From the inside out: Interoceptive feedback facilitates the integration of visceral signals for efficient sensory processing

Neuroscientific studies have mainly focused on the way humans perceive and interact with the external world. Recent work in the interoceptive domain indicates that the brain predictively models information from inside the body such as the heartbeat and that the efficiency with which this is executed can have implications for exteroceptive processing. However, to date direct evidence underpinning these hypotheses is lacking. Here, we show how the brain predictively refines neural resources to process afferent cardiac feedback and uses these interoceptive cues to enable more efficient processing of external sensory information. Participants completed a repetition-suppression paradigm consisting of a neutral repeating face. During the first face presentation, they heard auditory feedback of their heartbeat which either coincided with the systole of the cardiac cycle, the time at which cardiac events are registered by the brain or the diastole during which the brain receives no internal cardiac feedback. We used electroencephalography to measure the heartbeat evoked potential (HEP) as well as auditory (AEP) and visual evoked potentials (VEP). Exteroceptive cardiac feedback which coincided with the systole produced significantly higher HEP amplitudes relative to feedback timed to the diastole. Elevation of the HEP in this condition was followed by significant suppression of the VEP in response to the repeated neutral face and a stepwise decrease of AEP amplitude to repeated heartbeat feedback. Our results hereby show that exteroceptive heartbeat feedback coinciding with interoceptive signals at systole enhanced interoceptive cardiac processing. Furthermore, the same cue facilitating interoceptive integration enabled efficient suppression of a visual stimulus, as well as repetition suppression of the AEP across successive auditory heartbeat feedback. Our findings provide evidence that the alignment of external to internal signals can enhance the efficiency of interoceptive processing and that cues facilitating this process in either domain have beneficial effects for internal as well as external sensory processing

Exteroceptive expectations modulate interoceptive processing: repetition-suppression effects for visual and heartbeat evoked potentials

Interoception refers to the signaling of internal bodily commands. Here, we explore repetition suppression of intero- and exteroceptive neural markers to test whether the perception and predictability of exteroceptive stimulus material affects their expression. Participants completed a repetition suppression paradigm in which angry or neutral facial expressions repeated or alternated. Participants received either an implicit (experiment 1) or explicit (experiment 2) cue enabling the formation of expectations regarding the upcoming facial expression. We measured the heartbeat-evoked potential (HEP) indexing cardiac processing and visual evoked potentials (VEP) in response to viewing the second (repeated or alternated) face. Repeating angry facial expressions produced repetition suppression of both HEP and VEP amplitude while repeating neutral expressions led to repetition enhancement of HEP amplitude. This effect was magnified when participants were explicitly aware of predictive cues. Furthermore, repetition suppression of HEP amplitude correlated with neural attenuation of VEP activity. Results highlight repetition effects for interoceptive as well as exteroceptive neural markers and support top-down, expectation-based accounts of the phenomenon. Furthermore, results demonstrate that the perception of exteroceptive stimulus information has an effect on the processing of interoceptive signals and suggest a direct neural connection between the processing of external and internal sensory information

The Interaction between Interoceptive and Action States within a Framework of Predictive Coding

The notion of predictive coding assumes that perception is an iterative process between prior knowledge and sensory feedback. To date, this perspective has been primarily applied to exteroceptive perception as well as action and its associated phenomenological experiences such as agency. More recently, this predictive, inferential framework has been theoretically extended to interoception. This idea postulates that subjective feeling states are generated by top-down inferences made about internal and external causes of interoceptive afferents. While the processing of motor signals for action control and the emergence of selfhood have been studied extensively, the contributions of interoceptive input and especially the potential interaction of motor and interoceptive signals remain largely unaddressed. Here, we argue for a specific functional relation between motor and interoceptive awareness. Specifically, we implicate interoceptive predictions in the generation of subjective motor-related feeling states. Furthermore, we propose a distinction between reflexive and pre-reflexive modes of agentic action control and suggest that interoceptive input may affect each differently. Finally, we advocate the necessity of continuous interoceptive input for conscious forms of agentic action control. We conclude by discussing further research contributions that would allow for a fuller understanding of the interaction between agency and interoceptive awareness

Cardiac interoceptive learning is modulated by emotional valence perceived from facial expressions

Interoception refers to the processing of homeostatic bodily signals. Research demonstrates that interoceptive markers can be modulated via exteroceptive stimuli and suggests that the emotional content of this information may produce distinct interoceptive outcomes. Here, we explored the impact of differently valenced exteroceptive information on the processing of interoceptive signals. Participants completed a repetition-suppression paradigm viewing repeating or alternating faces. In experiment 1, faces wore either angry or pained expressions to explore the interoceptive response to different types of negative stimuli in the observer. In experiment 2, expressions were happy or sad to compare interoceptive processing of positive and negative information. We measured the heartbeat evoked potential (HEP) and visual evoked potentials (VEPs) as a respective marker of intero- and exteroceptive processing. We observed increased HEP amplitude to repeated sad and pained faces coupled with reduced HEP and VEP amplitude to repeated angry faces. No effects were observed for positive faces. However, we found a significant correlation between suppression of the HEP and VEP to repeating angry faces. Results highlight an effect of emotional expression on interoception and suggest an attentional trade-off between internal and external processing domains as a potential account of this phenomenon

