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Background: Near-infrared spectroscopy (NIRS) relative concentration signals contain 'noise' from physiological processes such as respiration and heart rate. Simultaneous assessment of NIRS and respiratory rate (RR) using a single sensor would facilitate a perfectly time-synced assessment of (cerebral) physiology. Our aim was to extract respiratory rate from cerebral NIRS intensity signals in neonates admitted to a neonatal intensive care unit (NICU). Methods: A novel algorithm, NRR (NIRS RR), is developed for extracting RR from NIRS signals recorded from critically ill neonates. In total, 19 measurements were recorded from ten neonates admitted to the NICU with a gestational age and birth weight of 38 ± 5 weeks and 3092 ± 990 g, respectively. We synchronously recorded NIRS and reference RR signals sampled at 100 Hz and 0.5 Hz, respectively. The performance of the NRR algorithm is assessed in terms of the agreement and linear correlation between the reference and extracted RRs, and it is compared statistically with that of two existing methods. Results: The NRR algorithm showed a mean error of 1.1 breaths per minute (BPM), a root mean square error of 3.8 BPM, and Bland-Altman limits of agreement of 6.7 BPM averaged over all measurements. In addition, a linear correlation of 84.5% (p < 0.01) was achieved between the reference and extracted RRs. The statistical analyses confirmed the significant (p < 0.05) outperformance of the NRR algorithm with respect to the existing methods. Conclusions: We showed the possibility of extracting RR from neonatal NIRS in an intensive care environment, which showed high correspondence with the reference RR recorded. Adding the NRR algorithm to a NIRS system provides the opportunity to record synchronously different physiological sources of information about cerebral perfusion and respiration by a single monitoring system. This allows for a concurrent integrated analysis of the impact of breathing (including apnea) on cerebral hemodynamics.

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OBJECTIVE: The employment of wearable systems for continuous monitoring of vital signs is increasing. However, due to substantial susceptibility of conventional bio-signals recorded by wearable systems to motion artifacts, estimation of the respiratory rate (RR) during physical activities is a challenging task. Alternatively, functional Near-Infrared Spectroscopy (fNIRS) can be used, which has been proven less vulnerable to the subject's movements. This paper proposes a fusion-based method for estimating RR during bicycling from fNIRS signals recorded by a wearable system. METHODS: Firstly, five respiratory modulations are extracted, based on amplitude, frequency, and intensity of the oxygenated hemoglobin concentration (O2Hb) signal. Secondly, the dominant frequency of each modulation is computed using the fast Fourier transform. Finally, dominant frequencies of all modulations are fused, based on averaging, to estimate RR. The performance of the proposed method was validated on 22 young healthy subjects, whose respiratory and fNIRS signals were simultaneously recorded during a bicycling task, and compared against a zero delay Fourier domain band-pass filter. RESULTS: The comparison between results obtained by the proposed method and band-pass filtering indicated the superiority of the former, with a lower mean absolute error (3.66 vs. 11.06 breaths per minute, p<0.05). The proposed fusion strategy also outperformed RR estimations based on the analysis of individual modulation. SIGNIFICANCE: This study orients towards the practical limitations of traditional bio-signals for RR estimation during physical activities.

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OBJECTIVE: Respiration is recognized as a systematic physiological interference in functional near-infrared spectroscopy (fNIRS). However, it remains unanswered as to whether it is possible to estimate the respiratory rate (RR) from such interference. Undoubtedly, RR estimation from fNIRS can provide complementary information that can be used alongside the cerebral activity analysis, e.g., sport studies. Thus, the objective of this paper is to propose a method for RR estimation from fNIRS. Our primary presumption is that changes in the baseline wander of oxygenated hemoglobin concentration (O2Hb) signal are related to RR. METHODS: fNIRS and respiratory signals were concurrently collected from subjects during controlled breathing tasks at a constant rate from 0.1 Hz to 0.4 Hz. Firstly, the signal quality index algorithm is employed to select the best O2Hb signal, and then a band-pass filter with cut-off frequencies from 0.05 to 2 Hz is used to remove very low- and high-frequency artifacts. Secondly, troughs of the filtered O2Hb signal are localized for synthesizing the baseline wander (S1) using cubic spline interpolation. Finally, the fast Fourier transform of the S1 signal is computed, and its dominant frequency is considered as RR. In this paper, two different datasets were employed, where the first one was used for the parameter adjustment of the proposed method, and the second one was solely used for testing. RESULTS: The low mean absolute error between the reference and estimated RRs for the first and second datasets (2.6 and 1.3 breaths per minute, respectively) indicates the feasibility of the proposed method for RR estimation from fNIRS. SIGNIFICANCE: This paper provides a novel view on the respiration interference as a source of complementary information in fNIRS.

