Publications by authors named "Jun Maruta"

30 Publications

  • Page 1 of 1

Visuomotor Synchronization: Military Normative Performance.

Mil Med 2021 Jul 28. Epub 2021 Jul 28.

Brain Trauma Foundation, Palo Alto, CA 94301, USA.

Introduction: Cognitive processes such as perception and reasoning are preceded and dependent on attention. Because of the close overlap between neural circuits of attention and eye movement, attention may be objectively quantified with recording of eye movements during an attention-dependent task. Our previous work demonstrated that performance scores on a circular visual tracking task that requires dynamic synchronization of the gaze with the target motion can be impacted by concussion, sleep deprivation, and attention deficit/hyperactivity disorder. The current study examined the characteristics of performance on a standardized predictive visual tracking task in a large sample from a U.S. Military population to provide military normative data.

Materials And Methods: The sample consisted of 1,594 active duty military service members of either sex aged 18-29 years old who were stationed at Fort Hood Army Base. The protocol was reviewed and approved by the U.S. Army Medical Research and Materiel Command Institutional Review Board. Demographic, medical, and military history data were collected using questionnaires, and performance-based data were collected using a circular visual tracking test and Trail Making Test. Differences in visual tracking performance by demographic characteristics were examined with a multivariate analysis of variance, as well as a Kolmogorov-Smirnov test and a rank-sum test. Associations with other measures were examined with a rank-sum test or Spearman correlations.

Results: Robust sex differences in visual tracking performance were found across the various statistical models, as well as age differences in several isolated comparisons. Accordingly, norms of performance scores, described in terms of percentile standings, were developed adjusting for age and sex. The effects of other measures on visual tracking performance were small or statistically non-significant. An examination of the score distributions of various metrics suggested that strategies preferred by men and women may optimize different aspects of visual tracking performance.

Conclusion: This large-scale quantification of attention, using dynamic visuomotor synchronization performance, provides rigorously characterized age- and sex-based military population norms. This study establishes analytics for assessing normal and impaired attention and detecting changes within individuals over time. Practical applications for combat readiness and surveillance of attention impairment from sleep insufficiency, concussion, medication, or attention disorders will be enhanced with portable, easily accessible, fast, and reliable dynamic eye-tracking technologies.
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http://dx.doi.org/10.1093/milmed/usab320DOI Listing
July 2021

The Scientific Contributions of Bernard Cohen (1929-2019).

Authors:
Jun Maruta

Front Neurol 2020 12;11:624243. Epub 2021 Jan 12.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Throughout Bernard Cohen's active career at Mount Sinai that lasted over a half century, he was involved in research on vestibular control of the oculomotor, body postural, and autonomic systems in animals and humans, contributing to our understanding of such maladies as motion sickness, mal de débarquement syndrome, and orthostatic syncope. This review is an attempt to trace and connect Cohen's varied research interests and his approaches to them. His influence was vast. His scientific contributions will continue to drive research directions for many years to come.
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http://dx.doi.org/10.3389/fneur.2020.624243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835511PMC
January 2021

Concussion Disrupts Normal Brain White Matter Microstructural Symmetry.

Front Neurol 2020 12;11:548220. Epub 2020 Nov 12.

Department Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States.

Injuries and illnesses can alter the normal bilateral symmetry of the brain, and determining the extent of this disruption may be useful in characterizing the pathology. One way of quantifying brain symmetry is in terms of bilateral correlation of diffusion tensor metrics between homologous white matter tracts. With this approach, we hypothesized that the brains of patients with a concussion are more asymmetrical than those of healthy individuals without a history of a concussion. We scanned the brains of 35 normal individuals and 15 emergency department patients with a recent concussion. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were determined for regions of interest (ROI) defined by a standard white-matter atlas that included 21 bilateral ROIs. For each ROI pair, bilateral correlation coefficients were calculated and compared between the two subject groups. A symmetry index, defined as the ratio between the difference and the sum of bilateral measures, was also calculated for each ROI pair and compared between the groups. We found that in normal subjects, the extent of symmetry varied among regions and individuals, and at least subtle forms of structural lateralization were common across regions. In patients, higher asymmetry was found overall as well as in the corticospinal tract specifically. Results indicate that a concussion can manifest in brain asymmetry that deviates from a normal state. The clinical utility of characterizing post-concussion pathology as abnormal brain asymmetry merits further exploration.
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http://dx.doi.org/10.3389/fneur.2020.548220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688463PMC
November 2020

Disrupted White Matter Microstructure of the Cerebellar Peduncles in Scholastic Athletes After Concussion.

Front Neurol 2019 15;10:518. Epub 2019 May 15.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States.

Concussion, or mild traumatic brain injury (mTBI), is a major public health concern, linked with persistent post-concussive syndrome, and chronic traumatic encephalopathy. At present, standard clinical imaging fails to reliably detect traumatic axonal injury associated with concussion and post-concussive symptoms. Diffusion tensor imaging (DTI) is an MR imaging technique that is sensitive to changes in white matter microstructure. Prior studies using DTI did not jointly investigate white matter microstructure in athletes, a population at high risk for concussive and subconcussive head traumas, with those in typical emergency room (ER) patients. In this study, we determine DTI scalar metrics in both ER patients and scholastic athletes who suffered concussions and compared them to those in age-matched healthy controls. In the early subacute post-concussion period, athletes demonstrated an elevated rate of regional decreases in axial diffusivity (AD) compared to controls. These regional decreases of AD were especially pronounced in the cerebellar peduncles, and were more frequent in athletes compared to the ER patient sample. The group differences may indicate differences in the mechanisms of the concussive impacts as well as possible compound effects of cumulative subconcussive impacts in athletes. The prevalence of white matter abnormality in cerebellar tracts lends credence to the hypothesis that post-concussive symptoms are caused by shearing of axons within an attention network mediated by the cerebellum, and warrant further study of the correlation between cerebellar DTI findings and clinical, neurocognitive, oculomotor, and vestibular outcomes in mTBI patients.
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http://dx.doi.org/10.3389/fneur.2019.00518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530417PMC
May 2019

Concussion Subtype Identification With the Rivermead Post-concussion Symptoms Questionnaire.

