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At least 55 records · Page 3

On the Efficacy of Isolating Shoulder and Elbow Movements with a Soft, Portable, and Wearable Robotic Device

Treatment intensity has a profound effect on motor recovery following neurological injury. The use of robotics has potential to automate these labor-intensive therapy procedures that are typically performed by physical therapists. Further, the use of wearable robotics offers an aspect of portability that may allow for rehabilitation outside the clinic. The authors have developed a soft, portable, lightweight upper extremity wearable robotic device to provide motor rehabilitation of patients with affected upper limbs due to traumatic brain injury (TBI). A key feature of the device demonstrated in this paper is the isolation of shoulder and elbow movements necessary for effective rehabilitation interventions. Herein is presented a feasibility study with one subject and demonstration of the device's ability to provide safe, comfortable, and controlled upper extremity movements. Moreover, it is shown that by decoupling shoulder and elbow motions, desired isolated joint actuation can be achieved.

Kadivar, Zahra↗

Process for Upgrading Cognitive Assessment Capabilities Onboard the International Space Station

MOTIVATION: Spaceflight poses varied and unique risks to the brain and cognitive functioning including radiation exposure, sleep disturbance, fatigue, fluid shifts (increased intracranial pressure), toxin exposure, elevated carbon dioxide, and traumatic brain injury, among others. These potential threats to cognitive functioning are capable of degrading performance and compromising mission success. Furthermore, the threats may increase in severity, and new types of threats may emerge for longer duration exploration missions. This presentation will describe the process used to identify gaps in our current approach, evaluate best practices in cognitive assessment, and transition new cognitive assessment tools to operational use. OVERVIEW: Risks to brain health and performance posed by spaceflight missions require sensitive tools to assess cognitive functioning of astronauts in flight. The Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) is the automated cognitive assessment tool currently deployed onboard the International Space Station (ISS). WinSCAT provides astronauts and flight surgeons with objective data to monitor neurocognitive functioning. WinSCAT assesses 5 discrete cognitive domains, is sensitive to changes in cognitive functioning, and was designed to be completed in less than 15 minutes. However, WinSCAT does not probe other areas of cognitive functioning that might be important to mission success. Researchers recently have developed batteries that may expand current capabilities, such as increased sensitivity to subtle fluctuations in cognitive functioning. Therefore, we engaged in a systematic process review in order to improve upon our current capabilities and incorporate new advances in cognitive assessment. This process included a literature review on newer measures of neurocognitive assessment, surveys of operational flight surgeons at NASA regarding needs and gaps in our capabilities, and expert panel review of candidate cognitive measures and assessment issues and procedures. SIGNIFICANCE: Our process and the results that flowed from it may be helpful to aeromedical professionals charged with transitioning research findings to operational use. Our specific findings regarding cognitive assessment tools are of significance to professionals who must assess readiness to perform in mission critical situations in environments involving threats to cognition and performance

Picano, J. J.↗

Brain-implantable multifunctional probe for simultaneous detection of glutamate and GABA neurotransmitters

We report Glutamate (GLU) and gamma-aminobutyric acid (GABA) are neurotransmitters (NTs) with an essential role in signal transmission in the brain. Brain disorders, such as epilepsy, Alzheimer's and Parkinson's diseases, and traumatic brain injury can be linked to imbalances in the GLU-GABA homeostasis that occurs in sub-second to seconds time frames. Current measurement techniques can detect these two NT concentrations simultaneously only in vitro. The present work reports on the fabrication of a silicon multifunctional biosensor microarray probe for sub-second simultaneous GLU-GABA detection in real-time, with excellent analyte sensitivity and selectivity and in vivo capabilities. The novel Si probes feature four surface-functionalized platinum ultramicroelectrodes (UMEs) for simultaneous amperometric detection of GLU and GABA with a sentinel, and a built-in microfluidic channel for the introduction of neurochemicals in the proximity of the UMEs. The microchannel also allows functioning of an On-Demand In-situ Calibrator that runs in-situ biosensor calibration. The probe exhibited excellent robustness at insertion in agarose-gel brain-tissue-mimicking test, and remarkably high hydrogen peroxide sensitivity (a by-product of GLU-GABA enzyme biosensor) with values on the order of 5000 nA μM -1 cm -2 and maximum sensitivities of 204 ± 15 nA μM -1 cm -2 and 37 ± 7 nA μM -1 cm -2 for GLU and GABA, respectively. Furthermore, the limit of detection of the biosensors reached as low as 7 nM, 165 nM and 750 nM for H 2 O 2 , GLU and GABA, respectively and a temporal resolution of hundreds of milliseconds during in vivo studies using freely moving rats.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Neurosciences & Neurology↗

The child in coma

Children in coma continue to pose medical, social, economic, ethical, moral, and legal problems. Modern life-support technology has aggravated these problems. Coma is viewed as a pathological state of unconsciousness from which the patient has not achieved arousal, and which calls for vigorous action to help him regain consciousness. There are two variables that have an especially important bearing on the ability to achieve arousal. These are: the character of the brain injury that caused the coma, and environmental factors that affect the patient after the injury.

