Hyper-brain hyper-frequency network topology dynamics when playing guitar in quartet.

Ensemble music performance is a highly coordinated form of social behavior requiring not only precise motor actions but also synchronization of different neural processes both within and between the brains of ensemble players. In previous analyses, which were restricted to within-frequency coupling (WFC), we showed that different frequencies participate in intra- and inter-brain coordination, exhibiting distinct network topology dynamics that underlie coordinated actions and interactions. However, many of the couplings both within and between brains are likely to operate across frequencies. Hence, to obtain a more complete picture of hyper-brain interaction when musicians play the guitar in a quartet, cross-frequency coupling (CFC) has to be considered as well. Furthermore, WFC and CFC can be used to construct hyper-brain hyper-frequency networks (HB-HFNs) integrating all the information flows between different oscillation frequencies, providing important details about ensemble interaction in terms of network topology dynamics (NTD). Here, we reanalyzed EEG (electroencephalogram) data obtained from four guitarists playing together in quartet to explore changes in HB-HFN topology dynamics and their relation to acoustic signals of the music. Our findings demonstrate that low-frequency oscillations (e.g., delta, theta, and alpha) play an integrative or pacemaker role in such complex networks and that HFN topology dynamics are specifically related to the guitar quartet playing dynamics assessed by sound properties. Simulations by link removal showed that the HB-HFN is relatively robust against loss of connections, especially when the strongest connections are preserved and when the loss of connections only affects the brain of one guitarist. We conclude that HB-HFNs capture neural mechanisms that support interpersonally coordinated action and behavioral synchrony.

Dynamics in interbrain synchronization while playing a piano duet.

Humans interact with each other through actions that are implemented by sensory and motor processes. To investigate the role of interbrain synchronization emerging during interpersonal action coordination, electroencephalography data from 13 pairs of pianists were recorded simultaneously while they performed a duet together. The study aimed to investigate whether interbrain phase couplings can be reduced to similar bottom-up driven processes during synchronous play, or rather represent cognitive top-down control required during periods of higher coordination demands. To induce such periods, one of the musicians acted as a confederate who deliberately desynchronized the play. As intended, on the behavioral level, the perturbation caused a breakdown in the synchronization of the musicians' play and in its stability across trials. On the brain level, interbrain synchrony, as measured by the interbrain phase coherence (IPC), increased in the delta and theta frequency bands during perturbation as compared to non-perturbed trials. Interestingly, this increase in IPC in the delta band was accompanied by the shift of the phase difference angle from in-phase toward anti-phase synchrony. In conclusion, the current study demonstrates that interbrain synchronization is based on the interpersonal temporal alignment of different brain mechanisms and is not simply reducible to similar sensory or motor responses.

Intra- and inter-brain coupling and activity dynamics during improvisational music therapy with a person with dementia: an explorative EEG-hyperscanning single case study.

Objective: Real-life research into the underlying neural dynamics of improvisational music therapy, used with various clinical populations, is largely lacking. This single case study explored within-session differences in musical features and in within- and between-brain coupling between a Person with Dementia (PwD) and a music therapist during a music therapy session. Methods: Dual-EEG from a music therapist and a PwD (male, 31 years) was recorded. Note density, pulse clarity and synchronicity were extracted from audio-visual data. Three music therapists identified moments of interest and no interest (MOI/MONI) in two drum improvisations. The Integrative Coupling Index, reflecting time-lagged neural synchronization, and musical features were compared between the MOI and MONI. Results: Between-brain coupling of 2 Hz activity was increased during the MOI, showing anteriority of the therapist's neural activity. Within-brain coupling for the PwD was stronger from frontal and central areas during the MOI, but within-brain coupling for the therapist was stronger during MONI. Differences in musical features indicated that both acted musically more similar to one another during the MOI. Conclusion: Within-session differences in neural synchronization and musical features highlight the dynamic nature of music therapy. Significance: The findings contribute to a better understanding of social and affective processes in the brain and (interactive) musical behaviors during specific moments in a real-life music therapy session. This may provide insights into the role of such moments for relational-therapeutic processes.