Front Neurol 2018 3;9:1034. Epub 2018 Dec 3.

Brain Trauma Foundation, New York, NY, United States.

Classifying concussion in key subtypes according to presenting symptomatology at an early post-injury stage is an emerging approach that may allow prediction of clinical trajectories and delivery of targeted treatments. The Rivermead Post-concussion Symptoms Questionnaire (RPQ) is a simple, freely available, and widely used tool for assessment of the presence and severity of various post-concussion symptoms. We aimed to probe the prevalence among athletes of symptom classes associated with identified concussion phenotypes using the RPQ at baseline and acutely after a concussion. Participants of organized sports aged 12-30 years were baseline-assessed with the expectation that some would experience a concussion during the study period. Concussed athletes were re-assessed within 2 weeks of their injuries. The RPQ was supplemented with three specific questions and reworded for baseline assessment. A binomial test was used to contrast the prevalence of an attribute in the concussed cohort against the probability established by the baseline observation. Three thousand and eighty-eight athletes were baseline-assessed and eighty-nine were re-assessed post-concussion. All concussed athletes endorsed having some elevated symptoms in the RPQ, and such endorsements were more prevalent than those among normal athletes. Moderate-to-severe post-concussion symptoms of specific classes tended to be endorsed with few additional symptoms of other classes of similar intensities. Elevated symptoms detected with the RPQ within as short as 2 weeks after a concussion may help delineate patients' clinical subtypes and guide their treatment. Further refinement of symptom questionnaires and use of objective measures will be needed to properly populate the concussion subtype classification.
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http://dx.doi.org/10.3389/fneur.2018.01034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287109PMC
December 2018

Association of Visual Tracking Metrics With Post-concussion Symptomatology.

Front Neurol 2018 26;9:611. Epub 2018 Jul 26.

Brain Trauma Foundation, New York, NY, United States.

Attention impairment may provide a cohesive neurobiological explanation for clusters of clinical symptoms that occur after a concussion; therefore, objective quantification of attention is needed. Visually tracking a moving target is an attention-dependent sensorimotor function, and eye movement can be recorded easily and objectively to quantify performance. Our previous work suggested the utility of gaze-target synchronization metrics of a predictive visual tracking task in concussion screening and recovery monitoring. Another objectively quantifiable performance measure frequently suggested for concussion screening is simple visuo-manual reaction time (simple reaction time, SRT). Here, we used visual tracking and SRT tasks to assess changes between pre- and within-2-week post-concussion performances and explore their relationships to post-concussion symptomatology. Athletes participating in organized competitive sports were recruited. Visual tracking and SRT records were collected from the recruited athlete pool as baseline measures over a 4-year period. When athletes experienced a concussion, they were re-assessed within 2 weeks of their injury. We present the data from a total of 29 concussed athletes. Post-concussion symptom burden was assessed with the Rivermead Post-Concussion Symptoms Questionnaire and subscales of the Brain Injury Screening Questionnaire. Post-concussion changes in visual tracking and SRT performance were examined using a paired -test. Correlations of changes in visual tracking and SRT performance to symptom burden were examined using Pearson's coefficients. Post-concussion changes in visual tracking performance were not consistent among the athletes. However, changes in several visual tracking metrics had moderate to strong correlations to symptom scales ( up to 0.68). On the other hand, while post-concussion SRT performance was reduced ( < 0.01), the changes in the performance metrics were not meaningfully correlated to symptomatology ( ≤ 0.33). Results suggest that visual tracking performance metrics reflect clinical symptoms when assessed within 2 weeks of concussion. Evaluation of concussion requires assessments in multiple domains because the clinical profiles are heterogeneous. While most individuals show recovery within a week of injury, others experience prolonged recovery periods. Visual tracking performance metrics may serve as a biomarker of debilitating symptoms of concussion implicating attention as a root cause of such pathologies.
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http://dx.doi.org/10.3389/fneur.2018.00611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070608PMC
July 2018

Visual Tracking in Development and Aging.

Front Neurol 2017 30;8:640. Epub 2017 Nov 30.

Brain Trauma Foundation, New York, NY, United States.

A moving target is visually tracked with a combination of smooth pursuit and saccades. Human visual tracking eye movement develops through early childhood and adolescence, and declines in senescence. However, the knowledge regarding performance changes over the life course is based on data from distinct age groups in isolation using different procedures, and thus is fragmented. We sought to describe the age-dependence of visual tracking performance across a wide age range and compare it to that of simple visuo-manual reaction time. We studied a cross-sectional sample of 143 subjects aged 7-82 years old (37% male). Eye movements were recorded using video-oculography, while subjects viewed a computer screen and tracked a small target moving along a circular trajectory at a constant speed. For simple reaction time (SRT) measures, series of key presses that subjects made in reaction to cue presentation on a computer monitor were recorded using a standard software. The positional precision and smooth pursuit velocity gain of visual tracking followed a U-shaped trend over age, with best performances achieved between the ages of 20 and 50 years old. A U-shaped trend was also found for mean reaction time in agreement with the existing literature. Inter-individual variability was evident at any age in both visual tracking and reaction time metrics. Despite the similarity in the overall developmental and aging trend, correlations were not found between visual tracking and reaction time performances after subtracting the effects of age. Furthermore, while a statistically significant difference between the sexes was found for mean SRT in the sample, a similar difference was not found for any of the visual tracking metrics. Therefore, the cognitive constructs and their neural substrates supporting visual tracking and reaction time performances appear largely independent. In summary, age is an important covariate for visual tracking performance, especially for a pediatric population. Since visual tracking performance metrics may provide signatures of abnormal neurological or cognitive states independent of reaction time-based metrics, further understanding of age-dependent variations in normal visual tracking behavior is necessary.
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http://dx.doi.org/10.3389/fneur.2017.00640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714854PMC
November 2017

