Scalp and skull influence on near infrared photon propagation in the Colin27 brain template.

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 ± 3.6 mm (range: 3.6-11.2mm), while the average skull thickness was 6.0 ± 1.9 mm (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.

Human cognitive performance in spaceflight and analogue environments.

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.

Nourishing the brain on deep space missions: nutritional psychiatry in promoting resilience.

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.

Test-re-test reliability of the Hopkins Verbal Learning Test-Revised in individuals with traumatic brain injury.

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.

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation.

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.

A controlled treatment study of internal memory strategies (I-MEMS) following traumatic brain injury.

OBJECTIVE: To evaluate the effects of participation in a memory group intervention focusing on internal strategy use on persons with traumatic brain injury-related memory impairment. PARTICIPANTS: Ninety-four adults with traumatic brain injury (54 in the experimental group and 40 controls) and resulting memory impairment, with severities ranging from mild to severe. All participants were at least 18 years of age at the time of injury and at least 1 year post injury at the time of study. DESIGN: Non randomized pre/posttest group comparison design. MAIN OUTCOME MEASURES: Hopkins Verbal Learning Test-Revised and Rivermead Behavioral Memory Test II. RESULTS: Participation in the memory group intervention was associated with improved memory performance immediately postintervention, and improvements were maintained 1 month postintervention. Severe injury was associated with less improvement in memory outcomes than mild and moderate injuries. Age and preinjury education were not related to outcome. CONCLUSIONS: Individuals with traumatic brain injury may benefit from memory group intervention focusing on internal strategy use. Study hypotheses should be retested using a randomized, controlled design, and further research is needed to better delineate influences on intervention candidacy and outcomes.

Test-re-test reliability of the virtual planning test in individuals with traumatic brain injury.

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.

Adaptive filtering to reduce global interference in non-invasive NIRS measures of brain activation: how well and when does it work?

In previous work we introduced a novel method for reducing global interference, based on adaptive filtering, to improve the contrast to noise ratio (CNR) of evoked hemodynamic responses measured non-invasively with near infrared spectroscopy (NIRS). Here, we address the issue of how to generally apply the proposed adaptive filtering method. A total of 156 evoked visual response measurements, collected from 15 individuals, were analyzed. The similarity (correlation) between measurements with far and near source-detector separations collected during the rest period before visual stimulation was used as indicator of global interference dominance. A detailed analysis of CNR improvement in oxy-hemoglobin (O(2)Hb) and deoxy-hemoglobin (HHb), as a function of the rest period correlation coefficient, is presented. Results show that for O(2)Hb measurements, 66% exhibited substantial global interference. For this dataset, dominated by global interference, 71% of the measurements revealed CNR improvements after adaptive filtering, with a mean CNR improvement of 60%. No CNR improvement was observed for HHb. This study corroborates our previous finding that adaptive filtering provides an effective method to increase CNR when there is strong global interference, and also provides a practical way for determining when and where to apply this technique.

Enhanced visual processing contributes to matrix reasoning in autism.

Recent behavioral investigations have revealed that autistics perform more proficiently on Raven's Standard Progressive Matrices (RSPM) than would be predicted by their Wechsler intelligence scores. A widely-used test of fluid reasoning and intelligence, the RSPM assays abilities to flexibly infer rules, manage goal hierarchies, and perform high-level abstractions. The neural substrates for these abilities are known to encompass a large frontoparietal network, with different processing models placing variable emphasis on the specific roles of the prefrontal or posterior regions. We used functional magnetic resonance imaging to explore the neural bases of autistics' RSPM problem solving. Fifteen autistic and eighteen non-autistic participants, matched on age, sex, manual preference and Wechsler IQ, completed 60 self-paced randomly-ordered RSPM items along with a visually similar 60-item pattern matching comparison task. Accuracy and response times did not differ between groups in the pattern matching task. In the RSPM task, autistics performed with similar accuracy, but with shorter response times, compared to their non-autistic controls. In both the entire sample and a subsample of participants additionally matched on RSPM performance to control for potential response time confounds, neural activity was similar in both groups for the pattern matching task. However, for the RSPM task, autistics displayed relatively increased task-related activity in extrastriate areas (BA18), and decreased activity in the lateral prefrontal cortex (BA9) and the medial posterior parietal cortex (BA7). Visual processing mechanisms may therefore play a more prominent role in reasoning in autistics.

Neurophysiological alterations during strategy-based verbal learning in traumatic brain injury.