Intra- and interbrain synchrony and hyperbrain network dynamics of a guitarist quartet and its audience during a concert.

Playing music in a concert represents a multilevel interaction between musicians and the audience, where interbrain synchronization might play an essential role. Here, we simultaneously recorded electroencephalographs (EEGs) from the brains of eight people during a concert: a quartet of professional guitarists and four participants in the audience. Using phase synchronization analyses between EEG signals within and between brains, we constructed hyperbrain networks, comprising synchronized brain activity across the eight brains, and analyzed them using a graph-theoretical approach. We found that strengths within and between brains in the delta band were higher in the quartet than in the public. Within-brain strengths were higher and between-brain strengths were lower in the music than in the applause condition, both particularly in the quartet group. These changes in coupling strength were accompanied by corresponding changes in the hyperbrain network topology, which were also frequency-specific. Moreover, the network topology and the dynamical structure of guitar sounds showed specific guitar-brain, guitar-guitar, and brain-brain directional associations, indicating multilevel dynamics with upward and downward causation. Finally, the hyperbrain networks exhibit modular structures that were more stable during music performance than during applause. Our findings illustrate complex hyperbrain network interactions in a quartet and its audience during a concert.

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors.

The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.

In touch: Cardiac and respiratory patterns synchronize during ensemble singing with physical contact.

Musical ensemble performances provide an ideal environment to gain knowledge about complex human interactions. Network structures of synchronization can reflect specific roles of individual performers on the one hand and a higher level of organization of all performers as a superordinate system on the other. This study builds on research on joint singing, using hyperscanning of respiration and heart rate variability (HRV) from eight professional singers. Singers performed polyphonic music, distributing their breathing within the same voice and singing without and with physical contact: that is touching each other's shoulder or waist. The idea of singing with touch was motivated by historical depictions of ensemble performances that showed singers touching each other. It raises the question of the potential benefit of touch for group performances. From a psycho-physiological point of view, physical contact should increase the synchronization of singing coordination. The results confirm previous findings on synchronization of respiration and HRV during choir singing and extend those findings to a non-homophonic musical repertoire while also revealing an increase in synchronization in respiration during physical contact. These effects were significant across different frequency ranges. The effect of physical contact was stronger when all singers were singing in comparison to the partial ensemble. Importantly, the synchronization could not be fully explained by the singing action (i.e., singing the same voice, or singing vs. listening) or by the standing position or touch. This finding suggests a higher level of organization of all singers, forming a superordinate system.

Epidemiological and evolutionary consequences of different types of CRISPR-Cas systems.

Bacteria have adaptive immunity against viruses (phages) in the form of CRISPR-Cas immune systems. Currently, 6 types of CRISPR-Cas systems are known and the molecular study of three of these has revealed important molecular differences. It is unknown if and how these molecular differences change the outcome of phage infection and the evolutionary pressure the CRISPR-Cas systems faces. To determine the importance of these molecular differences, we model a phage outbreak entering a population defending exclusively with a type I/II or a type III CRISPR-Cas system. We show that for type III CRISPR-Cas systems, rapid phage extinction is driven by the probability to acquire at least one resistance spacer. However, for type I/II CRISPR-Cas systems, rapid phage extinction is characterized by an a threshold-like behaviour: any acquisition probability below this threshold leads to phage survival whereas any acquisition probability above it, results in phage extinction. We also show that in the absence of autoimmunity, high acquisition rates evolve. However, when CRISPR-Cas systems are prone to autoimmunity, intermediate levels of acquisition are optimal during a phage outbreak. As we predict an optimal probability of spacer acquisition 2 factors of magnitude above the one that has been measured, we discuss the origin of such a discrepancy. Finally, we show that in a biologically relevant parameter range, a type III CRISPR-Cas system can outcompete a type I/II CRISPR-Cas system with a slightly higher probability of acquisition.

