Uncovering Hemispheric Asymmetry and Directed Oscillatory Brain-Heart Interplay in Anxiety Processing: An fMRI Study.

Brain-heart interactions (BHI) are critical for generating and processing emotions, including anxiety. Understanding specific neural correlates would be instrumental for greater comprehension and potential therapeutic interventions of anxiety disorders. While prior work has implicated the pontine structure as a central processor in cardiac regulation in anxiety, the distributed nature of anxiety processing across the cortex remains elusive. To address this, we performed a whole-brain-heart analysis using the full frequency directed transfer function to study resting-state spectral differences in BHI between high and low anxiety groups undergoing fMRI scans. Our findings revealed a hemispheric asymmetry in low-frequency interplay (0.05 Hz - 0.15 Hz) characterized by ascending BHI to the left insula and descending BHI from the right insula. Furthermore, we provide evidence supporting the "pacemaker hypothesis", highlighting the pons' function in regulating cardiac activity. Higher frequency interplay (0.2 Hz - 0.4Hz) demonstrate a preference for ascending interactions, particularly towards ventral prefrontal cortical activity in high anxiety groups, suggesting the heart's role in triggering a cognitive response to regulate anxiety. These findings highlight the impact of anxiety on BHI, contributing to a better understanding of its effect on the resting-state fMRI signal, with further implications for potential therapeutic interventions in treating anxiety disorders.

Intracortical brain-heart interplay: An EEG model source study of sympathovagal changes.

The interplay between cerebral and cardiovascular activity, known as the functional brain-heart interplay (BHI), and its temporal dynamics, have been linked to a plethora of physiological and pathological processes. Various computational models of the brain-heart axis have been proposed to estimate BHI non-invasively by taking advantage of the time resolution offered by electroencephalograph (EEG) signals. However, investigations into the specific intracortical sources responsible for this interplay have been limited, which significantly hampers existing BHI studies. This study proposes an analytical modeling framework for estimating the BHI at the source-brain level. This analysis relies on the low-resolution electromagnetic tomography sources localization from scalp electrophysiological recordings. BHI is then quantified as the functional correlation between the intracortical sources and cardiovascular dynamics. Using this approach, we aimed to evaluate the reliability of BHI estimates derived from source-localized EEG signals as compared with prior findings from neuroimaging methods. The proposed approach is validated using an experimental dataset gathered from 32 healthy individuals who underwent standard sympathovagal elicitation using a cold pressor test. Additional resting state data from 34 healthy individuals has been analysed to assess robustness and reproducibility of the methodology. Experimental results not only confirmed previous findings on activation of brain structures affecting cardiac dynamics (e.g., insula, amygdala, hippocampus, and anterior and mid-cingulate cortices) but also provided insights into the anatomical bases of brain-heart axis. In particular, we show that the bidirectional activity of electrophysiological pathways of functional brain-heart communication increases during cold pressure with respect to resting state, mainly targeting neural oscillations in the δ $$ \delta $$ , ß $$ \beta $$ , and γ $$ \gamma $$ bands. The proposed approach offers new perspectives for the investigation of functional BHI that could also shed light on various pathophysiological conditions.

Stochastic brain dynamics exhibits differential regional distribution and maturation-related changes.

Functional magnetic resonance imaging (fMRI) is a powerful non-invasive method for studying brain function by analyzing blood oxygenation level-dependent (BOLD) signals. These signals arise from intricate interplays of deterministic and stochastic biological elements. Quantifying the stochastic part is challenging due to its reliance on assumptions about the deterministic segment. We present a methodological framework to estimate intrinsic stochastic brain dynamics in fMRI data without assuming deterministic dynamics. Our approach utilizes Approximate Entropy and its behavior in noisy series to identify and characterize dynamical noise in unobservable fMRI dynamics. Applied to extensive fMRI datasets (645 Cam-CAN, 1086 Human Connectome Project subjects), we explore lifelong maturation of intrinsic brain noise. Findings indicate 10% to 60% of fMRI signal power is due to intrinsic stochastic brain elements, varying by age. These components demonstrate a physiological role of neural noise which shows a distinct distributions across brain regions and increase linearly during maturation.

Integrative neuro-cardiovascular dynamics in response to test anxiety: A brain-heart axis study.

