Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation.

The process of cellular respiration occurs for energy production through catabolic reactions, generally with glucose as the first process step. In the present work, we introduce a novel concept for understanding this process, based on our conclusion that glucose metabolism is coupled to the pentose phosphate pathway (PPP) and extra-mitochondrial oxidative phosphorylation in a closed-loop process. According to the current standard model of glycolysis, glucose is first converted to glucose 6-phosphate (glucose 6-P) and then to fructose 6-phosphate, glyceraldehyde 3-phosphate and pyruvate, which then enters the Krebs cycle in the mitochondria. However, it is more likely that the pyruvate will be converted to lactate. In the PPP, glucose 6-P is branched off from glycolysis and used to produce NADPH and ribulose 5-phosphate (ribulose 5-P). Ribulose 5-P can be converted to fructose 6-P and glyceraldehyde 3-P. In our view, a circular process can take place in which the ribulose 5-P produced by the PPP enters the glycolysis pathway and is then retrogradely converted to glucose 6-P. This process is repeated several times until the complete degradation of glucose 6-P. The role of mitochondria in this process is to degrade lipids by beta-oxidation and produce acetyl-CoA; the function of producing ATP appears to be only secondary. This proposed new concept of cellular bioenergetics allows the resolution of some previously unresolved controversies related to cellular respiration and provides a deeper understanding of metabolic processes in the cell, including new insights into the Warburg effect.

Cerebral, systemic physiological and behavioral responses to colored light exposure during a cognitive task: A SPA-fNIRS study.

Colored light has important implications for human health and well-being, as well as for the aesthetics and function of various environments. In addition to its effects on visual function, colored light has significant effects on cognitive performance, behavior and systemic physiology. The aim of the current study was to comprehensively investigate how colored light exposure (CLE) combined with a cognitive task (2-back) affects performance, cerebral hemodynamics, oxygenation, and systemic physiology as assessed by systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). 36 healthy subjects (22 female, 14 male, age 26.3 ± 5.7 years) were measured twice on two different days. They were exposed to the sequence of blue and red light or vice versa in a randomized crossover design. During the CLE, the subjects were asked to perform a 2-back task. The 2-back task performance was correlated with changes in the concentration of oxygenated hemoglobin in the prefrontal cortex (red: r = -0.37, p = 0.001; blue: r = -0.33, p = 0.004) and the high-frequency component of the heart rate variability (red: r = 0.35, p = 0.003; blue: r = 0.25, p = 0.04). These changes were independent of the CLE. Sequence-dependent effects were observed for fNIRS signals at the visual cortex (VC) and for electrodermal activity (EDA). While both colors caused relatively similar changes in the VC and EDA at the position of the first exposure, blue and red light caused greater changes in the VC and EDA, respectively, in the second exposure. There was no significant difference in the subjects' 2-back task performance between the CLE (p = 0.46). The results of this study provide new insights into how human physiology and behavior respond to colored light exposure. Our findings are important for understanding the impact of colored light in our daily lives and its potential applications in a variety of settings, including education, the workplace and healthcare.

Infradian Rhythms in Cerebrovascular Oxygenation and Blood Volume in Humans at Rest: A 5-Year Study.

BACKGROUND: All parameters of human physiology show chronobiological variability. While circadian (cycle length ~ 24 h) rhythms of the neuronal, hemodynamic and metabolic aspects of human brain activity are increasingly being explored, infradian (cycle length > 24 h) rhythms are largely unexplored. AIM: We investigated if cerebrovascular oxygen saturation (StO2) and blood volume ([tHb]) values measured over many years in many subjects during resting show infradian rhythmicity. SUBJECTS AND METHODS:  Absolute StO2 and [tHb] values (median over a 5 min resting-phase while sitting) were measured in 220 healthy subjects (age: 24.7 ± 3.6 years, 87 males, 133 females) 2-4 times on different days over the right and left frontal lobe (FL) and occipital lobe (OL) by employing frequency-domain NIRS as part of different systemic physiology augmented functional near-infrared spectroscopy, SPA-fNIRS, studies. The data set consisted of 708 single measurements performed over a timespan of 5 years (2017-2021). General additive models (GAM) and cosinor modelling were used to analyze the data. RESULTS:  The GAM analysis revealed (i) a non-linear trend in the StO2 and [tHb] values over the 5-year span, (ii) a circannual (cycle length ~ 12 months) rhythm in StO2 at the FL (amplitude (A): 3.4%, acrophase (φ): June) and OL (A: 1.5%, φ: May) as well as in [tHb] at the OL (A: 1.2 µM, bathyphase (θ): June), and (iii) a circasemiannual (cycle length ~ 6 months) rhythm in [tHb] at the FL (A: 2.7 µM, φ: March and September, respectively). Furthermore, the circannual oscillations of StO2 (at the FL) and [tHb] (at the OL) were statistically significantly correlated with the day length, outdoor temperature, humidity and air pressure. DISCUSSION AND CONCLUSION:  We conclude that absolute values of StO2 and [tHb] show chronobiological variability on the group-level with a long-term nonlinear trend as well as circannual/circasemiannual rhythmicity. These rhythms need to be taken into account when defining reference values for StO2 and [tHb] and may correlate with the variability of cerebrovascular disease incidents over the year.