Frequency Responses to Visual Tracking Stimuli May Be Affected by Concussion.

Mil Med 2017 03;182(S1):120-123

Brain Trauma Foundation, 1999 South Bascom Avenue, Suite 1040, Campbell, CA 95008.

Human visual tracking performance is known to be reduced with an increase of the target's speed and oscillation frequency, but changes in brain states following a concussion may alter these frequency responses. The goal of this study was to characterize and compare frequency-dependent smooth pursuit velocity degradation in normal subjects and patients who had chronic postconcussion symptoms, and also examine cases of acutely concussed patients. Eye movements were recorded while subjects tracked a target that moved along a circular trajectory of 10° radius at 0.33, 0.40, or 0.67 Hz. Performance was characterized by the gain of smooth pursuit velocity, with reduced gain indicating reduced performance. The difference between normal and chronic patient groups in the pattern of decrease in the gain of horizontal smooth pursuit velocity as a function of the stimulus frequency reflected patients performing more poorly than normal subjects at 0.4 Hz while both groups performing similarly at 0.33 or 0.67 Hz. The performance of acute patients may represent yet another type of frequency response. The findings suggest that there may be ranges of stimulus frequencies that differentiate the effects of concussion from normal individuals.
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http://dx.doi.org/10.7205/MILMED-D-16-00093DOI Listing
March 2017

Degradation of Binocular Coordination during Sleep Deprivation.

Front Neurol 2016 13;7:90. Epub 2016 Jun 13.

Brain Trauma Foundation, New York, NY, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.

To aid a clear and unified visual perception while tracking a moving target, both eyes must be coordinated, so the image of the target falls on approximately corresponding areas of the fovea of each eye. The movements of the two eyes are decoupled during sleep, suggesting a role of arousal in regulating binocular coordination. While the absence of visual input during sleep may also contribute to binocular decoupling, sleepiness is a state of reduced arousal that still allows for visual input, providing a context within which the role of arousal in binocular coordination can be studied. We examined the effects of sleep deprivation on binocular coordination using a test paradigm that we previously showed to be sensitive to sleep deprivation. We quantified binocular coordination with the SD of the distance between left and right gaze positions on the screen. We also quantified the stability of conjugate gaze on the target, i.e., gaze-target synchronization, with the SD of the distance between the binocular average gaze and the target. Sleep deprivation degraded the stability of both binocular coordination and gaze-target synchronization, but between these two forms of gaze control the horizontal and vertical components were affected differently, suggesting that disconjugate and conjugate eye movements are under different regulation of attentional arousal. The prominent association found between sleep deprivation and degradation of binocular coordination in the horizontal direction may be used for a fit-for-duty assessment.
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http://dx.doi.org/10.3389/fneur.2016.00090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904152PMC
July 2016

Chronic Post-Concussion Neurocognitive Deficits. II. Relationship with Persistent Symptoms.

Front Hum Neurosci 2016 15;10:45. Epub 2016 Feb 15.

Brain Trauma FoundationNew York, NY, USA; Department of Neurosurgery, Stanford UniversityStanford, CA, USA.

Individuals who sustain a concussion may continue to experience problems long after their injury. However, it has been postulated in the literature that the relationship between a concussive injury and persistent complaints attributed to it is mediated largely by the development of symptoms associated with posttraumatic stress disorder (PTSD) and depression. We sought to characterize cognitive deficits of adult patients who had persistent symptoms after a concussion and determine whether the original injury retains associations with these deficits after accounting for the developed symptoms that overlap with PTSD and depression. We compared the results of neurocognitive testing from 33 patients of both genders aged 18-55 at 3 months to 5 years post-injury with those from 140 control subjects. Statistical comparisons revealed that patients generally produced accurate responses on reaction time-based tests, but with reduced efficiency. On visual tracking, patients increased gaze position error variability following an attention demanding task, an effect that may reflect greater fatigability. When neurocognitive performance was examined in the context of demographic- and symptom-related variables, the original injury retained associations with reduced performance at a statistically significant level. For some patients, reduced cognitive efficiency and fatigability may represent key elements of interference when interacting with the environment, leading to varied paths of recovery after a concussion. Poor recovery may be better understood when these deficits are taken into consideration.
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http://dx.doi.org/10.3389/fnhum.2016.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753289PMC
February 2016

Chronic Post-Concussion Neurocognitive Deficits. I. Relationship with White Matter Integrity.

Front Hum Neurosci 2016 10;10:35. Epub 2016 Feb 10.

Department of Radiology and Biomedical Imaging, School of Medicine, University of California, San Francisco San Francisco, CA USA.

