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.

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.

Long-Term Blue Light Exposure Changes Frontal and Occipital Cerebral Hemodynamics: Not All Subjects React the Same.

BACKGROUND: In modern society, we are increasingly exposed to numerous sources of blue light, including screens (e.g., TVs, computers, laptops, smartphones, tablets) and light from fluorescent and LED lamps. Due to this wide range of applications, the effects of blue light exposure (BLE) on the human physiology need to be thoroughly studied. AIM: To investigate the impact of long-term BLE on frontal and occipital human cerebral hemodynamics and oxygenation using functional near-infrared spectroscopy (fNIRS) neuroimaging. MATERIALS AND METHODS: 32 healthy right-handed subjects (20 females, 12 males; age: 23.8 ± 2.2 years) were exposed to blue LED light for 15 minutes. Before (baseline, 8 min) and after (recovery, 10 min) the BLE, subjects were in darkness. We measured the concentration changes of oxyhemoglobin ([O2Hb]) and deoxyhemoglobin ([HHb]) at the prefrontal cortex (PFC) and visual cortex (VC) by fNIRS during the experiment. Subjects were then classified into different groups based on their hemodynamic response pattern of [O2Hb] at the PFC and VC during BLE. RESULTS: On the group level (32 subjects), we found an increase in [O2Hb] and a decrease in [HHb] at both cortices during BLE. Evoked changes of [O2Hb] were higher at the VC compared to the PFC. Eight different hemodynamic response patterns were detected in the subgroup analysis, while an increase of [O2Hb] in both cortices was the most common pattern (8 out of 32 cases, 25%) during BLE. DISCUSSION AND CONCLUSION: Our study showed that the hemodynamic and oxygenation changes at the PFC and VC during BLE (i) were generally higher in the VC compared to the PFC, (ii) showed an intersubject variability with respect to their magnitudes and shapes, and (iii) can be classified into eight groups. We conclude that blue light affects humans differently. It is essential to consider this when assessing the impact of the BLE on society.

Right-Left Asymmetry of Prefrontal Cerebral Oxygenation: Does it Depend on Systemic Physiological Activity, Absolute Tissue Oxygenation or Hemoglobin Concentration?

BACKGROUND: We have repeatedly observed a right-left asymmetry (RLA) of prefrontal cerebral oxygenation of subjects during the resting state. AIM: To clarify if the RLA is a reliably observable phenomenon at the group level and whether it is associated with systemic physiology, absolute tissue oxygen saturation (StO2) or total hemoglobin concentration ([tHb]). MATERIAL AND METHODS: StO2 and [tHb] values at the right and left prefrontal cortex (PFC) were calculated for two 5- min resting phases based on data from 76 single measurements (24 healthy adults, aged 22.0 ± 6.4 years). StO2 and [tHb] were measured with an ISS OxiplexTS frequency domain near-infrared spectroscopy device. In addition, end-tidal CO2 (PETCO2), heart rate (HR), respiration rate (RR) and the pulse-respiration quotient (PRQ = HR/RR) were measured and analyzed for the two phases. RESULTS: On the group level it was found that i) StO2 was higher at the right compared to the left PFC (for both phases), ii) RLA of StO2 (∆StO2 = StO2 (right)-StO2 (left) was independent of PETCO2, HR and PRQ, and iii) ∆StO2 was associated with absolute StO2 and [tHb] values (positively and negatively, respectively). DISCUSSION AND CONCLUSION: This study shows that i) RLA of StO2 at the PFC is a real phenomenon, and that ii) ∆StO2 at the group level does not depend on PETCO2, HR, RR or PRQ, but on absolute StO2 and [tHb]. We conclude that the RLA is a real effect, independent of systemic physiology, and most likely reflects genuine properties of the brain, i.e. different activity states of the two hemispheres.

Impact of Changes in Systemic Physiology on fNIRS/NIRS Signals: Analysis Based on Oblique Subspace Projections Decomposition.