Differences Between Good, Moderate and Poor Performers of a Verbal Fluency Task under Blue Light Exposure: An SPA-fNIRS Study.

Individuals have different performance levels for cognitive tasks. Are these performance levels reflected in physiological parameters? The aim of this study was to address this question by systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). We aimed to investigate whether different verbal fluency task (VFT) performances under blue light exposure were associated with different changes in cerebrovascular oxygenation and systemic physiological activity. The VFT performance of 32 healthy subjects (17 female, 15 male, age: 25.5 ± 4.3 years) was investigated under blue light exposure (120 lux). The VFT, which contained letter and category fluency tasks, lasted 9 min. There were rest periods without light exposure before and after the VFT for 8 min and 15 min, respectively. Based on their number of correct responses, subjects were classified into three groups, i.e., good, moderate, and poor performers. During the entire experiment, we simultaneously measured changes in cerebral and systemic physiological parameters using the SPA-fNIRS approach. We found that the better the subject's performance was, the smaller the task-evoked changes in cerebrovascular hemodynamics and oxygenation in the prefrontal cortex. Performance-dependent changes were also evident for skin conductance, arterial oxygen saturation and mean arterial pressure. This is the first VFT study that applies the comprehensive SPA-fNIRS approach to determine the relationship between task performance and changes in cerebral oxygenation and systemic physiology. Our study shows that these parameters are indeed related and the performance is reflected in the task-evoked cerebrovascular and systemic physiological changes.

The Significance of Lipids for the Absorption and Release of Oxygen in Biological Organisms.

A critically important step for the uptake and transport of oxygen (O2) in living organisms is the crossing of the phase boundary between gas (or water) and lipid/proteins in the cell. Classically, this transport across the phase boundary is explained as a transport by proteins or protein-based structures. In our contribution here, we want to show the significance of passive transport of O2 also (and in some cases probably predominantly) through lipids in many if not all aerobic organisms. In plants, the significance of lipids for gas exchange (absorption of CO2 and release of O2) is well recognized. The leaves of plants have a cuticle layer as the last film on both sides formed by polyesters and lipids. In animals, the skin has sebum as its last layer consisting of a mixture of neutral fatty esters, cholesterol and waxes which are also at the border between the cells of the body and the air. The last cellular layers of skin are not vascularized therefore their metabolism totally depends on this extravasal O2 absorption, which cannot be replenished by the bloodstream. The human body absorbs about 0.5% of O2 through the skin. In the brain, myelin, surrounding nerve cell axons and being formed by oligodendrocytes, is most probably also responsible for enabling O2 transport from the extracellular space to the cells (neurons). Myelin, being not vascularized and consisting of water, lipids and proteins, seems to absorb O2 in order to transport it to the nerve cell axon as well as to perform extramitochondrial oxidative phosphorylation inside the myelin structure around the axons (i.e., myelin synthesizes ATP) - similarly to the metabolic process occurring in concentric multilamellar structures of cyanobacteria. Another example is the gas transport in the lung where lipids play a crucial role in the surfactant ensuring incorporation of O2 in the alveoli where there are lamellar body and tubular myelin which form multilayered surface films at the air-membrane border of the alveolus. According to our view, the role played by lipids in the physical absorption of gases appears to be crucial to the existence of many, if not all, of the living aerobic species.

Effects of optogenetic and visual stimulation on gamma activity in the visual cortex.