We previously identified visual tracking deficits and associated degradation of integrity in specific white matter tracts as characteristics of concussion. We re-explored these characteristics in adult patients with persistent post-concussive symptoms using independent new data acquired during 2009-2012. Thirty-two patients and 126 normal controls underwent cognitive assessments and MR-DTI. After data collection, a subset of control subjects was selected to be individually paired with patients based on gender and age. We identified patients' cognitive deficits through pairwise comparisons between patients and matched control subjects. Within the remaining 94 normal subjects, we identified white matter tracts whose integrity correlated with metrics that indicated performance degradation in patients. We then tested for reduced integrity in these white matter tracts in patients relative to matched controls. Most patients showed no abnormality in MR images unlike the previous study. Patients' visual tracking was generally normal. Patients' response times in an attention task were slowed, but could not be explained as reduced integrity of white matter tracts relating to normal response timing. In the present patient cohort, we did not observe behavioral or anatomical deficits that we previously identified as characteristic of concussion. The recent cohort likely represented those with milder injury compared to the earlier cohort. The discrepancy may be explained by a change in the patient recruitment pool circa 2007 associated with an increase in public awareness of concussion.
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http://dx.doi.org/10.3389/fnhum.2016.00035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748060PMC
February 2016

Visuo-vestibular information processing by unipolar brush cells in the rabbit flocculus.

Cerebellum 2015 Oct;14(5):578-83

Department of Neuroscience & Physiology, New York University Medical School, New York, NY, 10016, USA.

The unipolar brush cell (UBC) is a glutamatergic granular layer interneuron that is predominantly located in the vestibulocerebellum and parts of the vermis. In rat and rabbit, we previously found using juxtacellular labeling combined with spontaneous activity recording that cells with highly regular spontaneous activity belong to the UBC category. Making use of this signature, we recorded from floccular UBCs in both anesthetized and awake rabbits while delivering visuo-vestibular stimulation by using sigmoidal rotation of the whole animal. In the anesthetized rabbit, the activity of the presumed UBC units displayed a wide variety of modulation profiles that could be related to aspects of head velocity or acceleration. These modulation profiles could also be found in the awake rabbit where, in addition, they could also carry an eye position signal. Furthermore, units in the awake rabbit could demonstrate rather long response latencies of up to 0.5 s. We suggest that the UBCs recorded in this study mostly belong to the type I UBC category (calretinin-positive) and that they can play diverse roles in floccular visuo-vestibular information processing, such as transformation of velocity-related signals to acceleration-related signals.
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http://dx.doi.org/10.1007/s12311-015-0710-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612327PMC
October 2015

Filling in the gaps: Anticipatory control of eye movements in chronic mild traumatic brain injury.

Neuroimage Clin 2015 22;8:210-23. Epub 2015 Apr 22.

Department of Radiology, University of California, San Diego, San Diego, CA, USA ; Radiology and Research Services, VA San Diego Healthcare System, San Diego, CA, USA.

A barrier in the diagnosis of mild traumatic brain injury (mTBI) stems from the lack of measures that are adequately sensitive in detecting mild head injuries. MRI and CT are typically negative in mTBI patients with persistent symptoms of post-concussive syndrome (PCS), and characteristic difficulties in sustaining attention often go undetected on neuropsychological testing, which can be insensitive to momentary lapses in concentration. Conversely, visual tracking strongly depends on sustained attention over time and is impaired in chronic mTBI patients, especially when tracking an occluded target. This finding suggests deficient internal anticipatory control in mTBI, the neural underpinnings of which are poorly understood. The present study investigated the neuronal bases for deficient anticipatory control during visual tracking in 25 chronic mTBI patients with persistent PCS symptoms and 25 healthy control subjects. The task was performed while undergoing magnetoencephalography (MEG), which allowed us to examine whether neural dysfunction associated with anticipatory control deficits was due to altered alpha, beta, and/or gamma activity. Neuropsychological examinations characterized cognition in both groups. During MEG recordings, subjects tracked a predictably moving target that was either continuously visible or randomly occluded (gap condition). MEG source-imaging analyses tested for group differences in alpha, beta, and gamma frequency bands. The results showed executive functioning, information processing speed, and verbal memory deficits in the mTBI group. Visual tracking was impaired in the mTBI group only in the gap condition. Patients showed greater error than controls before and during target occlusion, and were slower to resynchronize with the target when it reappeared. Impaired tracking concurred with abnormal beta activity, which was suppressed in the parietal cortex, especially the right hemisphere, and enhanced in left caudate and frontal-temporal areas. Regional beta-amplitude demonstrated high classification accuracy (92%) compared to eye-tracking (65%) and neuropsychological variables (80%). These findings show that deficient internal anticipatory control in mTBI is associated with altered beta activity, which is remarkably sensitive given the heterogeneity of injuries.
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http://dx.doi.org/10.1016/j.nicl.2015.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473731PMC
April 2016

Ocular disconjugacy cannot be measured without establishing a solid spatial reference.

Authors:
Jun Maruta

F1000Res 2015 17;4:71. Epub 2015 Mar 17.

Brain Trauma Foundation, One Broadway, 6th Floor, New York, NY 10007, USA.

This correspondence points out a need for clarification concerning the methodology utilized in the study "Eye tracking detects disconjugate eye movements associated with structural traumatic brain injury and concussion", recently published in Journal of Neurotrauma. The authors of the paper state that binocular eye movements were recorded using a single-camera video-oculography technique and that binocular disconjugate characteristics were analyzed without calibration of eye orientation. It is claimed that a variance-based disconjugacy metric was found to be sensitive to the severity of a concussive brain injury and to the status of recovery after the original injury. However, the reproducibility of the paper's findings may be challenged simply by the paucity of details in the methodological description. More importantly, from the information supplied or cited in the paper, it is difficult to evaluate the validity of the potentially interesting conclusions of the paper.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448744PMC
http://dx.doi.org/10.12688/f1000research.6162.2DOI Listing
June 2015

Abnormal White Matter Blood-Oxygen-Level-Dependent Signals in Chronic Mild Traumatic Brain Injury.

