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The grueling psychological demands of a journey into deep space coupled with ever-increasing distances away from home pose a unique problem: how can we best take advantage of the benefits of fresh foods in a place that has none? Here, we consider the biggest challenges associated with our current spaceflight food system, highlight the importance of supporting optimal brain health on missions into deep space, and discuss evidence about food components that impact brain health. We propose a future food system that leverages the gut microbiota that can be individually tailored to best support the brain and mental health of crews on deep space long-duration missions. Working toward this goal, we will also be making investments in sustainable means to nourish the crew that remains here on spaceship Earth. [ABSTRACT FROM AUTHOR]

For many cerebrovascular diseases both blood pressure (BP) and hemodynamic changes are important clinical variables. In this paper, we describe the development of a novel approach to noninvasively and simultaneously monitor cerebral hemodynamics, BP, and other important parameters at high temporal resolution (250 Hz sampling rate). In this approach, cerebral hemodynamics are acquired using near infrared spectroscopy based sensors and algorithms, whereas continuous BP is acquired by superficial temporal artery tonometry with pulse transit time based drift correction. The sensors, monitoring system, and data analysis algorithms used in the prototype for this approach are reported in detail in this paper. Preliminary performance tests demonstrated that we were able to simultaneously and noninvasively record and reveal cerebral hemodynamics and BP during people's daily activity. As examples, we report dynamic cerebral hemodynamic and BP fluctuations during postural changes and micturition. These preliminary results demonstrate the feasibility of our approach, and its unique power in catching hemodynamics and BP fluctuations during transient symptoms (such as syncope) and revealing the dynamic features of related events. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Spaceflight can strain astronaut physical, physiological, and mental well-being, whereas maintaining astronaut operational performance remains an essential goal. Although various cognitive tests have been used for spaceflight assessment, these have been challenged on their lack of operational relevance.METHODS: To address this gap, we developed and characterized the Robotic On-Board Trainer for Research (ROBoT-r) system, based on the Robotic On-Board Trainer (ROBoT) currently used for astronaut training on Canadarm2 track-and-capture activities. The task requires use of dual hand-controllers (6 degrees of freedom) to grapple an incoming vehicle in free-drift in a time-limited setting. After developing a platform for conducting research studies, characterization testing of ROBoT-r was completed by 14 astronaut-like volunteers (35 ± 11 yr; N = 5 women) over 16 sessions each.RESULTS: We describe the design and capabilities of the ROBoT-r system for conducting operationally relevant research on human performance. Version 6.2 of the system supports H-II Transfer Vehicle track-and-capture operations within a multimillion component, physics-enabled 3D model using NASA's DOUG graphics platform. It has configurable task initialization and auto-run capabilities, saves 38 variables continuously at 20 Hz throughout each run, provides the user quantitative feedback after each run, and provides summaries after each session. Detailed performance characterization data is reported for future experimental planning purposes.DISCUSSION: ROBoT-r's range of performance variables enables detailed and quantitative performance assessment. Its use in spaceflight will help provide insight into operational performance, as well as allowing investigators to compare these results with more traditional cognitive tests to help better understand the interaction between individual cognitive abilities and operational performance. [ABSTRACT FROM AUTHOR]

The brain is a central component of cognitive and physical human performance. Measures, including functional brain activation, cerebral perfusion, cerebral oxygenation, evoked electrical responses, and resting hemodynamic and electrical activity are all related to, or can predict, health status or performance decrements. However, measuring brain physiology typically requires large, stationary machines that are not suitable for mobile or self-monitoring. Moreover, when individuals are ambulatory, systemic physiological fluctuations- e.g., in heart rate, blood pressure, skin perfusion, and more-can interfere with noninvasive brain measurements. In efforts to address the physiological monitoring and performance assessment needs for astronauts during spaceflight, we have developed easy-to-use, wearable prototypes, such as NINscan, for near-infrared scanning, which can collect synchronized multimodal physiology data, including hemodynamic deep-tissue imaging (including brain and muscles), electroencephalography, electrocardiography, electromyography, electrooculography, accelerometry, gyroscopy, pressure, respiration, and temperature measurements. Given their self-contained and portable nature, these devices can be deployed in a much broader range of settings-including austere environments- thereby, enabling a wider range of novel medical and research physiology applications. We review these, including high-altitude assessments, self-deployable multimodal e.g., (polysomnographic) recordings in remote or low-resource environments, fluid shifts in variable-gravity, or spaceflight analog environments, intracranial brain motion during high-impact sports, and long-duration monitoring for clinical symptom-capture in various clinical conditions. In addition to further enhancing sensitivity and miniaturization, advanced computational algorithms could help support real-time feedback and alerts regarding performance and health. [ABSTRACT FROM AUTHOR]