Studying brain functions and activity during gamma oscillations can be a challenge because it requires careful planning to create the necessary conditions for a controlled experiment. Such an experiment consists of placing the brain into a gamma state and investigating cognitive processing with a careful design. Cortical oscillations in the gamma frequency range (30-80 Hz) play an essential role in a variety of cognitive processes, including visual processing and cognition. The present study aims to investigate the effects of a visual stimulus on the primary visual cortex under gamma oscillations. Specifically, we sought to explore the behavior of gamma oscillations triggered by optogenetic stimulation in the II and IV layers of the visual cortex, both with and without concurrent visual stimulation. Our results show that optogenetic stimulation increases the power of gamma oscillation in both layers of the visual cortex. However, the combined stimuli resulted in a reduction of gamma power in layer II and an increase and reinforcement in gamma power in layer IV. Modelling the results with the Wilson-Cowan model suggests changes in the input of the excitatory population due to the combined stimuli. In addition, our analysis of the data using the Lempel-Ziv complexity method supports our interpretations from the modeling. Thus, our results suggest that optogenetic stimulation enhances low gamma power in both layers of the visual cortex, while simultaneous visual stimulation has differing effects on the two layers, reducing gamma power in layer II and increasing it in layer IV.

How our hearts beat together: a study on physiological synchronization based on a self-paced joint motor task.

Cardiac physiological synchrony is regarded as an important component of social interaction due to its putative role in prosocial behaviour. Yet, the processes underlying physiological synchrony remain unclear. We aim to investigate these processes. 20 dyads (19 men, 21 women, age range 18-35) engaged in a self-paced interpersonal tapping synchronization task under different levels of tapping synchrony due to blocking of sensory communication channels. Applying wavelet transform coherence analysis, significant increases in heart rate synchronization from baseline to task execution were found with no statistically significant difference across conditions. Furthermore, the control analysis, which assessed synchrony between randomly combined dyads of participants showed no difference from the original dyads' synchrony. We showed that interindividual cardiac physiological synchrony during self-paced synchronized finger tapping resulted from a task-related stimulus equally shared by all individuals. We hypothesize that by applying mental effort to the task, individuals changed into a similar mental state, altering their cardiac regulation. This so-called psychophysiological mode provoked more uniform, less variable fluctuation patterns across all individuals leading to similar heart rate coherence independent of subsequent pairings. With this study, we provide new insights into cardiac physiological synchrony and highlight the importance of appropriate study design and control analysis.

Measuring acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans using TD-fNIRS.

Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n = 15, 8 females, 7 males, age 32.4 ± 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations, and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our study demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine in humans, and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings.

Effects of serotonergic psychedelics on mitochondria: Transdiagnostic implications for mitochondria-related pathologies.

The use of serotonergic psychedelics has gained increasing attention in research, clinical practice and society. Growing evidence suggests fast-acting, transdiagnostic health benefits of these 5-hydroxytryptamine 2A receptor agonists. Here, we provide a brief overview of their benefits for psychological, cardiovascular, metabolic, neurodegenerative, and immunological pathologies. We then review their effect on mitochondria including mitochondrial biogenesis, functioning and transport. Mitochondrial dysregulation is a transdiagnostic mechanism that contributes to the aforementioned pathologies. Hence, we postulate that psychedelic-induced effects on mitochondria partially underlie their transdiagnostic benefits. Based on this assumption, we propose new treatment indications for psychedelics and that the health benefits induced by psychedelics depend on patient-specific mitochondrial dysregulation.

COVID-19, post-acute COVID-19 syndrome (PACS, "long COVID") and post-COVID-19 vaccination syndrome (PCVS, "post-COVIDvac-syndrome"): Similarities and differences.

Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and over 13 billion COVID-19 vaccine doses have been administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to an acute disease, i.e. COVID-19, but also to a post-acute COVID-19 syndrome (PACS, "long COVID"). Currently, the side effects of COVID-19 vaccines are increasingly being noted and studied. Here, we summarise the currently available indications and discuss our conclusions that (i) these side effects have specific similarities and differences to acute COVID-19 and PACS, that (ii) a new term should be used to refer to these side effects (post-COVID-19 vaccination syndrome, PCVS, colloquially "post-COVIDvac-syndrome"), and that (iii) there is a need to distinguish between acute COVID-19 vaccination syndrome (ACVS) and post-acute COVID-19 vaccination syndrome (PACVS) - in analogy to acute COVID-19 and PACS ("long COVID"). Moreover, we address mixed forms of disease caused by natural SARS-CoV-2 infection and COVID-19 vaccination. We explain why it is important for medical diagnosis, care and research to use the new terms (PCVS, ACVS and PACVS) in order to avoid confusion and misinterpretation of the underlying causes of disease and to enable optimal medical therapy. We do not recommend to use the term "Post-Vac-Syndrome" as it is imprecise. The article also serves to address the current problem of "medical gaslighting" in relation to PACS and PCVS by raising awareness among the medical professionals and supplying appropriate terminology for disease.