J Neurotrauma 2015 Aug 6;32(16):1254-71. Epub 2015 May 6.

1 Department of Neurology, Washington University in St. Louis , St. Louis, Missouri.

Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI.
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http://dx.doi.org/10.1089/neu.2014.3547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601555PMC
August 2015

Possible Medication-Resistant Deficits in Adult ADHD.

J Atten Disord 2017 Dec 26;21(14):1169-1179. Epub 2014 Jun 26.

1 Brain Trauma Foundation, New York, NY, USA.

Objective: The nature of ADHD, especially in adulthood, is not well-understood. Therefore, we explored subcomponents of attention in adult ADHD.

Method: Twenty-three adults with ADHD were tested on neurocognitive and visual tracking performance both while on their regular prescription stimulant medication and while abstaining from the medication for 1 day. Pairwise comparisons to 46 two-for-one matched normal controls were made to detect medication-resistant effects of ADHD, and within-participant comparisons were made to detect medication-sensitive effects in patients.

Results: Even when on medication, patients performed more poorly than controls on a spatial working memory task, and on visual tracking and simple reaction time tasks immediately following other attention-demanding tasks. Patients' visual tracking performance degraded while off-medication in a manner consistent with reduced vigilance.

Conclusion: There may be persistent cognitive impairments in adult ADHD despite medication. In addition, the benefit of stimulants seems reduced under cognitive fatigue.
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http://dx.doi.org/10.1177/1087054714538659DOI Listing
December 2017

Detecting eye movement abnormalities from concussion.

Prog Neurol Surg 2014 6;28:226-33. Epub 2014 Jun 6.

Brain Trauma Foundation, Stanford University School of Medicine, Stanford, Calif., USA.

An attention-based biomarker may be useful for concussion screening. A key role of attention is to generate time-based expectancies of specific sensory information, and it is postulated that postconcussion cognitive impairments and symptoms may stem from a primary deficit in this predictive timing mechanism. There is a close relationship between gaze and attention, but in addressing predictive timing, there is a need for an appropriate testing paradigm and methods to quantify oculomotor anomalies. We have utilized a continuous predictive visual tracking paradigm because human visual tracking requires predicting the temporal course of a stimulus and dynamically synchronizing the required action with the stimulus. We have shown that concussion patients often show disrupted gaze-target synchronization characterized by large gaze position error variability and overall phase advancement. Various attention components interact with visual tracking, and thus there is a possibility that different neurological and physiological conditions produce identifiable visual tracking characteristics. Analyzing neuromotor functions, specifically oculomotor synchronization, can provide a fast, accurate, and reliable assessment of cognitive functions.
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http://dx.doi.org/10.1159/000358786DOI Listing
February 2015

Predictive visual tracking: specificity in mild traumatic brain injury and sleep deprivation.

Mil Med 2014 Jun;179(6):619-25

Brain Trauma Foundation, 7 World Trade Center, 34th Floor, 250 Greenwich Street, New York, NY 10007.

We tested whether reduced cognitive function associated with mild traumatic brain injury (mTBI) and sleep deprivation can be detected and distinguished using indices of predictive visual tracking. A circular visual tracking test was given to 13 patients with acute mTBI (recruited within 2 weeks of injury), 127 normal control subjects, and 43 healthy subjects who were fatigued by 26-hour sleep deprivation. Eye movement was monitored with video-oculography. In the mTBI-related portion of the study, visual tracking performance of acute mTBI patients was significantly worse than normal subjects (p < 0.001). In the sleep-deprivation-related portion of the study, no change was detected between the two baseline measures separated by 2 to 3 weeks, but the 26-hour sleep deprivation significantly degraded the visual tracking performance (p < 0.001). The mTBI subjects had substantially worse visual tracking than sleep-deprived subjects that could also be identified with different visual tracking indices, indicating possible different neurophysiological mechanisms. Results suggest that cognitive impairment associated with mTBI and fatigue may be triaged with the aid of visual tracking measures.
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http://dx.doi.org/10.7205/MILMED-D-13-00420DOI Listing
June 2014

Identifying Purkinje cells using only their spontaneous simple spike activity.

J Neurosci Methods 2014 Jul 28;232:173-80. Epub 2014 May 28.

Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, USA. Electronic address:

Background: We have extended our cerebellar cortical interneuron classification algorithm that uses statistics of spontaneous activity (Ruigrok et al., 2011) to include Purkinje cells. Purkinje cells were added because they do not always show a detectable complex spike, which is the accepted identification. The statistical measures used in the present study were obtained from morphologically identified interneurons and complex spike identified Purkinje cells, recorded from ketamine-xylazine anesthetized rats and rabbits, and from awake rabbits.

New Method: The new algorithm has an added decision step that classifies Purkinje cells using a combination of the median absolute difference from the median interspike interval (MAD) and the mean of the relative differences of successive interspike intervals (CV2). These measures reflect the high firing rate and intermediate regularity of Purkinje cell simple spike activity.

Results: Of 86 juxtacellularly labeled interneurons and 110 complex spike-identified Purkinje cells, 61 interneurons and 95 Purkinje cells were correctly classified, 22 interneurons and 13 Purkinje cells were deemed unclassifiable, and 3 interneurons and 2 Purkinje cells were incorrectly classified.

