Brain-heart interactions are modulated 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. 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.

Sleep slow oscillations favour local cortical plasticity underlying the consolidation of reinforced procedural learning in human sleep.

We investigated changes of slow-wave activity and sleep slow oscillations in the night following procedural learning boosted by reinforcement learning, and how these changes correlate with behavioural output. In the Task session, participants had to reach a visual target adapting cursor's movements to compensate an angular deviation introduced experimentally, while in the Control session no deviation was applied. The task was repeated at 13:00 hours, 17:00 hours and 23:00 hours before sleep, and at 08:00 hours after sleep. The deviation angle was set at 15° (13:00 hours and 17:00 hours) and increased to 45° (reinforcement) at 23:00 hours and 08:00 hours. Both for Task and Control nights, high-density electroencephalogram sleep recordings were carried out (23:30-19:30 hours). The Task night as compared with the Control night showed increases of: (a) slow-wave activity (absolute power) over the whole scalp; (b) slow-wave activity (relative power) in left centro-parietal areas; (c) sleep slow oscillations rate in sensorimotor and premotor areas; (d) amplitude of pre-down and up states in premotor regions, left sensorimotor and right parietal regions; (e) sigma crowning the up state in right parietal regions. After Task night, we found an improvement of task performance showing correlations with sleep slow oscillations rate in right premotor, sensorimotor and parietal regions. These findings suggest a key role of sleep slow oscillations in procedural memories consolidation. The diverse components of sleep slow oscillations selectively reflect the network activations related to the reinforced learning of a procedural visuomotor task. Indeed, areas specifically involved in the task stand out as those with a significant association between sleep slow oscillations rate and overnight improvement in task performance.

Attention to cardiac sensations enhances the heartbeat-evoked potential during exhalation.

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.

[Cardiac amyloidosis and aortic stenosis: what do we know?] / Amiloidosi cardiaca e stenosi valvolare aortica: quale legame?

Aortic valve stenosis and cardiac amyloidosis, particularly transthyretin-related, often coexist and share a common clinical and demographic profile. Several pathophysiological hypotheses have been proposed regarding the causes of this association, neither of which fully substantiated in practice. The key to detect the coexistence of cardiac amyloidosis and aortic valve stenosis lies in clinical suspicion. It is possible to hypothesize concurrent cardiac amyloidosis in patients with aortic valve stenosis with the aid of clinical, electrocardiographic, echocardiographic, and extracardiac "red flags". Subsequent non-invasive diagnostic steps are often sufficient to establish a definitive diagnosis. The early diagnosis of this condition is pivotal since the presence of dual pathology worsens patient's prognosis, especially without intervention. Available data on treatment show a better outcome in terms of survival and cardiovascular events in patients undergoing percutaneous correction of valvular heart disease rather than medical therapy alone, regardless of the presence of cardiac amyloidosis. Furthermore, it seems that cardiac amyloidosis does not impact survival after transcatheter aortic valve replacement, even if higher rates of rehospitalizations have been described. Indeed, percutaneous treatment of valvular heart disease is currently considered the primary therapeutic option. Subsequently a disease-modifying treatment for transthyretin amyloidosis may be considered in order to delay disease progression and improve outcomes, even if specific data are still lacking.

Report from a Tibetan Monastery: EEG neural correlates of concentrative and analytical meditation.

The positive effects of meditation on human wellbeing are indisputable, ranging from emotion regulation improvement to stress reduction and present-moment awareness enhancement. Changes in brain activity regulate and support these phenomena. However, the heterogeneity of meditation practices and their cultural background, as well as their poor categorization limit the generalization of results to all types of meditation. Here, we took advantage of a collaboration with the very singular and precious community of the Monks and Geshes of the Tibetan University of Sera-Jey in India to study the neural correlates of the two main types of meditation recognized in Tibetan Buddhism, namely concentrative and analytical meditation. Twenty-three meditators with different levels of expertise underwent to an ecological (i.e., within the monastery) EEG acquisition consisting of an analytical and/or concentrative meditation session at "their best," and with the only constraint of performing a 5-min-long baseline at the beginning of the session. Time-varying power-spectral-density estimates of each session were compared against the baseline (i.e., within session) and between conditions (i.e., analytical vs. concentrative). Our results showed that concentrative meditation elicited more numerous and marked changes in the EEG power compared to analytical meditation, and mainly in the form of an increase in the theta, alpha and beta frequency ranges. Moreover, the full immersion in the Monastery life allowed to share the results and discuss their interpretation with the best scholars of the Monastic University, ensuring the identification of the most expert meditators, as well as to highlight better the differences between the different types of meditation practiced by each of them.

Characterization and natural history of different phenotypes in hereditary transthyretin amyloidosis: 40-year experience at a single Italian referral centre.

