Investigating cortical activity during cybersickness by fNIRS.

This study investigated brain responses during cybersickness in healthy adults using functional near-infrared spectroscopy (fNIRS). Thirty participants wore a head-mounted display and observed a virtual roller coaster scene that induced cybersickness. Cortical activation during the virtual roller coaster task was measured using fNIRS. Cybersickness symptoms were evaluated using a Simulator Sickness Questionnaire (SSQ) administered after the virtual rollercoaster. Pearson correlations were performed for cybersickness symptoms and the beta coefficients of hemodynamic responses. The group analysis of oxyhemoglobin (HbO) and total hemoglobin (HbT) levels revealed deactivation in the bilateral angular gyrus during cybersickness. In the Pearson correlation analyses, the HbO and HbT beta coefficients in the bilateral angular gyrus had a significant positive correlation with the total SSQ and disorientation. These results indicated that the angular gyrus was associated with cybersickness. These findings suggest that the hemodynamic response in the angular gyrus could be a biomarker for evaluating cybersickness symptoms.

MiR-497-5p ameliorates the oxyhemoglobin-induced subarachnoid hemorrhage injury in vitro by targeting orthodenticle homeobox protein 1 (Otx1) to activate the Nrf2/HO-1 pathway.

Subarachnoid hemorrhage (SAH) is a neurological disorder that severely damages the brain and causes cognitive impairment. MicroRNAs are critical regulators in a variety of neurological diseases. MiR-497-5p has been found to be downregulated in the aneurysm vessel walls obtained from patients with aneurysmal subarachnoid hemorrhage, but its functions and mechanisms in SAH have not been reported. Therefore, this study was designed to investigate the effect of miR-497-5p and its related mechanisms in SAH. We established an in vitro SAH model by exposing PC12 cells to oxyhemoglobin (oxyHb). We found that miR-497-5p was downregulated in SAH serum and oxyHb-treated PC12 cells, and its overexpression inhibited the oxyHb-induced apoptosis, inflammatory response and oxidative stress via activation of the Nrf2 pathway. Mechanistically, the targeting relationship between miR-497-5p and Otx1 was verified by luciferase reporter assays. Moreover, Otx1 upregulation abolished the protective effects of miR-497-5p upregulation against oxyHb-induced apoptosis, inflammation and oxidative stress in PC12 cells. Collectively, our findings indicate that miR-497-5p could inhibit the oxyHb-induced SAH damage by targeting Otx1 to activate the Nrf2/HO-1 pathway, which provides a potential therapeutic target for SAH treatment.

Non-invasive assessment of periodontal inflammation by continuum-removal hemodynamic spectral indices.

BACKGROUND: Hyperspectral techniques have aroused great interest in non-invasively measuring periodontal tissue hemodynamics. However, current studies mainly focused on three typical inflammation stages (healthy, gingivitis and periodontitis) and practical approaches for using optical spectroscopy for early and precisely detection of periodontal inflammation at finer disease stages have not been well studied. METHODS: This study provided novel spectroscopic insights into periodontitis at different stages of disease, and developed six simple but physically meaning hemodynamic spectral indices (HSIs) including four spectral absorption depths of oxyhemoglobin ( D HbO 2 ), deoxyhemoglobin ( D Hb ), total hemoglobin ( t Hb ) and tissue water ( D water ), and two normalized difference indices of oxyhemoglobin( N D HbO 2 I ) and deoxyhemoglobin ( N D Hb I ) from continuum-removal spectra (400-1700 nm) of periodontal tissue collected from 47 systemically healthy subjects over different severities from healthy, gingivitis, slight, moderate to severe periodontitis for early and precision diagnostics of periodontitis. Typical statistical analyses were conducted to explore the effectiveness of the proposed HSIs. RESULTS: D Hb and t Hb exerted significant increasing trends as inflammation progressed, whereas D HbO 2 exhibited significant difference (P < 0.05) from the healthy sites only at moderate and severe periodontitis and D water presented unstable sensitives to disease severity. By contrast, N D HbO 2 I and N D Hb I showed more steadily downward trends as severity increased, and demonstrated the highest correlations with clinical gold standard parameters. Particularly, the proposed normalized HSIs ( N D HbO 2 I and N D Hb I ) yielded high correlations of - 0.49 and - 0.44 with probing depth, respectively, far outperforming results achieved by previous studies. The performances of the HSIs were also confirmed using the periodontal therapy group. CONCLUSIONS: These results indicated great potentials of combination optical spectroscopy and smart devices to non-invasively probe periodontitis at earlier stages using the simple and practical HSIs. Trial registration This study was retrospectively registered in the Chinese Clinical Trial Registry on October 24, 2021, and the clinical registration number is ChiCTR2100052306.

