Oxygenated Hemoglobin Signals Research Articles

The neurovascular couplings between electrophysiological and hemodynamic activities in anticipatory selective attention.

Selective attention is thought to involve target enhancement and distractor inhibition processes. Here, we recorded simultaneous electroencephalographic (EEG) and functional near-infrared spectroscopy (fNIRS) data from human adults when they were pre-cued by the visual field of coming target, distractor, or both of them. From the EEG data, we found alpha power relatively decreased contralaterally to the to-be-attended target, as reflected by the positive-going alpha modulation index. Late alpha power relatively increased contralaterally to the to-be-suppressed distractor, as reflected by the negative-going alpha modulation index. From the fNIRS data, we found enhancements of hemodynamic activity over the contralateral hemisphere in response to both the target and the distractor anticipation but within nonoverlapping posterior brain regions. More importantly, we described the specific neurovascular modulation between alpha power and oxygenated hemoglobin signal, which showed a positive coupling effect during target anticipation and a negative coupling effect during distractor anticipation. Such flexible neurovascular couplings between EEG oscillation and hemodynamic activity seem to play an essential role in the final behavioral outcomes. These results provide unique neurovascular evidence for the dissociation of the mechanisms of target enhancement and distractor inhibition. Individual behavioral differences can be related to individual differences in neurovascular coupling.

Use of Virtual Reality Working Memory Task and Functional Near-Infrared Spectroscopy to Assess Brain Hemodynamic Responses to Methylphenidate in ADHD Children.

Virtual reality (VR) neuropsychological tests have emerged as a method to explore drug effects in real-life contexts in attention deficit hyperactivity disorder (ADHD) children. Functional near-infrared spectroscopy (fNIRS) is a useful tool to measure brain activity during VR tasks in ADHD children with motor restlessness. The present study aimed to explore the acute effects of methylphenidate (MPH) on behavioral performance and brain activity during a VR-based working memory task simulating real-life classroom settings in ADHD children. In total, 23 children with ADHD performed a VR n-back task before and 2 h after MPH administration concurrent with measurements of oxygenated hemoglobin signal changes with fNIRS. Altogether, 12 healthy control (HC) subjects participated in the same task but did not receive MPH treatment. Reaction time (RT) was shortened after MPH treatment in the 1-back condition, but changes in brain activation were not observed. In the 2-back condition, activation of the left dorsolateral prefrontal cortex (DLPFC) and bilateral medial prefrontal cortex (mPFC) was decreased alongside behavioral changes such as shorter RT, lower RT variability, and higher accuracy after MPH administration. Bilateral mPFC activation in the 2-back condition inversely correlated with task accuracy in the pre-MPH condition; this inverse correlation was not observed after MPH administration. In ADHD children, deactivation of the default mode network mediated by mPFC reduced during high working memory load, which was restored through MPH treatment. Our results suggest that the combination of VR classroom tasks and fNIRS examination makes it easy to assess drug effects on brain activity in ADHD children in settings simulating real-life.

FNIRS-based Neurorobotic Interface for gait rehabilitation

BackgroundIn this paper, a novel functional near-infrared spectroscopy (fNIRS)-based brain-computer interface (BCI) framework for control of prosthetic legs and rehabilitation of patients suffering from locomotive disorders is presented.MethodsfNIRS signals are used to initiate and stop the gait cycle, while a nonlinear proportional derivative computed torque controller (PD-CTC) with gravity compensation is used to control the torques of hip and knee joints for minimization of position error. In the present study, the brain signals of walking intention and rest tasks were acquired from the left hemisphere’s primary motor cortex for nine subjects. Thereafter, for removal of motion artifacts and physiological noises, the performances of six different filters (i.e. Kalman, Wiener, Gaussian, hemodynamic response filter (hrf), Band-pass, finite impulse response) were evaluated. Then, six different features were extracted from oxygenated hemoglobin signals, and their different combinations were used for classification. Also, the classification performances of five different classifiers (i.e. k-Nearest Neighbour, quadratic discriminant analysis, linear discriminant analysis (LDA), Naïve Bayes, support vector machine (SVM)) were tested.ResultsThe classification accuracies obtained from SVM using the hrf were significantly higher (p < 0.01) than those of the other classifier/ filter combinations. Those accuracies were 77.5, 72.5, 68.3, 74.2, 73.3, 80.8, 65, 76.7, and 86.7% for the nine subjects, respectively.ConclusionThe control commands generated using the classifiers initiated and stopped the gait cycle of the prosthetic leg, the knee and hip torques of which were controlled using the PD-CTC to minimize the position error. The proposed scheme can be effectively used for neurofeedback training and rehabilitation of lower-limb amputees and paralyzed patients.