AIMS: Hereditary transthyretin amyloidosis (ATTRv) is one of the leading aetiologies of systemic amyloidosis with more than 135 mutations described and a broad spectrum of clinical manifestations. We aimed to provide a systematic description of a population of individuals carrying pathogenic mutations of transthyretin (TTR) gene and to investigate the major clinical events during follow-up. METHODS AND RESULTS: This was an observational, retrospective, cohort study including consecutive patients with mutations of TTR gene, admitted to a tertiary referral centre in Bologna, Italy, between 1984 and 2022. Three hundred twenty-five patients were included: 106 asymptomatic carriers, 49 cardiac phenotype, 49 neurological phenotype, and 121 mixed phenotype. Twenty-two different mutations were found, with Ile68Leu (41.8%), Val30Met (19%), and Glu89Gln (10%) being the most common. After a median follow-up of 51 months, 111 patients (38.3%) died and 9 (11.5%) of the 78 asymptomatic carriers developed ATTRv. Carriers had a prognosis comparable with healthy population, while no significant differences were seen among the three phenotypes adjusted by age. Age at diagnosis, New York Heart Association class III, left ventricular ejection fraction, modified polyneuropathy disability score IV, and disease-modifying therapy were independently associated with survival. CONCLUSION: This study offers a wide and comprehensive overview of ATTRv from the point of view of a tertiary referral centre in Italy. Three main phenotypes can be identified (cardiac, neurological, and mixed) with specific clinical and instrumental features. Family screening programmes are essential to identify paucisymptomatic affected patients or unaffected carriers of the mutation, to be followed through the years. Lastly, disease-modifying therapy represents an evolving cornerstone of the management of ATTRv, with a great impact on mortality.

A total of 325 consecutive patients harbouring a pathogenic mutation in the TTR gene, admitted to a tertiary referral centre in Bologna, Italy, between 1984 and 2022, were included in the study.These patients exhibited significant clinical diversity: 106 were asymptomatic carriers, 49 presented with a cardiac phenotype, 49 had a neurological phenotype, and 121 had a mixed phenotype.Asymptomatic carriers demonstrated a prognosis comparable with healthy population, but some of them may develop signs and symptoms of the disease during follow-up.Survival curves adjusted by age are similar among the three phenotypes.Age at diagnosis, New York Heart Association class, modified polyneuropathy disability score, left ventricular ejection fraction, and disease-modifying therapy were identified as independent factors associated with prognosis.

Time-varying information measures: an adaptive estimation of information storage with application to brain-heart interactions.

Network Physiology is a rapidly growing field of study that aims to understand how physiological systems interact to maintain health. Within the information theory framework the information storage (IS) allows to measure the regularity and predictability of a dynamic process under stationarity assumption. However, this assumption does not allow to track over time the transient pathways occurring in the dynamical activity of a physiological system. To address this limitation, we propose a time-varying approach based on the recursive least squares algorithm (RLS) for estimating IS at each time instant, in non-stationary conditions. We tested this approach in simulated time-varying dynamics and in the analysis of electroencephalographic (EEG) signals recorded from healthy volunteers and timed with the heartbeat to investigate brain-heart interactions. In simulations, we show that the proposed approach allows to track both abrupt and slow changes in the information stored in a physiological system. These changes are reflected in its evolution and variability over time. The analysis of brain-heart interactions reveals marked differences across the cardiac cycle phases of the variability of the time-varying IS. On the other hand, the average IS values exhibit a weak modulation over parieto-occiptal areas of the scalp. Our study highlights the importance of developing more advanced methods for measuring IS that account for non-stationarity in physiological systems. The proposed time-varying approach based on RLS represents a useful tool for identifying spatio-temporal dynamics within the neurocardiac system and can contribute to the understanding of brain-heart interactions.

The impact of cardiac phases on multisensory integration.

The brain continuously processes information coming from both the external environment and visceral signals generated by the body. This constant information exchange between the body and the brain allows signals originating from the oscillatory activity of the heart, among others, to influence perception. Here, we investigated how the cardiac phase modulates multisensory integration, which is the process that allows information from multiple senses to combine non-linearly to reduce environmental uncertainty. Forty healthy participants completed a Simple Detection Task with unimodal (Auditory, Visual, Tactile) and bimodal (Audio-Tactile, Audio-Visual, Visuo-Tactile) stimuli presented 250 ms and 500 ms after the R-peak of the electrocardiogram, that is, systole and diastole, respectively. First, we found a nonspecific effect of the cardiac cycle phases on detection of both unimodal and bimodal stimuli. Reaction times were faster for stimuli presented during diastole, compared to systole. Then, applying the Race Model Inequality approach to quantify multisensory integration, Audio-Tactile and Visuo-Tactile, but not Audio-Visual stimuli, showed higher integration when presented during diastole than during systole. These findings indicate that the impact of the cardiac phase on multisensory integration may be specific for stimuli including somatosensory (i.e., tactile) inputs. This suggests that the heartbeat-related noise, which according to the interoceptive predictive coding theory suppresses somatosensory inputs, also affects multisensory integration during systole. In conclusion, our data extend the interoceptive predictive coding theory to the multisensory domain. From a more mechanistic view, they may reflect a reduced optimization of neural oscillations orchestrating multisensory integration during systole.