Comparison With Existing Methods: The new algorithm improves on our previous algorithm because it includes Purkinje cells. This algorithm is the only one for the cerebellum that does not presume anatomical knowledge of whether the cells are in the molecular layer or the granular layer.

Conclusions: These results strengthen the view that the new decision algorithm is useful for identifying neurons recorded at all cerebellar depths, particularly those neurons recorded in the rabbit vestibulocerebellum.
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http://dx.doi.org/10.1016/j.jneumeth.2014.04.031DOI Listing
July 2014

Attention and visual tracking degradation during acute sleep deprivation in a military sample.

Aviat Space Environ Med 2014 May;85(5):497-503

Background: Fatigue due to sleep restriction places individuals at elevated risk for accidents, degraded health, and impaired physical and mental performance. Early detection of fatigue-related performance decrements is an important component of injury prevention and can help to ensure optimal performance and mission readiness. This study used a predictive visual tracking task and a computer-based measure of attention to characterize fatigue-related attention decrements in healthy Army personnel during acute sleep deprivation.

Methods: Serving as subjects in this laboratory-based study were 87 male and female service members between the ages of 18 and 50 with no history of brain injury with loss of consciousness, substance abuse, or significant psychiatric or neurologic diagnoses. Subjects underwent 26 h of sleep deprivation, during which eye movement measures from a continuous circular visual tracking task and attention measures (reaction time, accuracy) from the Attention Network Test (ANT) were collected at baseline, 20 h awake, and between 24 to 26 h awake.

Results: Increases in the variability of gaze positional errors (46-47%), as well as reaction time-based ANT measures (9-65%), were observed across 26 h of sleep deprivation. Accuracy of ANT responses declined across this same period (11%).

Discussion: Performance measures of predictive visual tracking accurately reflect impaired attention due to acute sleep deprivation and provide a promising approach for assessing readiness in personnel serving in diverse occupational areas, including flight and ground support crews.
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http://dx.doi.org/10.3357/asem.3882.2014DOI Listing
May 2014

Adaptation of visual tracking synchronization after one night of sleep deprivation.

Exp Brain Res 2014 Jan 11;232(1):121-31. Epub 2013 Oct 11.

Brain Trauma Foundation, 7 World Trade Center, 34th Floor, 250 Greenwich Street, New York, NY, 10007, USA,

The temporal delay between sensory input and motor execution is a fundamental constraint in interactions with the environment. Predicting the temporal course of a stimulus and dynamically synchronizing the required action with the stimulus are critical for offsetting this constraint, and this prediction-synchronization capacity can be tested using visual tracking of a target with predictable motion. Although the role of temporal prediction in visual tracking is assumed, little is known of how internal predictions interact with the behavioral outcome or how changes in the cognitive state influence such interaction. We quantified and compared the predictive visual tracking performance of military volunteers before and after one night of sleep deprivation. The moment-to-moment synchronization of visual tracking during sleep deprivation deteriorated with sensitivity changes greater than 40 %. However, increased anticipatory saccades maintained the overall temporal accuracy with near zero phase error. Results suggest that acute sleep deprivation induces instability in visuomotor prediction, but there is compensatory visuomotor adaptation. Detection of these visual tracking features may aid in the identification of insufficient sleep.
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http://dx.doi.org/10.1007/s00221-013-3725-8DOI Listing
January 2014

The Network Modification (NeMo) Tool: elucidating the effect of white matter integrity changes on cortical and subcortical structural connectivity.

Brain Connect 2013 ;3(5):451-63

1 Imaging and Data Evaluation and Analysis Laboratory (IDEAL), Department of Radiology and the Brain and Mind Research Institute, Weill Cornell Medical College , New York, New York.

Accurate prediction of brain dysfunction caused by disease or injury requires the quantification of resultant neural connectivity changes compared with the normal state. There are many methods with which to assess anatomical changes in structural or diffusion magnetic resonance imaging, but most overlook the topology of white matter (WM) connections that make up the healthy brain network. Here, a new neuroimaging software pipeline called the Network Modification (NeMo) Tool is presented that associates alterations in WM integrity with expected changes in neural connectivity between gray matter regions. The NeMo Tool uses a large reference set of healthy tractograms to assess implied network changes arising from a particular pattern of WM alteration on a region- and network-wise level. In this way, WM integrity changes can be extrapolated to the cortices and deep brain nuclei, enabling assessment of functional and cognitive alterations. Unlike current techniques that assess network dysfunction, the NeMo tool does not require tractography in pathological brains for which the algorithms may be unreliable or diffusion data are unavailable. The versatility of the NeMo Tool is demonstrated by applying it to data from patients with Alzheimer's disease, fronto-temporal dementia, normal pressure hydrocephalus, and mild traumatic brain injury. This tool fills a gap in the quantitative neuroimaging field by enabling an investigation of morphological and functional implications of changes in structural WM integrity.
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http://dx.doi.org/10.1089/brain.2013.0147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796322PMC
May 2014

Dynamic visuomotor synchronization: quantification of predictive timing.

Behav Res Methods 2013 Mar;45(1):289-300

Brain Trauma Foundation, 7 World Trade Center, 250 Greenwich Street, New York, NY 10007, USA.