BACKGROUND: Verbal learning and strategic processing deficits are common sequelae of traumatic brain injury (TBI); however, the neurophysiological mechanisms underlying such deficits remain poorly understood. METHODS: We performed functional magnetic resonance imaging (fMRI) in 25 individuals with chronic TBI (>1 year after injury) and 20 matched healthy controls. Subjects were scanned while encoding word lists, with free recall and recognition assessed after each scanning run. To vary the strategic processing load, participants learned semantically unrelated words (Unrelated condition), semantically related words under null instruction conditions (Spontaneous condition), and semantically related words following training on the use of a semantic clustering strategy (Directed condition). RESULTS: Behavioral performance on recall, recognition, and semantic clustering improved significantly as follows: Unrelated < Spontaneous < Directed. Individuals with TBI exhibited impaired yet parallel behavioral performance relative to control participants. The fMRI measures of brain activity during verbal encoding revealed decreased activity in participants with TBI relative to controls in left dorsolateral prefrontal cortex (DLPFC; BA 9) and in a region spanning the left angular and supramarginal gyri (BA 39/40). Functional connectivity analysis revealed evidence of a functional-but not anatomical-breakdown in the connectivity between the DLPFC and other regions specifically when participants with TBI were directed to use the semantic encoding strategy. CONCLUSION: After TBI, the DLPFC appears to be decoupled from other active brain regions specifically when strategic control is required. We hypothesize that approaches designed to help re-couple DLPFC under such conditions may aid TBI cognitive rehabilitation.

Operationally Relevant Behavior Assessment Using the Robotic On-Board Trainer for Research (ROBoT-r).

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.Ivkovic V, Sommers B, Cefaratti DA, Newman G, Thomas DW, Alexander DG, Strangman GE. Operationally relevant behavior assessment using the Robotic On-Board Trainer for Research (ROBoT-r). Aerosp Med Hum Perform. 2019; 90(9):819-825.

Technology Development for Simultaneous Wearable Monitoring of Cerebral Hemodynamics and Blood Pressure.

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.

Auditory stimulus repetition effects on cortical hemoglobin oxygenation: a near-infrared spectroscopy investigation.

The cortical response to repeated sensory stimuli plateaus (or declines) as repetition frequencies increase beyond 2-8 Hz. This study examined the underlying changes in cortical oxygenated and deoxygenated hemoglobin associated with this phenomenon using near-infrared spectroscopy. The optical signal was measured from 11 healthy volunteers listening to noise-burst trains presented at 2, 10, and 35 Hz. In a bilateral region consistent with the posterior superior temporal gyrus there was an inverse relationship between deoxyhemoglobin concentration change and stimulus frequency: greatest at 2 Hz, intermediate at 10 Hz, and smallest at 35 Hz. These findings provide preliminary support for a relationship between the perceptual characteristics of auditory stimuli and modulation of cortical oxygenation as measured via an emerging neuromonitoring technique.

Prediction of memory rehabilitation outcomes in traumatic brain injury by using functional magnetic resonance imaging.

OBJECTIVE: To evaluate the ability of functional magnetic resonance imaging (fMRI) measures collected from people with traumatic brain injury (TBI) to provide predictive value for rehabilitation outcomes over and above standard predictors. DESIGN: Prospective study. SETTING: Academic medical center. PARTICIPANTS: Persons (N=54) with TBI greater than 1 year postinjury. INTERVENTION: A novel 12-session group rehabilitation program focusing on internal strategies to improve memory. MAIN OUTCOME MEASURE: The Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall score. RESULTS: fMRI measures were collected while participants performed a strategically directed word memorization task. Prediction models were multiple linear regressions with the following primary predictors of outcome: age, education, injury severity, preintervention HVLT-R, and task-related fMRI activation of the left dorsolateral and left ventrolateral prefrontal cortex (VLPFC). Baseline HVLT-R was a significant predictor of outcome (P=.007), as was injury severity (for severe vs mild, P=.049). We also found a significant quadratic (inverted-U) effect of fMRI in the VLPFC (P=.007). CONCLUSIONS: This study supports previous evidence that left prefrontal activity is related to strategic verbal learning, and the magnitude of this activation predicted success in response to cognitive memory rehabilitation strategies. Extreme under- or overactivation of VLPFC was associated with less successful learning after rehabilitation. Further study is necessary to clarify this relationship and to expand and optimize the possible uses of functional imaging to guide rehabilitation therapies.

Wearable brain imaging with multimodal physiological monitoring.

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.

Adaptive filtering to reduce global interference in evoked brain activity detection: a human subject case study.

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.

Adaptive filtering for global interference cancellation and real-time recovery of evoked brain activity: a Monte Carlo simulation study.

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.

Increased cerebral blood volume pulsatility during head-down tilt with elevated carbon dioxide: the SPACECOT Study.

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 double-blind 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.NEW & NOTEWORTHY Cerebral blood volume (CBV) pulsatility-as measured by near-infrared spectroscopy-increases over time during -12° head-down tilt at both cardiac and Mayer wave frequencies. CBV pulsatility appeared to increase more under elevated (0.5%) CO2 at Mayer wave frequencies in some individuals. If similar dynamic pulsatility increases occur in astronauts, there is the potential to initiate vascular and possibly other remodeling processes that lead to symptoms associated with sustained increases in intracranial pressure.

Ambulatory diffuse optical tomography and multimodality physiological monitoring system for muscle and exercise applications.

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.

Acute Mountain Sickness Symptoms Depend on Normobaric versus Hypobaric Hypoxia.

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.