Neural Correlates of Non-ordinary States of Consciousness in Pranayama Practitioners: The Role of Slow Nasal Breathing.

The modulatory effect of nasal respiration on integrative brain functions and hence consciousness has recently been unambiguously demonstrated. This effect is sustained by the olfactory epithelium mechanical sensitivity complemented by the existence of massive projections between the olfactory bulb and the prefrontal cortex. However, studies on slow nasal breathing (SNB) in the context of contemplative practices have sustained the fundamental role of respiratory vagal stimulation, with little attention to the contribution of the olfactory epithelium mechanical stimulation. This study aims at disentangling the effects of olfactory epithelium stimulation (proper of nasal breathing) from those related to respiratory vagal stimulation (common to slow nasal and mouth breathing). We investigated the psychophysiological (cardio-respiratory and electroencephalographic parameters) and phenomenological (perceived state of consciousness) aftereffects of SNB (epithelium mechanical - 2.5 breaths/min) in 12 experienced meditators. We compared the nasal breathing aftereffects with those observed after a session of mouth breathing at the same respiratory rate and with those related to a resting state condition. SNB induced (1) slowing of electroencephalography (EEG) activities (delta-theta bands) in prefrontal regions, (2) a widespread increase of theta and high-beta connectivity complemented by an increase of phase-amplitude coupling between the two bands in prefrontal and posterior regions belonging to the Default Mode Network, (3) an increase of high-beta networks small-worldness. (4) a higher perception of being in a non-ordinary state of consciousness. The emerging scenario strongly suggests that the effects of SNB, beyond the relative contribution of vagal stimulation, are mainly ascribable to olfactory epithelium stimulation. In conclusion, slow Pranayama breathing modulates brain activity and hence subjective experience up to the point of inducing a non-ordinary state of consciousness.

Mutual interaction between visual homeostatic plasticity and sleep in adult humans.

Sleep and plasticity are highly interrelated, as sleep slow oscillations and sleep spindles are associated with consolidation of Hebbian-based processes. However, in adult humans, visual cortical plasticity is mainly sustained by homeostatic mechanisms, for which the role of sleep is still largely unknown. Here, we demonstrate that non-REM sleep stabilizes homeostatic plasticity of ocular dominance induced in adult humans by short-term monocular deprivation: the counterintuitive and otherwise transient boost of the deprived eye was preserved at the morning awakening (>6 hr after deprivation). Subjects exhibiting a stronger boost of the deprived eye after sleep had increased sleep spindle density in frontopolar electrodes, suggesting the involvement of distributed processes. Crucially, the individual susceptibility to visual homeostatic plasticity soon after deprivation correlated with the changes in sleep slow oscillations and spindle power in occipital sites, consistent with a modulation in early occipital visual cortex.

A Systematic Review on the Role of Substance Consumption in Work-Related Road Traffic Crashes Reveals the Importance of Biopsychosocial Factors in Prevention.

OBJECTIVE: Since many jobs imply driving, a relevant part of all road traffic crashes (RTC) is related to work. Statistics considering all crashes suggest that they are significantly associated with consumption of substances, but the root causes are not yet clear. The objective of the present paper was to systematically review the scientific literature concerning substances consumption and work-related RTC. We queried the PubMed and Scopus electronic databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were included if they reported all necessary data and survived a quality assessment. We selected a final sample of 30 articles from an initial pool of 7113. As hypothesized, taking any of the considered substances was found to increase the risk of work-related RTC. Descriptive statistics on work-related RTC showed a higher average positivity rate for medicines (14.8%) than for alcohol (3.02%) and drugs (0.84%). Interestingly, the impact of some medications found an unconvincing explanation in the mere occurrence of side effects, and it suggests that psychosocial and/or medical conditions could be better predictors of RTC. We therefore propose an intervention and prevention model that also considers biopsychosocial factors, for which further studies are needed in future research.

Systematic Review of Studies on Subliminal Exposure to Phobic Stimuli: Integrating Therapeutic Models for Specific Phobias.