Astronauts aboard the International Space Station (ISS) have exhibited hyperopic shifts, posterior eye globe flattening, dilated optic nerve sheaths, and even optic disk swelling from spaceflight. Elevated intracranial pressure (ICP) consequent to cephalad fluid shifts is commonly hypothesized as contributing to these ocular changes. Head-down tilt (HDT) is frequently utilized as an Earth-based analog to study similar fluid shifts. Sealed environments like the ISS also exhibit elevated CO2, a potent arteriolar vasodilator that could further affect cerebral blood volume (CBV) and cerebral blood flow, intracranial compliance, and ICP. A collaborative pilot study between the National Space Biomedical Research Institute and the German Aerospace Center tested the hypotheses that 1) HDT and elevated CO2 physiologically interact and 2) cerebrovascular pulsatility is related to HDT and/or elevated CO2. In a doubleblind crossover study (n = 6), we measured CBV pulsatility via near-infrared spectroscopy, alongside noninvasive ICP and intraocular pressure (IOP) during 28-h -12° HDT at both nominal (0.04%) and elevated (0.5%) ambient CO2. In our cohort, CBV pulsatility increased significantly over time at cardiac frequencies (0.031 ± 0.009 μM/h increase in total hemoglobin concentration pulsatility amplitude) and Mayer wave frequencies (0.019 ± 0.005 μM/h increase). The HDT-CO2 interaction on pulsatility was not robust but rather driven by one individual. Significant differences between atmospheres were not detected in ICP or IOP. Further work is needed to determine whether individual differences in pulsatility responses to CO2 relate to visual changes in space. [ABSTRACT FROM AUTHOR]

Acute mountain sickness (AMS), characterized by headache, nausea, fatigue, and dizziness when unacclimatized individuals rapidly ascend to high altitude, is exacerbated by exercise and can be disabling. Although AMS is observed in both normobaric (NH) and hypobaric hypoxia (HH), recent evidence suggests that NH and HH produce different physiological responses. We evaluated whether AMS symptoms were different in NH and HH during the initial stages of exposure and if the assessment tool mattered. Seventy-two 8 h exposures to normobaric normoxia (NN), NH, or HH were experienced by 36 subjects. The Environmental Symptoms Questionnaire (ESQ) and Lake Louise Self-report (LLS) were administered, resulting in a total of 360 assessments, with each subject answering the questionnaire 5 times during each of their 2 exposure days. Classification tree analysis indicated that symptoms contributing most to AMS were different in NH (namely, feeling sick and shortness of breath) compared to HH (characterized most by feeling faint, appetite loss, light headedness, and dim vision). However, the differences were not detected using the LLS. These results suggest that during the initial hours of exposure (1) AMS in HH may be a qualitatively different experience than in NH and (2) NH and HH may not be interchangeable environments. [ABSTRACT FROM AUTHOR]

