A proof-of-concept randomized crossover clinical trial of a first-in-class vasopressin 1a receptor antagonist for PTSD: Design, methods, and recruitment.

Background: Almost eight million Americans suffer from Posttraumatic Stress Disorder (PTSD). Current PTSD drug therapies rely on repurposed antidepressants and anxiolytics, which produce undesirable side effects and have recognized compliance issues. Vasopressin represents a promising and novel target for pharmacological intervention. Logistical issues implementing a clinical trial for a novel PTSD pharmaceutical are relatively uncharted territory as trials concerning a new agent have not been published in the past several decades. All published trials have repurposed FDA-approved psychoactive medications with known risk profiles. Our recruitment challenges are discussed in this context. Methods: An 18-week proof-of-concept randomized crossover clinical trial of a first-in-class vasopressin 1a receptor antagonist (SRX246) for PTSD was conducted. All participants received SRX246 for 8 weeks, the placebo for 8 weeks, and the drug vs. placebo arms were compared. Participants were assessed every 2 weeks for PTSD symptoms as well as other medication effects. Results were expected to provide an initial demonstration of safety and tolerability in this clinical population and potentially clinical efficacy in SRX246-treated patients measured by Clinician Administered PTSD Scale (CAPS) score changes, clinical impression, and other indices compared to placebo. The primary hypothesis was that SRX246 would result in a clinically meaningful 10-point reduction in mean CAPS score compared to placebo. Discussion: This study is the first to investigate an oral vasopressin 1a receptor antagonist for PTSD. As a wave of PTSD clinical trials with new pharmaceutical compounds are beginning now, lessons learned from our recruitment challenges may be invaluable to these endeavors.

Traumatic brain injury history and baseline symptoms outweigh sex differences for risk of concussion in a sample of collegiate athletes.

OBJECTIVE: To test the hypothesis that a history of traumatic brain injury (TBI) prior to the collegiate pre-season is associated with risk for re-injury. We also investigate sex differences, cognitive functioning, and self-reported concussion symptoms and their associations with concussion risk. METHODS: A longitudinal cohort study consisting of collegiate athletes (n = 212) who completed consecutive preseason evaluations (P1 and P2) between 2012 and 2015, averaging 12.9 (SD = 4.2) months apart. RESULTS: There were 40 new concussions recorded between P1 and P2, 21 (53%) of which were among athletes who reported a lifetime history of mild TBI/concussion at P1. New P1-P2 concussions occurred in 24% of female athletes (n = 23) and 15% of male athletes (n = 17). History of TBI and female sex were significant predictors of new concussion between P1 and P2; however, in adjusted models, the inclusion of Impulse Control and PCSS Total symptom scores attenuated the effect of sex on the risk for new injury. CONCLUSION: Collegiate athletes with a lifetime history of TBI had a significantly higher risk of sustaining a subsequent concussion. Pre-season emotional and somatic symptomology may contribute to incident concussion risk. The findings highlight the importance of considering lifetime head injury exposure and baseline symptomatology when interpreting sex differences and evaluating concussion risk.

Screening for Brain Injury Sustained in the Context of Intimate Partner Violence (IPV): Measure Development and Preliminary Utility of the Brain Injury Screening Questionnaire IPV Module.