Neural Synchrony and Network Dynamics in Social Interaction: A Hyper-Brain Cell Assembly Hypothesis.

Mounting neurophysiological evidence suggests that interpersonal interaction relies on continual communication between cell assemblies within interacting brains and continual adjustments of these neuronal dynamic states between the brains. In this Hypothesis and Theory article, a Hyper-Brain Cell Assembly Hypothesis is suggested on the basis of a conceptual review of neural synchrony and network dynamics and their roles in emerging cell assemblies within the interacting brains. The proposed hypothesis states that such cell assemblies can emerge not only within, but also between the interacting brains. More precisely, the hyper-brain cell assembly encompasses and integrates oscillatory activity within and between brains, and represents a common hyper-brain unit, which has a certain relation to social behavior and interaction. Hyper-brain modules or communities, comprising nodes across two or several brains, are considered as one of the possible representations of the hypothesized hyper-brain cell assemblies, which can also have a multidimensional or multilayer structure. It is concluded that the neuronal dynamics during interpersonal interaction is brain-wide, i.e., it is based on common neuronal activity of several brains or, more generally, of the coupled physiological systems including brains.

The Impact of Genital Ulcers on HIV Transmission Has Been Underestimated-A Critical Review.

In the early 1990s, several observational studies determined that genital ulcer disease (GUD), in either the index or the exposed person, facilitates HIV transmission. Several meta-analyses have since presented associated risk ratios (RR) over the baseline per-act transmission probability (PATP) usually in the range of 2-5. Here we review all relevant observational studies and meta-analyses, and show that the estimation of RRs was, in most cases, biased by assuming the presence of GUD at any time during long follow-up periods, while active genital ulcers were present in a small proportion of the time. Only two studies measured the GUD co-factor effect in PATPs focusing on acts in which ulcers were present, and both found much higher RRs (in the range 11-112). We demonstrate that these high RRs can be reconciled with the studies on which currently accepted low RRs were based, if the calculations are restricted to the actual GUD episodes. Our results indicate that the effect of genital ulcers on the PATP of HIV might be much greater than currently accepted. We conclude that the medical community should work on the assumption that HIV risk is very high during active genital ulcers.

Probing associations between interbrain synchronization and interpersonal action coordination during guitar playing.

Playing music in an ensemble is a highly coordinated human action involving musicians' brain-body interactions at different levels of physical and cortical organization in time and space. It has been suggested that interbrain phase synchronization plays an essential role in musical interaction. In this study, we aimed to explore associations between interbrain synchronization and interpersonal action coordination, using electroencephalographic recordings of the brain activity of guitarists playing in a duet as well as the acoustic recordings of their music. By applying phase synchronization algorithms to the musicians' brain activities and the sounds produced during guitar playing, we show that synchronous brain activity is strongly related to instrument sounds and behavioral play-onset synchrony, as indicated by phase alignment in relation to the time differences in play onsets and an angular-linear correlation between phase and time differences across trials and guitarist pairs. Interestingly, this correlation was especially strong in the first part of the music piece, when the guitarists seem to adjust their coordinated play onsets and brain rhythms actively. This suggests that the methods capturing intra- and interbrain synchronization and its relations to coordinated playing provide crucial information about the underlying mechanisms of interpersonal action coordination.

Interpersonal synchrony when singing in a choir.

Singing in a choir has long been known to enhance well-being and protect mental health. Clearly, the experience of a uniquely harmonious social activity is very satisfying for the singers. How might this come about? One of the important factors positively associated with well-being is interpersonal action coordination allowing the choir to function as a whole. This review focuses on temporal coordination dynamics of physiological systems and/or subsystems forming part or the core of the functional substrate of choir singing. These coordination dynamics will be evaluated with respect to the concept of a superordinate system, or superorganism, based on the principles of self-organization and circular causality. We conclude that choral singing is a dynamic process requiring tight interpersonal action coordination that is characterized by coupled physiological systems and specific network topology dynamics, representing a potent biomarker for social interaction.