Activation and depression of neural and hemodynamic responses induced by the intracortical microstimulation and visual stimulation in the mouse visual cortex.

Objective. Intracortical microstimulation (ICMS) can be an effective method for restoring sensory perception in contemporary brain-machine interfaces. However, the mechanisms underlying better control of neuronal responses remain poorly understood, as well as the relationship between neuronal activity and other concomitant phenomena occurring around the stimulation site.Approach. Different microstimulation frequencies were investigatedin vivoon Thy1-GCaMP6s mice using widefield and two-photon imaging to evaluate the evoked excitatory neural responses across multiple spatial scales as well as the induced hemodynamic responses. Specifically, we quantified stimulation-induced neuronal activation and depression in the mouse visual cortex and measured hemodynamic oxyhemoglobin and deoxyhemoglobin signals using mesoscopic-scale widefield imaging.Main results. Our calcium imaging findings revealed a preference for lower-frequency stimulation in driving stronger neuronal activation. A depressive response following the neural activation preferred a slightly higher frequency stimulation compared to the activation. Hemodynamic signals exhibited a comparable spatial spread to neural calcium signals. Oxyhemoglobin concentration around the stimulation site remained elevated during the post-activation (depression) period. Somatic and neuropil calcium responses measured by two-photon microscopy showed similar dependence on stimulation parameters, although the magnitudes measured in soma was greater than in neuropil. Furthermore, higher-frequency stimulation induced a more pronounced activation in soma compared to neuropil, while depression was predominantly induced in soma irrespective of stimulation frequencies.Significance. These results suggest that the mechanism underlying depression differs from activation, requiring ample oxygen supply, and affecting neurons. Our findings provide a novel understanding of evoked excitatory neuronal activity induced by ICMS and offer insights into neuro-devices that utilize both activation and depression phenomena to achieve desired neural responses.

Melanin bias in pulse oximetry explained by light source spectral bandwidth.

BACKGROUND: Pulse oximetry uses noninvasive optical measurements of light transmission from each of two sources through vascularised living tissue over the cardiac cycle (SpO2). From those measurements, the relative amount of oxygenated haemoglobin (SaO2) in circulating blood can be deduced. Recent reports have shown that, compared with SaO2 measurements from blood samples, SpO2 measurements are biased erroneously high for patients with dark skin. METHODS: We developed a new method, spectrally resolved photoplethysmography (srPPG), to examine how spectral bandwidth affects the transmission of polychromatic light through the fingertip across the cardiac cycle. We measured and recorded the spectral transmission through the fingertip as the O2 concentration in inspired air was reduced. We applied digital spectral filters of two different bandwidths, narrow or broad, to the same srPPG recordings to determine whether SpO2 readings systematically varied for the two bandwidths. The srPPG method also allowed us to measure the fractional amount of melanin in the optical path. The effect of melanin content on the ratio of SpO2 readings for narrow and broad spectral bandwidths was analysed. RESULTS: We hypothesised, based upon the Beer-Lambert law, and then showed experimentally, that the light emission spectra of light-emitting diode light sources, as used in commercial pulse oximeters, result in erroneously high SpO2 measurements for patients having greater melanin concentrations in their skin than those of the subject pool used for instrument calibration. CONCLUSIONS: To eliminate melanin bias, pulse oximeters should use much narrower spectral bandwidths than those used in current models.