Abstract Intimate partner violence (IPV) is associated with risk for multi-etiology brain injury (BI), including repetitive head impacts, isolated traumatic brain injuries (TBI), and anoxic/hypoxic injury secondary to nonfatal strangulation (NFS). IPV-related injuries are often unreported, but evidence suggests that survivors are more likely to report when asked directly. There are currently no validated tools for screening of brain injury related to IPV that meet World Health Organization guidelines for this population. Here, we describe measure development methods and preliminary utility of the Brain Injury Screening Questionnaire IPV (BISQ-IPV) module. We culled items from existing IPV and TBI screening tools and sought two rounds of stakeholder feedback regarding content coverage, terminology, and safety of administration. The resulting stakeholder-informed BISQ-IPV module is a seven-item self-report measure that uses contextual cues (e.g., being shoved, shaken, strangled) to query lifetime history of IPV-related head/neck injury. We introduced the BISQ-IPV module into the Late Effects of TBI (LETBI) study to investigate rates of violent and IPV-specific head/neck injury reporting in a TBI sample. Among those who completed the BISQ-IPV module (n = 142), 8% of the sample (and 20% of women) reported IPV-related TBI, and 15% of the sample (34% of women) reported IPV-related head or neck injury events that did not result in loss or alteration of consciousness. No men reported NFS; one woman reported inferred BI secondary to NFS, and 6% of women reported NFS events. Those who endorsed IPV-BI were all women, many were highly educated, and many reported low incomes. We then compared reporting of violent TBIs and head/neck injury events among individuals who completed the core BISQ wherein IPV is not specifically queried (administered from 2015-2018; n = 156) to that of individuals who completed the core BISQ preceded by the BISQ-IPV module (BISQ+IPV, administered from 2019-2021; n = 142). We found that 9% of those who completed the core BISQ reported violent TBI (e.g., abuse, assault), whereas 19% of those who completed the BISQ+IPV immediately preceding the core BISQ reported non-IPV-related violent TBI on the core BISQ. These findings suggest that standard TBI screening tools are inadequate for identifying IPV-BI and structured cueing of IPV-related contexts yields greater reporting of both IPV- and non-IPV-related violent BI. When not queried directly, IPV-BI remains a hidden variable in TBI research studies.

Visuomotor Synchronization: Military Normative Performance.

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.

International Survey of Antiseizure Medication Use in Patients with Complicated Mild Traumatic Brain Injury: A New York Neurotrauma Consortium Study.

BACKGROUND: Seizures and epilepsy after traumatic brain injury (TBI) negatively affect quality of life and longevity. Antiseizure medication (ASM) prophylaxis after severe TBI is associated with improved outcomes; these medications are rarely used in mild TBI. However, a paucity of research is available to inform ASM use in complicated mild TBI (cmTBI) and no empirically based clinical care guidelines for ASM use in cmTBI exist. We aim to identify seizure prevention and management strategies used by clinicians experienced in treating patients with cmTBI to characterize standard care and inform a systematic approach to clinical decision making regarding ASM prophylaxis. METHODS: We recruited a multidisciplinary international cohort through professional organizational listservs and social media platforms. Our questionnaire assessed factors influencing ASM prophylaxis after cmTBI at the individual, institutional, and health system-wide levels. RESULTS: Ninety-two providers with experience managing cmTBI completed the survey. We found a striking diversity of ASM use in cmTBI, with 30% of respondents reporting no/infrequent use and 42% reporting frequent use; these tendencies did not differ by provider or institutional characteristics. Certain conditions universally increased or decreased the likelihood of ASM use and represent consensus. Based on survey results, ASMs are commonly used in patients with cmTBI who experience acute secondary seizure or select positive neuroimaging findings; we advise caution in elderly patients and those with concomitant neuropsychiatric illness. CONCLUSIONS: This study is the first to characterize factors influencing clinical decision making in ASM prophylaxis after cmTBI based on multidisciplinary multicenter provider practices. Prospective controlled studies are necessary to inform standardized guideline development.

Enhancing exposure therapy for posttraumatic stress disorder (PTSD): a randomized clinical trial of virtual reality and imaginal exposure with a cognitive enhancer.

Posttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17-5.86], p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = -8.87 [95% CI -11.33 to -6.40], p < 0.001, ES = -0.44). The main effect of DCS vs. placebo was not significant. Augmentation by MDD interaction (p = 0.073) suggested that depressed participants improved more on placebo (M = -8.43 [95% CI -10.98 to -5.88], p < 0.001, ES = -0.42); DCS and placebo were equally effective for nondepressed participants. There was an apparent moderating effect of BDNF Val66Met polymorphism on DCS augmentation (ES = 0.67). Met66 allele carriers improved more on DCS (ES = -0.25). FAAH 385 A carriers improved more than non-carriers (ES = 0.33), particularly those with MDD (ES = 0.62). This study provides a step toward precision therapeutics for PTSD by demonstrating that comorbid MDD and genetic markers may help guide treatment selection.ClinicalTrials.gov Identifier: NCT01352637.

Evaluating the clinical benefit of brain-computer interfaces for control of a personal computer.