Measurements of cerebral and muscle oxygenation (StO2) and perfusion ([tHb]) with functional near-infrared spectroscopy (fNIRS) and near infrared spectroscopy (NIRS), respectively, can be influenced by changes in systemic physiology. The aim of our study was to apply the oblique subspace projections signal decomposition (OSPSD) to find the contribution from systemic physiology, i.e. heart rate (HR), electrocardiography (ECG)-derived respiration (EDR) and partial pressure of carbon dioxide (pCO2) to StO2 and [tHb] signals measured on the prefrontal cortex (PFC) and calf muscle. OSPSD was applied to two datasets (n1 = 42, n2 = 79 measurements) from two fNIRS/NIRS speech studies. We found that (i) all StO2 and [tHb] signals contained components related to changes in systemic physiology, (ii) the contribution from systemic physiology varied strongly between subjects, and (iii) changes in systemic physiology generally influenced fNIRS signals on the left and right PFC to a similar degree.

Absolute Values of Optical Properties (µa, µÎ„s, µeff and DPF) of Human Head Tissue: Dependence on Head Region and Individual.

BACKGROUND: Absolute optical properties (i.e., the absorption coefficient, µa, and the reduced scattering coefficient, [Formula: see text]) of head tissue can be measured with frequency-domain near-infrared spectroscopy (FD-NIRS). AIM: We investigated how the absolute optical properties depend on the individual subject and the head region. MATERIALS AND METHODS: The data set used for the analysis comprised 31 single FD-NIRS measurements of 14 healthy subjects (9 men, 5 women, aged 33.4 ± 10.5 years). From an 8-min measurement (resting-state; FD-NIRS device: Imagent, ISS Inc.; bilateral over the prefrontal cortex, PFC, and visual cortex, VC) median values were calculated for µa and [Formula: see text] as well as the effective attenuation coefficient (µeff) and the differential pathlength factor (DPF). The measurement was done for each subject one to three times with at least 24 h between the measurements. RESULTS: (i) A Bayesian ANOVA analysis revealed that head region and subject were the most significant main effects on µa, [Formula: see text] and µeff, as well as DPF, respectively. (ii) At the VC, µa, [Formula: see text] and µeff had higher values compared to the PFC. (iii) The differences in the optical properties between PFC and VC were age-dependent. (iv) All optical properties also were age-dependent. This was strongest for the properties of the PFC compared to the VC. DISCUSSION AND CONCLUSION: Our analysis demonstrates that all optical head tissue properties (µa, [Formula: see text], µeff and DPF) were dependent on the head region, individual subject and age. The optical properties of the head are like a 'fingerprint' for the individual subject. Assuming constant optical properties for the whole head should be carefully reconsidered.

Long-Term Changes in Optical Properties (µa, µ's, µeff and DPF) of Human Head Tissue During Functional Neuroimaging Experiments.

Frequency-domain near-infrared spectroscopy (FD-NIRS) enables to measure absolute optical properties (i.e. the absorption coefficient, µa, and the reduced scattering coefficient, [Formula: see text]) of the brain tissue. The aim of this study was to investigate how the optical properties changed during the course of a functional NIRS experiment. The analyzed dataset comprised of FD-NIRS measurements of 14 healthy subjects (9 males, 5 females, aged: 33.4 ± 10.5 years, range: 24-57 years old). Each measurement lasted 33 min, i.e. 8 min baseline in darkness, 10 min intermittent light stimulation, and 15 min recovery in darkness. Optical tissue properties were obtained bilaterally over the prefrontal cortex (PFC) and visual cortex (VC) with FD-NIRS (Imagent, ISS Inc., USA). Changes in µa and [Formula: see text] were directly measured and two parameters were calculated, i.e. the differential pathlength factor (DPF) and the effective attenuation coefficient (µeff). Differences in the behavior of the optical changes were observed when comparing group-averaged data versus single datasets: no clear overall trend was presented in the group data, whereas a clear long-term trend was visible in almost all of the single measurements. Interestingly, the changes in [Formula: see text] statistically significantly correlated with µa, positively in the PFC and negatively in the VC. Our analysis demonstrates that all optical brain tissue properties (µa, [Formula: see text], µeff and DPF) change during these functional neuroimaging experiments. The change in [Formula: see text] is not random but follows a trend, which depends on the single experiment and measurement location. The change in the scattering properties of the brain tissue during a functional experiment is not negligible. The assumption [Formula: see text] ≈ const during an experiment is valid for group-averaged data but not for data from single experiments.