Combined frequency domain near-infrared spectroscopy and diffuse correlation spectroscopy system for comprehensive metabolic monitoring of inspiratory muscles during loading.

Significance: Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critically ill patients. The process of weaning patients from MV can be long and arduous and can lead to serious complications for many patients. Despite the known importance of inspiratory muscle function in the success of weaning, current clinical standards do not include direct monitoring of these muscles. Aim: The goal of this project was to develop and validate a combined frequency domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) system for the noninvasive characterization of inspiratory muscle response to a load. Approach: The system was fabricated by combining a custom digital FD-NIRS and DCS system. It was validated via liquid phantom titrations and a healthy volunteer study. The sternocleidomastoid (SCM), an accessory muscle of inspiration, was monitored during a short loading period in fourteen young, healthy volunteers. Volunteers performed two different respiratory exercises, a moderate load and a high load, which consisted of a one-minute baseline, a one-minute load, and a six-minute recovery period. Results: The system has low crosstalk between absorption, reduced scattering, and flow when tested in a set of liquid titrations. Faster dynamics were observed for changes in blood flow index (BFi), and metabolic rate of oxygen (MRO2) compared with hemoglobin + myoglobin (Hb+Mb) based parameters after the onset of loads in males. Additionally, larger percent changes in BFi, and MRO2 were observed compared with Hb+Mb parameters in both males and females. There were also sex differences in baseline values of oxygenated Hb+Mb, total Hb+Mb, and tissue saturation. Conclusions: The dynamic characteristics of Hb+Mb concentration and blood flow were distinct during loading of the SCM, suggesting that the combination of FD-NIRS and DCS may provide a more complete picture of inspiratory muscle dynamics.

Histidine Protonation States Regulate the State Transition from R State Hemoglobin.

The objective of our work is to investigate the impact of pH on the structural changes of hemoglobin that affect its O2 affinity, known as the Bohr effect. We conducted molecular dynamics (MD) simulations to explore the transition between various hemoglobin states based on the protonation states (PSs) of two histidine residues (ßHis143 and ßHis146). We conducted the MD simulations from the R and R2 states with three sets of PSs assuming pH values of 7.0, 6.5, and 5.5, aiming to investigate the influence of pH on hemoglobin behavior. Our results demonstrated that the protonated His residues promote the state transition from the R state to the R2 state and encourage elongation of the distance between the ß1-ß2 subunits by weakening the inter-subunit interactions in the R state. These observations, aligning with the experimental evidence, indicate that the R2 state typically crystallizes under low pH conditions. Our findings suggest that the relationship between the PSs and the structural stability of the R state plays a role in the acid and alkaline Bohr effect.

New view on the compatibility of hemoglobin function in the erythrocytes.

OBJECTIVE: Aim: To study the process of hemoglobin oxidation and the enzymatic reactions associated with it. PATIENTS AND METHODS: Materials and Methods: Heparinized human blood (15 IU/ml) was obtained from the clinical department. The concentration of oxy- and methemoglobin, auto-oxidation of hemoglobin was determined spectrophotometrically spectrophotometrically. Autooxidation of hemoglobin was recorded spectrophotometrically, and protein concentration was determined by the Lowry method. Monooxygenase activity of hemoglobin was also measured by the method described by Lowry spectrophotometrically. The concentration of O2 and H2O2 in the reaction media was determined on a biomicroanalyzer OR 210/3 (Redelkis). RESULTS: Results: The obtained experimental data allow us to propose a mechanism of "spontaneous autooxidation" of oxyhemoglobin, which can be described by the following equations: Hb2+O2 → Hb3+ + O2 - (1) Hb2+O2 + 2e - + 2H+ →Hb3+ + H2O2 (2) Hb2+O2 + 2e - + 2H+ →Hb2+ + H2O2 (3) Hb2+ + O2 →Hb2+O2 (4) Spectral characteristics of the process of "spontaneous auto-oxidation" indicate the formation of a metform of hemoglobin, the depletion of oxygen by the system was established, at pH 5.6, an increase in the monooxygenase activity of hemoglobin is observed 3-4 times compared to the physiological level. CONCLUSION: Сonclusions: In addition to the main, previously known functions of hemoglobin (gas transport, peroxidase, monooxygenase), it catalyzes a two-electron oxidase reaction in which O2 is reduced to H2O2. This is confirmed by experimental data on the formation of one of the products of "spontaneous autoxidation" of oxyhemoglobin _ deoxyform at pH 5.6 _ 8.9.