From Localized Mild Hyperthermia to Improved Tumor Oxygenation: Physiological Mechanisms Critically Involved in Oncologic Thermo-Radio-Immunotherapy.

(1) Background: Mild hyperthermia (mHT, 39-42 °C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy. mHT triggers a series of therapeutically relevant biological mechanisms, e.g., it can act as a radiosensitizer by improving tumor oxygenation, the latter generally believed to be the commensurate result of increased blood flow, and it can positively modulate protective anticancer immune responses. However, the extent and kinetics of tumor blood flow (TBF) changes and tumor oxygenation are variable during and after the application of mHT. The interpretation of these spatiotemporal heterogeneities is currently not yet fully clarified. (2) Aim and methods: We have undertaken a systematic literature review and herein provide a comprehensive insight into the potential impact of mHT on the clinical benefits of therapeutic modalities such as radio- and immuno-therapy. (3) Results: mHT-induced increases in TBF are multifactorial and differ both spatially and with time. In the short term, changes are preferentially caused by vasodilation of co-opted vessels and of upstream normal tissue vessels as well as by improved hemorheology. Sustained TBF increases are thought to result from a drastic reduction of interstitial pressure, thus restoring adequate perfusion pressures and/or HIF-1α- and VEGF-mediated activation of angiogenesis. The enhanced oxygenation is not only the result of mHT-increased TBF and, thus, oxygen availability but also of heat-induced higher O2 diffusivities, acidosis- and heat-related enhanced O2 unloading from red blood cells. (4) Conclusions: Enhancement of tumor oxygenation achieved by mHT cannot be fully explained by TBF changes alone. Instead, a series of additional, complexly linked physiological mechanisms are crucial for enhancing tumor oxygenation, almost doubling the initial O2 tensions in tumors.

The significance of bioelectricity on all levels of organization of an organism. Part 1: From the subcellular level to cells.

Bioelectricity plays an essential role in the structural and functional organization of biological organisms. In this first article of our three-part series, we summarize the importance of bioelectricity for the basic structural level of biological organization, i.e. from the subcellular level (charges, ion channels, molecules and cell organelles) to cells.

Psychedelics and fNIRS neuroimaging: exploring new opportunities.

In this Outlook paper, we explain to the optical neuroimaging community as well as the psychedelic research community the great potential of using optical neuroimaging with functional near-infrared spectroscopy (fNIRS) to further explore the changes in brain activity induced by psychedelics. We explain why we believe now is the time to exploit the momentum of the current resurgence of research on the effects of psychedelics and the momentum of the increasing progress and popularity of the fNIRS technique to establish fNIRS in psychedelic research. With this article, we hope to contribute to this development.

Changes in Cerebral Oxygenation and Systemic Physiology During a Verbal Fluency Task: Differences Between Men and Women.