We systematically review 26 papers investigating subjective, behavioral, and psychophysiological correlates of subliminal exposure to phobic stimuli in phobic patients. Stimulations were found to elicit: (1) cardiac defense responses, (2) specific brain activations of both subcortical (e.g., amygdala) and cortical structures, (3) skin conductance reactions, only when stimuli lasted >20 ms and were administered with intertrial interval >20 s. While not inducing the distress caused by current (supraliminal) exposure therapies, exposure to subliminal phobic stimuli still results in successful extinction of both psychophysiological and behavioral correlates: however, it hardly improves subjective fear. We integrate those results with recent bifactorial models of emotional regulation, proposing a new form of exposure therapy whose effectiveness and acceptability should be maximized by a preliminary subliminal stimulation. Systematic Review Registration: identifier [CRD42021129234].

The Consciousness State of Traditional Nidrâ Yoga/Modern Yoga Nidra: Phenomenological Characterization and Preliminary Insights from an EEG Study.

Nidrâ yoga is an ancient yogic practice capable of inducing altered states of consciousness characterized by deep relaxation, strong concentration, acute self-awareness, and joy. In modern contemplative neuroscience language, it is known by the name yoga nidra, and few studies have investigated its phenomenological and psychophysiological effects. Six healthy volunteers (four females aged 31-74) performed 12 yoga nidra sessions guided by an expert during a 6-day retreat. Each session consisted of 10 minutes in a resting state (baseline) followed by 2 hours of yoga nidra. Psychometric data regarding dissociative experiences (Clinician Administered Dissociative States Scale) and the state of consciousness (Phenomenology of Consciousness Inventory) were collected after baseline and yoga nidra, while high-density EEG was recorded during the entire session. During nidra sessions, no sleep hallmarks (i.e., K-complexes and sleep spindles) were detected by the EEG in any subject. Psychometric data we re analyzed using a Wilcoxon signed-rank test corrected with the false discovery rate approach for multiple comparisons. Compared to baseline, yoga nidra practice was related to: (1) increased dissociative effects (p = 0.022); (2) perception of being in an altered state of consciousness (p = 0.026); (3) alterations in perceived body image (p = 0.022); (4) increased "meaningfulness" attributed to the experience (p = 0.026); (5) reduced rational thinking (p = 0.029); and (6) reduced volitional thought control (p = 0.026). First-person experience is discussed in relation to descriptive EEG power spectral density analysis, which was performed in one subject because of severe EEG artifacts in the other recordings; that subject showed, compared to baseline: (1) early increase of alpha and beta power, followed by a progressive widespread reduction; (2) widespread early increase of theta power, followed by a progressive reduction; and (3) widespread increase of gamma power in the latest stages. The present preliminary results enrich the knowledge of yoga nidra, elucidating its phenomenology and suggesting some psychophysiological correlates that future studies may address.

How Breath-Control Can Change Your Life: A Systematic Review on Psycho-Physiological Correlates of Slow Breathing.

Background: The psycho-physiological changes in brain-body interaction observed in most of meditative and relaxing practices rely on voluntary slowing down of breath frequency. However, the identification of mechanisms linking breath control to its psychophysiological effects is still under debate. This systematic review is aimed at unveiling psychophysiological mechanisms underlying slow breathing techniques (<10 breaths/minute) and their effects on healthy subjects. Methods: A systematic search of MEDLINE and SCOPUS databases, using keywords related to both breathing techniques and to their psychophysiological outcomes, focusing on cardio-respiratory and central nervous system, has been conducted. From a pool of 2,461 abstracts only 15 articles met eligibility criteria and were included in the review. The present systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: The main effects of slow breathing techniques cover autonomic and central nervous systems activities as well as the psychological status. Slow breathing techniques promote autonomic changes increasing Heart Rate Variability and Respiratory Sinus Arrhythmia paralleled by Central Nervous System (CNS) activity modifications. EEG studies show an increase in alpha and a decrease in theta power. Anatomically, the only available fMRI study highlights increased activity in cortical (e.g., prefrontal, motor, and parietal cortices) and subcortical (e.g., pons, thalamus, sub-parabrachial nucleus, periaqueductal gray, and hypothalamus) structures. Psychological/behavioral outputs related to the abovementioned changes are increased comfort, relaxation, pleasantness, vigor and alertness, and reduced symptoms of arousal, anxiety, depression, anger, and confusion. Conclusions: Slow breathing techniques act enhancing autonomic, cerebral and psychological flexibility in a scenario of mutual interactions: we found evidence of links between parasympathetic activity (increased HRV and LF power), CNS activities (increased EEG alpha power and decreased EEG theta power) related to emotional control and psychological well-being in healthy subjects. Our hypothesis considers two different mechanisms for explaining psychophysiological changes induced by voluntary control of slow breathing: one is related to a voluntary regulation of internal bodily states (enteroception), the other is associated to the role of mechanoceptors within the nasal vault in translating slow breathing in a modulation of olfactory bulb activity, which in turn tunes the activity of the entire cortical mantle.