Arterial oxygen desaturation during moderate hypoxia hinders sensorimotor performance.

INTRODUCTION: Moderate hypoxia may impact cognitive and sensorimotor performance prior to self-recognized impairments. Therefore, rapid and objective assessment tools to identify people at risk of impaired function during moderate hypoxia is needed. PURPOSE: Test the hypothesis that reductions in arterial oxygen saturation during moderate normobaric hypoxia (FiO2 = 14%) decreases gamified sensorimotor performance as measured by alterations of motor acuity. METHODS: Following three consecutive days of practice, thirty healthy adults (25 ± 5 y, 10 females) completed three bouts of the tablet-based gamified assessment (Statespace Labs, Inc.) of motor acuity at Baseline and 60 and 90 min after exposure to 13.8 ± 0.2% (hypoxia) and 20.1 ± 0.4% (normoxia) oxygen. The gamified assessment involved moving the tablet to aim and shoot at targets. Both conditions were completed on the same day and were administered in a single-blind, block randomized manner. Performance metrics included shot time and shot variability. Arterial oxyhemoglobin saturation estimated via forehead pulse oximetry (SpO2). Data were analyzed using linear mixed effects models. RESULTS: Compared to normoxia (99±1%), SpO2 was lower (p<0.001) at 60 (89±3%) and 90 (90±2%) min of hypoxia. Shot time was unaffected by decreases in SpO2 (0.012, p = 0.19). Nor was shot time affected by the interaction between SpO2 decrease and baseline performance (0.006, p = 0.46). Shot variability was greater (i.e., less precision, worse performance) with decreases in SpO2 (0.023, p = 0.02) and depended on the interaction between SpO2 decrease and baseline performance (0.029, p< 0.01). CONCLUSION: Decreases in SpO2 during moderate hypoxic exposure hinders sensorimotor performance via decreased motor acuity, i.e., greater variability (less precision) with no change in speed with differing decreases in SpO2. Thus, personnel who are exposed to moderate hypoxia and have greater decreases in SpO2 exhibit lower motor acuity, i.e., less precise movements even though decision time and movement speed are unaffected.

Near-infrared spectroscopy data for foot skin oxygen saturation in healthy subjects.

Our objective was to evaluate normative data for near-infrared spectroscopy (NIRS) in 110 healthy volunteers by Fitzpatrick skin type (FST) and region of the foot. We obtained measurements of the dorsum and plantar foot using a commercially available device (SnapshotNIR, Kent Imaging, Calgary Canada). On the dorsum of the foot, people with FST6 had significantly lower oxygen saturation compared to FST1-5 (p < 0.001), lower oxyhaemoglobin compared to FST2-5 (p = 0.001), but there was no difference in deoxyhaemoglobin. No differences were found on the plantar foot. When comparing dorsal and plantar foot, there was higher oxyhaemoglobin (0.40 ± 0.09 vs. 0.51 ± 0.12, p < 0.001) and deoxyhaemoglobin (0.16 ± 0.05 vs. 0.21 ± 0.05, p < 0.001) on the plantar foot, but no differences in oxygen saturation (dorsal 70.7 ± 10.8, plantar 70.0 ± 9.5, p = 0.414). In 6.4% of feet, there were black areas, for which no NIRS measurements could be generated. All areas with no data were on the dorsal foot and only found in FST 5-6. People with FST6 had significantly larger areas with no data compared to FST 5 (22.2 cm2 ± 20.4 vs. 1.9 cm2 ± 0.90, p = 0.007). These findings should be considered when using NIRS technology. Skin pigmentation should be evaluated in future NIRS studies.

Effects of Age on the Auditory Cortex During Speech Perception in Noise: Evidence From Functional Near-Infrared Spectroscopy.