Abstract 1863: Non-invasive imaging of colitis using multispectral optoacoustic tomography

Abstract Background: Currently, several non-invasive modalities, including MRI and PET, are being investigated to identify early intestinal inflammation, longitudinally monitor disease status, or detect dysplastic changes in patients with inflammatory bowel disease (IBD). Currently, multispectral optoacoustic tomography (MSOT; often in combination with ultrasound) has been used to effectively image tumor xenografts as well as several orthotopic tumor models, including pancreatic adenocarcinoma, but not to specifically assess inflammatory or dysplastic changes in the bowel in murine models. Here, we assess the applicability and utility of (MSOT) in evaluating the presence and severity of colitis. Methods: Nine 6-7 week old C57B/6 mice underwent antibiotic depletion of gastrointestinal flora before inoculation with enterotoxic Bacteroides fragilis to induce colitis. Mice were then anesthetized, depilated, imaged from their superior thorax to inferior pelvis using MSOT. Mice were evaluated prior to bacterial inoculation, 2 days after inoculation, and 7 days after inoculation. MSOT values for oxygenated and deoxygenated hemoglobin were determined using MSOT imaging software and compared using linear regression. At each timepoint, three mice underwent colonoscopy prior to euthanasia and colon processing for histology. Results: Mice with bacterially-induced colitis demonstrated a temporally-associated increase in mesenteric and colonic vascularity, with an increase in mean signal intensity of oxygenated hemoglobin (1.150 vs. 2.716 MSOT a.u. compared to controls; p=0.004) by MSOT two days after inoculation. These findings were significantly more prominent 7 days after inoculation, with increased mean signal intensity of oxygenated hemoglobin (1.150 vs. 2.716 vs. 3.422 MSOT a.u. for controls vs. 2 days post-ETBF vs. 7 days post-ETBF, p=0.0002) and the development of punctate vascular lesions on the colonic surface. Compared to untreated controls, mice at 2 days and 7 days post ETBF inoculation demonstrated an increased colitis score on colonoscopy (1.5 vs. 2.5 vs. 5.5), which correlated well with MSOT findings of mean oxygenated hemoglobin signal intensity (r=0.82, p=0.013). These findings were also associated with inflammatory changes observed on histologic analysis. Conclusions: MSOT represents a non-invasive diagnostic modality that effectively identifies colitis in a murine model. With improvements in depth of tissue penetration, MSOT may hold potential as a sensitive, accurate, non-invasive imaging tool in evaluation of both disease status and early detection of malignancy in patients with IBD. Citation Format: Neal Bhutiani, William Grizzle, Susan Galandiuk, Dennis Otali, Gerald Dryden, Nejat Egilmez, Lacey R. Mcnally. Non-invasive imaging of colitis using multispectral optoacoustic tomography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1863. doi:10.1158/1538-7445.AM2017-1863

Evaluation of different classification methods for the diagnosis of schizophrenia based on functional near-infrared spectroscopy.

Based on near-infrared spectroscopy (NIRS), recent converging evidence has been observed that patients with schizophrenia exhibit abnormal functional activities in the prefrontal cortex during a verbal fluency task (VFT). Therefore, some studies have attempted to employ NIRS measurements to differentiate schizophrenia patients from healthy controls with different classification methods. However, no systematic evaluation was conducted to compare their respective classification performances on the same study population. In this study, we evaluated the classification performance of four classification methods (including linear discriminant analysis, k-nearest neighbors, Gaussian process classifier, and support vector machines) on an NIRS-aided schizophrenia diagnosis. We recruited a large sample of 120 schizophrenia patients and 120 healthy controls and measured the hemoglobin response in the prefrontal cortex during the VFT using a multichannel NIRS system. Features for classification were extracted from three types of NIRS data in each channel. We subsequently performed a principal component analysis (PCA) for feature selection prior to comparison of the different classification methods. We achieved a maximum accuracy of 85.83% and an overall mean accuracy of 83.37% using a PCA-based feature selection on oxygenated hemoglobin signals and support vector machine classifier. This is the first comprehensive evaluation of different classification methods for the diagnosis of schizophrenia based on different types of NIRS signals. Our results suggested that, using the appropriate classification method, NIRS has the potential capacity to be an effective objective biomarker for the diagnosis of schizophrenia.