Ambulatory diffuse optical tomography (aDOT) is based on near-infrared spectroscopy (NIRS) and enables three-dimensional imaging of regional hemodynamics and oxygen consumption during a person’s normal activities. Although NIRS has been previously used for muscle assessment, it has been notably limited in terms of the number of channels measured, the extent to which subjects can be ambulatory, and/or the ability to simultaneously acquire synchronized auxiliary data such as electromyography (EMG) or electrocardiography (ECG). We describe the development of a prototype aDOT system, called NINscan-M, capable of ambulatory tomographic imaging as well as simultaneous auxiliary multimodal physiological monitoring. Powered by four AA size batteries and weighing 577 g, the NINscan-M prototype can synchronously record 64-channel NIRS imaging data, eight channels of EMG, ECG, or other analog signals, plus force, acceleration, rotation, and temperature for 24+ h at up to 250 Hz. We describe the system’s design, characterization, and performance characteristics. We also describe examples of isometric, cycle ergometer, and free-running ambulatory exercise to demonstrate tomographic imaging at 25 Hz. NINscan-M represents a multiuse tool for muscle physiology studies as well as clinical muscle assessment. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study simultaneously quantified the effects of normobaric hypoxia (NH), hypobaric hypoxia (HH), exercise duration, and exposure time on acute mountain sickness severity (AMS-C). METHODS: Thirty-six subjects (27.7 ± 7.8 yr) participated in a partial repeated measures study, completing two of six conditions: normobaric normoxia (NN: 300 m/984 ft equivalent), NH or HH (Po2 = 91 mmHg; 4400 m/14,436 ft equivalent), combined with moderate intensity cycling for 10 or 60 min. Subjects completed the Environmental Symptoms Questionnaire and oxygen saturation (Spo2) was measured before, 1.5 h, 4 h, and 6.5 h into an 8-h exposure, and 1.5 h post-exposure. We fit multiple linear regression models with cluster adjusted standard errors on the exposure times using NH, HH, and long exercise as indicator variables, and AMS-C as the outcome variable. The Spo2 and pre-exposure AMS-C score were used as covariates. RESULTS: NH and HH led to substantial and progressively increasing AMS-C, but NN did not. The effect of HH on AMS-C was significantly different from NH, with AMS-C in HH being 1.6 times higher than in NH. HH led to significantly increasing AMS-C, regardless of the exercise duration, while NH only did so in combination with longer exercise. DISCUSSION: Increases in AMS-C were each independently related to NH, HH, and long duration exercise, with HH affecting AMS-C more severely. This suggests that hypobaria may affect AMS development above the level induced by hypoxia alone. This further suggests that NH and HH may not be interchangeable for studying AMS and that exercise duration may impact physiological responses. [ABSTRACT FROM AUTHOR]

The feasibility and utility of wearable 24-h multimodality neuromonitoring during daily activities are demonstrated. We have developed a fourth-generation ambulatory near infrared spectroscopy device, namely NINscan 4. NINscan 4 enables recording of brain function (via cerebral hemodynamics), systemic hemodynamics, electrocardiography, and actigraphy simultaneously and continuously for up to 24 h at 250-Hz sampling rate, during (and with minor restriction to) daily activities. We present initial 24-h human subject test results, with example analysis including (1) comparison of cerebral perfusion and oxygenation changes during wakefulness and sleep over a 24-h period and (2) capturing of hemodynamic changes prior, during and after sudden waken up in the night during sleep. These results demonstrate the first ambulatory 24-h cerebral and systemic hemodynamics monitoring, and its unique advantages including long-term data collection and analysis capability, ability to catch unpredictable transient events during activities of daily living, as well as coregistered multimodality analysis capabilities. These results also demonstrate that NINscan 4's motion artifact at 1- head move- g ment is smaller than physiological hemodynamic fluctuations during motionless sleep. The broader potential of this technology is also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Near-infrared neuromonitoring (NIN) is based on near-infrared spectroscopy (NIRS) measurements performed through the intact scalp and skull. Despite the important effects of overlying tissue layers on the measurement of brain hemodynamics, the influence of scalp and skull on NIN sensitivity are not well characterized. Using 3555 Monte Carlo simulations, we estimated the sensitivity of individual continuous-wave NIRS measurements to brain activity over the entire adult human head by introducing a small absorption perturbation to brain gray matter and quantifying the influence of scalp and skull thickness on this sensitivity. After segmenting the Colin27 template into five tissue types (scalp, skull, cerebrospinal fluid, gray matter and white matter), the average scalp thickness was 6.9±3.6mm (range: 3.6–11.2mm), while the average skull thickness was 6.0±1.9mm (range: 2.5–10.5mm). Mean NIN sensitivity – defined as the partial path length through gray matter divided by the total photon path length – ranged from 0.06 (i.e., 6% of total path length) at a 20mm source–detector separation, to over 0.19 at 50mm separations. NIN sensitivity varied substantially around the head, with occipital pole exhibiting the highest NIRS sensitivity to gray matter, whereas inferior frontal regions had the lowest sensitivity. Increased scalp and skull thickness were strongly associated with decreased sensitivity to brain tissue. Scalp thickness always exhibited a slightly larger effect on sensitivity than skull thickness, but the effect of both varied with SD separation. We quantitatively characterize sensitivity around the head as well as the effects of scalp and skull, which can be used to interpret NIN brain activation studies as well as guide the design, development and optimization of NIRS devices and sensors. [Copyright &y& Elsevier]