Test anxiety (TA), a recognized form of social anxiety, is the most prominent cause of anxiety among students and, if left unmanaged, can escalate to psychiatric disorders. TA profoundly impacts both central and autonomic nervous systems, presenting as a dual manifestation of cognitive and autonomic components. While limited studies have explored the physiological underpinnings of TA, none have directly investigated the intricate interplay between the CNS and ANS in this context. In this study, we introduce a non-invasive, integrated neuro-cardiovascular approach to comprehensively characterize the physiological responses of 27 healthy subjects subjected to test anxiety induced via a simulated exam scenario. Our experimental findings highlight that an isolated analysis of electroencephalographic and heart rate variability data fails to capture the intricate information provided by a brain-heart axis assessment, which incorporates an analysis of the dynamic interaction between the brain and heart. With respect to resting state, the simulated examination induced a decrease in the neural control onto heartbeat dynamics at all frequencies, while the studying condition induced a decrease in the ascending heart-to-brain interplay at EEG oscillations up to 12Hz. This underscores the significance of adopting a multisystem perspective in understanding the complex and especially functional directional mechanisms underlying test anxiety.

Physiological Noise: Definition, Estimation, and Characterization in Complex Biomedical Signals.

BACKGROUND: Nonlinear physiological systems exhibit complex dynamics driven by intrinsic dynamical noise. In cases where there is no specific knowledge or assumption about system dynamics, such as in physiological systems, it is not possible to formally estimate noise. AIM: We introduce a formal method to estimate the power of dynamical noise, referred to as physiological noise, in a closed form, without specific knowledge of the system dynamics. METHODOLOGY: Assuming that noise can be modeled as a sequence of independent, identically distributed (IID) random variables on a probability space, we demonstrate that physiological noise can be estimated through a nonlinear entropy profile. We estimated noise from synthetic maps that included autoregressive, logistic, and Pomeau-Manneville systems under various conditions. Noise estimation is performed on 70 heart rate variability series from healthy and pathological subjects, and 32 electroencephalographic (EEG) healthy series. RESULTS: Our results showed that the proposed model-free method can discern different noise levels without any prior knowledge of the system dynamics. Physiological noise accounts for around 11% of the overall power observed in EEG signals and approximately 32% to 65% of the power related to heartbeat dynamics. Cardiovascular noise increases in pathological conditions compared to healthy dynamics, and cortical brain noise increases during mental arithmetic computations over the prefrontal and occipital regions. Brain noise is differently distributed across cortical regions. CONCLUSION: Physiological noise is very part neurobiological dynamics and can be measured using the proposed framework in any biomedical series.

Towards the definition of Microstates of the Cortical Brain-Heart Axis.

Brain microstates are defined as states with quasi-stable scalp activity topography and have been widely studied in literature. Whether those states are brain-specific or extend to the body level is unknown yet. We investigate the extension of cortical microstates to the peripheral autonomic nerve, specifically at the brain-heart axis level as a functional state of the central autonomic network. To achieve this, we combined Electroencephalographic (EEG) and heart rate variability (HRV) series from 36 healthy volunteers undergoing a cognitive workload elicitation after a resting state. Our results showed the existence of microstates at the functional brain-heart axis with spatio-temporal and quasi-stable states that exclusively pertained to the efferent direction from the brain to the heart. Some of the identified microstates are specific for neural or cardiovascular frequency bands, while others topographies are recurrent over the EEG and HRV spectra. Furthermore, some of the identified brain-heart microstates were associated with specific experimental conditions, while others were nonspecific to tasks. Our findings support the hypothesis that EEG microstates extend to the brain-heart axis level and may be exploited in future neuroscience and clinical research.

Characterization of Physiological Noise in Complex Cardiovascular Variability Series.

The cardiovascular system can be analyzed using spectral, nonlinear, and complexity metrics. Nevertheless, dynamical noise may significantly impact these quantifiers. To our knowledge, there has been no attempt to quantify the intrinsic cardiovascular system noise driving heartbeat dynamics. To this end, this study presents a novel, model-free framework to define and quantify physiological noise using nonlinear Approximate Entropy profile. The framework was tested using analytical noisy series and then applied to real Heart Rate Variability (HRV) series gathered from a publicly-available dataset of recordings from 19 young and 19 elderly subjects watching the movie "Fantasia". Results suggest that physiological noise may account for over 15% of cardiovascular dynamics and is influenced by aging, with decreased cardiac noise in the elderly compared to the young subjects. Our findings indicate that physiological noise is a crucial factor in characterizing cardiovascular dynamics, and current spectral, nonlinear, and complexity assessments should take into account underlying dynamical noise estimates.