Newly Discovered Archival Data Show Coincidence of a Peak of Sexually Transmitted Diseases with the Early Epicenter of Pandemic HIV-1.

To which extent STDs facilitated HIV-1 adaptation to humans, sparking the pandemic, is still unknown. We searched colonial medical records from 1906-1958 for Leopoldville, Belgian Congo, which was the initial epicenter of pandemic HIV-1, compiling counts of treated STD cases in both Africans and Europeans. Almost all Europeans were being treated, while for Africans, generalized treatment started only in 1929. Treated STD counts in Europeans thus reflect STD infection rates more accurately compared to counts in Africans. In Africans, the highest recorded STD treatment incidence was in 1929-1935, declining to low levels in the 1950s. In Europeans, the recorded treatment incidences were highest during the period 1910-1920, far exceeding those in Africans. Europeans were overwhelmingly male and had frequent sexual contact with African females. Consequently, high STD incidence among Europeans must have coincided with high prevalence and incidence in the city's African population. The data strongly suggest the worst STD period was 1910-1920 for both Africans and Europeans, which coincides with the estimated origin of pandemic HIV-1. Given the strong effect of STD coinfections on HIV transmission, these new data support our hypothesis of a causal effect of STDs on the epidemic emergence of HIV-1.

Interactive brains, social minds: Neural and physiological mechanisms of interpersonal action coordination.

It is now widely accepted that inter-brain synchronization is an important and inevitable mechanism of interpersonal action coordination and social interaction behavior. This review of the current literature focuses first on the forward model for interpersonal action coordination and functional system theory for biological systems, two broadly similar concepts for adaptive system behavior. Further, we review interacting-brain and/or hyper-brain dynamics studies, to show the interplay between intra- and inter-brain connectivity resulting in hyper-brain network structure and network topology dynamics, and consider the functioning of interacting brains as a superordinate system. The concept of a superordinate system, or superorganism, is then evaluated with respect to neuronal and physiological systems group dynamics, which show further accompanying mechanisms of interpersonal interaction. We note that fundamental problems need to be resolved to better understand the neural mechanisms of interpersonal action coordination.

Comparison of two simulators for individual based models in HIV epidemiology in a population with HSV 2 in Yaoundé (Cameroon).

Model comparisons have been widely used to guide intervention strategies to control infectious diseases. Agreement between different models is crucial for providing robust evidence for policy-makers because differences in model properties can influence their predictions. In this study, we compared models implemented by two individual-based model simulators for HIV epidemiology in a heterosexual population with Herpes simplex virus type-2 (HSV-2). For each model simulator, we constructed four models, starting from a simplified basic model and stepwise including more model complexity. For the resulting eight models, the predictions of the impact of behavioural interventions on the HIV epidemic in Yaoundé-Cameroon were compared. The results show that differences in model assumptions and model complexity can influence the size of the predicted impact of the intervention, as well as the predicted qualitative behaviour of the HIV epidemic after the intervention. These differences in predictions of an intervention were also observed for two models that agreed in their predictions of the HIV epidemic in the absence of that intervention. Without additional data, it is impossible to determine which of these two models is the most reliable. These findings highlight the importance of making more data available for the calibration and validation of epidemiological models.

Interacting brains coming in sync through their minds: an interbrain neurofeedback study.

Neurophysiological evidence shows that interpersonal action coordination is accompanied by interbrain synchronization (IBS). However, the functional significance of this association remains unclear. Using two experimental designs, we explored whether IBS is amenable to neurofeedback (NFB). Feedback was provided either as two balls approaching each other (so-called ball design), or as two pendula, each reflecting the oscillatory activity of one of the two participants (so-called pendulum design). The NFB was provided at delta (i.e., 2.5 Hz) and theta (i.e., 5 Hz) electroencephalography frequencies, and manipulated by enhanced and inverse feedback. We showed that the participants were able to increase IBS by using NFB, especially when it was fed back at the theta frequency. Apart from intra- and interbrain coupling, other oscillatory activities (e.g., power spectral density, peak amplitude, and peak frequency) also changed during the task compared with the rest. Moreover, all the measures showed specific correlations with the subjective postsurvey item scores, reflecting subjective feeling and appraisal. We conclude that the use of IBS for NFB might help in specifying the contribution of IBS to interpersonal action coordination and in providing important information about the neural mechanisms of social interaction and the causal dimension of IBS.