Understanding the spatial and depth sensitivity of non-invasive near-infrared spectroscopy (NIRS) measurements to brain tissue–i.e., near-infrared neuromonitoring (NIN) – is essential for designing experiments as well as interpreting research findings. However, a thorough characterization of such sensitivity in realistic head models has remained unavailable. In this study, we conducted 3,555 Monte Carlo (MC) simulations to densely cover the scalp of a well-characterized, adult male template brain (Colin27). We sought to evaluate: (i) the spatial sensitivity profile of NIRS to brain tissue as a function of source-detector separation, (ii) the NIRS sensitivity to brain tissue as a function of depth in this realistic and complex head model, and (iii) the effect of NIRS instrument sensitivity on detecting brain activation. We found that increasing the source-detector (SD) separation from 20 to 65 mm provides monotonic increases in sensitivity to brain tissue. For every 10 mm increase in SD separation (up to ∼45 mm), sensitivity to gray matter increased an additional 4%. Our analyses also demonstrate that sensitivity in depth (S) decreases exponentially, with a “rule-of-thumb” formula S = 0.75*0.85depth. Thus, while the depth sensitivity of NIRS is not strictly limited, NIN signals in adult humans are strongly biased towards the outermost 10–15 mm of intracranial space. These general results, along with the detailed quantitation of sensitivity estimates around the head, can provide detailed guidance for interpreting the likely sources of NIRS signals, as well as help NIRS investigators design and plan better NIRS experiments, head probes and instruments. [ABSTRACT FROM AUTHOR]

Primary objective: To determine test-re-test reliability of the Hopkins Verbal Learning Test-Revised (HVLT-R) in a group of individuals with traumatic brain injury (TBI). Research design: Single-group repeated measures design. Methods and procedures: Seventy-five individuals with TBI were administered the HVLT-R twice, with 6-8 weeks between the two test sessions. Main outcomes and results: Test-re-test reliability on HVLT-R scoring parameters ranged from 0.537-0.818, with seven of the eight scoring parameters exhibiting r > 0.6. At re-test, scores did not significantly change on any of the eight HVLT-R scoring parameters. Conclusions: HVLT-R use with individuals with TBI is supported. Test-re-test reliability of total recall and delayed recall sub-scores was particularly high. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) commonly results in residual memory difficulties. Such deficits are amenable to cognitive rehabilitation, but optimal selection of rehabilitation interventions remains a challenge. We hypothesized that diffusion tensor imaging (DTI) could be used to predict which individuals were likely to benefit from a specific memory rehabilitation intervention. Thirty-seven individuals with TBI, of all severities, first underwent DTI scanning, along with 18 matched controls. Participants with TBI then attended a 12-session memory intervention emphasizing internal memory strategies (I-MEMS). Primary outcome measures (HVLT, RBMT) were collected at the time of DTI scanning, and both immediately and one month post-therapy. In contrast to typical neuroimaging analysis, fractional anisotropy (FA) was used to predict long-term outcome scores, adjusting for typical predictors (injury severity, age, education, time since injury, pretest score). FA of the parahippocampal white matter was a significant negative predictor of HVLT, while the anterior corpus callosum, left anterior internal capsule, and right anterior corona radiata were negative predictors of RBMT outcome. The importance of these predictors rivaled those of pretest scores. Thus, FA measures may provide substantial predictive value for other cognitive interventions as well. The reason why higher FA was associated with less successful response to cognitive intervention remains unclear and will require further study. [ABSTRACT FROM AUTHOR]