A Unified Framework for Investigating Aperiodic and Periodic Components in the Hearbeat Dynamics Spectrum: a Feasibility Study.

Heart Rate Variability (HRV) series is a widely used, non-invasive, and easy-to-acquire time-resolved signal for evaluating autonomic control on cardiovascular activity. Despite the recognition that heartbeat dynamics contains both periodic and aperiodic components, the majority of HRV modeling studies concentrate on only one component. On the one hand, there are models based on self-similarity and 1/f behavior that focus on the aperiodic component; on the other hand, there is the conventional division of the spectral domain into narrow-band oscillations, which considers HRV as a combination of periodic components. Taking inspiration from a recent parametrization of EEG power spectra, here we evaluate the applicability of a unified modeling framework to quantitatively assess heartbeat dynamics spectra as a mixture of aperiodic and periodic components. The proposed model is applied on publicly-available, real HRV series collected during postural changes from 10 healthy subjects. Results show that the proposed modeling effectively characterizes different experimental conditions and may complement HRV standard analysis defined in the frequency domain.

Complex Brain-Heart Mapping in Mental and Physical Stress.

OBJECTIVE: The central and autonomic nervous systems are deemed complex dynamic systems, wherein each system as a whole shows features that the individual system sub-components do not. They also continuously interact to maintain body homeostasis and appropriate react to endogenous and exogenous stimuli. Such interactions are comprehensively referred to functional brain-heart interplay (BHI). Nevertheless, it remains uncertain whether this interaction also exhibits complex characteristics, that is, whether the dynamics of the entire nervous system inherently demonstrate complex behavior, or if such complexity is solely a trait of the central and autonomic systems. Here, we performed complexity mapping of the BHI dynamics under mental and physical stress conditions. METHODS AND PROCEDURES: Electroencephalographic and heart rate variability series were obtained from 56 healthy individuals performing mental arithmetic or cold-pressure tasks, and physiological series were properly combined to derive directional BHI series, whose complexity was quantified through fuzzy entropy. RESULTS: The experimental results showed that BHI complexity is mainly modulated in the efferent functional direction from the brain to the heart, and mainly targets vagal oscillations during mental stress and sympathovagal oscillations during physical stress. CONCLUSION: We conclude that the complexity of BHI mapping may provide insightful information on the dynamics of both central and autonomic activity, as well as on their continuous interaction. CLINICAL IMPACT: This research enhances our comprehension of the reciprocal interactions between central and autonomic systems, potentially paving the way for more accurate diagnoses and targeted treatments of cardiovascular, neurological, and psychiatric disorders.

Nonlinear neural patterns are revealed in high frequency functional near infrared spectroscopy analysis.

Functional Near Infrared Spectroscopy (fNIRS) is a useful tool for measuring hemoglobin concentration. Linear theory of the hemodynamic response function supports low frequency analysis (<0.2 Hz). However, we hypothesized that nonlinearities, arising from the complex neurovascular interactions sustaining vasomotor tone, may be revealed in higher frequency components of fNIRS signals. To test this hypothesis, we simulated nonlinear hemodynamic models to explore how blood flow autoregulation changes may alter evoked neurovascular signals in high frequencies. Next, we analyzed experimental fNIRS data to compare neural representations between fast (0.2-0.6 Hz) and slow (<0.2 Hz) waves, demonstrating that only nonlinear representations quantified by sample entropy are distinct between these frequency bands. Finally, we performed group-level distance correlation analysis to show that the cortical distribution of activity is independent only in the nonlinear analysis of fast and slow waves. Our study highlights the importance of analyzing nonlinear higher frequency effects seen in fNIRS for a comprehensive analysis of cortical neurovascular activity. Furthermore, it motivates further exploration of the nonlinear dynamics driving regional blood flow and hemoglobin concentrations.

Predictors of the Use of a Mental Health-Focused eHealth System in Patients With Breast and Prostate Cancer: Bayesian Structural Equation Modeling Analysis of a Prospective Study.