When a moving target is tracked visually, spatial and temporal predictions are used to circumvent the neural delay required for the visuomotor processing. In particular, the internally generated predictions must be synchronized with the external stimulus during continuous tracking. We examined the utility of a circular visual-tracking paradigm for assessment of predictive timing, using normal human subjects. Disruptions of gaze-target synchronization were associated with anticipatory saccades that caused the gaze to be temporarily ahead of the target along the circular trajectory. These anticipatory saccades indicated preserved spatial prediction but suggested impaired predictive timing. We quantified gaze-target synchronization with several indices, whose distributions across subjects were such that instances of extremely poor performance were identifiable outside the margin of error determined by test-retest measures. Because predictive timing is an important element of attention functioning, the visual-tracking paradigm and dynamic synchronization indices described here may be useful for attention assessment.
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http://dx.doi.org/10.3758/s13428-012-0248-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578718PMC
March 2013

The generation and validation of white matter connectivity importance maps.

Neuroimage 2011 Sep 29;58(1):109-21. Epub 2011 Jun 29.

Dept. of Radiology, Weill Cornell Medical College, New York, NY 10065, USA.

Both the size and location of injury in the brain influences the type and severity of cognitive or sensorimotor dysfunction. However, even with advances in MR imaging and analysis, the correspondence between lesion location and clinical deficit remains poorly understood. Here, structural and diffusion images from 14 healthy subjects are used to create spatially unbiased white matter connectivity importance maps that quantify the amount of disruption to the overall brain network that would be incurred if that region were compromised. Some regions in the white matter that were identified as highly important by such maps have been implicated in strategic infarct dementia and linked to various attention tasks in previous studies. Validation of the maps is performed by investigating the correlations of the importance maps' predicted cognitive deficits in a group of 15 traumatic brain injury patients with their cognitive test scores measuring attention and memory. While no correlation was found between amount of white matter injury and cognitive test scores, significant correlations (r>0.68, p<0.006) were found when including location information contained in the importance maps. These tools could be used by physicians to improve surgical planning, diagnosis, and assessment of disease severity in a variety of pathologies like multiple sclerosis, trauma, and stroke.
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http://dx.doi.org/10.1016/j.neuroimage.2011.05.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144270PMC
September 2011

A unified science of concussion.

Ann N Y Acad Sci 2010 Oct;1208:58-66

Brain Trauma Foundation, New York, New York 10007, USA.

The etiology, imaging, and behavioral assessment of mild traumatic brain injury (mTBI) are daunting fields, given the lack of a cohesive neurobiological explanation for the observed cognitive deficits seen following mTBI. Although subjective patient self-report is the leading method of diagnosing mTBI, current scientific evidence suggests that quantitative measures of predictive timing, such as visual tracking, could be a useful adjunct to guide the assessment of attention and to screen for advanced brain imaging. Magnetic resonance diffusion tensor imaging (DTI) has demonstrated that mTBI is associated with widespread microstructural changes that include those in the frontal white matter tracts. Deficits observed during predictive visual tracking correlate with DTI findings that show lesions localized in neural pathways subserving the cognitive functions often disrupted in mTBI. Unifying the anatomical and behavioral approaches, the emerging evidence supports an explanation for mTBI that the observed cognitive impairments are a result of predictive timing deficits caused by shearing injuries in the frontal white matter tracts.
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http://dx.doi.org/10.1111/j.1749-6632.2010.05695.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021720PMC
October 2010

Visual tracking synchronization as a metric for concussion screening.

J Head Trauma Rehabil 2010 Jul-Aug;25(4):293-305

Brain Trauma Foundation, New York, NY 10007, USA.

Our goal was to determine whether performance variability during predictive visual tracking can provide a screening measure for mild traumatic brain injury (mTBI). Seventeen subjects with chronic postconcussive syndrome and 9 healthy control subjects were included in this study. Eye movements were recorded with video-oculography as the subject visually tracked a target that moved through a circular trajectory. We compared the variability of gaze positional errors relative to the target with the microstructural integrity of white matter tracts as measured by the fractional anisotropy (FA) parameter of diffusion tensor imaging. Gaze error variability was significantly correlated with the mean FA values of the right anterior corona radiata (ACR) and the left superior cerebellar peduncle, tracts that support spatial processing and sustenance of attention, and the genu of the corpus callosum. Because the ACR and the genu are among the most frequently damaged white matter tracts in mTBI, the correlations imply that gaze error variability during visual tracking may provide a useful screening tool for mTBI. Gaze error variability was also significantly correlated with attention and working memory measures in neurocognitive testing; thus, measurement of visual tracking performance is promising as a fast and practical screening tool for mTBI.
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http://dx.doi.org/10.1097/HTR.0b013e3181e67936DOI Listing
October 2010

Intraburst and interburst signaling by climbing fibers.

J Neurosci 2007 Oct;27(42):11263-70

Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA.

Although cerebellar Purkinje cell complex spikes occur at low frequency (approximately 1/s), each complex spike is often associated with a high-frequency burst (approximately 500/s) of climbing fiber spikes. We examined the possibility that signals are present within the climbing fiber bursts. By intracellularly recording from depolarized, nonspiking Purkinje cells in anesthetized pigmented rabbits, climbing fiber burst patterns were investigated by determining the number of components in the induced compound EPSPs during spontaneous activity and during visual stimulation. For our sample of 43 cells, >70% of all EPSPs were of the compound type composed of two or three EPSPs. During spontaneous activity, the number of components in each compound EPSP was not related to the latency to the succeeding compound EPSP. Conversely, the number of components in each compound EPSP was related to its latency after the preceding compound EPSP. This latency increased from 0.62 s for one-component EPSPs to 1.69 s for compound EPSPs with four or more components. The effect of visual stimulation on the climbing fiber activity was studied in 19 floccular Purkinje cells whose low-frequency interburst climbing fiber response was modulated by movement about the vertical axis. During sinusoidal oscillation (0.1 Hz, +/-10 degrees), compound EPSPs with a larger number of components tended to be more prevalent during movement in the excitatory direction than in the inhibitory direction. Thus, climbing fibers can, in addition to modulation of their low interburst frequency, transmit signals in the form of the number of spikes within each high-frequency burst.
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http://dx.doi.org/10.1523/JNEUROSCI.2559-07.2007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6673016PMC
October 2007

Vertical (Z-axis) acceleration alters the ocular response to linear acceleration in the rabbit.

