Biology subjects

Ferri, F.

Publications and source records attributed to Ferri, F..

15 recordsLinked to original sources

bioRxiv2025

Breathing strategies to influence perception: Evidence for interoceptive and exteroceptive active sensing

Recent research indicates that humans continuously and automatically modulate their breathing to temporally align exteroceptive stimuli with specific phases of the respiratory cycle. This process has been interpreted as a form of active sensing and is associated with faster responses and improved perceptual accuracy. While converging evidence suggests that respiration also shapes interoceptive processing at both neural and behavioural levels, it remains unclear whether individuals actively adjust their breathing to optimize interoceptive performance. In this study, we examined whether healthy participants modulated their respiration during an interoceptive (heartbeat discrimination) and an exteroceptive (tactile detection) task. We analysed respiration both in terms of time-locked activity and inter-trial phase coherence relative to stimulus onset and assessed their relationship with perceptual accuracy. Our results demonstrated that participants systematically adjust their breathing in both amplitude and phase, synchronizing respiration to the anticipated (i.e., cued) onset of stimuli in both tasks. Crucially, task performance was enhanced during exhalation compared to inhalation, suggesting that respiratory modulation supports the perception of both interoceptive and exteroceptive signals. Significance statementThis study reveals that humans not only synchronize their breathing to anticipated external and internal stimuli, but also perform better when perceiving them during exhalation. By showing that respiration is modulated in both interoceptive and exteroceptive contexts, our findings extend the concept of active sensing to internal bodily awareness. This has important implications for understanding the dynamic interplay between physiology and perception and may guide interventions aimed at improving clinical outcomes in conditions where interoception is disrupted.

neuroscience↗

bioRxiv2025

Cardio-respiratory interactions in interoceptive perception: The role of heartbeat-modulated cortical oscillations

The cardiovascular and respiratory systems are anatomically and functionally integrated within the cardio-respiratory system. This close connection suggests that breathing continuously shapes cardiac interoceptive perception. Previously, we demonstrated cardio-respiratory interoceptive interactions in the heartbeat-evoked potential, a neural marker of cortical processing of cardiac signals. Specifically, we observed enhanced late heartbeat-evoked potential positivity and greater interoceptive accuracy during exhalation compared to inhalation in participants engaged in cardiac interoceptive tasks. Here, we extended these findings to the time-frequency domain by reanalysing our previous dataset. We investigated heartbeat-modulated cortical oscillations, examining power, inter-trial coherence, and functional connectivity across the respiratory cycle at rest, during a cardiac interoceptive task (heartbeat counting), and an exteroceptive control task (cardiac-tone counting). Results revealed that during the heartbeat counting task, late heartbeat-related power, inter-trial coherence, and functional connectivity increased during exhalation compared to inhalation, particularly in the alpha and theta frequency bands. These effects were primarily localized to right fronto-centro-parietal electrodes. Furthermore, we identified interactive relationships between heartbeat-evoked potential and heartbeat-modulated cortical oscillations in the alpha band that predicted interoceptive accuracy. These relationships were independent of cardiac physiology and were absent in the exteroceptive task. We proposed a model of cardio-respiratory interactions within the framework of interoceptive predictive coding, suggesting that these interactions occur at multiple levels of the interoceptive hierarchy: peripheral, brainstem, and cortical. Our interpretation highlights the role of heartbeat-related alpha-band modulations in enhancing the precision-weighting of cardiac prediction errors, thereby facilitating attentional allocation to interoceptive signals and the suppression of task-irrelevant distractors, particularly during exhalation.

neuroscience↗

bioRxiv2025

Respiration facilitates behaviour during multisensory integration

The brain processes information from the external environment alongside signals generated by the body. Among bodily rhythms, respiration emerges as a key modulator of sensory processing. Multisensory integration, the non-linear combination of information from multiple senses to reduce environmental uncertainty, may be influenced by respiratory dynamics. This study investigated how respiration modulates reaction times and multisensory integration in a simple detection task. Forty healthy participants were presented with unimodal (Auditory, Visual, Tactile) and bimodal (Audio-Tactile, Audio-Visual, Visuo-Tactile) stimuli while their respiratory activity was recorded. Results revealed that reaction times systematically varied with respiration, with faster responses during peak inspiration and early expiration but slower responses during the expiration-to-inspiration transition. Applying the race model inequality approach to quantify multisensory integration, we found that Audio-Tactile and Audio-Visual stimuli exhibited the highest integration during the expiration-to-inspiration phase. These findings conceivably reflect respiration phase-locked changes in cortical excitability which in turn, orchestrates multisensory integration. Interestingly, participants also tended to adapt their respiratory cycles, aligning response onsets preferentially with early expiration. This suggests that, rather than a mere bottom-up mechanism, respiration is actively adjusted to maximise the signal-to-noise balance between interoceptive and exteroceptive signals.