OBJECTIVES: Age-related speech perception difficulties may be related to a decline in central auditory processing abilities, particularly in noisy or challenging environments. However, how the activation patterns related to speech stimulation in different noise situations change with normal aging has yet to be elucidated. In this study, we aimed to investigate the effects of noisy environments and aging on patterns of auditory cortical activation. DESIGN: We analyzed the functional near-infrared spectroscopy signals of 20 young adults, 21 middle-aged adults, and 21 elderly adults, and evaluated their cortical response patterns to speech stimuli under five different signal to noise ratios (SNRs). In addition, we analyzed the behavior score, activation intensity, oxyhemoglobin variability, and dominant hemisphere, to investigate the effects of aging and noisy environments on auditory cortical activation. RESULTS: Activation intensity and oxyhemoglobin variability both showed a decreasing trend with aging at an SNR of 0 dB; we also identified a strong correlation between activation intensity and age under this condition. However, we observed an inconsistent activation pattern when the SNR was 5 dB. Furthermore, our analysis revealed that the left hemisphere may be more susceptible to aging than the right hemisphere. Activation in the right hemisphere was more evident in older adults than in the left hemisphere; in contrast, younger adults showed leftward lateralization. CONCLUSIONS: Our analysis showed that with aging, auditory cortical regions gradually become inflexible in noisy environments. Furthermore, changes in cortical activation patterns with aging may be related to SNR conditions, and that understandable speech with a low SNR ratio but still understandable may induce the highest level of activation. We also found that the left hemisphere was more affected by aging than the right hemisphere in speech perception tasks; the left-sided dominance observed in younger individuals gradually shifted to the right hemisphere with aging.

Effects of High-Intensity Inspiratory Muscle Warm-Up on High-Intensity Exercise Performance and Muscle Oxygenation.

PURPOSE: An inspiratory muscle warm-up (IMW) improves inspiratory muscle function, but the effects of high-intensity exercise are inconsistent. We aimed to determine the effects of high-intensity IMW on high-intensity exercise performance and muscle oxygenation. METHODS: Ten healthy men (maximal oxygen uptake [V˙O2max] 52.2 [5.0] mL·kg-1·min-1) performed constant-load exercise to exhaustion on a cycle ergometer at V˙O2max under 2 IMW conditions: a placebo condition (PLA) and a high-intensity IMW condition (HIGH). The inspiratory loads were set at 15% and 80% of maximal inspiratory pressure, respectively. Maximal inspiratory pressure was measured before and after IMW. Oxyhemoglobin was measured in the vastus lateralis by near-infrared spectroscopy during exercise. Rating of perceived exertion (RPE) for a leg was measured after 1 and 2 minutes of exercise. RESULTS: Exercise tolerance was significantly higher under HIGH than PLA (228 [49] s vs 218 [49] s, P = .003). Maximal inspiratory pressure was significantly increased by IMW under HIGH (from 125 [20] to 136 [25] cm H2O, P = .031). Oxyhemoglobin was significantly higher under HIGH than PLA at 80% of the total duration of exercise (P = .048). RPE for the leg was significantly lower under HIGH than PLA after 2 minutes of exercise (P = .019). CONCLUSIONS: Given that oxyhemoglobin is an index of local oxygen supply, the results of this study suggest that high-intensity IMW increases the oxygen supply to active limbs. It may also reflect a reduction in RPE in the leg. In addition, high-intensity IMW may improve exercise performance.

Brain control of dual-task walking can be improved in aging and neurological disease.