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

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We propose the signal quality index (SQI) algorithm as a novel tool for quantitatively assessing the functional near infrared spectroscopy (fNIRS) signal quality in a numeric scale from 1 (very low quality) to 5 (very high quality). The algorithm comprises two preprocessing steps followed by three consecutive rating stages. The results on a dataset annotated by independent fNIRS experts showed SQI performed significantly better (p<0.05) than PHOEBE (placing headgear optodes efficiently before experimentation) and SCI (scalp coupling index), two existing algorithms, in both quantitatively rating and binary classifying the fNIRS signal quality. Employment of the proposed algorithm to estimate the signal quality before processing the fNIRS signals increases certainty in the interpretations.

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PURPOSE: Cerebral oxygenation as measured by near-infrared spectroscopy (NIRS) might be useful to discriminate between physiological and pathological responses after standing up in individuals with orthostatic hypotension. This study addressed the physiological sensitivity of the cerebral oxygenation responses as measured by NIRS to different types and speeds of postural changes in healthy adults and assessed the reliability of these responses. METHODS: Cerebral oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb) and tissue saturation index (TSI) were measured bilaterally on the forehead of 15 healthy individuals (12 male, age range 18-27) using NIRS. Participants performed three repeats of sit to stand, and slow and rapid supine to stand movements. Responses were defined as the difference between mean, minimum and maximum O2Hb, HHb and TSI values after standing up and baseline. Test-retest, interobserver and intersensor reliabilities were addressed using intraclass correlation coefficients (ICCs). RESULTS: The minimum O2Hb response was most sensitive to postural changes and showed significant differences (- 4.09 µmol/L, p < 0.001) between standing up from sitting and supine position, but not between standing up at different speeds (- 0.31 µmol/L, p = 0.70). The minimum O2Hb response was the most reliable parameter (ICC > 0.6). CONCLUSIONS: In healthy individuals, NIRS-based cerebral oxygenation parameters are sensitive to postural change and discriminate between standing up from supine and sitting position with minimum O2Hb response as the most sensitive and reliable parameter. The results underpin the potential value for future clinical use of NIRS in individuals with orthostatic hypotension.

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When healthy subjects stand up, it is associated with a reduction in cerebral blood velocity and oxygenation although cerebral autoregulation would be considered to prevent a decrease in cerebral perfusion. Aging is associated with a higher incidence of falls, and in the elderly falls may occur particularly during the adaptation to postural change. This study evaluated the cerebrovascular adaptation to postural change in 15 healthy younger (YNG) vs. 15 older (OLD) subjects by recordings of the near-infrared spectroscopy-determined cerebral oxygenation (cO2Hb) and the transcranial Doppler-determined mean middle cerebral artery blood velocity (MCA V(mean)). In OLD (59 (52-65) years) vs. YNG (29 (27-33) years), the initial postural decline in mean arterial pressure (-52 ± 3% vs. -67 ± 3%), cO2Hb (-3.4 ± 2.5 µmoll(-1) vs. -5.3 ± 1.7 µmoll(-1)) and MCA V(mean) (-16 ± 4% vs. -29 ± 3%) was smaller. The decline in MCA V(mean) was related to the reduction in MAP. During prolonged orthostatic stress, the decline in MCA V(mean)and cO(2)Hb in OLD remained smaller. We conclude that with healthy aging the postural reduction in cerebral perfusion becomes less prominent.

