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.

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.

Neurofluid coupling during sleep and wake states.

BACKGROUND: In clinical populations, the movement of cerebrospinal fluid (CSF) during sleep is a growing area of research with potential mechanistic connections in both neurodegenerative (e.g., Alzheimer's Disease) and neurodevelopmental disorders. However, we know relatively little about the processes that influence CSF movement. To inform clinical intervention targets this study assesses the coupling between (a) real-time CSF movement, (b) neuronal-driven movement, and (c) non-neuronal systemic physiology driven movement. METHODS: This study included eight young, healthy volunteers, with concurrently acquired neurofluid dynamics using functional Magnetic Resonance Imaging (MRI), neural activity using Electroencephalography (EEG), and non-neuronal systemic physiology with peripheral functional Near-Infrared Spectroscopy (fNIRS). Neuronal and non-neuronal drivers were assessed temporally; wherein, EEG measured slow wave activity that preceded CSF movement was considered neuronally driven. Similarly, slow wave oscillations (assessed via fNIRS) that coupled with CSF movement were considered non-neuronal systemic physiology driven. RESULTS AND CONCLUSIONS: Our results document neural contributions to CSF movement were only present during light NREM sleep but low-frequency non-neuronal oscillations were strongly coupled with CSF movement in all assessed states - awake, NREM-1, NREM-2. The clinical/research implications of these findings are two-fold. First, neuronal-driven oscillations contribute to CSF movement outside of deep sleep (NREM-3); therefore, interventions aimed at increasing CSF movement may yield meaningful increases with the promotion of NREM sleep more generally - a focus on NREM S3 may not be needed. Second, non-neuronal systemic oscillations contribute across wake and sleep stages; therefore, interventions may increase CSF movement by manipulating systemic physiology.

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.

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.

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.

The Role of Systemic Physiology in Individual Hemodynamic Responses Measured on the Head Due to Long-Term Stimulation Involving Colored Light Exposure and a Cognitive Task: An SPA-fNIRS Study.

In our previous investigations using systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) neuroimaging, we found larger variability between subjects in changes of cerebral hemodynamics and oxygenation induced by an intricate experimental paradigm involving colored light exposure and a cognitive task. We aimed to investigate the role the activity of the systemic physiology has on individual variations in the fNIRS data. Thirty-two healthy subjects (17 female, 15 male and age: 25.5 ± 4.3 years) were exposed to blue and red light for 9 min (colored light exposure, CLE) while performing a verbal fluency task (VFT). We found that (i), at the group level, the visual cortex showed a stronger deoxyhemoglobin concentration response during blue light exposure than during red light exposure, and (ii) this relationship was influenced by individually different baseline blood pressure values. Furthermore, we found other correlations between changes in fNIRS signals and changes in systemic physiology. Our study demonstrates the usefulness and necessity of the SPA-fNIRS approach to gain insights into the individual variability of hemodynamic responses measured with fNIRS, especially in the case of an intricate experimental paradigm (i.e., CLE-VFT) as used in our study.

Systemic physiology augmented functional near-infrared spectroscopy hyperscanning: a first evaluation investigating entrainment of spontaneous activity of brain and body physiology between subjects.

Significance: Functional near-infrared spectroscopy (fNIRS) enables measuring the brain activity of two subjects while they interact, i.e., the hyperscanning approach. Aim: In our exploratory study, we extended classical fNIRS hyperscanning by adding systemic physiological measures to obtain systemic physiology augmented fNIRS (SPA-fNIRS) hyperscanning while blocking and not blocking the visual communication between the subjects. This approach enables access brain-to-brain, brain-to-body, and body-to-body coupling between the subjects simultaneously. Approach: Twenty-four pairs of subjects participated in the experiment. The paradigm consisted of two subjects that sat in front of each other and had their eyes closed for 10 min, followed by a phase of 10 min where they made eye contact. Brain and body activity was measured continuously by SPA-fNIRS. Results: Our study shows that making eye contact for a prolonged time causes significant changes in brain-to-brain, brain-to-body, and body-to-body coupling, indicating that eye contact is followed by entrainment of the physiology between subjects. Subjects that knew each other generally showed a larger trend to change between the two conditions. Conclusions: The main point of this study is to introduce a new framework to investigate brain-to-brain, body-to-body, and brain-to-body coupling through a simple social experimental paradigm. The study revealed that eye contact leads to significant synchronization of spontaneous activity of the brain and body physiology. Our study is the first that employed the SPA-fNIRS approach and showed its usefulness to investigate complex interpersonal physiological changes.

Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy.

Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest.

Cerebral and systemic physiological effects of wearing face masks in young adults.

The COVID-19 pandemic led to widespread mandates requiring the wearing of face masks, which led to debates on their benefits and possible adverse effects. To that end, the physiological effects at the systemic and at the brain level are of interest. We have investigated the effect of commonly available face masks (FFP2 and surgical) on cerebral hemodynamics and oxygenation, particularly microvascular cerebral blood flow (CBF) and blood/tissue oxygen saturation (StO2), measured by transcranial hybrid near-infrared spectroscopies and on systemic physiology in 13 healthy adults (ages: 23 to 33 y). The results indicate small but significant changes in cerebral hemodynamics while wearing a mask. However, these changes are comparable to those of daily life activities. This platform and the protocol provides the basis for large or targeted studies of the effects of mask wearing in different populations and while performing critical tasks.

Individual Differences in Hemodynamic Responses Measured on the Head Due to a Long-Term Stimulation Involving Colored Light Exposure and a Cognitive Task: A SPA-fNIRS Study.

When brain activity is measured by neuroimaging, the canonical hemodynamic response (increase in oxygenated hemoglobin ([O2Hb]) and decrease in deoxygenated hemoglobin ([HHb]) is not always seen in every subject. The reason for this intersubject-variability of the responses is still not completely understood. This study is performed with 32 healthy subjects, using the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. We investigate the intersubject variability of hemodynamic and systemic physiological responses, due to a verbal fluency task (VFT) under colored light exposure (CLE; blue and red). Five and seven different hemodynamic response patterns were detected in the subgroup analysis of the blue and red light exposure, respectively. We also found that arterial oxygen saturation and mean arterial pressure were positively correlated with [O2Hb] at the prefrontal cortex during the CLE-VFT independent of the color of light and classification of the subjects. Our study finds that there is substantial intersubject-variability of cerebral hemodynamic responses, which is partially explained by subject-specific systemic physiological changes induced by the CLE-VFT. This means that both subgroup analyses and the additional assessment of systemic physiology are of crucial importance to achieve a comprehensive understanding of the effects of a CLE-VFT on human subjects.

The Legacy of Sickness Behaviors.

Systemic infections of all types lead to a syndrome known as sickness behaviors. Changes in the behavior of febrile humans and animals formed the original basis for this concept. Body temperature is behaviorally regulated in both endotherms and ectotherms. However, infections cause other changes in body functions, including sleep disruption, anorexia, cognitive and memory deficits and disorientation. The brain mediates this entire cluster of symptoms, even though most major infections occur outside the brain. The true importance of sickness behaviors is not the numerous discoveries of symptoms that affect all of us when we get sick. Instead, the legacy of 30 years of research in sickness behaviors is that it established the physiologic importance of reciprocal communication systems between the immune system and the brain. This conceptual advance remains in its infancy.

Frontal cerebral oxygenation asymmetry: intersubject variability and dependence on systemic physiology, season, and time of day.