The peak prevalence of multiple sclerosis has shifted into older age groups, but co-occurring and possibly synergistic motoric and cognitive declines in this patient population are poorly understood. Dual-task-walking performance, subserved by the prefrontal cortex, and compromised in multiple sclerosis and aging, predicts health outcomes. Whether acute practice can improve dual-task walking performance and prefrontal cortex hemodynamic response efficiency in multiple sclerosis has not been reported. To address this gap in the literature, the current study examined task- and practice-related effects on dual-task-walking and associated brain activation in older adults with multiple sclerosis and controls. Multiple sclerosis (n = 94, mean age = 64.76 ± 4.19 years) and control (n = 104, mean age = 68.18 ± 7.01 years) participants were tested under three experimental conditions (dual-task-walk, single-task-walk, and single-task-alpha) administered over three repeated counterbalanced trials. Functional near-infrared-spectroscopy was used to evaluate task- and practice-related changes in prefrontal cortex oxygenated hemoglobin. Gait and cognitive performances declined, and prefrontal cortex oxygenated hemoglobin was higher in dual compared to both single task conditions in both groups. Gait and cognitive performances improved over trials in both groups. There were greater declines over trials in oxygenated hemoglobin in dual-task-walk compared to single-task-walk in both groups. Among controls, but not multiple sclerosis participants, declines over trials in oxygenated hemoglobin were greater in dual-task-walk compared to single-task-alpha. Dual-task walking and associated prefrontal cortex activation efficiency improved during a single session, but improvement in neural resource utilization, although significant, was attenuated in multiple sclerosis participants. These findings suggest encouraging brain adaptability in aging and neurological disease.

Multilevel Pain Assessment with Functional Near-Infrared Spectroscopy: Evaluating ΔHBO2 and ΔHHB Measures for Comprehensive Analysis.

Assessing pain in non-verbal patients is challenging, often depending on clinical judgment which can be unreliable due to fluctuations in vital signs caused by underlying medical conditions. To date, there is a notable absence of objective diagnostic tests to aid healthcare practitioners in pain assessment, especially affecting critically-ill or advanced dementia patients. Neurophysiological information, i.e., functional near-infrared spectroscopy (fNIRS) or electroencephalogram (EEG), unveils the brain's active regions and patterns, revealing the neural mechanisms behind the experience and processing of pain. This study focuses on assessing pain via the analysis of fNIRS signals combined with machine learning, utilising multiple fNIRS measures including oxygenated haemoglobin (ΔHBO2) and deoxygenated haemoglobin (ΔHHB). Initially, a channel selection process filters out highly contaminated channels with high-frequency and high-amplitude artifacts from the 24-channel fNIRS data. The remaining channels are then preprocessed by applying a low-pass filter and common average referencing to remove cardio-respiratory artifacts and common gain noise, respectively. Subsequently, the preprocessed channels are averaged to create a single time series vector for both ΔHBO2 and ΔHHB measures. From each measure, ten statistical features are extracted and fusion occurs at the feature level, resulting in a fused feature vector. The most relevant features, selected using the Minimum Redundancy Maximum Relevance method, are passed to a Support Vector Machines classifier. Using leave-one-subject-out cross validation, the system achieved an accuracy of 68.51%±9.02% in a multi-class task (No Pain, Low Pain, and High Pain) using a fusion of ΔHBO2 and ΔHHB. These two measures collectively demonstrated superior performance compared to when they were used independently. This study contributes to the pursuit of an objective pain assessment and proposes a potential biomarker for human pain using fNIRS.

Mild cognitive impairment estimation based on functional near-infrared spectroscopy.

Patients with mild cognitive impairment (MCI) are at a high risk of developing future dementia. However, early identification and active intervention could potentially reduce its morbidity and the incidence of dementia. Functional near-infrared spectroscopy (fNIRS) has been proposed as a noninvasive modality for detecting oxygenation changes in the time-varying hemodynamics of the prefrontal cortex. This study sought to provide an effective method for detecting patients with MCI using fNIRS and the Wisconsin card sorting test (WCST) to evaluate changes in blood oxygenation. The results revealed that all groups with a lower mini-mental state examination grade had a higher increase in HHb concentration during a modified WCST (MCST). The increase in the change in oxygenated hemoglobin concentration in the stroke group was smaller than that in the normal group due to weak cerebrovascular reactivity.

Validation of a mobile fNIRS device for measuring working memory load in the prefrontal cortex.