Primary objective: To determine test–re-test reliability of the VIrtual Planning Test (VIP) in a group of individuals with traumatic brain injury (TBI). Research design: Single-group repeated measures design. Methods and procedures: Seventy-five individuals with TBI were administered the VIP, with 6–8 weeks between the two test sessions. Main outcomes and results: Test–re-test reliability on VIP scoring parameters—as measured by Pearson correlation coefficients—ranged from 0.341–0.855, with five of the seven scoring parameters exhibiting r > 0.6. Conclusions: Based on the findings of the current study, the VIP has overall moderate test–re-test reliability when administered to individuals with TBI. Some VIP scoring parameters, i.e. Total correct/accuracy and Total absence, demonstrated high test–re-test reliability. Others, i.e. Planning time and Total wrong order, demonstrated low test–re-test reliability. [ABSTRACT FROM AUTHOR]

Ultrasound is an important theragnostic modality in modern medicine. Technical advancement of both acoustic focusing and transcranial delivery have enabled administration of ultrasound waves to localized brain areas with few millimeters of spatial specificity and penetration depth sufficient to reach the thalamus. Transcranial focused ultrasound (tFUS) given at a low acoustic intensity has been shown to increase or suppress the excitability of region-specific brain areas. The neuromodulatory effects can outlast the sonication, suggesting the possibility of inducing neural plasticity needed for neurorehabilitation. Increasing numbers of studies have shown the efficacy and excellent safety profile of the technique, yet comparisons among the safety-related parameters have not been compiled. This review aims to provide safety information and perspectives of tFUS brain stimulation. First, the acoustic parameters most relevant to thermal/mechanical tissue damage are discussed along with regulated parameters for existing ultrasound therapies/diagnostic imaging. Subsequently, the parameters used in studies of large animals, non-human primates, and humans are surveyed and summarized in terms of the acoustic intensity and the mechanical index. The pulse-mode operation and the use of low ultrasound frequency for tFUS-mediated brain stimulation warrant the establishment of new safety guidelines/recommendations for the use of the technique among healthy volunteers, with additional cautionary requirements for its clinical translation., Competing Interests: Conflict of Interest: The authors have no potential conflicts of interest to disclose., (Copyright © 2021. Korean Society for Neurorehabilitation.)

Ambulatory diffuse optical tomography (aDOT) is based on near-infrared spectroscopy (NIRS) and enables three-dimensional imaging of regional hemodynamics and oxygen consumption during a person’s normal activities. Although NIRS has been previously used for muscle assessment, it has been notably limited in terms of the number of channels measured, the extent to which subjects can be ambulatory, and/or the ability to simultaneously acquire synchronized auxiliary data such as electromyography (EMG) or electrocardiography (ECG). We describe the development of a prototype aDOT system, called NINscan-M, capable of ambulatory tomographic imaging as well as simultaneous auxiliary multimodal physiological monitoring. Powered by four AA size batteries and weighing 577 g, the NINscan-M prototype can synchronously record 64-channel NIRS imaging data, eight channels of EMG, ECG, or other analog signals, plus force, acceleration, rotation, and temperature for 24+ h at up to 250 Hz. We describe the system’s design, characterization, and performance characteristics. We also describe examples of isometric, cycle ergometer, and free-running ambulatory exercise to demonstrate tomographic imaging at 25 Hz. NINscan-M represents a multiuse tool for muscle physiology studies as well as clinical muscle assessment.