BACKGROUND: Sex differences in behavioural performance of a cognitive task have been repeatedly reported in the literature. Whether such differences are also relevant for evoked cerebral haemodynamic and oxygenation responses as well as systemic physiological changes is a topic of ongoing investigations. AIM: We investigated whether changes in cerebral oxygenation and systemic physiological activity are sex-dependent during a verbal fluency task (VFT). SUBJECTS AND METHODS: VFT performance and changes in cerebral oxygenation and systemic physiology were investigated in 32 healthy right-handed adults (17 females, 15 males, age: 25.5 ± 4.3 years). The total duration of the VFT was 9 min. During this phase, subjects were also exposed to blue light (peak wavelength: 450 nm, illuminance: 120 lux). Before and after the VFT, subjects were in darkness. In this study, we used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. Absolute concentration changes of oxyhaemoglobin ([O2Hb]), deoxyhaemoglobin ([HHb]), total haemoglobin ([tHb]), as well as tissue oxygen saturation (StO2) were measured bilaterally over the prefrontal cortex (PFC) and visual cortex (VC). Systemic physiological parameters were also recorded in parallel (e.g., end-tidal CO2, heart rate, respiration rate, skin conductance). RESULTS: We found that: (i) Females were better VFT performers in comparison to males. (ii) Changes in [O2Hb] and [HHb] in the VC were higher for males compared to females during the VFT under blue light exposure. (iii) Lower and higher StO2 changes were detected for males compared to females in the PFC and VC, respectively. (iv) Sex-dependent changes were also evident for end-tidal CO2, heart rate, respiration rate, and pulse-respiration quotient. CONCLUSIONS: Our study showed that sex differences are not only observed in task performance but also in the magnitudes of changes in cerebral and physiological parameters. The findings of the current study emphasise that sex differences in brain activation and systemic physiological activity need to be considered when interpreting functional neuroimaging data. These findings offer a broad range of implications for educational purposes and facilitate a better understanding of the effects of sex on behavioural performance as well as human physiology.

Frontal Cerebral Oxygenation in Humans at Rest: A Mirror Symmetry in the Correlation with Cardiorespiratory Activity.

BACKGROUND: Although several studies published reference values for frontal cerebral tissue oxygen saturation (StO2) measured with near-infrared spectroscopy (NIRS) based cerebral oximetry, a detailed investigation, whether and which factors from systemic physiology are related to the individual StO2 values, is missing. AIM: We investigated how the state of the cardiorespiratory system is linked to StO2 values at rest. SUBJECTS AND METHODS: Absolute StO2 values (median over a 5 min resting-phase while sitting) were obtained from 126 healthy subjects (age: 24.0 ± 0.2 years, 45 males, 81 females) over the left and right prefrontal cortex (PFC) by employing frequency-domain NIRS as part of a systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) study. In addition, heart rate (HR) and respiration rate (RR) were measured, and the pulse respiration quotient (PRQ) was determined (PRQ = HR/RR). General additive models (GAM) were used to analyse the data. RESULTS: The GAM analysis revealed a specific relationship between the overall PFC StO2 values (mean over right and left PFC) and the variables HR and RR: HR was positively correlated with mean StO2, while RR showed no correlation. In the mirror case, RR was negatively linearly correlated with the frontal cerebral oxygenation asymmetry (FCOA), which was not correlated with HR. The right PFC StO2 was not linked to the RR, whereas the left PFC StO2 was. Positive correlations of the PRQ with the mean PFC StO2 as well as the FCOA were also found. GAM modelling revealed that the individual FCOA values are explained to a large extent (deviance explained: 88.8%) by the individual mean PFC StO2 and PRQ. We conclude that (i) the state of the cardiorespiratory system is significantly correlated with StO2 values and (ii) there is a mirror symmetry with regard to the impact of cardiorespiratory parameters on the mean PFC StO2 and FCOA.

Cross-Frequency Coupling Between Brain and Body Biosignals: A Systemic Physiology Augmented Functional Near-Infrared Spectroscopy Hyperscanning Study.

BACKGROUND: Understanding the brain and body processes during interaction or cooperation between two or more subjects is an important topic in current neuroscientific research. In a previous study, we introduced a novel approach that enables investigation of the coupling of biosignals (brain and systemic physiology, SP) from two subjects: systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) hyperscanning. AIM: The aim was to extend our signal analysis approach by the cross-frequency time-dependent wavelet transform coherence (WTC) of the fNIRS and SP biosignals to gain new insights into the nature and cause of functional hyperconnectivity. SUBJECTS AND METHODS: 24 pairs of adults took part in a closed-eye versus prolonged eye-contact task of 10 min each. Brain and body activity was measured continuously by SPA-fNIRS hyperscanning. We calculated the time-dependent WTC of the biosignals for four different frequency bands: very low-frequency band (VLF, 0.002-0.08 Hz), low-frequency band 1 (LF1, 0.015-0.15 Hz), low-frequency band 2 (LF2, 0.08-0.15 Hz) and heart rate band (HR, 1-2 Hz). We then performed the cross-frequency correlated-coherence coupling analysis. RESULTS: A stronger cross-frequency coupling during the eye-contact condition (between 99 pairs of biosignals) was found than during the eye-closed condition (between 50 pairs of biosignals). Prolonged eye contact led to entrainment of the brain and body between different frequency bands and two subjects. The strongest hyperconnectivity was between the LF1-VLF frequency band. DISCUSSION AND CONCLUSION: With this exploratory study, we reveal further benefits of the SPA-fNIRS approach for future hyperscanning studies.