Cortical changes underlying balance recovery in patients with hemiplegic stroke

Balance problems are a major sequelae of stroke and are implicated in poor recovery of activities of daily living. In a cross-sectional study, using 50-channel event-related functional near-infrared spectroscopy we previously reported a significant correlation between individual balance ability after stroke and postural perturbation-related cortical activation in the supplementary motor area (SMA) and the prefrontal cortex. However, the neural mechanisms underlying balance recovery after stroke remain unclear. Herein, we examined the cortical involvement in balance recovery after stroke by determining longitudinal regional cortical activation changes in patients with hemiplegic stroke. Twenty patients with subcortical stroke admitted to our hospital for post-acute inpatient rehabilitation participated in this study. Before and after intensive inpatient physical and occupational therapy rehabilitation, we evaluated cortical activation associated with external postural perturbations induced by combined brisk forward and backward movement on a platform. Postural perturbation-related cortical activation in the SMA of the affected and unaffected hemispheres was significantly increased after intensive rehabilitation. The increment of the postural-perturbation-related oxygenated hemoglobin signals in the SMA of the unaffected hemisphere was significantly correlated with the gain in balance function measured by the Berg Balance Scale. These findings support the conclusion that the SMA plays an important role in postural balance control, and suggest that the SMA is a crucial area for balance recovery after hemiplegic stroke.

9. Saccade abnormalities in Gilles de la Tourette syndrome

Human brain mapping with near infrared spectroscopy (NIRS) measurements poses two major problems that limit its effectiveness for localizing cortical activation. One is lower spatial resolution and the other is artifacts due to physiological noises most exemplified by non-cortical skin blood flow changes. In this study, we propose a novel solution for these problems by simultaneously implementing a high-density probe arrangement and independent component analysis (ICA)-based signal processing. To achieve high spatial information density, oxygenated hemoglobin signals during a fast-finger-tapping (4 Hz) task were measured with double-density optical topography (DDOT), which consists of data from two alternately embedded single-density optical topographies (SDOT). Then, the measured signals were subjected to ICA to extract the signal components representing cortical activation. DDOT data can be decomposed into two different sets of SDOT data. Comparisons between SDOT and DDOT data revealed that DDOT portrayed both the spatially focused activation and the temporal structure relevant to hemodynamic response, whereas the SDOT data could only portray one or the other. The spatial resolution of DDOT might appear excessive, but it does indeed enable more efficient source separation than SDOT, leading to more robust spatial and temporal analyzes.

Cortical control of postural balance in patients with hemiplegic stroke

Despite its remarkable effect on the activities of daily living, the precise mechanism underlying balance control after stroke remains to be elucidated. In this study, we investigated the cortical activation induced by postural perturbation in 20 patients with stroke using a 50-channel event-related functional near-infrared spectroscopy. A combination of brisk forward and backward movements of a platform without any prior cue was used as an external postural perturbation. Multi-participant analysis of oxygenated hemoglobin signals showed postural perturbation-related cortical activation in the prefrontal cortical areas in both hemispheres as well as the premotor and parietal association cortical areas in the unaffected hemisphere. Regression analysis using the individual Berg Balance Scale as the regressor showed a significant positive correlation between balance ability and the postural perturbation-related changes in oxygenated hemoglobin signals in the supplementary motor areas and prefrontal cortical areas in both hemispheres. Consistent with the previous findings in healthy participants, these findings suggest that the broad cortical network, including the prefrontal, premotor, supplementary motor, and parietal cortical areas in both hemispheres, was essential for balance control even in poststroke patients.

Neurofeedback Using Real-Time Near-Infrared Spectroscopy Enhances Motor Imagery Related Cortical Activation

Accumulating evidence indicates that motor imagery and motor execution share common neural networks. Accordingly, mental practices in the form of motor imagery have been implemented in rehabilitation regimes of stroke patients with favorable results. Because direct monitoring of motor imagery is difficult, feedback of cortical activities related to motor imagery (neurofeedback) could help to enhance efficacy of mental practice with motor imagery. To determine the feasibility and efficacy of a real-time neurofeedback system mediated by near-infrared spectroscopy (NIRS), two separate experiments were performed. Experiment 1 was used in five subjects to evaluate whether real-time cortical oxygenated hemoglobin signal feedback during a motor execution task correlated with reference hemoglobin signals computed off-line. Results demonstrated that the NIRS-mediated neurofeedback system reliably detected oxygenated hemoglobin signal changes in real-time. In Experiment 2, 21 subjects performed motor imagery of finger movements with feedback from relevant cortical signals and irrelevant sham signals. Real neurofeedback induced significantly greater activation of the contralateral premotor cortex and greater self-assessment scores for kinesthetic motor imagery compared with sham feedback. These findings suggested the feasibility and potential effectiveness of a NIRS-mediated real-time neurofeedback system on performance of kinesthetic motor imagery. However, these results warrant further clinical trials to determine whether this system could enhance the effects of mental practice in stroke patients.

