des protocoles classiques de conditionnement pavlovien. Enfin, cette revue mettra en lumière de nouvelles études expérimentales permettant d'aborder des questions auparavant difficiles à étudier chez l'animal. Nous examinerons notamment les liens entre respiration et maintien des états de peur, offrant une explication potentielle à l'efficacité des techniques de méditation et de contrôle de la respiration dans la régulation des émotions. De plus, nous présenterons des résultats récents sur le décodage de l'activité neuronale liée aux représentations internes chez l'animal, offrant ainsi la possibilité d'étudier les ruminations, symptômes caractéristiques du TSPT qui étaient auparavant inaccessibles à l'expérimentation animale.

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Autism Spectrum Disorder (ASD) is characterized by rigidity of routines and restricted interests, and atypical social communication and interaction. Recent evidence for altered synchronization of neuro-oscillatory brain activity with regularities in the environment and of altered peripheral nervous system function in ASD present promising novel directions for studying pathophysiology and its relationship to ASD clinical phenotype. Human cognition and action are significantly influenced by physiological rhythmic processes that are generated by both the central nervous system (CNS) and the autonomic nervous system (ANS). Normally, perception occurs in a dynamic context, where brain oscillations and autonomic signals synchronize with external events to optimally receive temporally predictable rhythmic information, leading to improved performance. The recent findings on the time-sensitive coupling between the brain and the periphery in effective perception and successful social interactions in typically developed highlight studying the interactions within the brain-body-environment triad as a critical direction in the study of ASD. Here we offer a novel perspective of autism as a case where the temporal dynamics of brain-body-environment coupling is impaired. We present evidence from the literature to support the idea that in autism the nervous system fails to operate in an adaptive manner to synchronize with temporally predictable events in the environment to optimize perception and behavior. This framework could potentially lead to novel biomarkers of hallmark deficits in ASD such as cognitive rigidity and altered social interaction.

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SKORA, L.I., J.J.A. LIVERMORE and K. Roelofs. The functional role of cardiac activity in perception and action. NEUROSCI BIOBEHAV REV X(X) XXX-XXX, 2022. Patterns of cardiac activity continuously vary with environmental demands, accelerating or decelerating depending on circumstances. Simultaneously, cardiac cycle affects a host of higher-order processes, where systolic baroreceptor activation largely impairs processing. However, a unified functional perspective on the role of cardiac signal in perception and action has been lacking. Here, we combine the existing strands of literature and use threat-, anticipation-, and error-related cardiac deceleration to show that deceleration is an adaptive mechanism dynamically attenuating the baroreceptor signal associated with each heartbeat to minimise its impact on exteroceptive processing. This mechanism allows to enhance attention afforded to external signal and prepare an appropriate course of action. Conversely, acceleration is associated with a reduced need to attend externally, enhanced action tendencies and behavioural readjustment. This novel account demonstrates that dynamic adjustments in heart rate serve the purpose of regulating the level of precision afforded to internal versus external evidence in order to optimise perception and action. This highlights that the importance of cardiac signal in adaptive behaviour lies in its dynamic regulation.

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Heart rate has natural fluctuations that are typically ascribed to autonomic function. Recent evidence suggests that conscious processing can affect the timing of the heartbeat. We hypothesized that heart rate is modulated by conscious processing and therefore dependent on attentional focus. To test this, we leverage the observation that neural processes synchronize between subjects by presenting an identical narrative stimulus. As predicted, we find significant inter-subject correlation of heart rate (ISC-HR) when subjects are presented with an auditory or audiovisual narrative. Consistent with our hypothesis, we find that ISC-HR is reduced when subjects are distracted from the narrative, and higher ISC-HR predicts better recall of the narrative. Finally, patients with disorders of consciousness have lower ISC-HR, as compared to healthy individuals. We conclude that heart rate fluctuations are partially driven by conscious processing, depend on attentional state, and may represent a simple metric to assess conscious state in unresponsive patients.

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Recent studies suggest that vagus nerve stimulation (VNS) promotes cognitive and behavioral restoration after traumatic brain injuries. As vagus nerve has wide effects over the brain and visceral organs, stimulation of the sensory/visceral afferents might have a therapeutic potential to modulate the level of consciousness. One of the most important challenges in studying consciousness is objective evaluation of the consciousness level. Brain complexity that can be measured through Lempel-Ziv complexity (LZC) index was used as a novel mathematical approach for objective measurement of consciousness. The main goal of our study was to examine the effects of VNS on LZC index of consciousness. In this study, we did VNS on the anesthetized rats, and simultaneously LFPs recording was performed in two different cortical areas of primary somatosensory (S1) or visual (V1) cortex. LZC and the amplitude of slow waves were computed during different periods of VNS. We found that the LZC index during VNS period was significantly higher in both of the cortical areas of S1 and V1. Slow-wave activity decreased during VNS in S1, while there was no significant change in V1. Our findings showed that VNS can augment the consciousness level, and LZC index is a more sensitive parameter for detecting the level of consciousness.