BACKGROUND: eHealth systems have been increasingly used to manage depressive symptoms in patients with somatic illnesses. However, understanding the factors that drive their use, particularly among patients with breast and prostate cancer, remains a critical area of research. OBJECTIVE: This study aimed to determine the factors influencing use of the NEVERMIND eHealth system among patients with breast and prostate cancer over 12 weeks, with a focus on the Technology Acceptance Model. METHODS: Data from the NEVERMIND trial, which included 129 patients with breast and prostate cancer, were retrieved. At baseline, participants completed questionnaires detailing demographic data and measuring depressive and stress symptoms using the Beck Depression Inventory-II and the Depression, Anxiety, and Stress Scale-21, respectively. Over a 12-week period, patients engaged with the NEVERMIND system, with follow-up questionnaires administered at 4 weeks and after 12 weeks assessing the system's perceived ease of use and usefulness. Use log data were collected at the 2- and 12-week marks. The relationships among sex, education, baseline depressive and stress symptoms, perceived ease of use, perceived usefulness (PU), and system use at various stages were examined using Bayesian structural equation modeling in a path analysis, a technique that differs from traditional frequentist methods. RESULTS: The path analysis was conducted among 100 patients with breast and prostate cancer, with 66% (n=66) being female and 81% (n=81) having a college education. Patients reported good mental health scores, with low levels of depression and stress at baseline. System use was approximately 6 days in the initial 2 weeks and 45 days over the 12-week study period. The results revealed that PU was the strongest predictor of system use at 12 weeks (ßuse at 12 weeks is predicted by PU at 12 weeks=.384), whereas system use at 2 weeks moderately predicted system use at 12 weeks (ßuse at 12 weeks is predicted by use at 2 weeks=.239). Notably, there were uncertain associations between baseline variables (education, sex, and mental health symptoms) and system use at 2 weeks, indicating a need for better predictors for early system use. CONCLUSIONS: This study underscores the importance of PU and early engagement in patient engagement with eHealth systems such as NEVERMIND. This suggests that, in general eHealth implementations, caregivers should educate patients about the benefits and functionalities of such systems, thus enhancing their understanding of potential health impacts. Concentrating resources on promoting early engagement is also essential given its influence on sustained use. Further research is necessary to clarify the remaining uncertainties, enabling us to refine our strategies and maximize the benefits of eHealth systems in health care settings.

Microstates of the cortical brain-heart axis.

Electroencephalographic (EEG) microstates are brain states with quasi-stable scalp topography. Whether such states extend to the body level, that is, the peripheral autonomic nerves, remains unknown. We hypothesized that microstates extend at the brain-heart axis level as a functional state of the central autonomic network. Thus, we combined the EEG and heartbeat dynamics series to estimate the directional information transfer originating in the cortex targeting the sympathovagal and parasympathetic activity oscillations and vice versa for the afferent functional direction. Data were from two groups of participants: 36 healthy volunteers who were subjected to cognitive workload induced by mental arithmetic, and 26 participants who underwent physical stress induced by a cold pressure test. All participants were healthy at the time of the study. Based on statistical testing and goodness-of-fit evaluations, we demonstrated the existence of microstates of the functional brain-heart axis, with emphasis on the cerebral cortex, since the microstates are derived from EEG. Such nervous-system microstates are spatio-temporal quasi-stable states that exclusively refer to the efferent brain-to-heart direction. We demonstrated brain-heart microstates that could be associated with specific experimental conditions as well as brain-heart microstates that are non-specific to tasks.

Depression as a cardiovascular disorder: central-autonomic network, brain-heart axis, and vagal perspectives of low mood.

If depressive symptoms are not caused by the physiological effects of a substance or other medical or neurological conditions, they are generally classified as mental disorders that target the central nervous system. However, recent evidence suggests that peripheral neural dynamics on cardiovascular control play a causal role in regulating and processing emotions. In this perspective, we explore the dynamics of the Central-Autonomic Network (CAN) and related brain-heart interplay (BHI), highlighting their psychophysiological correlates and clinical symptoms of depression. Thus, we suggest that depression may arise from dysregulated cardiac vagal and sympathovagal dynamics that lead to CAN and BHI dysfunctions. Therefore, treatments for depression should target the nervous system as a whole, with particular emphasis on regulating vagal and BHI dynamics.

Altering Time Perception in Virtual Reality Through Multimodal Visual-Tactile Kappa Effect.