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Leg crossing increases arterial pressure and combats symptomatic orthostatic hypotension in patients with sympathetic failure. This study compared the central and cerebrovascular effects of leg crossing in patients with sympathetic failure and healthy controls. We addressed the relationship between MCA Vmean (middle cerebral artery blood velocity; using transcranial Doppler ultrasound), frontal lobe oxygenation [O2Hb (oxyhaemoglobin)] and MAP (mean arterial pressure), CO (cardiac output) and TPR (total peripheral resistance) in six patients (aged 37-67 years; three women) and age- and gender-matched controls during leg crossing. In the patients, leg crossing increased MAP from 58 (42-79) to 72 (52-89) compared with 84 (70-95) to 90 (74-94) mmHg in the controls. MCA Vmean increased from 55 (38-77) to 63 (45-80) and from 56 (46-77) to 64 (46-80) cm/s respectively (P<0.05), with a larger rise in O2Hb [1.12 (0.52-3.27)] in the patients compared with the controls [0.83 (-0.11 to 2.04) micromol/l]. In the control subjects, CO increased 11% (P<0.05) with no change in TPR. By contrast, in the patients, CO increased 9% (P<0.05), but also TPR increased by 13% (P<0.05). In conclusion, leg crossing improves cerebral perfusion and oxygenation both in patients with sympathetic failure and in healthy subjects. However, in healthy subjects, cerebral perfusion and oxygenation were improved by a rise in CO without significant changes in TPR or MAP, whereas in patients with sympathetic failure, cerebral perfusion and oxygenation were improved through a rise in MAP due to increments in both CO and TPR.

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Despite the social impact of repetitive strain injury (RSI), little is known about its pathophysiological mechanism. The main objective of this study was to assess the local muscle oxygenation (mVO2) and blood flow (mBF) of the forearm in individuals with RSI during isometric contractions of the forearm. We employed the non-invasive optical technique near-infrared spectroscopy to assess forearm VO2 and BF. These variables were assessed at 10%, 20%, and 40% of their individual maximal voluntary strength. Twenty-two patients with RSI symptoms in both arms (bilateral RSI) and 30 healthy age-matched subjects participated in this cross-sectional study. The results showed lower mVO2 during exercise and a reduced mBF after exercise. The results suggest that mVO2 and mVO2 are lower in the forearms of individuals with RSI compared with their controls at similar working intensities. This finding indicates that the underlying vasculature may be impaired. Although these findings contribute to the understanding of RSI, future research is necessary to further unravel the mechanisms of this area.

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Patients with left ventricular dysfunction may have different orthostatic responses of blood pressure (BP) and cerebral oxygenation than healthy elderly subjects. We investigated orthostatic changes in systemic haemodynamic variables and cerebral oxygenation in 21 elderly patients with heart failure New York Heart Association class I-III in stable condition (age 70-83 years) after withdrawal of furosemide and captopril for 2 weeks, and in 18 healthy elderly subjects (age 70-84 years). Frontal cortical concentration changes of oxyhaemoglobin ([O2Hb]) and deoxyhaemoglobin ([HHb]) were continuously measured by near-infrared spectrophotometry and BP changes by Finapres before and during 10 min of standing. Upon standing [O2Hb] reflecting blood flow, changed by -1.2 +/- 0.9 micromol L-1 (mean +/- SEM) in the patients, whereas it decreased by -4.5 +/- 0.6 micromol L-1 (P<0.01) in the healthy subjects after standing (P<0.05 between groups). [HHb] reflecting the sum of cerebral blood flow, arterial oxygen saturation and cerebral oxygen uptake, increased by 1.5 +/- 0.5 micromol L-1 (P<0.05) and 1.7 +/- 0.6 micromol L-1 (P<0.05), respectively. Compared with healthy elderly subjects, elderly patients with left ventricular dysfunction showed smaller orthostatic [O2Hb] decreases (P<0.01), in relation to higher orthostatic BP rises (P<0.05). These findings indicate that BP changes and an altered cardiovascular balance may influence orthostatic cortical haemodynamic responses in elderly subjects.

