Cluster permutation analysis for EEG series based on non-parametric Wilcoxon–Mann–Whitney statistical tests

Cluster-based permutation tests are widely used in neuroscience studies for the analysis of high-dimensional electroencephalography (EEG) and event-related potential (ERP) data as it may address the multiple comparison problem without reducing the statistical power. However, classical cluster-based permutation analysis relies on parametric t-tests, whose assumptions may not be verified in case of non-normality of the data distribution and alternative options may be considered. To overcome this limitation, here we present a new software for a cluster permutation analysis for EEG series based on non-parametric Wilcoxon–Mann–Whitney tests. We tested both t-test and non-parametric Wilcoxon implementations in two independent datasets of ERPs and EEG spectral data: while t-test-based and non-parametric Wilcoxon-based cluster analyses showed similar results in case of ERP data, the t-test implementation was not able to find clustered effects in case of spectral data. We encourage the use of non-parametric statistics for a cluster permutation analysis of EEG data, and we provide a publicly available software for this computation

Methodological Considerations on EEG Electrical Reference: A Functional Brain-Heart Interplay Study

The growing interest in the study of functional brain-heart interplay (BHI) has motivated the development of novel methodological frameworks for its quantification. While a combination of electroencephalography (EEG) and heartbeat-derived series has been widely used, the role of EEG preprocessing on a BHI quantification is yet unknown. To this extent, here we investigate on four different EEG electrical referencing techniques associated with BHI quantifications over 4-minute resting-state in 15 healthy subjects. BHI methods include the synthetic data generation model, heartbeat-evoked potentials, heartbeat-evoked oscillations, and maximal information coefficient (MIC). EEG signals were offline referenced under the Cz channel, common average, mastoids average, and Laplacian method, and statistical comparisons were performed to assess similarities between references and between BHI techniques. Results show a topographical agreement between BHI estimation methods depending on the specific EEG reference. Major differences between BHI methods occur with the Laplacian reference, while major differences between EEG references are with the MIC analysis. We conclude that the choice of EEG electrical reference may significantly affect a functional BHI quantification

Multivariate Pattern Analysis of Entropy estimates in Fast- and Slow-Wave Functional Near Infrared Spectroscopy: A Preliminary Cognitive Stress study

Functional near infrared spectroscopy (fNIRS) is a modality that can measure shallow cortical brain signals and also contains pulsatile oscillations that originate from heartbeat dynamics. In particular, while fNIRS slow waves (0 Hz to 0.6 Hz) refer to the standard hemodynamic signal, fast-wave (0.8 Hz to 3 Hz) fNIRS signals refer to cardiac oscillations. Using a cognitive stress experiment paradigm with mental arithmetic, the aim of this study was to assess differences in cortical activity when using slow-wave or fast-wave fNIRS signals. Furthermore, we aimed to see whether fNIRS fast and slow waves provide different information to discriminate mental arithmetic tasks from baseline. We used data from 10 healthy subjects from an open dataset performing mental arithmetic tasks and assessed fNIRS signals using mean values in the time domain, as well as complexity estimates including sample, fuzzy, and distribution entropy. A searchlight representational similarity analysis with pairwise t-test group analysis was performed to compare the representational dissimilarity matrices of each searchlight center. We found significant representational differences between fNIRS fast and slow waves for all complexity estimates, at different brain regions. On the other hand, no statistical differences were observed for mean values. We conclude that entropy analysis of fNIRS data may be more sensitive than traditional methods like mean analysis at detecting the additional information provided by fast-wave signals for discriminating mental arithmetic tasks and warrants further research

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 (Formula presented.), (Formula presented.), and (Formula presented.) bands. The proposed approach offers new perspectives for the investigation of functional BHI that could also shed light on various pathophysiological conditions

The Role of EEG Electrical Reference in the Assessment of Functional Brain-Heart Interplay: A Preliminary Study

Recent studies have proposed computational models for a functional brain-heart interplay (BHI) assessment based on electroencephalography (EEG). Nevertheless, the role of the EEG electrical reference on such BHI estimates has not been investigated yet. Here we present a pilot study assessing BHI in 4 minutes resting-state in 10 healthy subjects through methods including heartbeat-evoked potentials (HEP) and oscillations, Maximal Information Coefficient, and our recently proposed model based on Synthetic Data Generation (SDG). EEG signals were re-referenced to the Cz channel, common average, mastoids, and Laplacian. Results for EEG power in the alpha band indicate that the most significant differences between BHI methods are with the Laplacian reference while a higher agreement exists between HEP and SDG approaches