Behavioral changes before lockdown and decreased retail and recreation mobility during lockdown contributed most to controlling COVID-19 in Western countries.

BACKGROUND: The COVID-19 pandemic has prompted a lockdown in many countries to control the exponential spread of the SARS-CoV-2 virus, hereby reducing the time-varying basic reproduction number (Rt) to below one. Governments are looking for evidence to balance the demand of their citizens to ease some of the restriction, against the fear of a new peak in infections. In this study, we wanted to quantify the relative contribution of mobility restrictions, and that of behavioral changes that occurred already before the lockdowns, on the reduction of transmission during lockdowns in Western countries in early 2020. METHODS: Incidence data of cases and deaths from the first wave of infections for 35 Western countries (32 European, plus Israel, USA and Canada) were analyzed using epidemiological compartment models in a Bayesian framework. Mobility data was used to estimate the timing of changes associated with a lockdown, and was correlated with estimated reductions of Rt. RESULTS: Across all countries, the initial median estimate for Rt was 3.6 (95% IQR 2.4-5.2), and it was reduced to 0.78 (95% IQR 0.58-1.01) during lockdown. 48% (18-65%) of the reduction occurred already in the week before lockdown, with lockdown itself causing the remaining drop in transmission. A lower Rt during lockdown was independently associated with an increased time spent at home (0.21 per 10% more time, p < 0.007), and decreased mobility related to retail and recreation (0.07 per 10% less mobility, p < 0.008). CONCLUSIONS: In a Western population unaware of the risk, SARS-CoV-2 can be highly contagious with a reproduction number R0 > 5. Our results are consistent with evidence that recreational activities (including restaurant and bar visits) enable super-spreading events. Exiting from lockdown therefore requires continued physical distancing and tight control on this kind of activities.

FcRn Overexpression Expands Diversity of the Humoral Immune Response in bFcRn Transgenic Mice.

The neonatal Fc receptor (FcRn) plays key roles in IgG and albumin homeostasis, maternal IgG transport, and antigen presentation of IgG-opsonized antigens. Previously, we reported that transgenic (Tg) mice that overexpress bovine FcRn (bFcRn) have augmented T-dependent humoral immune response with increased IgG protection, higher level of antigen-specific antibodies, greater number of antigen-specific B cells, and effective immune response even against weakly immunogenic epitopes. In this study we analyzed the diversity of the humoral immune response of bFcRn Tg mice, using a length distribution analysis (spectratyping) and next generation sequencing (NGS) of the immunoglobulin heavy chain variable regions. Our analysis showed that in response to immunization with ovalbumin or transfected cells that expressed a unique membrane protein, our Tg animals developed a more diverse plasma cell repertoire than controls, which manifested in greater numbers of different clones, and clusters with fewer highly expanded large clones, as identified by the variable region (CDR3) of the immunoglobulin heavy chain. The increased antibody diversity in Tg mice after immunization was observed at both IgM and IgG levels, indicating that the increased humoral immune diversity in Tg mice is due to a higher number of both activated, antigen-specific naïve and isotype switched B cells. We thus demonstrated that the BCR repertoire of the immunized bFcRn Tg animals is more diverse compared to wild type mice, which likely makes these Tg mice a better choice for monoclonal antibody production against challenging antigens, including the extracellular regions of cell membrane proteins.

Transmitted drug resistance in newly diagnosed and treatment-naïve HIV type 1-infected patients in Hungary.