Machine Learning Distinguishes Familiar from Unfamiliar Pairs of Subjects Performing an Eye Contact Task: A Systemic Physiology Augmented Functional Near-Infrared Spectroscopy Hyperscanning Study.

BACKGROUND: Eye contact is an important aspect of human communication and social interactions. Changes in brain and systemic physiological activity associated with interactions between humans can be measured with systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) hyperscanning, enabling inter-brain and inter-body synchronisation to be determined. In a previous study, we found that pairs of subjects that are socially connected show higher brain and body synchrony. AIM: To enable a deeper understanding, our aim was to build and automatically detect the best set of features to distinguish between two different groups (familiar and unfamiliar pairs). MATERIAL AND METHODS: We defined several features based on the Spearman correlation and wavelet transform coherence (WTC) of biosignals measured on 23 pairs of subjects (13 familiar and 10 unfamiliar pairs) during eye contact for 10 min. Additional custom features that identify the maximum brain-to-body coupling instants between pairs were generated. RESULTS: After testing on combinations of different feature extraction methods, four subsets of features with the strongest discrimination power were taken into account to train a decision tree (DT) machine learning (ML) algorithm. We have obtained 95.65% classification accuracy using a leave-one-out cross-validation. The coupling features which represent the two maximum mean values resulting from the sum of 7 time-dependent WTC signals (oxyhaemoglobin concentration of the right prefrontal region, total haemoglobin concentration of the left and right prefrontal region, heart rate, electrodermal activity on the left and right wrist, and skin temperature on the right wrist) played an essential role in the classification accuracy. CONCLUSION: Training the DT-ML algorithm with combined brain and systemic physiology data provided higher accuracy than training it only with brain or systemic data alone. The results demonstrate the power of the SPA-fNIRS hyperscanning approach and the potential in applying ML to investigate the strength of social bonds in a wide range of social interaction contexts.

Intersubject Variability in Cerebrovascular Hemodynamics and Systemic Physiology during a Verbal Fluency Task under Colored Light Exposure: Clustering of Subjects by Unsupervised Machine Learning.

There is large intersubject variability in cerebrovascular hemodynamic and systemic physiological responses induced by a verbal fluency task (VFT) under colored light exposure (CLE). We hypothesized that machine learning would enable us to classify the response patterns and provide new insights into the common response patterns between subjects. In total, 32 healthy subjects (15 men and 17 women, age: 25.5 ± 4.3 years) were exposed to two different light colors (red vs. blue) in a randomized cross-over study design for 9 min while performing a VFT. We used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach to measure cerebrovascular hemodynamics and oxygenation at the prefrontal cortex (PFC) and visual cortex (VC) concurrently with systemic physiological parameters. We found that subjects were suitably classified by unsupervised machine learning into different groups according to the changes in the following parameters: end-tidal carbon dioxide, arterial oxygen saturation, skin conductance, oxygenated hemoglobin in the VC, and deoxygenated hemoglobin in the PFC. With hard clustering methods, three and five different groups of subjects were found for the blue and red light exposure, respectively. Our results highlight the fact that humans show specific reactivity types to the CLE-VFT experimental paradigm.

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.

Systemic physiology augmented functional near-infrared spectroscopy: a powerful approach to study the embodied human brain.

In this Outlook paper, we explain why an accurate physiological interpretation of functional near-infrared spectroscopy (fNIRS) neuroimaging signals is facilitated when systemic physiological activity (e.g., cardiorespiratory and autonomic activity) is measured simultaneously by employing systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). The rationale for SPA-fNIRS is twofold: (i) SPA-fNIRS enables a more complete interpretation and understanding of the fNIRS signals measured at the head since they contain components originating from neurovascular coupling and from systemic physiological sources. The systemic physiology signals measured with SPA-fNIRS can be used for regressing out physiological confounding components in fNIRS signals. Misinterpretations can thus be minimized. (ii) SPA-fNIRS enables to study the embodied brain by linking the brain with the physiological state of the entire body, allowing novel insights into their complex interplay. We envisage the SPA-fNIRS approach will become increasingly important in the future.