Search

It has been suggested that our perception of the internal milieu, or the body's internal state, is shaped by our beliefs and previous knowledge about the body's expected state, rather than being solely based on actual interoceptive experiences. This study investigated whether heartbeat perception could be illusorily distorted towards prior subjective beliefs, such that threat expectations suffice to induce a misperception of heartbeat frequency. Participants were instructed to focus on their cardiac activity and report their heartbeat, either tapping along to it (Experiment 1) or silently counting (Experiment 2) while ECG was recorded. While completing this task, different cues provided valid predictive information about the intensity of an upcoming cutaneous stimulation (high- vs. low- pain). Results showed that participants expected a heart rate increase over the anticipation of high- vs. low-pain stimuli and that this belief was perceptually instantiated, as suggested by their interoceptive reports. Importantly, the perceived increase was not mirrored by the real heart rate. Perceptual modulations were absent when participants executed the same task but with an exteroceptive stimulus (Experiment 3). The findings reveal, for the first time, an interoceptive illusion of increased heartbeats elicited by threat expectancy and shed new light on interoceptive processes through the lenses of Bayesian predictive processes, providing tantalizing insights into how such illusory phenomena may intersect with the recognition and regulation of people's internal states., Competing Interests: Declaration of competing interest The authors declare no competing financial or academic interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Respiration and cardiac activity intricately interact through complex physiological mechanisms. The heartbeat-evoked potential (HEP) is an EEG fluctuation reflecting the cortical processing of cardiac signals. We recently found higher HEP amplitude during exhalation than inhalation during a task involving attention to cardiac sensations. This may have been due to reduced cardiac perception during inhalation and heightened perception during exhalation through attentional mechanisms. To investigate relationships between HEP, attention, and respiration, we introduced an experimental setup that included tasks related to cardiac and respiratory interoceptive and exteroceptive attention. Results revealed HEP amplitude increases during the interoceptive tasks over fronto-central electrodes. When respiratory phases were taken into account, HEP increases were primarily driven by heartbeats recorded during exhalation, specifically during the cardiac interoceptive task, while inhalation had minimal impact. These findings emphasize the role of respiration in cardiac interoceptive attention and could have implications for respiratory interventions to fine-tune cardiac interoception., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Respiration and heartbeat continuously interact within the living organism at many different levels, representing two of the main oscillatory rhythms of the body and providing major sources of interoceptive information to the brain. Despite the modulatory effect of respiration on exteroception and cognition has been recently established in humans, its role in shaping interoceptive perception has been scarcely investigated so far. In two independent studies, we investigated the effect of spontaneous breathing on cardiac interoception by assessing the Heartbeat Evoked Potential (HEP) in healthy humans. In Study 1, we compared HEP activity for heartbeats occurred during inhalation and exhalation in 40 volunteers at rest. We found higher HEP amplitude during exhalation, compared to inhalation, over fronto-centro-parietal areas. This suggests increased brain-heart interactions and improved cortical processing of the heartbeats during exhalation. Further analyses revealed that this effect was moderated by heart rate changes. In Study 2, we tested the respiratory phase-dependent modulation of HEP activity in 20 volunteers during Exteroceptive and Interoceptive conditions of the Heartbeat Detection (HBD) task. In these conditions, participants were requested to tap at each heartbeat, either listened to or felt, respectively. Results showed higher HEP activity and higher detection accuracy at exhalation than inhalation in the Interoceptive condition only. Direct comparisons of Interoceptive and Exteroceptive conditions confirmed stronger respiratory phase-dependent modulation of HEP and accuracy when attention was directed towards the interoceptive stimuli. Moreover, HEP changes during the Interoceptive condition were independent of heart physiology, but were positively correlated with higher detection accuracy at exhalation than inhalation. This suggests a link between optimization of cortical processing of cardiac signals and detection of heartbeats across the respiratory cycle. Overall, we provide data showing that respiration shapes cardiac interoception at the neurophysiological and behavioural levels. Specifically, exhalation may allow attentional shift towards the internal bodily states., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2022. Published by Elsevier Inc.)

The necessity to improve in vitro cell screening assays is becoming ever more important. Pharmaceutical companies, research laboratories and hospitals require technologies that help to speed up conventional screening and therapeutic procedures to produce more data in a short time in a realistic and reliable manner. The design of new solutions for test biomaterials and active molecules is one of the urgent problems of preclinical screening and the limited correlation between in vitro and in vivo data remains one of the major issues. The establishment of the most suitable in vitro model provides reduction in times, costs and, last but not least, in the number of animal experiments as recommended by the 3Rs (replace, reduce, refine) ethical guiding principles for testing involving animals. Although two-dimensional (2D) traditional cell screening assays are generally cheap and practical to manage, they have strong limitations, as cells, within the transition from the three-dimensional (3D) in vivo to the 2D in vitro growth conditions, do not properly mimic the real morphologies and physiology of their native tissues. In the study of human pathologies, especially, animal experiments provide data closer to what happens in the target organ or apparatus, but they imply slow and costly procedures and they generally do not fully accomplish the 3Rs recommendations, i.e., the amount of laboratory animals and the stress that they undergo must be minimized. Microfluidic devices seem to offer different advantages in relation to the mentioned issues. This review aims to describe the critical issues connected with the conventional cells culture and screening procedures, showing what happens in the in vivo physiological micro and nano environment also from a physical point of view. During the discussion, some microfluidic tools and their components are described to explain how these devices can circumvent the actual limitations described in the introduction.

Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury., (© 2022. The Author(s).)