Sensitivity to CT-optimal, Affective Touch Depends on Adult Attachment Style

Affective touch supports affiliative bonds and social cognition. In particular, gentle, stroking touch, which has recently been associated with the C Tactile (CT) system, is typically perceived as pleasant and prosocial. However, it remains unknown whether pre-existing models of social relating influence the perception of CT-optimal touch. In this study (N = 44 adults), we examined how individual differences in attachment styles relate to the perception of CT-optimal touch, as well as to a different modality of interoception, namely heartbeat perception. Using the gold-standard assessment of attachment (Adult Attachment Interview), we found that insecure attachment was associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Acknowledging the different traditions in measuring attachment, we also used a well-validated self-report questionnaire that pertains to explicit representations of current close relationships. Using this measure, we found that higher scores in attachment anxiety (but not attachment avoidance) were associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Attachment patterns (in both measures) were not related to cardiac perception accuracy. These results corroborate and extend previous literature on CT-optimal touch and its relation with affiliative bonds and social cognition. Given that attachment was not related to perceived cardiac accuracy, these findings point to the specificity of the relationship between CT-optimal touch and attachment

An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations.

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis

Sensitivity to CT-optimal, Affective Touch Depends on Adult Attachment Style

Affective touch supports affiliative bonds and social cognition. In particular, gentle, stroking touch, which has recently been associated with the C Tactile (CT) system, is typically perceived as pleasant and prosocial. However, it remains unknown whether pre-existing models of social relating influence the perception of CT-optimal touch. In this study (N = 44 adults), we examined how individual differences in attachment styles relate to the perception of CT-optimal touch, as well as to a different modality of interoception, namely heartbeat perception. Using the gold-standard assessment of attachment (Adult Attachment Interview), we found that insecure attachment was associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Acknowledging the different traditions in measuring attachment, we also used a well-validated self-report questionnaire that pertains to explicit representations of current close relationships. Using this measure, we found that higher scores in attachment anxiety (but not attachment avoidance) were associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Attachment patterns (in both measures) were not related to cardiac perception accuracy. These results corroborate and extend previous literature on CT-optimal touch and its relation with affiliative bonds and social cognition. Given that attachment was not related to perceived cardiac accuracy, these findings point to the specificity of the relationship between CT-optimal touch and attachment

Affective interoceptive inference: Evidence from heart-beat evoked brain potentials.

The perception of internal bodily signals (interoception) is central to many theories of emotion and embodied cognition. According to recent theoretical views, the sensory processing of visceral signals such as one's own heartbeat is determined by top-down predictions about the expected interoceptive state of the body (interoceptive inference). In this EEG study we examined neural responses to heartbeats following expected and unexpected emotional stimuli. We used a modified stimulus repetition task in which pairs of facial expressions were presented with repeating or alternating emotional content, and we manipulated the emotional valence and the likelihood of stimulus repetition. We found that affective predictions of external socially relevant information modulated the heartbeat-evoked potential, a marker of cardiac interoception. Crucially, the HEP changes highly relied on the expected emotional content of the facial expression. Thus, expected negative faces led to a decreased HEP amplitude, whereas such an effect was not observed after an expected neutral face. These results suggest that valence-specific affective predictions, and their uniquely associated predicted bodily sensory state, can reduce or amplify cardiac interoceptive responses. In addition, the affective repetition effects were dependent on repetition probability, highlighting the influence of top-down exteroceptive predictions on interoception. Our results are in line with recent models of interoception supporting the idea that predicted bodily states influence sensory processing of salient external information

Development of candidate rotavirus vaccines derived from neonatal strains in India

The need for a rotavirus vaccine in India is based on the enormous burden associated with the <100,000 deaths due to rotavirus diarrhea that occur annually among Indian children. Two rotavirus strains identified during nosocomial outbreaks of rotavirus infection in New Delhi and Bangalore, India, more than a decade ago are being developed as live oral vaccines. Infected newborns had no symptoms, shed virus for up to 2 weeks after infection, mounted a robust immune response, and demonstrated protection against severe rotavirus diarrhea after reinfection. The 2 strains are naturally occurring bovine-human reassortants. The New Delhi strain, 116E, is characterized as having a P[11],G9 genotype, and the Bangalore strain, I321, is characterized as having a P[11],G10 genotype. The strains have been prepared as pilot lots for clinical trials to be conducted in New Delhi. This unique project, which is developing a new rotavirus vaccine in India with the use of Indian strains, an Indian manufacturer, and an Indian clinical development program, aims to expedite introduction of rotavirus vaccines in India

Potential for La Crosse virus segment reassortment in nature

The evolutionary success of La Crosse virus (LACV, family Bunyaviridae) is due to its ability to adapt to changing conditions through intramolecular genetic changes and segment reassortment. Vertical transmission of LACV in mosquitoes increases the potential for segment reassortment. Studies were conducted to determine if segment reassortment was occurring in naturally infected Aedes triseriatus from Wisconsin and Minnesota in 2000, 2004, 2006 and 2007. Mosquito eggs were collected from various sites in Wisconsin and Minnesota. They were reared in the laboratory and adults were tested for LACV antigen by immunofluorescence assay. RNA was isolated from the abdomen of infected mosquitoes and portions of the small (S), medium (M) and large (L) viral genome segments were amplified by RT-PCR and sequenced. Overall, the viral sequences from 40 infected mosquitoes and 5 virus isolates were analyzed. Phylogenetic and linkage disequilibrium analyses revealed that approximately 25% of infected mosquitoes and viruses contained reassorted genome segments, suggesting that LACV segment reassortment is frequent in nature