neuroscience↗

bioRxiv2024

Reduced learning rate and E/I imbalance drive Peripersonal Space boundaries expansion in Schizophrenia

Abnormal encoding of peripersonal space (PPS) is believed to affect bodily self disruptions in schizophrenia (SCZ). Empirical studies show that SCZ patients exhibit a narrower PPS than controls but maintain its plasticity. Computational research links this smaller PPS to increased excitation of sensory neurons and reduced feedforward synaptic density. However, it is unclear how such differences influence learning during the expansion of PPS boundaries. We hypothesise that Hebbian plasticity can account for PPS expansion after active tool use training. To explore the effect of such mechanisms on PPS plasticity, we developed a SCZ network model which was fit to behavioural data before and after tool manipulation. We found that PPS expansion occurs in spite of E/I imbalance or reduced synaptic density, but does not match the post-training PPS representation of patients. A better fit was obtained after altering plasticity by either reducing the learning rate, increasing the forgetting rate or increasing the plasticity threshold. We discuss our findings in terms of dysfunctional plasticity in SCZ and highlight the key challenges in identifying the neurobiological correlates of reduced plasticity within PPS networks. Because current empirical data supports multiple viable mechanisms, we propose experiments to distinguish between the proposed plasticity accounts and clarify mixed findings on PPS representation in SCZ. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/604515v2_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@14ee71forg.highwire.dtl.DTLVardef@127c3aborg.highwire.dtl.DTLVardef@19f1338org.highwire.dtl.DTLVardef@a6e437_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIUsing a peripersonal space network model, we found that PPS expansion after tool-use occurs in spite of E/I imbalance or reduced synaptic density. C_LIO_LIReduced feedforward synaptic plasticity is required to match the post-training PPS representation of patients. C_LIO_LISuch reduction of synaptic plasticity could be achieved by either reducing the learning rate, increasing the forgetting rate or increasing the plasticity threshold relative to a healthy control model. C_LIO_LIOur model predicts that measuring PPS at intermediate time points during a longer stimulation protocol would help distinguish between these plasticity differences. C_LI

neuroscience↗

bioRxiv2024

Excitation/Inhibition imbalance impairs multisensory causal inference by increasing the proneness to experience the sound-induced flash illusion in the schizophrenia spectrum

The spectrum of schizophrenia is characterised by an altered sense of self with known impairments in tactile sensitivity, proprioception, body-self boundaries, and self-recognition. These are thought to be produced by failures in multisensory integration mechanisms, commonly observed as enlarged temporal binding windows during audiovisual illusion tasks. To our knowledge, there is an absence of computational explanations for multisensory integration deficits in patients with schizophrenia and individuals with high schizotypy, particularly at the neurobiological level. We implemented a multisensory causal inference network to reproduce the responses of individuals who scored low in schizotypy in a simulated double flash illusion task. Next, we explored the effects of recurrent excitation, cross-modal and feedback weights, and synaptic density on the visual illusory responses of the network. Using quantitative fitting to empirical data, we found that an increase in the weights of the recurrent excitatory connectivity in the network enlarges the temporal binding window and increases the overall proneness to experience the illusion, matching the responses of individuals scoring high in schizotypy. Moreover, we found that an increase in excitation increases the probability of inferring a common cause from the stimuli. We propose an E/I imbalance account of reduced temporal discrimination in the SCZ spectrum and discuss possible links with Bayesian theories of schizophrenia. We highlight the importance of adopting a multisensory causal inference perspective to address body-related symptomatology of schizophrenia.