Brain-computer interfaces (BCIs) enabling the control of a personal computer could provide myriad benefits to individuals with disabilities including paralysis. However, to realize this potential, these BCIs must gain regulatory approval and be made clinically available beyond research participation. Therefore, a transition from engineering-oriented to clinically oriented outcome measures will be required in the evaluation of BCIs. This review examined how to assess the clinical benefit of BCIs for the control of a personal computer. We report that: (a) a variety of different patient-reported outcome measures can be used to evaluate improvements inhow a patient feels, and we offer some considerations that should guide instrument selection. (b) Activities of daily living can be assessed to demonstrate improvements inhow a patient functions, however, new instruments that are sensitive to increases in functional independence via the ability to perform digital tasks may be needed. (c) Benefits tohow a patient surviveshas not previously been evaluated but establishing patient-initiated communication channels using BCIs might facilitate quantifiable improvements in health outcomes.

Understanding loss to follow-up in a longitudinal study of people with traumatic brain injury.

OBJECTIVE: To examine factors related to attrition in a traumatic brain injury (TBI) study sample assessed up to 15 years after injury. PARTICIPANTS: One thousand twenty-eight participants with TBI who completed the year 1 follow-up assessment at a TBI Model Systems Center between 1992 and 2018. METHOD: Secondary analysis of data from a prospective longitudinal cohort study considering follow-up data collection completion status at years 1, 2, 5, 10, and 15. RESULTS: In univariable analyses, multiple factors were associated with loss to follow-up (LOFU) including being a member of a socially disadvantaged group, substance use history, residence, payor, cause of injury, and results of earlier follow-up attempts. In a multiple logistic regression analysis examining the prediction of follow-up condition at 10 or 15 years post-injury, only payor and race/ethnicity were significant predictors. Hispanic ethnicity was associated with higher odds of LOFU, and these participants often spoke Spanish and were born outside of the United States. CONCLUSIONS: The findings suggest a need to understand sociodemographic variables and their influence on participant attrition in longitudinal TBI research. With a better understanding of these predictors, procedures can be developed to address retention of participants who are identified as being at increased risk for study drop out.

Postintensive Care Syndrome in Survivors of Critical Illness Related to Coronavirus Disease 2019: Cohort Study From a New York City Critical Care Recovery Clinic.

OBJECTIVE: Determine the characteristics of postintensive care syndrome in the cognitive, physical, and psychiatric domains in coronavirus disease 2019 ICU survivors. DESIGN: Single-center descriptive cohort study from April 21, to July 7, 2020. SETTING: Critical care recovery clinic at The Mount Sinai Hospital in New York City. PATIENTS: Adults who had critical illness due to coronavirus disease 2019 requiring an ICU stay of 7 days or more and who agreed to a telehealth follow-up in the critical care recovery clinic 1-month post hospital discharge. INTERVENTIONS: None. MEASURES AND MAIN RESULTS: Patient-reported outcome measures assessing physical and psychiatric domains were collected electronically, a cognitive test was performed by a clinician, and clinical data were obtained through electronic medical records. Outcome measures assessed postintensive care syndrome symptoms in the physical (Modified Rankin Scale, Dalhousie Clinical Frailty Scale, Neuro-Quality of Life Upper Extremity and Lower Extremity Function, Neuro-Quality of Life Fatigue), psychiatric (Insomnia Severity Scale; Patient Health Questionnaire-9; and Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), and cognitive (Telephone Montreal Cognitive Assessment) domains. The 3-Level Version of Euro-QoL-5D was used to assess the physical and psychiatric domains. A diagnosis of postintensive care syndrome was made in cases with evidence of impairment in at least one postintensive care syndrome domain. We included 45 patients with a mean (sd) age of 54 (13) years, and 73% were male. Ninety-one percent of coronavirus disease 2019 ICU survivors fit diagnostic criteria for postintensive care syndrome. 86.7 % had impairments in the physical domain, 22 (48%) reported impairments in the psychiatric domain, and four (8%) had impairments on cognitive screening. We found that 58% had some degree of mobility impairment. In the psychiatric domain, 38% exhibited at least mild depression, and 18 % moderate to severe depression. Eighteen percent presented Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, scores suggestive of posttraumatic stress syndrome diagnosis. In the Telephone Montreal Cognitive Assessment, 9% had impaired cognition. CONCLUSIONS: Survivors of critical illness related to coronavirus disease 2019 are at high risk of developing postintensive care syndrome. These findings highlight the importance of planning for appropriate post-ICU care to diagnose and treat this population.