Lewinn, E. B.↗

Noninvasive Intracranial Volume and Pressure Measurements Using Ultrasound (Head and Spinal)

Prevention of secondary brain injuries following head trauma can be accomplished most easily when intracranial pressure (ICP) is monitored. However, current measurement techniques are invasive and thus not practical in the combat environment. The Pulsed Phase Lock Loop device, which was developed and patented by consultants Drs. Yost and Cantrell, uses a unique, noninvasive ultrasonic phase comparison method to measure slight changes in cranial volume which occur with changes in ICP. Year two studies included whole body head-up and head-down tilting effects on intracranial compliance and pressure in six healthy volunteers.

Hargens, Alan R.↗

Entrepreneurial Aspirations

Recom Technologies, Inc., was established in 1980 by Jack Lee, a former NASA contractor. After forming the new company, Recom was awarded NASA contracts, which eventually grew to 50 percent of the company's business. Two companies have spun-off from Recom, both of which have their basis in NASA technology. The first is Attention Control Systems, Inc. with utilizes intelligent planning software that Recom developed for NASA Ames Computational Sciences Division in a hand-held planner used as an aid in cognitive rehabilitation of brain injury patients. The second is MiraNet, Inc. who uses CLIPS as the foundation for WEXpert, the first rules based help system on the Web.

Source record↗

Moving Ahead With Eye Power

NASA's Jet Propulsion Laboratory's collaborated with LC Technologies, Inc., to improve LCT's Eyegaze Communication System, an eye tracker that enables people with severe cerebral palsy, muscular dystrophy, multiple sclerosis, strokes, brain injuries, spinal cord injuries, and ALS (amyotrophic lateral sclerosis) to communicate and control their environment using their eye movements. To operate the system, the user sits in front of the computer monitor while the camera focuses on one eye. By looking at control keys on the monitor for a fraction of a second, the user can 'talk' with speech synthesis, type, operate a telephone, access the Internet and e-mail, and run computer software. Nothing is attached to the user's head or body, and the improved size and portability allow the system to be mounted on a wheelchair. LCT and JPL are working on several other areas of improvement that have commercial add-on potential.

Source record↗

Signal Processing Methods Monitor Cranial Pressure

Dr. Norden Huang, of Goddard Space Flight Center, invented a set of algorithms (called the Hilbert-Huang Transform, or HHT) for analyzing nonlinear and nonstationary signals that developed into a user-friendly signal processing technology for analyzing time-varying processes. At an auction managed by Ocean Tomo Federal Services LLC, licenses of 10 U.S. patents and 1 domestic patent application related to HHT were sold to DynaDx Corporation, of Mountain View, California. DynaDx is now using the licensed NASA technology for medical diagnosis and prediction of brain blood flow-related problems, such as stroke, dementia, and traumatic brain injury.

Source record↗

Neuropsychological Testing of Astronauts

The Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) is a computer program that administers a battery of five timed neuro-cognitive tests. WinSCAT was developed to give astronauts an objective and automated means of assessing their cognitive functioning during space flight, as compared with their own baseline performances measured during similar prior testing on the ground. WinSCAT is also intended for use by flight surgeons to assess cognitive impairment after exposure of astronauts to such cognitive assaults as head trauma, decompression sickness, and exposure to toxic gas. The tests were selected from among a group of tests, denoted the Automated Neuropsychological Assessment Metrics, that were created by the United States Navy and Army for use in evaluating the cognitive impairment of military personnel who have been subjected to medication or are suspected to have sustained brain injuries. These tests have been validated in a variety of clinical settings and are now in the public domain. The tests are presented in a Microsoft Windows shell that facilitates administration and enables immediate reporting of test scores in numerical and graphical forms.