Significance: Our study reveals that frontal cerebral oxygenation asymmetry (FCOA), i.e. a difference in the oxygenation between the right and left prefrontal cortex (PFC), is a real phenomenon in healthy human subjects at rest. Aim: To investigate FCOA, we performed a study with 134 healthy right-handed subjects with the systemic physiology augmented functional near infrared spectroscopy (SPA-fNIRS) approach. Approach: Subjects were measured 2 to 4 times on different days resulting in an unprecedented number of 518 single measurements of the absolute values of tissue oxygen saturation ( StO 2 ) and total hemoglobin concentration ([tHb]) of the right and left PFC. Measurements were performed with frequency-domain functional near-infrared spectroscopy. In addition, the cardiorespiratory parameters were measured simultaneously. Results: We found that (i) subjects showed an FCOA (higher StO 2 on the right PFC), but not for tHb; (ii) intrasubject variability was excellent for both StO 2 and tHb, and fair for FCOA; (iii)  StO 2 correlated significantly with blood CO 2 concentration, [tHb] with heart rate, respiration rate (RR), and the pulse-respiration quotient (PRQ), and FCOA with RR and PRQ; (iv) FCOA and StO 2 were dependent on season and time of day, respectively; (v) FCOA was negatively correlated with the room temperature; and (vi)  StO 2 and tHb were not correlated with the subjects mood but with their chronotype, whereas FCOA was not dependent on the chronotype. Conclusion: Our study demonstrates that FCOA is real, and it provides unique insights into this remarkable phenomenon.

Effect of short-term colored-light exposure on cerebral hemodynamics and oxygenation, and systemic physiological activity.

There is not yet a comprehensive view of how the color of light affects the cerebral and systemic physiology in humans. The aim was to address this deficit through basic research. Since cerebral and systemic physiological parameters are likely to interact, it was necessary to establish an approach, which we have termed "systemic-physiology-augmented functional near-infrared spectroscopy (SPA-fNIRS) neuroimaging." This multimodal approach measures the systemic and cerebral physiological response to exposure to light of different colors. In 14 healthy subjects (9 men, 5 women, age: [Formula: see text] years, range: 24 to 57 years) exposed to red, green, and blue light (10-min intermittent wide-field visual color stimulation; [Formula: see text] blocks of visual stimulation), brain hemodynamics and oxygenation were measured by fNIRS on the prefrontal cortex (PFC) and visual cortex (VC) simultaneously, in addition with systemic parameters. This study demonstrated that (i) all colors elicited responses in the VC, whereas only blue evoked a response in the PFC; (ii) there was a color-dependent effect on cardiorespiratory activity; (iii) there was significant change in neurosystemic functional connectivity; (iv) cerebral hemodynamic responses in the PFC and changes in the cardiovascular system were gender and age dependent; and (v) electrodermal activity and psychological state showed no stimulus-evoked changes, and there was no dependence on color of light, age, and gender. We showed that short-term light exposure caused color-dependent responses in cerebral hemodynamics/oxygenation as well as cardiorespiratory dynamics. Additionally, we showed that neurosystemic functional connectivity changes even during apparently stress-free tasks-an important consideration when using any of the hemodynamic neuroimaging methods (e.g. functional magnetic resonance imaging, positron emission tomography, and fNIRS). Our findings are important for future basic research and clinical applications as well as being relevant for everyday life.

Short separation regression improves statistical significance and better localizes the hemodynamic response obtained by near-infrared spectroscopy for tasks with differing autonomic responses.

Autonomic nervous system response is known to be highly task-dependent. The sensitivity of near-infrared spectroscopy (NIRS) measurements to superficial layers, particularly to the scalp, makes it highly susceptible to systemic physiological changes. Thus, one critical step in NIRS data processing is to remove the contribution of superficial layers to the NIRS signal and to obtain the actual brain response. This can be achieved using short separation channels that are sensitive only to the hemodynamics in the scalp. We investigated the contribution of hemodynamic fluctuations due to autonomous nervous system activation during various tasks. Our results provide clear demonstrations of the critical role of using short separation channels in NIRS measurements to disentangle differing autonomic responses from the brain activation signal of interest.