Reinjury After Moderate to Severe TBI: Rates and Risk Factors in the NIDILRR Traumatic Brain Injury Model Systems.

OBJECTIVES: To compare characteristics of those who do and do not sustain subsequent traumatic brain injuries (TBIs) following index TBI and to identify reinjury risk factors. DESIGN: Secondary data analysis of an ongoing longitudinal cohort study. SETTING: TBI Model Systems Centers. PARTICIPANTS: In total, 11 353 individuals aged 16+ years. MAIN OUTCOME MEASURES: Ohio State University TBI Identification Method. RESULTS: In total, 7.9% of individuals reported sustaining a TBI post-index TBI. Twenty percent of reinjuries occurred within a year of the index TBI. Reinjury risk followed an approximate U-shaped distribution such that risk was higher in the first year, declined 2 to 10 years postinjury, and then increased after 10 years. A multivariable Weibull model identified predictors of reinjury: younger (<29 years) and middle-aged and older (50+ years) age at index TBI relative to middle age, pre-index TBI, pre-index alcohol and illicit drug use, incarceration history, and less severe index TBI. CONCLUSIONS: A subset of individuals who receive inpatient rehabilitation for TBI are at an increased risk for reinjury, and an injury-prone phenotype may be characterized by engagement in risk behaviors. Factors associated with reinjury risk may differ for younger versus middle-aged and older adults. Findings underscore the need for empirically informed risk stratification models to identify TBI survivors at risk for reinjury.

The Effects of Early Mobilization on Patients Requiring Extended Mechanical Ventilation Across Multiple ICUs.

OBJECTIVES: 1) To successfully implement early mobilization of individuals with prolonged mechanical ventilation in multiple ICUs at a tertiary care hospital and 2) to reduce length of stay and improve quality of care to individuals in the ICUs. DESIGN: Comparative effectiveness cohort study based on a quality improvement project. SETTING: Five ICUs at a tertiary care hospital. PATIENTS: A total of 541 mechanically ventilated patients over a 2-year period (2014-2015): 280 and 261, respectively. Age ranged from 19 to 94 years (mean, 63.84; sd, 14.96). INTERVENTIONS: A hospital-based initiative spurred development of a multidisciplinary team, tasked with establishing early mobilization in ICUs. MEASUREMENTS AND MAIN RESULTS: Early mobilization in the ICUs was evaluated by the number of physical therapy consults, length of stay, individual treatment sessions utilizing functional outcomes, and follow-up visits. Implementation of an early mobilization protocol across all ICUs led to a significant increase in the number of physical therapy consults, a significant decrease in ICU and overall lengths of stay, significantly shorter days to implement physical therapy, and a significantly higher physical therapy follow-up rate. CONCLUSIONS: Mobilizing individuals in an intensive care setting decreases length of stay and hospital costs. With an interdisciplinary team to plan, implement, and evaluate stages of the program, a successful early mobilization program can be implemented across all ICUs simultaneously and affect change in patients who will require prolonged mechanical ventilation.

An interview based approach to the anorectal portion of the International Standards of Neurological Classification of Spinal Cord Injury Exam (I-A-ISNCSCI): a pilot study.

STUDY DESIGN: Prospective, single-blinded study. OBJECTIVE: To design and evaluate the use of an interview based version of the anorectal portion of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam in the acute inpatient rehabilitation (AIR) setting. SETTING: AIR unit. METHODS: Participants admitted to AIR underwent standard ISNCSCI exams (S-ISNCSCI) as part of routine inpatient care within 3 days of being administered an interview version of the anorectal portion of the ISNCSCI (I-A-ISNCSCI). Agreement between the anorectal portion of the S-ISNCSCI (S-A-ISNCSCI) and the I-A-ISNCSCI was evaluated. RESULTS: Forty of forty-five enrolled participants completed the assessments. Agreement between the I-A-ISNCSCI and S-A-ISNCSCI was substantial for anorectal sensation to light touch (k = 0.71, 95% CI 0.52-0.90, N = 36), pin prick (k = 0.68, 95% CI 0.48-0.87, N = 38), deep anal pressure (k = 0.77, 95% CI 0.53-1.00, N = 37), and completeness of injury based on combined sacral sensory criteria (k = 0.72, 95% CI 0.47-0.97, N = 40); and fair for voluntary anal contraction (k = 0.29, 95% CI -0.01 to 0.59, N = 36). Responses of "I don't know" were excluded from agreement analyses. CONCLUSIONS: This pilot study was a first step in developing interview based tools such as the I-A-ISNCSCI in an AIR setting providing convenient access to individuals with SCI and their direct feedback. The study design introduces potential recall bias and may not match true clinical situations such as remote follow-up of neurological changes for chronic patients. The use of interview based tools for assessing individuals with SCI remains worthy of further study.