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The organisation of language in the brain of multilingual people remains controversial. Using a high temporal resolution 12-channel near-infrared continuous wave spectroscopy system, we have demonstrated that it is possible to monitor non-invasively, comfortably and, without the interferences due to intrinsic limitations of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), cortical oxygenation changes in the Broca's area in response to translation of short sentences and language switching. Eight Dutch students proficient in English translated aloud from their native language into English or vice versa or alternating (switching) short visually presented sentences. These tasks provoked, in the left inferior frontal cortex which includes the Broca's area, a consistent and incremental rise in oxyhaemoglobin accompanied by a smaller decrease in deoxyhaemoglobin. The investigated cortical areas surrounding the Broca's area showed no uniform and consistent oxygenation changes upon the three different translation tasks. These results confirm that Broca's area is involved in the translation process and its so called activation is unaffected by the direction of the translation. In addition, these results strengthen the role of near-infrared multi-point measurements as a powerful tool for investigating the spatial and temporal features of the cortical oxygenation changes during language processing.

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Elderly patients with heart failure are at risk of postprandial hypotension (PPH), orthostatic hypotension (OH), and concomitant cerebral oxygenation changes because of altered cardiovascular balance and the use of cardiovascular medications, such as furosemide and captopril. In 24 patients with heart failure (New York Heart Association class II to III, in stable condition, and receiving cardiovascular medication [aged 70 to 83 years]), blood pressure (BP) was measured by Finapres, and cortical concentrations of oxyhemoglobin and deoxyhemoglobin were measured using near-infrared spectroscopy during standing and after a 292-kcal carbohydrate meal. Tests were performed before and during therapy with furosemide 40 mg once daily (n = 11) or captopril 6.25 and 12.5 mg twice daily (n = 13) in a double-blind randomized trial. Before treatment, 13 of 24 patients had PPH, and 2 of 24 patients had OH. The first dose of furosemide significantly decreased postprandial systolic BP (p <0.05) and postprandial frontal cortical oxygenation (p <0.05), whereas the first dose of captopril did not. Furosemide and captopril did not significantly affect postprandial or orthostatic BP or cortical oxygenation after 2 weeks of treatment. Thus, PPH is a common phenomenon in elderly patients with heart failure, whereas OH is not. The first dose of furosemide 40 mg decreased postprandial systolic BP and frontal cortical oxygenation, in contrast with the first dose of captopril 6.25 mg and 2-week treatment with furosemide 40 mg once daily or captopril 12.5 mg twice daily. These findings indicate that initiating furosemide treatment worsens PPH, and furosemide is less safe in elderly patients with heart failure.

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The aim of this study was to investigate the performance of in vivo quantitative near-infrared spectroscopy (NIRS) in skeletal muscle at various workloads. NIRS was used for the quantitative measurement of O2 consumption (mVO2) in the human flexor digitorum superficialis muscle at rest and during rhythmic isometric handgrip exercise in a broad range of work intensities (10-90% MVC=maximum voluntary contraction force). Six subjects were tested on three separate days. No significant differences were found in mVO2 measured over different days with the exception of the highest workload. The within-subject variability for each workload measured over the three measurements days ranged from 15.7 to 25.6% and did not increase at the high workloads. The mVO2 was 0.14 +/- 0.01 mlO2 min-1 100 g-1 at rest and increased roughly 19 times to 2.68 +/- 0.58 mlO2 min-1 100 g-1 at 72% MVC. These results show that local muscle oxygen consumption at rest as well as during exercise at a broad range of work intensities can be measured reliably by NIRS, applied to a uniform selected subject population. This is of great importance as direct local measurement of mVO2 during exercise is not possible with the conventional techniques. The method is robust enough to measure over separate days and at various workloads and can therefore contribute to a better understanding of human physiology in both the normal and pathological state of the muscle.