The perception of time is highly subjective and intertwined with space perception. In a well-known perceptual illusion, called Kappa effect, the distance between consecutive stimuli is modified to induce time distortions in the perceived inter-stimulus interval that are proportional to the distance between the stimuli. However, to the best of our knowledge, this effect has not been characterized and exploited in virtual reality (VR) within a multisensory elicitation framework. This paper investigates the Kappa effect elicited by concurrent visual-tactile stimuli delivered to the forearm, through a multimodal VR interface. This paper compares the outcomes of an experiment in VR with the results of the same experiment performed in the "physical world", where a multimodal interface was applied to participants' forearm to deliver controlled visual-tactile stimuli. Our results suggest that a multimodal Kappa effect can be elicited both in VR and in the physical world relying on concurrent visual-tactile stimulation. Moreover, our results confirm the existence of a relation between the ability of participants in discriminating the duration of time intervals and the magnitude of the experienced Kappa effect. These outcomes can be exploited to modulate the subjective perception of time in VR, paving the path toward more personalised human-computer interaction.

Nervous-System-Wise Functional Estimation of Directed Brain-Heart Interplay Through Microstate Occurrences.

BACKGROUND: The quantification of functional brain-heart interplay (BHI) through analysis of the dynamics of the central and autonomic nervous systems provides effective biomarkers for cognitive, emotional, and autonomic state changes. Several computational models have been proposed to estimate BHI, focusing on a single sensor, brain region, or frequency activity. However, no models currently provide a directional estimation of such interplay at the organ level. OBJECTIVE: This study proposes an analysis framework to estimate BHI that quantifies the directional information flow between whole-brain and heartbeat dynamics. METHODS: System-wise directed functional estimation is performed through an ad-hoc symbolic transfer entropy implementation, which leverages on EEG-derived microstate series and on partition of heart rate variability series. The proposed framework is validated on two different experimental datasets: the first investigates the cognitive workload performed through mental arithmetic and the second focuses on an autonomic maneuver using a cold pressor test (CPT). RESULTS: The experimental results highlight a significant bidirectional increase in BHI during cognitive workload with respect to the preceding resting phase and a higher descending interplay during a CPT compared to the preceding rest and following recovery phases. These changes are not detected by the intrinsic self entropy of isolated cortical and heartbeat dynamics. CONCLUSION: This study corroborates the literature on the BHI phenomenon under these experimental conditions and the new perspective provides novel insights from an organ-level viewpoint. SIGNIFICANCE: A system-wise perspective of the BHI phenomenon may provide new insights into physiological and pathological processes that may not be completely understood at a lower level/scale of analysis.

From local counterfactuals to global feature importance: efficient, robust, and model-agnostic explanations for brain connectivity networks.

BACKGROUND: Explainable artificial intelligence (XAI) is a technology that can enhance trust in mental state classifications by providing explanations for the reasoning behind artificial intelligence (AI) models outputs, especially for high-dimensional and highly-correlated brain signals. Feature importance and counterfactual explanations are two common approaches to generate these explanations, but both have drawbacks. While feature importance methods, such as shapley additive explanations (SHAP), can be computationally expensive and sensitive to feature correlation, counterfactual explanations only explain a single outcome instead of the entire model. METHODS: To overcome these limitations, we propose a new procedure for computing global feature importance that involves aggregating local counterfactual explanations. This approach is specifically tailored to fMRI signals and is based on the hypothesis that instances close to the decision boundary and their counterfactuals mainly differ in the features identified as most important for the downstream classification task. We refer to this proposed feature importance measure as Boundary Crossing Solo Ratio (BoCSoR), since it quantifies the frequency with which a change in each feature in isolation leads to a change in classification outcome, i.e., the crossing of the model's decision boundary. RESULTS AND CONCLUSIONS: Experimental results on synthetic data and real publicly available fMRI data from the Human Connect project show that the proposed BoCSoR measure is more robust to feature correlation and less computationally expensive than state-of-the-art methods. Additionally, it is equally effective in providing an explanation for the behavior of any AI model for brain signals. These properties are crucial for medical decision support systems, where many different features are often extracted from the same physiological measures and a gold standard is absent. Consequently, computing feature importance may become computationally expensive, and there may be a high probability of mutual correlation among features, leading to unreliable results from state-of-the-art XAI methods.