Flynn, Christopher↗

Brain Gene Expression Signatures From Cerebrospinal Fluid Exosome RNA Profiling

While the Visual Impairment and Intracranial Pressure (VIIP) syndrome observations have focused on ocular symptoms, spaceflight has been also associated with a number of other performance and neurologic signs, such as headaches, cognitive changes, vertigo, nausea, sleep/circadian disruption and mood alterations, which, albeit likely multifactorial, can also result from elevation of intracranial pressure (ICP). We therefore hypothesize that these various symptoms are caused by disturbances in the neurophysiology of the brain structures and are correlated with molecular markers in the cerebrospinal fluid (CSF) as indicators of neurophysiological changes. Exosomes are 30-200 nm microvesicles shed into all biofluids, including blood, urine, and CSF, carrying a highly rich source of intact protein and RNA cargo. Exosomes have been identified in human CSF, and their proteome and RNA pool is a potential new reservoir for biomarker discovery in neurological disorders. The purpose of this study is to investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension -IIH), a condition which shares some of the neuroophthalmological features of VIIP, as a first step toward obtaining evidence suggesting that cognitive function and ICP levels can be correlated with biomarkers in the CSF. Our preliminary work, reported last year, validated the exosomal technology applicable to CSF analysis and demonstrated that it was possible to obtain gene expression evidence of inflammation processes in traumatic brain injury patients. We are now recruiting patients with suspected IIH requiring lumbar puncture at Baylor College of Medicine. Both CSF (5 ml) and human plasma (10 ml) are being collected in order to compare the pattern of differentially expressed genes observed in CSF and in blood. Since blood is much more accessible than CSF, we would like to determine whether plasma biomarkers for elevated ICP can be identified. This may eventually lead to a blood test to diagnose intracranial hypertension.

Zanello, S. B.↗

Noninvasive Breath Analysis Using NASA E-Nose Technology for Health Assessment

Clinical breath analysis is based on the fact that many important metabolites and biomarker molecules are present at detectable levels in exhaled breath, and many of these molecules correlate with human disease or correlate with physiological states that could lead to a decline in health. Presented is a technology that utilizes an array of chemical sensors combined with humidity, temperature and pressure for real time breath analysis to correlate the chemical information in the breath with the state and functioning of different human organs. For example, a marker for pulmonary inflammation processes of the lower respiratory tract, e.g. asthma, is the increase of the nitrogen oxide (NO) concentration in breath. Other volatile biomarkers may correlate with infectious process, metabolic conditions and inflammatory diseases, such as traumatic brain injury (TBI). This technology is also called "electronic nose" (E-Nose) in the sense that the device can mimic human nose to smell odors using a pattern recognition technique to analyze the sensor array data. Breath sampling is non-invasive and can be analyzed in real-time.

Li, Jing↗

Correlated Changes in Retinal Thickness and Visuomotor Function in Asymptomatic Plaquenil Toxicity Patients

We have previously shown that a 5-minute eye-movement test can capture a number of largely independent “oculometric” parameters of human visual/visuomotor function (Liston & Stone, 2014). This test has been successfully used to characterize mild neural impairment due to traumatic brain injury, sleep and circadian disruption, and alcohol consumption (Liston et al., 2017; Stone et al, 2019; Tyson et al, 2021). Here, we extend this approach to study patients at risk of progressive posterior-segment illness to see how oculometrics relate to standard clinical ophthalmological measures. Five female patients (<20:40 BCVA, 34-60 years old) undergoing hydroxychloroquine treatment (2-7mg/kg/day for 10-23 years for rheumatologic illness) have participated thus far. Under monocular viewing conditions in randomized order, they tracked a moving spot undergoing radial step-ramp motion in one of 90 randomized directions, at one of 5 randomized speeds, starting at random times (for details, see Stone et al, 2019). We computed nine independent oculometrics (latency, initial acceleration, steady-state gain, proportion smooth, saccadic rate, saccadic amplitude, direction noise, speed responsiveness, and speed noise). Spectral-domain optical coherence tomography (Zeiss, Dublin, CA) was used to measure the average thickness of the nine Early Treatment Diabetic Retinopathy Study macular sectors from the internal limiting membrane to the retinal pigmented epithelium. We used Pearson’s correlation between retinal thickness and our oculometrics with t-statistics to test separate one-sided hypotheses across 10 retinae. Our preliminary analysis found significant changes in several different aspects of visuomotor performance. Most notably, latency increased, initial acceleration decreased, and steady-state pursuit gain decreased as retinal thickness decreased (r2 = 0.364, 0.579, and 0.692; one-tailed P = 0.032, 0.005, and 0.001, respectively). Speed responsiveness appeared to decrease, but this effect was marginal for our current sample (r2 = 0.253, P = 0.069). Lastly, direction discrimination and saccadic behavior appeared unchanged. We conclude that oculometrics may provide sensitive measures of changes in retinal thickness. More importantly, oculometrics have the potential to detect impairment before it becomes evident with standard clinical imaging tools, while also providing insight into the behavioral implications of any resulting deficits in visual/visuomotor function.

eye movements↗

Oculometric Detection and Characterization of Sub-Clinical Visual/Visuomotor Impairment