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Near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) both allow non-invasive monitoring of cerebral cortical oxygenation responses to various stimuli. To compare these methods in elderly subjects and to determine the effect of age on cortical oxygenation responses, we determined motor-task-related changes in deoxyhemoglobin concentration ([HHb]) over the left motor cortex in six healthy young subjects (age 35 +/- 9 years, mean +/- SD) and five healthy elderly subjects (age 73 +/- 3 years) by NIRS and blood-oxygen-level-dependent (BOLD) fMRI simultaneously. The motor-task consisted of seven cycles of 20-sec periods of contralateral finger-tapping at a rate as fast as possible alternated with 40-sec periods of rest. Time-locked averages over the seven cycles were used for further analysis. Task-related decreases in [HHb] over the motor cortex were measured by NIRS, with maximum changes of -0.83 +/- 0.38 mumol/L (P < 0.01) for the young and -0.32 +/- 0.17 mumol/L (P < 0.05) for the elderly subjects. The BOLD-fMRI signal increased over the cortex volume under investigation with NIRS, with maximum changes of 2.11 +/- 0.72% (P < 0.01) for the young and 1.75 +/- 0.71% (P < 0.01) for the elderly subjects. NIRS and BOLD-fMRI measurements showed good correlation in the young (r = -0.70, r(2) = 0.48, P < 0.001) and elderly subjects (r = -0.82, r(2) = 0.67, P < 0.001). Additionally, NIRS measurements demonstrated age-dependent decreases in task-related cerebral oxygenation responses (P < 0.05), whereas fMRI measurements demonstrated smaller areas of cortical activation in the elderly subjects (P < 0.05). These findings demonstrate that NIRS and fMRI similarly assess cortical oxygenation changes in young subjects and also in elderly subjects. In addition, cortical oxygenation responses to brain activation alter with aging.

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STUDY OBJECTIVES: Effects of chronic metabolic alkalosis and acidosis and their relation to central chemoregulation may differ between normocapnic and chronic hypercapnic patients with COPD. The relationship between responses of inspired ventilation (VI), mouth occlusion pressure (P(0.1)), and cerebral blood volume (CBV), to short-term changes in arterial PCO(2) was measured. PATIENTS AND METHODS: Seventeen patients with chronic hypercapnia and COPD (PaCO(2) > 6.0 kPa) and 16 normocapnic patients with COPD (PaCO(2) < or = 6.0 kPa) [FEV(1) 27% predicted] were studied under baseline metabolic conditions and after 1 week of treatment with oral furosemide, 40 mg/d, or acetazolamide, 500 mg/d. Hypercapnia (change in end-tidal carbon dioxide > 1 kPa) was induced by administering adequate amounts of carbon dioxide in the inspired air. CBV was measured using near-infrared spectroscopy. RESULTS: Compared with baseline metabolic condition, chronic metabolic acidosis and alkalosis did not change ventilatory (Delta VI/Delta PaCO(2)) and cerebrovascular (Delta CBV/Delta PaCO(2)) reactivity. Base excess (BE) decreased by 6.8 +/- 1.1 mEq/L and 6.9 +/- 1.6 mEq/L, respectively, in the normocapnic and chronic hypercapnic COPD groups during metabolic acidosis, resulting in a not-quite-significant leftward shift of both the ventilatory and cerebrovascular carbon dioxide response curve. BE increased by 2.3 +/- 1.2 mEq/L and 1.2 +/- 1.3 mEq/L, respectively, during chronic metabolic alkalosis in both COPD groups, without concomitant shift. Poor correlations between ventilatory and cerebrovascular carbon dioxide responsiveness (Delta CBV/Delta PaCO(2) and Delta VI/Delta PaCO(2), Delta CBV/Delta PaCO(2) and Delta P(0.1)/Delta PaCO(2), respectively) were found irrespective of baseline, respiratory condition, and induced metabolic state. CONCLUSIONS: Normocapnic and chronic hypercapnic COPD patients have the same ventilatory and cerebrovascular carbon dioxide responsiveness irrespective of induced metabolic state.

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