Maintaining intact cognitive performance is a high priority for space exploration. This review seeks to summarize the cumulative results of existing studies of cognitive performance in spaceflight and analogue environments. We focused on long-duration (>21 d) studies for which no review has previously been conducted. There were 11 published studies identified for long-duration spaceflight (N = 42 subjects) as well as 21 shorter spaceflight studies (N = 70 subjects). Overall, spaceflight cognitive studies ranged from 6-438 d in duration. Some 55 spaceflight analogue studies were also identified, ranging from 6 to 520 d. The diverse nature of experimental procedures and protocols precluded formal meta-analysis. In general, the available evidence fails to strongly support or refute the existence of specific cognitive deficits in low Earth orbit during long-duration spaceflight, which may be due in large part to small numbers of subjects. The studies consistently suggest that novel environments (spaceflight or other) induce variable alterations in cognitive performance across individuals, consistent with known astronaut experiences. This highlights the need to better quantify the magnitude and scope of this interindividual variability, and understand its underlying factors, when predicting in-flight cognitive functioning for extended periods.

The feasibility and utility of wearable 24-h multimodality neuromonitoring during daily activities are demonstrated. We have developed a fourth-generation ambulatory near infrared spectroscopy device, namely NINscan 4. NINscan 4 enables recording of brain function (via cerebral hemodynamics), systemic hemodynamics, electrocardiography, and actigraphy simultaneously and continuously for up to 24 h at 250-Hz sampling rate, during (and with minor restriction to) daily activities. We present initial 24-h human subject test results, with example analysis including (1) comparison of cerebral perfusion and oxygenation changes during wakefulness and sleep over a 24-h period and (2) capturing of hemodynamic changes prior, during and after sudden waken up in the night during sleep. These results demonstrate the first ambulatory 24-h cerebral and systemic hemodynamics monitoring, and its unique advantages including long-term data collection and analysis capability, ability to catch unpredictable transient events during activities of daily living, as well as coregistered multimodality analysis capabilities. These results also demonstrate that NINscan 4's motion artifact at 1-g head movement is smaller than physiological hemodynamic fluctuations during motionless sleep. The broader potential of this technology is also discussed.

Ambulatory near-infrared spectroscopy (aNIRS) enables recording of systemic or tissue-specific hemodynamics and oxygenation during a person's normal activities. It has particular potential for the diagnosis and management of health problems with unpredictable and transient hemodynamic symptoms, or medical conditions requiring continuous, long-duration monitoring. aNIRS is also needed in conditions where regular monitoring or imaging cannot be applied, including remote environments such as during spaceflight or at high altitude. One key to the successful application of aNIRS is reducing the impact of motion artifacts in aNIRS recordings. In this paper, we describe the development of a novel prototype aNIRS monitor, called NINscan, and our efforts to reduce motion artifacts in aNIRS monitoring. Powered by 2 AA size batteries and weighting 350 g, NINscan records NIRS, ECG, respiration, and acceleration for up to 14 h at a 250 Hz sampling rate. The system's performance and resistance to motion is demonstrated by long term quantitative phantom tests, Valsalva maneuver tests, and multiparameter monitoring during parabolic flight and high altitude hiking. To the best of our knowledge, this is the first report of multiparameter aNIRS monitoring and its application in parabolic flight.