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique that measures cortical blood flow to infer neural activation. Traditionally limited to laboratory settings due to high costs and complex operation, recent advancements have introduced mobile fNIRS devices, significantly broadening the scope of potential research participants. This study validates the use of the Mendi, a two-channel mobile fNIRS system, for measuring prefrontal oxyhemoglobin concentration changes during an n-back task. We manipulated task difficulty through different n-back levels (one-back versus three-back), revealing increased oxyhemoglobin concentrations in the prefrontal cortex during the more demanding three-back task compared to the one-back task. This finding demonstrates the Mendi's ability to distinguish between low and high cognitive task loads. Behavioural data, showing a decrease in accuracy under high load conditions, further corroborates these neuroimaging findings. Our study validates the Mendi mobile fNIRS system as an effective tool for assessing working memory load and underscores its potential in enhancing neuroscientific research accessibility. The user-friendly and cost-effective nature of mobile fNIRS systems like the Mendi opens up neuroscientific research to a diverse set of participants, enabling the investigation of neural processes in real-world environments across a variety of demographic groups.

Relationship between cognitive function and brain activation in major depressive disorder patients with and without insomnia: A functional near-infrared spectroscopy (fNIRS) study.

BACKGROUND: Patients with major depressive disorder (MDD) frequently present with sleep disturbances and cognitive impairment. The purpose of this study was to investigate whether cognitive impairment is more severe in MDD patients with insomnia, and the underlying neural mechanisms. METHODS: A total of 41 MDD patients with insomnia and 43 MDD patients without insomnia were recruited. We used functional near-infrared spectroscopy (fNIRS) to assess changes in oxyhemoglobin (Oxy-Hb) concentrations in the brain of patients while performing a verbal fluency task (VFT). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), cognitive function by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and severity of depression by the Hamilton Depression Scale (HAMD). RESULTS: Compared to MDD patients without insomnia, those with insomnia had lower scores on the RBANS total and immediate memory, visuospatial/constructional, and delayed memory subscales, as well as lower oxy-Hb concentrations in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral medial prefrontal cortex (mPFC).Further correlation analysis showed that there was a significant correlation between the RBANS total score in all brain regions except left mPFC in MDD patients with insomnia(all p < 0.05). Further multiple linear regression showed that Oxy-Hb concentrations of left DLPFC were independently associated with RBANS total score. CONCLUSION: Our study suggests that MDD patients with insomnia have more cognitive impairment, which is associated with impaired frontal brain activity. Our findings may provide new insights to understand the underlying neural mechanisms of both disorders MDD patients and provide potential clinical value for developing treatment strategies for insomnia in MDD patients.

The abnormal brain activation pattern of adolescents with major depressive disorder based on working memory tasks: A fNIRS study.

OBJECTIVE: Although studies have confirmed that working memory (WM) is impaired among adults with major depressive disorder (MDD), generalizing these neurocognitive impairments to adolescents with MDD would be tenuous. Therefore, separate studies for adolescents with MDD are needed. Relatively little is known about the neural processes associated with WM dysfunction in adolescents with MDD. Thus, we examined whether adolescents with MDD have abnormal brain activation patterns compared to healthy controls (HC) during WM tasks and whether it was possible to distinguish adolescents with MDD and HC based on mean oxy-hemoglobin (Oxy-Hb) changes. METHOD: A total of 87 adolescents with MDD and 63 HC were recruited. Functional near-infrared spectroscopy (fNIRS) was performed to monitor the concentrations of Oxy-Hb in the frontotemporal lobe while participants performed three WM tasks in order to examine WM impairments in adolescents with depression. RESULTS: The mean changes in Oxy-Hb concentrations in the left prefrontal cortex and right prefrontal cortex were higher among HC than among patients during the encoding and maintenance phase under each WM-load task. Machine learning was used to distinguish adolescents with MDD and HC based on Oxy-Hb changes, with a moderate area under the curve of 0.84. CONCLUSIONS: This study revealed WM defects in adolescents with MDD compared to HC based on mean Oxy-Hb changes, which can be valuable for distinguishing adolescents with MDD from HC.

Alpha-Asarone Ameliorates Neurological Dysfunction of Subarachnoid Hemorrhagic Rats in Both Acute and Recovery Phases via Regulating the CaMKII-Dependent Pathways.