"INTEGRO INTEGRated Psychotherapeutic InterventiOn" on the Management of Chronic Pain in Patients with Fibromyalgia: The Role of the Therapeutic Relationship.

Fibromyalgia (FM) is a chronic disease characterized by a heterogeneous set of physical and psychological conditions. The chronic experience of disability felt by patients and the impact on quality of life (QoL) of the disease may worsen the cognitive reappraisal ability and contribute to maintaining an altered pain modulation mechanism. This paper presents the study protocol of an INTEGRated psychotherapeutic interventiOn on the management of chronic pain in patients with fibromyalgia (INTEGRO). The aim of the study is to investigate the efficacy of an integrated psychotherapeutic intervention focused on pain management on QoL and pain perception, in a pilot sample of 45 FM patients with idiopathic chronic pain. The contribution of perceived therapeutic relationship (alliance) and physiological attunement, in both the patient and therapist, will be considered as possible mediators of intervention efficacy. Attachment dimensions, traumatic experiences, difficulties in emotion regulation, mindfulness attitude and psychophysiological profile will also be considered as covariates. The objectives are to evaluate longitudinally if patients will experience an increase in QoL perception (primary endpoint), pain-managing self-efficacy and emotion-regulation abilities as well as a reduction in pain intensity (secondary endpoints), considering the mediating role of perceived therapeutic alliance and physiological attunement in both the patient and therapist.

Characterization of autonomic states by complex sympathetic and parasympathetic dynamics.

Assessment of heartbeat dynamics provides a promising framework for non-invasive monitoring of cardiovascular and autonomic states. Nevertheless, the non-specificity of such measurements among clinical populations and healthy conditions associated with different autonomic states severely limits their applicability and exploitation in naturalistic conditions. This limitation arises especially when pathological or postural change-related sympathetic hyperactivity is compared to autonomic changes across age and experimental conditions. In this frame, we investigate the intrinsic irregularity and complexity of cardiac sympathetic and vagal activity series in different populations, which are associated with different cardiac autonomic dynamics. Sample entropy, fuzzy entropy, and distribution entropy are calculated on the recently proposed sympathetic and parasympathetic activity indices (SAI and PAI) series, which are derived from publicly available heartbeat series of congestive heart failure patients, elderly and young subjects watching a movie in the supine position, and healthy subjects undergoing slow postural changes. Results show statistically significant differences between pathological/old subjects and young subjects in the resting state and during slow tilt, with interesting trends in SAI- and PAI-related entropy values. Moreover, while CHF patients and healthy subjects in upright position show the higher cardiac sympathetic activity, elderly and young subjects in resting state showed higher vagal activity. We conclude that quantification of intrinsic cardiac complexity from sympathetic and vagal dynamics may provide new physiology insights and improve on the non-specificity of heartbeat-derived biomarkers.

Dynamic fluctuations in ascending heart-to-brain communication under mental stress.

Dynamical information exchange between central and autonomic nervous systems, as referred to functional brain-heart interplay, occurs during emotional and physical arousal. It is well documented that physical and mental stress lead to sympathetic activation. Nevertheless, the role of autonomic inputs in nervous system-wise communication under mental stress is yet unknown. In this study, we estimated the causal and bidirectional neural modulations between electroencephalogram (EEG) oscillations and peripheral sympathetic and parasympathetic activities using a recently proposed computational framework for a functional brain-heart interplay assessment, namely the sympathovagal synthetic data generation model. Mental stress was elicited in 37 healthy volunteers by increasing their cognitive demands throughout three tasks associated with increased stress levels. Stress elicitation induced an increased variability in sympathovagal markers, as well as increased variability in the directional brain-heart interplay. The observed heart-to-brain interplay was primarily from sympathetic activity targeting a wide range of EEG oscillations, whereas variability in the efferent direction seemed mainly related to EEG oscillations in the γ band. These findings extend current knowledge on stress physiology, which mainly referred to top-down neural dynamics. Our results suggest that mental stress may not cause an increase in sympathetic activity exclusively as it initiates a dynamic fluctuation within brain-body networks including bidirectional interactions at a brain-heart level. We conclude that directional brain-heart interplay measurements may provide suitable biomarkers for a quantitative stress assessment and bodily feedback may modulate the perceived stress caused by increased cognitive demand.