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Forrest Gump or The Matrix? Preference-based decisions are subjective and entail self-reflection. However, these self-related features are unaccounted for by known neural mechanisms of valuation and choice. Self-related processes have been linked to a basic interoceptive biological mechanism, the neural monitoring of heartbeats, in particular in ventromedial prefrontal cortex (vmPFC), a region also involved in value encoding. We thus hypothesized a functional coupling between the neural monitoring of heartbeats and the precision of value encoding in vmPFC. Human participants of both sexes were presented with pairs of movie titles. They indicated either which movie they preferred or performed a control objective visual discrimination that did not require self-reflection. Using magnetoencephalography, we measured heartbeat-evoked responses (HERs) before option presentation and confirmed that HERs in vmPFC were larger when preparing for the subjective, self-related task. We retrieved the expected cortical value network during choice with time-resolved statistical modeling. Crucially, we show that larger HERs before option presentation are followed by stronger value encoding during choice in vmPFC. This effect is independent of overall vmPFC baseline activity. The neural interaction between HERs and value encoding predicted preference-based choice consistency over time, accounting for both interindividual differences and trial-to-trial fluctuations within individuals. Neither cardiac activity nor arousal fluctuations could account for any of the effects. HERs did not interact with the encoding of perceptual evidence in the discrimination task. Our results show that the self-reflection underlying preference-based decisions involves HERs, and that HER integration to subjective value encoding in vmPFC contributes to preference stability.SIGNIFICANCE STATEMENT Deciding whether you prefer Forrest Gump or The Matrix is based on subjective values, which only you, the decision-maker, can estimate and compare, by asking yourself. Yet, how self-reflection is biologically implemented and its contribution to subjective valuation are not known. We show that in ventromedial prefrontal cortex, the neural response to heartbeats, an interoceptive self-related process, influences the cortical representation of subjective value. The neural interaction between the cortical monitoring of heartbeats and value encoding predicts choice consistency (i.e., whether you consistently prefer Forrest Gump over Matrix over time. Our results pave the way for the quantification of self-related processes in decision-making and may shed new light on the relationship between maladaptive decisions and impaired interoception.

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When patients present with persistent bodily complaints that cannot be explained by a symptom-linked organic pathology (medically unexplained symptoms), they are diagnosed with 'functional' somatic syndromes (FSS). Despite their prevalence, the management of FSS is notoriously challenging in clinical practice. This may be because FSS are heterogeneous disorders in terms of etiopathogenesis. They include patients with primarily peripheral dysfunction, primarily centrally driven somatic symptoms, and a mix of both. Brain-imaging studies, particularly data-driven pattern recognition methods using machine learning algorithms, could provide brain-based biomarkers for these clinical conditions. In this review, we provide an overview of our brain imaging data on brain-body interactions in one of the most well-known FSS, irritable bowel syndrome (IBS), and discuss the possible development of a brain-based biomarker for FSS. Anticipation of unpredictable pain, which commonly elicits fear in FSS patients, induced increased activity in brain areas associated with hypervigilance during rectal distention and non-distention conditions in IBS. This was coupled with dysfunctional inhibitory influence of the medial prefrontal cortex (mPFC) and pregenual anterior cingulate cortex (pACC) on stress regulation systems, resulting in the activated autonomic nervous system (ANS) and neuroendocrine system stimulated by corticotropin-releasing hormone (CRH). IBS subjects with higher alexithymia, a risk factor for FSS, showed stronger activity in the insula during rectal distention but reduced subjective sensitivity. Reduced top-down regulation of the ANS and CRH system by mPFC and pACC, discordance between the insula response to stimulation and subjective sensation of pain, and stronger threat responses in hypervigilance-related areas may be a candidate brain-based biomarker.

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Electroencephalographic and magnetoencephalographic data have characterized two types of brain-body interactions observed during various types of motor actions, "corticokinematic" and "corticomuscular" coupling. Here, we review the literature on these interactions in healthy individuals, discuss several open debates, and outline current limitations and directions for future research. Corticokinematic coupling (commonly referred to as corticokinematic coherence) probes the relationship between activity of sensorimotor network nodes and various movement-related signals (e.g., speed, velocity, acceleration). It is mainly driven by movement rhythmicity during active, passive, and observed dynamic motor actions. It typically predominates at the primary sensorimotor cortex contralateral to the moving limb, occurs at movement frequency and its harmonics, and predominantly reflects the cortical processing of proprioceptive feedback driven by movement rhythmicity in a broad range of dynamic motor actions. Corticomuscular coupling (commonly referred to as corticomuscular coherence) probes the interaction between sensorimotor cortical rhythms and electromyographic (EMG) activity that mainly occurs during steady isometric muscle contraction. We will here focus on the ~20-Hz coupling that is observed during weak isometric contraction and is linked to the modulation of the descending motor command by the ~20-Hz sensorimotor rhythm. This review argues that corticokinematic and corticomuscular couplings have different neural bases. Corticokinematic coupling is mainly driven by afferent signals, while corticomuscular coupling is mainly (but not solely) driven by efferent signals. This distinction should be considered when investigating interactions between brain and body movements.

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This perspective emphasizes that the brain-machine interface (BMI) research has the potential to clarify major mysteries of the brain and that such clarification of the mysteries by neuroscience is needed to develop BMIs. I enumerate five principal mysteries. The first is "how is information encoded in the brain?" This is the fundamental question for understanding what our minds are and is related to the verification of Hebb's cell assembly theory. The second is "how is information distributed in the brain?" This is also a reconsideration of the functional localization of the brain. The third is "what is the function of the ongoing activity of the brain?" This is the problem of how the brain is active during no-task periods and what meaning such spontaneous activity has. The fourth is "how does the bodily behavior affect the brain function?" This is the problem of brain-body interaction, and obtaining a new "body" by a BMI leads to a possibility of changes in the owner's brain. The last is "to what extent can the brain induce plasticity?" Most BMIs require changes in the brain's neuronal activity to realize higher performance, and the neuronal operant conditioning inherent in the BMIs further enhances changes in the activity.