neuroscience↗

bioRxiv2023

Multi-target mode of action of Sulfodyne(R), a stabilized Sulforaphane, against pathogenic effects of SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown that, except vaccination, few therapeutics options for its treatment or prevention are available. Among the pathways that can be targeted for COVID-19 treatment, the Keap1/Nrf2 pathway seems of high interest as it regulates redox homeostasis and inflammation that are altered during SARS-CoV-2 infection. Here, we use three potent activators of the Keap1/Nrf2 pathway and showed that Sulfodyne(R), a stabilized natural Sulforaphane preparation with optimal bioavailability, had the highest antiviral activity in pulmonary or colonic epithelial cell lines even when added late after SARS-CoV-2 infection. This antiviral activity was not dependent on NRF2 activity but associated with action on ER stress and mTOR signaling that are activated during SARS-CoV-2 infection. Sulfodyne(R) also decreased the inflammatory response of epithelial cell lines infected by SARS-CoV-2 independently of SARS-CoV-2 replication and reduced the activation of human monocytes that are recruited after infection of epithelial cells by SARS-CoV-2. Administration of Sulfodyne(R) had little effects on SARS-CoV-2 replication in mice and hamsters infected with SARS-CoV-2 but significantly reduced weight loss and disease severity. Altogether, these results pinpoint the natural compound Sulfodyne(R) as a potent therapeutic agent of COVID-19 symptomatology. Author SummaryAccumulating evidence shows that oxidative stress coupled with the systemic inflammation contribute to COVID-19 pathogenesis. As the Keap1/Nrf2 pathway is the major regulator of redox homeostasis and promotes resolution of inflammation and as lung biopsies from COVID-19 patients showed a decreased NRF2 target gene signature, pharmacological agents that are known to activate NRF2 are good candidates for COVID-19 treatment. We show herein that Sulfodyne(R), an NRF2 activator that consists in a stabilized Sulforaphane preparation with optimal bioavailability, impairs SARS-CoV-2 replication in colonic or pulmonary epithelial cells. We show that this antiviral activity of Sulfodyne(R) is not dependent of NRF2 activation, characterize the pathways associated with the Sulfodyne(R) antiviral activity and show that Sulfodyne(R) displays multiple actions that result in a decrease of the inflammation associated with SARS-CoV-2 infection. Finally, we show that Sulfodyne(R) decreases the pathogenesis of mice or hamster infected with SARS-CoV-2. Overall, this study provides mechanistic explanations of the action of Sulfodyne(R) during SARS-CoV-2 infection and suggests that Sulfodyne(R) is a potential therapeutic agent of COVID-19 pathogenesis.

cell biology↗

bioRxiv2023

The interplay between focus of attention, respiratory phases, and the Heartbeat Evoked Potential

The Heartbeat Evoked Potential (HEP) is an EEG fluctuation that reflects the cortical processing of cardiac signals. HEP amplitude increases during various tasks involving cardiac interoception. Recent research has also indicated that HEP amplitude and cardiac interoceptive accuracy are higher during exhalation compared to inhalation. This difference may be due to the suppression of heartbeat-related sensations during inhalation and the amplification of sensations during exhalation through attentional mechanisms. Despite significant advancements in HEP research, the interactions between the HEP, interoceptive attention, and respiration are still unclear. In this study, we developed a novel experimental paradigm to investigate the relationship between HEP amplitude and respiratory phases during tasks that involve attention to cardiac interoception, non-cardiac interoception (specifically, respiration), and exteroceptive stimuli. The tasks included the Heartbeat Counting Task and the Breath Counting Task as interoceptive tasks, as well as the Cardiac-Tone Counting Task and the Breath-Tone Counting Task as exteroceptive tasks. Results demonstrated significant increases in HEP amplitude during the Heartbeat Counting Task compared to the Cardiac-Tone Counting Task and the Breath Counting Task, mostly observed over fronto-central electrodes in a late time-window. Notably, the amplitude increases during the Heartbeat Counting Task were primarily driven by HEPs recorded during exhalation, while inhalation had minimal impact. These findings align with the predictive coding model of interoceptive perception, suggesting that HEP amplitude reflects a precision-weighting process of prediction errors related to cardiac sensations that is specifically influenced by attention directed toward the heart. Furthermore, our findings emphasize the crucial role of exhalation in this precision-weighting process. These results may have considerable implications for the development of respiratory interventions to fine-tune cardiac interoception.

neuroscience↗

bioRxiv2023

Local and Global Measures of Information Storage for the Assessment of Heartbeat-Evoked Cortical Responses

ObjectiveBrain-heart interactions involve bidirectional effects produced by bottom-up input at each heartbeat, and top-down neural regulatory responses of the brain. While the cortical processing of the heartbeat is usually investigated through the analysis of the Heartbeat Evoked Potential, in this study we propose an alternative approach based on the variability in the predictability of the brain dynamics induced by the heartbeat. MethodsIn a group of eighteen subjects in whom simultaneous recording of the electroencephalogram (EEG) and electrocardiogram was performed in a resting-state, we analyzed the temporal profile of the local Information Storage (IS) to detect changes in the regularity of EEG signals in time windows associated with different phases of the cardiac cycle at rest. ResultsThe average values of the local IS were significantly higher in the parieto-occipital areas of the scalp, suggesting an activation of the Default Mode Network, regardless of the cardiac cycle phase. In contrast, the variability of the local IS showed marked differences across the cardiac cycle phases. ConclusionOur results suggest that cardiac activity influences the predictive information of EEG dynamics differently in the various phases of the cardiac cycle. SignificanceThe variability of local IS measures can represent a useful index to identify spatio-temporal dynamics within the neurocardiac system, which generally remain overlooked by the more widely employed global measures.

neuroscience↗

bioRxiv2023

Exposure to false cardiac feedback alters pain perception and anticipatory cardiac frequency.