Cognitive deficits following traumatic brain injury (TBI) commonly include difficulties with memory, attention, and executive dysfunction. These deficits are amenable to cognitive rehabilitation, but optimally selecting rehabilitation programs for individual patients remains a challenge. Recent methods for quantifying regional brain morphometry allow for automated quantification of tissue volumes in numerous distinct brain structures. We hypothesized that such quantitative structural information could help identify individuals more or less likely to benefit from memory rehabilitation. Fifty individuals with TBI of all severities who reported having memory difficulties first underwent structural MRI scanning. They then participated in a 12 session memory rehabilitation program emphasizing internal memory strategies (I-MEMS). Primary outcome measures (HVLT, RBMT) were collected at the time of the MRI scan, immediately following therapy, and again at 1-month post-therapy. Regional brain volumes were used to predict outcome, adjusting for standard predictors (e.g., injury severity, age, education, pretest scores). We identified several brain regions that provided significant predictions of rehabilitation outcome, including the volume of the hippocampus, the lateral prefrontal cortex, the thalamus, and several subregions of the cingulate cortex. The prediction range of regional brain volumes were in some cases nearly equal in magnitude to prediction ranges provided by pretest scores on the outcome variable. We conclude that specific cerebral networks including these regions may contribute to learning during I-MEMS rehabilitation, and suggest that morphometric measures may provide substantial predictive value for rehabilitation outcome in other cognitive interventions as well.

There has been substantial recent growth in the use of non-invasive optical brain imaging in studies of human brain function in health and disease. Near-infrared neuroimaging (NIN) is one of the most promising of these techniques and, although NIN hardware continues to evolve at a rapid pace, software tools supporting optical data acquisition, image processing, statistical modeling, and visualization remain less refined. Python, a modular and computationally efficient development language, can support functional neuroimaging studies of diverse design and implementation. In particular, Python's easily readable syntax and modular architecture allow swift prototyping followed by efficient transition to stable production systems. As an introduction to our ongoing efforts to develop Python software tools for structural and functional neuroimaging, we discuss: (i) the role of non-invasive diffuse optical imaging in measuring brain function, (ii) the key computational requirements to support NIN experiments, (iii) our collection of software tools to support NIN, called NinPy, and (iv) future extensions of these tools that will allow integration of optical with other structural and functional neuroimaging data sources. Source code for the software discussed here will be made available at www.nmr.mgh.harvard.edu/Neural_SystemsGroup/software.html.

Following previous Monte Carlo simulations, we describe in detail an example of detecting evoked visual hemodynamic responses in a human subject as a preliminary demonstration of the novel global interference cancellation technology. The raw time series of oxyhemoglobin (O(2)Hb) and deoxyhemoglobin (HHb) changes, their block averaged results before and after adaptive filtering, together with the power spectral density analysis are presented. Simultaneous respiration and EKG recordings suggested that spontaneous low-frequency oscillation and cardiac activity were the major sources of global interference in our test. When global interference dominates (e.g., for O(2)Hb in our data, judged by power spectral density analysis), adaptive filtering effectively reduced this interference, doubling the contrast-to-noise ratio (CNR) for evoked visual response detection. When global interference is not obvious (e.g., in our HHb data), adaptive filtering provided no CNR improvement. The results also showed that the hemodynamic changes in the superficial layers and the estimated total global interference in the target measurement were highly correlated (r=0.96), which explains why this global interference cancellation method should work well when global interference is dominating. In addition, the results suggested that association between the superficial layer hemodynamics and the total global interference is time-varying.

The sensitivity of near-infrared spectroscopy (NIRS) to evoked brain activity is reduced by physiological interference in at least two locations: 1. the superficial scalp and skull layers, and 2. in brain tissue itself. These interferences are generally termed as "global interferences" or "systemic interferences," and arise from cardiac activity, respiration, and other homeostatic processes. We present a novel method for global interference reduction and real-time recovery of evoked brain activity, based on the combination of a multiseparation probe configuration and adaptive filtering. Monte Carlo simulations demonstrate that this method can be effective in reducing the global interference and recovering otherwise obscured evoked brain activity. We also demonstrate that the physiological interference in the superficial layers is the major component of global interference. Thus, a measurement of superficial layer hemodynamics (e.g., using a short source-detector separation) makes a good reference in adaptive interference cancellation. The adaptive-filtering-based algorithm is shown to be resistant to errors in source-detector position information as well as to errors in the differential pathlength factor (DPF). The technique can be performed in real time, an important feature required for applications such as brain activity localization, biofeedback, and potential neuroprosthetic devices.