It has long been known that qualitative abnormalities in eye movements can be used to diagnose overt brain pathologies (Diefendorf & Dodge, 1908; Fox & Holmes, 1926; Leigh & Zee, 2015). Here, we will examine the use of a set of quantitative measures of the human behavioral response (oculometrics) in a 5-minute radial ocular tracking task (Krukowski & Stone, 2005) with sufficient temporal, spatial, and directional uncertainty to minimize the contribution of a priori prediction or anticipation, and to emphasize the use of a posteriori visual processing of the stimulus trajectory (Liston & Stone, 2014). The derived oculometrics provide a largely independent, reliable set of metrics that are sensitive enough to detect mild sub-clinical impairment across a range of possible neural loci (Stone et al., 2019) with the pattern of impairment across the set providing specificity as to its nature (Tyson et al., 2023). We will review our earlier findings where oculometrics have been used to detect mild impairment due to traumatic brain injury, sleep loss, and low-dose alcohol (Liston et al., 2017; Stone et al., 2019; Tyson et al., 2021). We will also report on a recent clinical study of asymptomatic patients at risk of retinal pathology (Leung et al., 2022) and show that oculometrics can detect and characterize substantive loss of visual function in the absence of clinical indicators of pathology. We conclude that oculometric testing could be used as a routine non-invasive ophthalmological or neurological tool to aid in the early detection and diagnosis of neural injury, toxicity, or disease.

eye movements↗

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. DISCUSSION: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study.

Rana, Brinda K.↗

The Biomechanics of Indirect Traumatic Optic Neuropathy Using a Computational Head Model With a Biofidelic Orbit

Indirect traumatic optic neuropathy (ITON) is an injury to the optic nerve due to head trauma and usually results in partial or complete loss of vision. In order to advance a mechanistic understanding of the injury to the optic nerve, we developed a head model with a biofidelic orbit. Head impacts were simulated under controlled conditions of impactor velocity. The locations of impact were varied to include frontal, lateral, and posterior parts of the head. Impact studies were conducted using two types of impactors that differed in their rigidity relative to the skull. The simulated results from both the impactors suggest that forehead impacts are those to which the optic nerve is most vulnerable. The mode and location of optic nerve injury is significantly different between the impacting conditions. Simulated results using a relatively rigid impactor (metal cylinder) suggest optic nerve injury initiates at the location of the intracranial end of the optic canal and spreads to the regions of the optic nerve in the vicinity of the optic canal. In this case, the deformation of the skull at the optic canal, resulting in deformation of the optic nerve, was the primary mode of injury. On the other hand, simulated results using a relatively compliant impactor (soccer ball) suggest that primary mode of injury comes from the brain tugging upon the optic nerve (from where it is affixed to the intracranial end of the optic canal) during coup countercoup motion of the brain. This study represents the first published effort to employ a biofidelic simulation of the full length of the optic nerve in which the orbit is integrated within the whole head.

59 BASIC BIOLOGICAL SCIENCES↗

Is the spatial distribution of brain lesions associated with closed-head injury predictive of subsequent development of attention-deficit/hyperactivity disorder? Analysis with brain-image database

PURPOSE: To determine whether there is an association between the spatial distribution of lesions detected at magnetic resonance (MR) imaging of the brain in children after closed-head injury and the development of secondary attention-deficit/hyperactivity disorder (ADHD). MATERIALS AND METHODS: Data obtained from 76 children without prior history of ADHD were analyzed. MR images were obtained 3 months after closed-head injury. After manual delineation of lesions, images were registered to the Talairach coordinate system. For each subject, registered images and secondary ADHD status were integrated into a brain-image database, which contains depiction (visualization) and statistical analysis software. Using this database, we assessed visually the spatial distributions of lesions and performed statistical analysis of image and clinical variables. RESULTS: Of the 76 children, 15 developed secondary ADHD. Depiction of the data suggested that children who developed secondary ADHD had more lesions in the right putamen than children who did not develop secondary ADHD; this impression was confirmed statistically. After Bonferroni correction, we could not demonstrate significant differences between secondary ADHD status and lesion burdens for the right caudate nucleus or the right globus pallidus. CONCLUSION: Closed-head injury-induced lesions in the right putamen in children are associated with subsequent development of secondary ADHD. Depiction software is useful in guiding statistical analysis of image data.

NASA Discipline Neuroscience↗

Project BIOCORE /M212/, a biological cosmic ray experiment - Procedures, summary, and conclusions

The primary objective of the experiment was to determine whether a specific portion of the high Z-high energy (HZE) galactic cosmic ray particle spectrum, especially particles with Z no less than 6, can produce microscopically visible injury of brain and eye tissues. Pocket mice (Perognathus longimembris), obtained from the California desert, were selected as the biological target. Five of these mice were flown on Apollo XVII. Not only the brain and eyes but also many other tissues of these animals were studied for evidence of cosmic ray particle damage. The lack of prior experimental evidence as to the character of the potential injury induced by HZE particles required reliance on the physical characteristics of particle radiation in ascertaining the probable nature of the injury. These characteristics and the key aspects of the experiment are summarized in this paper. Subsequent articles in this special supplement give details of the biological, engineering, and dosimetric aspects of BIOCORE together with the results.

Haymaker, W.↗