Early brain injury (EBI) is the leading cause of poor prognosis for patients suffering from subarachnoid hemorrhage (SAH), particularly learning and memory deficits in the repair phase. A recent report has involved calcium/calmodulin-dependent protein kinase II (CaMKII) in the pathophysiological process underlying SAH-induced EBI. Alpha-asarone (ASA), a major compound isolated from the Chinese medicinal herb Acorus tatarinowii Schott, was proven to reduce secondary brain injury by decreasing CaMKII over-phosphorylation in rats' model of intracerebral hemorrhage in our previous report. However, the effect of ASA on SAH remains unclear, and the role of CaMKII in both acute and recovery stages of SAH needs further investigation. In this work, we first established a classic SAH rat model by endovascular perforation and intraperitoneally administrated different ASA doses (10, 20, and 40 mg/kg) 2 h after successful modeling. Then, the short- and long-term neurobehavioral performances were blindly evaluated to confirm ASA's efficacy against SAH. Subsequently, we explored ASA's therapeutic mechanism in both acute and recovery stages using histopathological examination, TUNEL staining, flow cytometry, Western-blot, double-immunofluorescence staining, and transmission electron microscopy (TEM) observation. Finally, KN93, a selective CaMKII inhibitor, was applied in oxyhemoglobin-damaged HT22 cells to explore the role of CaMKII in ASA's neuroprotective effect. The results demonstrated that ASA alleviated short- and long-term neurological dysfunction, reduced mortality and seizure rate within 24 h, and prolonged 14-day survival in SAH rats. Histopathological examination showed a reduction of neuronal damage and a restoration of the hippocampal structure after ASA treatment in both acute and recovery phases of SAH. In the acute stage, the Western-blot and flow cytometer analyses showed that ASA restored E/I balance, reduced calcium overload and CaMKII phosphorylation, and inhibited mitochondrion-involved apoptosis, thus preventing neuronal damage and apoptosis underlying EBI post-SAH. In the recovery stage, the TEM observation, double-immunofluorescence staining, and Western-blot analyses indicated that ASA increased the numbers of synapses and enhanced synaptic plasticity in the ipsilateral hippocampi, probably by promoting NR2B/CaMKII interaction and activating subsequent CREB/BDNF/TrkB signaling pathways. Furthermore, KN93 notably reversed ASA's neuroprotective effect on oxyhemoglobin-damaged HT22 cells, confirming CaMKII a potential target for ASA's efficacy against SAH. Our study confirmed for the first time that ASA ameliorated the SAH rats' neurobehavioral deterioration, possibly via modulating CaMKII-involved pathways. These findings provided a promising candidate for the clinical treatment of SAH and shed light on future drug discovery against SAH.

Oxyhaemoglobin saturation NIR-IIb imaging for assessing cancer metabolism and predicting the response to immunotherapy.

In vivo quantitative assessment of oxyhaemoglobin saturation (sO2) status in tumour-associated vessels could provide insights into cancer metabolism and behaviour. Here we develop a non-invasive in vivo sO2 imaging technique to visualize the sO2 levels of healthy and tumour tissue based on photoluminescence bioimaging in the near-infrared IIb (NIR-IIb; 1,500-1,700 nm) window. Real-time dynamic sO2 imaging with a high frame rate (33 Hz) reveals the cerebral arteries and veins through intact mouse scalp/skull, and this imaging is consistent with the haemodynamic analysis results. Utilizing our non-invasive sO2 imaging, the tumour-associated-vessel sO2 levels of various cancer models are evaluated. A positive correlation between the tumour-associated-vessel sO2 levels and the basal oxygen consumption rate of corresponding cancer cells at the early stages of tumorigenesis suggests that cancer cells modulate the tumour metabolic microenvironment. We also find that a positive therapeutic response to the checkpoint blockade cancer immunotherapy could lead to a dramatic decrease of the tumour-associated-vessel sO2 levels. Two-plex dynamic NIR-IIb imaging can be used to simultaneously observe tumour-vessel sO2 and PD-L1, allowing a more accurate prediction of immunotherapy response.