Clinically-oriented monitoring of acute effects of methylphenidate on cerebral hemodynamics in ADHD children using fNIRS

ObjectiveAttention Deficit Hyperactivity Disorder (ADHD), a common developmental syndrome with inattention, hyperactivity, and impulsivity, is typically treated with the psychostimulant drug, methylphenidate (MPH). We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to search for a clinically implementable biological marker for the acute MPH effect on ADHD children. MethodsFollowing an MPH washout period, twelve ADHD children performed a go/no-go task before and 1.5h after MPH intake. fNIRS was used to monitor the lateral prefrontal cortical hemodynamics of ADHD children performing a go/no-go task. ResultsThere was no significant activation in the lateral prefrontal cortices examined before MPH intake. However, after MPH intake, significant MPH-elicited activation (oxygenated hemoglobin signal increase) was detected in the right lateral prefrontal cortex (LPFC) implicated with response inhibition functions. There was a large significant correlation between increases in task performance and activation in the right LPFC. ConclusionsThe improved cognitive performance was associated with activation in the right LPFC, which might serve as a biological marker to monitor the effect of MPH in ADHD children. SignificanceMPH-effect assessment in ADHD children using fNIRS can be performed within a 3h stay at a hospital during a single visit, and thus may be integrated into clinical practice.

Large-Scale Brain Networks Underlying Language Acquisition in Early Infancy

A critical issue in human development is that of whether the language-related areas in the left frontal and temporal regions work as a functional network in preverbal infants. Here, we used 94-channel near-infrared spectroscopy to reveal the functional networks in the brains of sleeping 3-month-old infants with and without presenting speech sounds. During the first 3 min, we measured spontaneous brain activation (period 1). After period 1, we provided stimuli by playing Japanese sentences for 3 min (period 2). Finally, we measured brain activation for 3 min without providing the stimulus (period 3), as in period 1. We found that not only the bilateral temporal and temporoparietal regions but also the prefrontal and occipital regions showed oxygenated hemoglobin signal increases and deoxygenated hemoglobin signal decreases when speech sounds were presented to infants. By calculating time-lagged cross-correlations and coherences of oxy-Hb signals between channels, we tested the functional connectivity for the three periods. The oxy-Hb signals in neighboring channels, as well as their homologous channels in the contralateral hemisphere, showed high correlation coefficients in period 1. Similar correlations were observed in period 2; however, the number of channels showing high correlations was higher in the ipsilateral hemisphere, especially in the anterior–posterior direction. The functional connectivity in period 3 showed a close relationship between the frontal and temporal regions, which was less prominent in period 1, indicating that these regions form the functional networks and work as a hysteresis system that has memory of the previous inputs. We propose a hypothesis that the spatiotemporally large-scale brain networks, including the frontal and temporal regions, underlie speech processing in infants and they might play important roles in language acquisition during infancy.

Measurement of neuronal activity in a macaque monkey in response to animate images using near-infrared spectroscopy (NIRS)

Near-infrared spectroscopy (NIRS) has been used extensively for functional neuroimaging over the past decade, in part because it is considered a powerful tool for investigating brain function in human infants and young children, for whom other neuroimaging techniques are not suitable. In particular, several studies have measured hemodynamic responses in the occipital region in infants upon exposure to visual stimuli. In the present study, we used a multi-channel NIRS to measure neuronal activity in a macaque monkey who was trained to watch videos showing various circus animals performing acrobatic activities without fixing the head position of the monkey. Cortical activity from the occipital region was measured first by placing a probe comprising a 3 × 5 array of emitters and detectors (2 × 4 cm) on the area (area 17), and the robustness and stability of the results were confirmed across sessions. Cortical responses were then measured from the dorsofrontal region. The oxygenated hemoglobin signals increased in area 9 and decreased in area 8b in response to viewing the videos. The results suggest that these regions are involved in cognitive processing of visually presented stimuli. The monkey showed positive responsiveness to the stimuli from the affective standpoint, but its attentional response to them was an inhibitory one.