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 concentration

Functional assessment of bidirectional cortical and peripheral neural control on heartbeat dynamics: A brain-heart study on thermal stress

The study of functional Brain-Heart Interplay (BHI) from non-invasive recordings has gained much interest in recent years. Previous endeavors aimed at understanding how the two dynamical systems exchange information, providing novel holistic biomarkers and important insights on essential cognitive aspects and neural system functioning. However, the interplay between cardiac sympathovagal and cortical oscillations still has much room for further investigation. In this study, we introduce a new computational framework for a functional BHI assessment, namely the Sympatho-Vagal Synthetic Data Generation Model, combining cortical (electroencephalography, EEG) and peripheral (cardiac sympathovagal) neural dynamics. The causal, bidirectional neural control on heartbeat dynamics was quantified on data gathered from 26 human volunteers undergoing a cold-pressor test. Results show that thermal stress induces heart-to-brain functional interplay sustained by EEG oscillations in the delta and gamma bands, primarily originating from sympathetic activity, whereas brain-to-heart interplay originates over central brain regions through sympathovagal control. The proposed methodology provides a viable computational tool for the functional assessment of the causal interplay between cortical and cardiac neural control

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 c 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

Confounding effects of heart rate, breathing rate, and frontal fNIRS on interoception

Recent studies have established that cardiac and respiratory phases can modulate perception and related neural dynamics. While heart rate and respiratory sinus arrhythmia possibly affect interoception biomarkers, such as heartbeat-evoked potentials, the relative changes in heart rate and cardiorespiratory dynamics in interoceptive processes have not yet been investigated. In this study, we investigated the variation in heart and breathing rates, as well as higher functional dynamics including cardiorespiratory correlation and frontal hemodynamics measured with fNIRS, during a heartbeat counting task. To further investigate the functional physiology linked to changes in vagal activity caused by specific breathing rates, we performed the heartbeat counting task together with a controlled breathing rate task. The results demonstrate that focusing on heartbeats decreases breathing and heart rates in comparison, which may be part of the physiological mechanisms related to “listening” to the heart, the focus of attention, and self-awareness. Focusing on heartbeats was also observed to increase frontal connectivity, supporting the role of frontal structures in the neural monitoring of visceral inputs. However, cardiorespiratory correlation is affected by both heartbeats counting and controlled breathing tasks. Based on these results, we concluded that variations in heart and breathing rates are confounding factors in the assessment of interoceptive abilities and relative fluctuations in breathing and heart rates should be considered to be a mode of covariate measurement of interoceptive processes

De Novo Unbalanced Translocations in Prader-Willi and Angelman Syndrome Might Be the Reciprocal Product of inv dup(15)s

The 15q11-q13 region is characterized by high instability, caused by the presence of several paralogous segmental duplications. Although most mechanisms dealing with cryptic deletions and amplifications have been at least partly characterized, little is known about the rare translocations involving this region. We characterized at the molecular level five unbalanced translocations, including a jumping one, having most of 15q transposed to the end of another chromosome, whereas the der(15)(pter->q11-q13) was missing. Imbalances were associated either with Prader-Willi or Angelman syndrome. Array-CGH demonstrated the absence of any copy number changes in the recipient chromosome in three cases, while one carried a cryptic terminal deletion and another a large terminal deletion, already diagnosed by classical cytogenetics. We cloned the breakpoint junctions in two cases, whereas cloning was impaired by complex regional genomic architecture and mosaicism in the others. Our results strongly indicate that some of our translocations originated through a prezygotic/postzygotic two-hit mechanism starting with the formation of an acentric 15qter->q1::q1->qter representing the reciprocal product of the inv dup(15) supernumerary marker chromosome. An embryo with such an acentric chromosome plus a normal chromosome 15 inherited from the other parent could survive only if partial trisomy 15 rescue would occur through elimination of part of the acentric chromosome, stabilization of the remaining portion with telomere capture, and formation of a derivative chromosome. All these events likely do not happen concurrently in a single cell but are rather the result of successive stabilization attempts occurring in different cells of which only the fittest will finally survive. Accordingly, jumping translocations might represent successful rescue attempts in different cells rather than transfer of the same 15q portion to different chromosomes. We also hypothesize that neocentromerization of the original acentric chromosome during early embryogenesis may be required to avoid its loss before cell survival is finally assured