Exp Brain Res 2008 Feb 10;185(1):87-99. Epub 2007 Oct 10.

Department of Neurology, Mount Sinai School of Medicine, Box 1135, 1 Gustave L. Levy Place, New York, NY 10029, USA.

Whether ocular orientation to gravity is produced solely by linear acceleration in the horizontal plane of the head or depends on both horizontal and vertical components of the acceleration of gravity is controversial. Here, we compared orienting eye movements of rabbits during head tilt to those produced by centrifugation that generated centripetal acceleration along the naso-occipital (X-), bitemporal (Y-) and vertical (Z-) axes in a constant gravitational field. Sensitivities of ocular counter-pitch and vergence during pitch tilts were approximately 25 degrees /g and approximately 26 degrees /g, respectively, and of ocular counter-roll during roll tilts was approximately 20 degrees /g. During X-axis centripetal acceleration with 1 g of gravity along the Z-axis, pitch and vergence sensitivities were reduced to approximately 13 degrees /g and approximately 16 degrees /g. Similarly, Y-axis acceleration with 1g along the Z-axis reduced the roll sensitivity to approximately 16 degrees /g. Modulation of Z-axis centripetal acceleration caused sensitivities to drop by approximately 6 degrees /g in pitch, approximately 2 degrees /g in vergence, and approximately 5 degrees /g in roll. Thus, the constant 1g acceleration along the Z-axis reduced the sensitivity of ocular orientation to linear accelerations in the horizontal plane. Orienting responses were also modulated by varying the head Z-axis acceleration; the sensitivity of response to Z-axis acceleration was linearly related to the response to static tilt. Although the sign of the Z-axis modulation is opposite in the lateral-eyed rabbit from that in frontal-eyed species, these data provide evidence that the brain uses both the horizontal and the vertical components of acceleration from the otolith organs to determine the magnitude of ocular orientation in response to linear acceleration.
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http://dx.doi.org/10.1007/s00221-007-1138-2DOI Listing
February 2008

Eye velocity asymmetry, ocular orientation, and convergence induced by angular rotation in the rabbit.

Vision Res 2006 Mar 7;46(6-7):961-9. Epub 2005 Dec 7.

Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.

We studied ocular asymmetries and orienting responses induced by angular rotation in rabbits with binocular video recordings. Slow phase velocities were significantly larger in the eye moving temporonasally than nasotemporally. The eyes also converged and pitched down during rotation, which increased and refocused binocular overlap in the visual fields. Eye position also shifted into the slow phase direction. Vergence and pitch outlasted the induced nystagmus, suggesting that they were generated by a separate vestibulo-oculomotor subsystem(s). Thus, mechanisms in the rabbit increase compensatory eye velocity in the eye that leads into the direction of rotation and enhance binocular vision.
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http://dx.doi.org/10.1016/j.visres.2005.10.015DOI Listing
March 2006

Orienting eye movements and nystagmus produced by translation while rotating (TWR).

Exp Brain Res 2005 Jun 9;163(3):273-83. Epub 2005 Feb 9.

Department of Neurology and Physiology and Biophysics, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA.

Sinusoidal translation while rotating at constant angular velocity about a vertical axis (translation while rotating, TWR) produces centripetal and translational accelerations along the direction of translation and an orthogonal Coriolis acceleration due to the translation in the rotating frame. Thus, a Coriolis acceleration is produced along the bitemporal axis when oscillating along the naso-occipital axis, and along the naso-occipital axis when oscillating along the bitemporal axis. Together, these components generate an elliptically rotating acceleration vector that revolves around the head in the direction of rotation at the frequency of oscillation. Here we studied the orienting and compensatory responses of rabbits during TWR. Combinations of centripetal and translational accelerations were held constant at 0.5 g, and oscillation frequencies were varied from 0.01-0.33 Hz. The amplitude of the Coriolis acceleration increased with the frequency of translation. Naso-occipital translation caused vergence and pitch at all frequencies and roll at higher frequencies, and bitemporal translation produced roll at all frequencies and vergence and pitch at higher frequencies. The sensitivity of each ocular orienting component to linear acceleration was comparable across the different oscillation frequencies. TWR also induced continuous yaw nystagmus with slow phase velocity in the direction of rotation of the acceleration vector. Thresholds for appearance of nystagmus were 0.05 Hz, corresponding to a Coriolis acceleration of 0.06 g. Mean slow phase velocity for a rotating linear acceleration vector produced by 0.5 g along the translation axis and 0.34 g of Coriolis acceleration along the orthogonal axis were approximately 9 degrees /s. Eye velocities during TWR were similar to those generated by off-vertical axis rotation (OVAR), but were opposite in direction with regard to head rotation, following the direction of the rotating acceleration vector in both paradigms. Both are produced by activation of velocity storage in the vestibular system. One important difference between TWR and OVAR is that the head is always upright with regard to gravity during TWR. We speculate that the brain may use these low amplitude rotating linear accelerations to generate eye velocities that help to orient gaze when making turns during normal locomotion.
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http://dx.doi.org/10.1007/s00221-004-2178-5DOI Listing
June 2005
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