Spectral changes of near-infrared spectroscopy signals in migraineurs with aura reveal an impaired carbon dioxide-regulatory mechanism

Subjects suffering from migraine with aura (MwA) present an altered cerebral autoregulation during migraine attacks. It is still unclear whether MwA sufferers present a normal autoregulation during attack-free periods. In this study, we characterized cerebral autoregulation in the frequency domain by analyzing the spontaneous oscillations superimposed on the cerebral hemodynamic signals, as detected by near-infrared spectroscopy (NIRS). Ten healthy women (age: 38.4 +/- 9.5 years) and ten women suffering from MwA (age: 35.2 +/- 10.5 years) underwent NIRS recording in resting conditions and during breath-holding (BH). Being the NIRS signals during BH nonstationary, we used the Choi-Williams time-frequency distribution to perform spectral analysis. We considered 256 s of signals and quantified the variation in the power of the very-low frequencies (VLF: 20-40 mHz) and of the low frequencies (LF: 40-140 mHz) as response to BH. Results showed that BH increases the power in the LF band both in healthy and MwA subjects. Considering the signal of the deoxygenated hemoglobin, the average power increase in the LF band was equal to 20% +/- 15.4% for the healthy group and significantly lower, 4.8% +/- 8.3%, in the MwA group (Student's t test, P < 0.02). No significant difference was observed in the VLF band or in the oxygenated hemoglobin signal power variations of the LF and VLF bands. The resulting data reveal a possible impairment in the carbon dioxide-regulatory mechanism in MwA subjects.

Near-Infrared Spectroscopy Monitoring of Brain Oxygen in Infant Cardiac Surgery

The use of near-infrared spectroscopy for monitoring cerebral oxygenation during different types of cardiopulmonary bypass was evaluated in 24 patients aged 5 to 13 months. They underwent open-heart surgery under cardiopulmonary bypass with moderate hypothermia, deep hypothermia with low flow, or deep hypothermia with circulatory arrest. Near-infrared spectroscopy data were compared with electroencephalography and biochemical indicators (neuron-specific enolase, lactate). Near-infrared spectroscopy data showed no correlation with biochemical indicators in patients undergoing cardiopulmonary bypass with moderate hypothermia or deep hypothermia with low flow. In the deep hypothermia with circulatory arrest group, the oxygenated hemoglobin signal declined to a nadir during circulatory arrest. The period from reaching the nadir until reperfusion and the minimum values of oxygenated hemoglobin correlated closely with increases in neuron-specific enolase and lactate. All patients with an oxygenated hemoglobin-signal nadir time < 35 min were free from behavioral evidence of brain injury. The oxygenated hemoglobin-signal nadir time may be useful in predicting the safe duration of circulatory arrest.

Prediction of safe duration of hypothermic circulatory arrest by near-infrared spectroscopy

Objective: Hypothermic circulatory arrest is widely used for adults with aortic arch disease as well as for children with congenital heart disease. At present, no method exists for monitoring safe duration of circulatory arrest. Near-infrared spectroscopy is a new technique for noninvasive monitoring of cerebral oxygenation and energy state. In the current study, the relationship between near-infrared spectroscopy data and neurologic outcome was evaluated in a survival piglet model with hypothermic circulatory arrest. Methods: Thirty-six piglets (9.36 ± 0.16 kg) underwent circulatory arrest under varying conditions with continuous monitoring by near-infrared spectroscopy (temperature 15°C or 25°C, hematocrit value 20% or 30%, circulatory arrest time 60, 80, or 100 minutes). Each setting included 3 animals. Neurologic recovery was evaluated daily by neurologic deficit score and overall performance category. Brain was fixed in situ on postoperative day 4 and examined by histologic score. Results: Oxygenated hemoglobin signal declined to a plateau (nadir) during circulatory arrest. Time to nadir was significantly shorter with lower hematocrit value (P <.001) and higher temperature (P <.01). Duration from reaching nadir until reperfusion (“oxygenated hemoglobin signal nadir time”) was significantly related to histologic score (rs = 0.826), neurologic deficit score (rs = 0.717 on postoperative day 1; 0.716 on postoperative day 4), and overall performance category (rs = 0.642 on postoperative day 1; 0.702 on postoperative day 4) (P <.001). All animals in which oxygenated hemoglobin signal nadir time was less than 25 minutes were free of behavioral or histologic evidence of brain injury. Conclusion: Oxygenated hemoglobin signal nadir time determined by near-infrared spectroscopy monitoring is a useful predictor of safe duration of circulatory arrest. Safe duration of hypothermic circulatory arrest is strongly influenced by perfusate hematocrit value and temperature during circulatory arrest.J Thorac Cardiovasc Surg 2001;122:339-50