OBJECTIVES: Transmitted human immunodeficiency virus type 1 (HIV-1) drug resistance (TDR) may affect the success of first-line antiretroviral treatment. This study aimed to monitor the presence of HIV-1 strains carrying transmitted drug resistance-associated mutations (TDRMs) in newly diagnosed and treatment-naïve patients in Hungary. METHODS: This study included 168 HIV-infected individuals diagnosed between 2013-2017; most of them (93.5%) belonged to the homo/bisexual population. HIV-1 subtypes and TDRMs were determined by analysing the protease and reverse transcriptase coding regions of the pol gene by the Stanford HIV Drug Resistance Database. Transmission clusters among patients were identified using phylogenetic analysis. RESULTS: Although subtype B HIV-1 strains were predominant (87.5%), non-B subtypes including F, A, CRF01_AE, CRF02_AG, D and G were also recorded, especially in young adults. The overall prevalence of TDR was 10.7% (18 of 168; 95% CI: 6.9-16.3%). Subtype B HIV-1 strains carried most of the TDRMs (94.4%). Nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were the most prevalent indicators of TDR (16 of 168; 9.5%; 95% CI: 5.9-14.9%), followed by mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (2 of 168; 1.2%; 95% CI: 0.3-4.2%) and protease inhibitors (PIs) (1 of 168, 0.6%; 95% CI: 0.1-3.3%). Phylogenetic analysis revealed that most NRTI-associated resistance mutations were associated with a single monophyletic clade, suggesting early single-source introduction and ongoing spread of this drug-resistant HIV-1 strain. CONCLUSIONS: Onward transmission of drug-resistant subtype B HIV-1 strains accounted for the majority of TDRs observed among treatment-naïve HIV-infected individuals in Hungary.

Network topology dynamics of circulating biomarkers and cognitive performance in older Cytomegalovirus-seropositive or -seronegative men and women.

BACKGROUND: Cytokines are signaling molecules operating within complex cascade patterns and having exceptional modulatory functions. They impact various physiological processes such as neuroendocrine and metabolic interactions, neurotrophins' metabolism, neuroplasticity, and may affect behavior and cognition. In our previous study, we found that sex and Cytomegalovirus (CMV)-serostatus may modulate levels of circulating pro- and anti-inflammatory cytokines, metabolic factors, immune cells, and cognitive performance, as well as associations between them. RESULTS: In the present study, we used a graph-theoretical approach to investigate the network topology dynamics of 22 circulating biomarkers and 11 measures of cognitive performance in 161 older participants recruited to undergo a six-months training intervention. For network construction, we applied coefficient of determination (R 2 ) that was calculated for all possible pairs of variables (N = 33) in four groups (CMV- men and women; CMV+ men and women). Network topology has been evaluated by clustering coefficient (CC) and characteristic path length (CPL) as well as local (E local ) and global (E global ) efficiency, showing the degree of network segregation (CC and E local ) and integration (CPL and E global ). We found that networks under consideration showed small-world networks properties with more random characteristics. Mean CC, as well as local and global efficiency were highest and CPL shortest in CMV- males (having lowest inflammatory status and highest cognitive performance). CMV- and CMV+ females did not show any significant differences. Modularity analyses showed that the networks exhibit in all cases highly differentiated modular organization (with Q-value ranged between 0.397 and 0.453). CONCLUSIONS: In this work, we found that segregation and integration properties of the network were notably stronger in the group with balanced inflammatory status. We were also able to confirm our previous findings that CMV-infection and sex modulate multiple circulating biomarkers and cognitive performance and that balanced inflammatory and metabolic status in elderly contributes to better cognitive functioning. Thus, network analyses provide a useful strategy for visualization and quantitative description of multiple interactions between various circulating pro- and anti-inflammatory biomarkers, hormones, neurotrophic and metabolic factors, immune cells, and measures of cognitive performance and can be in general applied for analyzing interactions between different physiological systems.