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.

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.

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.

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.

Color-dependent changes in humans during a verbal fluency task under colored light exposure assessed by SPA-fNIRS.

Light evokes robust visual and nonvisual physiological and psychological effects in humans, such as emotional and behavioral responses, as well as changes in cognitive brain activity and performance. The aim of this study was to investigate how colored light exposure (CLE) and a verbal fluency task (VFT) interact and affect cerebral hemodynamics, oxygenation, and systemic physiology as determined by systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). 32 healthy adults (17 female, 15 male, age: 25.5 ± 4.3 years) were exposed to blue and red light for 9 min while performing a VFT. Before and after the CLE, subjects were in darkness. We found that this long-term CLE-VFT paradigm elicited distinct changes in the prefrontal cortex and in most systemic physiological parameters. The subjects' performance depended significantly on the type of VFT and the sex of the subject. Compared to red light, blue evoked stronger responses in cerebral hemodynamics and oxygenation in the visual cortex. Color-dependent changes were evident in the recovery phase of several systemic physiological parameters. This study showed that the CLE has effects that endure at least 15 min after cessation of the CLE. This underlines the importance of considering the persistent influence of colored light on brain function, cognition, and systemic physiology in everyday life.

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.

New Directions in Exercise Prescription: Is There a Role for Brain-Derived Parameters Obtained by Functional Near-Infrared Spectroscopy?

In the literature, it is well established that regular physical exercise is a powerful strategy to promote brain health and to improve cognitive performance. However, exact knowledge about which exercise prescription would be optimal in the setting of exercise-cognition science is lacking. While there is a strong theoretical rationale for using indicators of internal load (e.g., heart rate) in exercise prescription, the most suitable parameters have yet to be determined. In this perspective article, we discuss the role of brain-derived parameters (e.g., brain activity) as valuable indicators of internal load which can be beneficial for individualizing the exercise prescription in exercise-cognition research. Therefore, we focus on the application of functional near-infrared spectroscopy (fNIRS), since this neuroimaging modality provides specific advantages, making it well suited for monitoring cortical hemodynamics as a proxy of brain activity during physical exercise.

Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells?

Recently accumulating evidence has put into question the role of large multinucleated giant cells (MNGCs) around bone biomaterials. While cells derived from the monocyte/macrophage lineage are one of the first cell types in contact with implanted biomaterials, it was originally thought that specifically in bone tissues, all giant cells were bone-resorbing osteoclasts whereas foreign body giant cells (FBGCs) were found associated with a connective tissue foreign body reaction resulting in fibrous encapsulation and/or material rejection. Despite the great majority of bone grafting materials routinely found with large osteoclasts, a special subclass of bone biomaterials has more recently been found surrounded by large giant cells virtually incapable of resorbing bone grafts even years after their implantation. While original hypotheses believed that a 'foreign body reaction' may be taking place, histological data retrieved from human samples years after their implantation have put these original hypotheses into question by demonstrating better and more stable long-term bone volume around certain bone grafts. Exactly how or why this 'special' subclass of giant cells is capable of maintaining long-term bone volume, or methods to scientifically distinguish them from osteoclasts remains extremely poorly studied. The aim of this review article was to gather the current available literature on giant cell markers and differences in expression patterns between osteoclasts and MNGCs utilizing 19 specific markers including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed. STATEMENT OF SIGNIFICANCE: This review article presents 19 specific cell-surface markers to distinguish between osteoclasts and MNGCs including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (often previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed. The proposed concepts and guidelines aims to guide the next wave of research facilitating the differentiation between osteoclast/MNGCs formation, as well as provides the basis for increasing our understanding of the exact function of MNGCs in bone tissue/biomaterial homeostasis.