The experience of pain, like other interoceptive processes, has recently been conceptualized in terms of predictive coding and free energy frameworks. In these views, the brain integrates sensory, proprioceptive, and interoceptive signals to generate probabilistic inferences about upcoming events, which shape both the state and the perception of our inner body. Here we ask whether it is possible to induce pain expectations by providing false faster (vs. slower) acoustic cardiac feedback before administering electrical cutaneous shocks. We test whether these expectations will shape both the perception of pain and the bodys physiological state toward prior predictions. Results confirmed that faster cardiac feedback elicited pain expectations that affected both perceptual pain judgments and the bodys physiological response. Perceptual pain judgments were biased towards the expected level of pain, such that participants illusorily perceived identical noxious stimuli as more intense and unpleasant. Physiological changes mirrored the predicted level of pain, such that participants actual cardiac response in anticipation of pain stimuli showed a deceleration in heart rate, in line with the well-known orienting cardiac response in anticipation of threatening stimuli (Experiment 1). In a control experiment, such perceptual and cardiac modulations were dramatically reduced when the feedback reproduced an exteroceptive, instead of interoceptive, cardiac feedback (Experiment 2). These findings show that cardiac perception can be understood as interoceptive inference that modulates both our perception and the physiological state of the body, thereby actively generating the interoceptive and autonomic consequences that have been predicted.

neuroscience↗

bioRxiv2022

Heart Is Deceitful Above All Things: illusory perception of heartbeat is induced by pain expectation.

The perception of the internal milieu is thought to reflect beliefs and prior knowledge about the expected state of the body, rather than only actual interoceptive states. This study investigated whether heartbeat perception could be illusorily distorted towards prior subjective beliefs, such that threat expectations suffice to induce a false perception of increased 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 shown 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 peoples internal states.

neuroscience↗

bioRxiv2022

Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter

AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-{beta} amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during chronic inflammation. The disease can be transmitted horizontally, likely facilitated by prion-like mechanism, in captive animals leading to extreme disease prevalence, e.g. 70% in captive cheetah and 57-73% in domestic short hair (DSH) cats kept in shelters. Herein, we present the 3.3 [A] cryo-EM structure of an AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure. The structure reveals a cross-{beta} architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a distinct amyloid fold. Based on shared disease profiles and almost identical protein sequences, we propose a similar amyloid fold of deposits identified previously in captive cheetah.

biophysics↗

bioRxiv2022

AA-amyloidosis in cats (Felis catus) housed in shelters

Systemic AA-amyloidosis is a protein-misfolding disease that is characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. In domestic short-hair cats, AA-amyloidosis has only been anecdotally reported and is considered a rare disease. Here we report that an astonishing 57-73% of early deceased short-hair cats kept in three independent shelters suffer from amyloid deposition in the liver, spleen, or kidney. Histopathology and mass spectrometry of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B=0.026, CI95%=0.007-0.046; p=0.010). Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease.

pathology↗

bioRxiv2022

Brain-heart interactions are optimized across the respiratory cycle via interoceptive attention

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. 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. These effects were positively correlated, suggesting a link between optimization of both cortical processing of cardiac signals and perception of heartbeats across the respiratory cycle. 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. 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.

neuroscience↗

bioRxiv2020

Influence of E/I balance and pruning in peri-personal space differences in schizophrenia: a computational approach

The encoding of the space close to the body, named peri-personal space (PPS), is thought to play a crucial role in the unusual experiences of the self observed in schizophrenia (SCZ). However, it is unclear why SCZ patients and high schizotypal (H-SPQ) individuals present a narrower PPS and why the boundaries of the PPS are more sharply defined in patients. We hypothesise that the unusual PPS representation observed in SCZ is caused by an imbalance of excitation and inhibition (E/I) in recurrent synapses of unisensory neurons or an impairment of bottom-up and top-down connectivity between unisensory and multisensory neurons. These hypotheses were tested computationally by manipulating the effects of E/I imbalance, feedback weights and synaptic density in the network. Using simulations we explored the effects of such impairments in the PPS representation generated by the network and fitted the model to behavioural data. We found that increased excitation of sensory neurons could account for the smaller PPS observed in SCZ and H-SPQ, whereas a decrease of synaptic density caused the sharp definition of the PPS observed in SCZ. We propose a novel conceptual model of PPS representation in the SCZ spectrum that can account for alterations in self-world demarcation, failures in tactile discrimination and symptoms observed in patients.

neuroscience↗

bioRxiv2020

Cortical Silent Period duration reflects inter-individual differences in action stopping performance.

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate of motor inhibition within the primary motor cortex (M1), such as the Cortical Silent period (CSP). CSPs length is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, we here explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the length of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSPs length and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.

neuroscience↗