Enhanced exposure therapy for combat-related Posttraumatic Stress Disorder (PTSD): Study protocol for a randomized controlled trial.

BACKGROUND: PTSD, which has been identified in up to 23% of post-9-11 veterans, often results in a chronic, pernicious course. Thus, effective treatments are imperative. The Institute of Medicine (IOM) concluded that the only intervention for PTSD with sufficient evidence to conclude efficacy is exposure therapy. This Phase III trial compares the efficacy of exposure therapy for combat-related PTSD delivered in two different formats- via virtual reality exposure therapy (VRE) or prolonged exposure therapy (PE)- combined with D-Cycloserine (DCS), a cognitive enhancer shown to facilitate the extinction of fear. METHODS/DESIGN: Military personnel of any duty status and civilians deployed to Iraq and Afghanistan were eligible. Participants were randomly assigned to 9 sessions of exposure therapy (VRE or PE) and medication (50 mg DCS or placebo). Participants were treated at three geographically diverse sites. Participants were re-assessed at 3-months post-treatment. The co-primary hypotheses are that (1) DCS will augment response to exposure therapy (both VRE and PE) on PTSD symptoms; (2) VRE will be associated with greater improvement than PE. Genetic and psychophysiological markers will be evaluated as potential moderators and mediators of treatment outcomes as well as secondary outcomes. DISCUSSION: This study is the first to compare the relative efficacy of DCS-augmented VRE versus PE on PTSD symptoms. The design has several advantages: participants received an active, effective treatment and predictors of response to treatment included genetic and psychobiological measures. The results may directly influence the future delivery of services, and contribute to the development of a standardized treatment protocol. TRIAL REGISTRATION: NCT01352637.

Association of Visual Tracking Metrics With Post-concussion Symptomatology.

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 t-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 (r up to 0.68). On the other hand, while post-concussion SRT performance was reduced (p < 0.01), the changes in the performance metrics were not meaningfully correlated to symptomatology (r ≤ 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.

Visual Tracking in Development and Aging.

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.

Improving Emotion Regulation Following Web-Based Group Intervention for Individuals With Traumatic Brain Injury.

OBJECTIVE: Preliminary evaluation of the efficacy of a Web-based group intervention (Online EmReg) to improve emotion regulation (ER) in individuals with traumatic brain injury (TBI). DESIGN: Pre-/post-within-subject design with baseline, end-of-treatment, and 12-week follow-up assessments. PARTICIPANTS: Ninety-one individuals with TBI and deficits in ER. INTERVENTION: Twenty-four sessions of training in ER skills delivered by group videoconference. MEASURES: Difficulties in Emotion Regulation Scale (DERS), Positive Affect Negative Affect Schedule (PANAS), Satisfaction With Life Scale (SWLS), Problem Solving Inventory (PSI), Social Problem Solving Inventory-Revised: Short Form (SPSI-R:S), and Dysexecutive Questionnaire (DEX). RESULTS: Significant changes with large effect sizes were found for the DERS at the 12-week follow-up assessment. Significant and moderate changes were found on the SWLS, DEX, PSI, and subscales of the PANAS and SPSI-R:S. CONCLUSIONS: Online EmReg appears to be a promising method of delivering a group intervention to improve ER following TBI.

Response of School Districts to the New York State Concussion Awareness and Management Act: Review of Policies and Procedures.

BACKGROUND: By 2014, all states implemented concussion laws that schools must translate into daily practice; yet, limited knowledge exists regarding implementation of these laws. We examined the extent to which concussion management policies and procedure (P&P) documents of New York State school districts comply with the State's Concussion Awareness and Management Act (the Act). We also aimed to identify barriers to compliance. METHODS: Forty-seven school districts provided P&P documents. We examined compliance with the Act and the relationship between compliance and each district's demographics. RESULTS: Compliance varied across school districts, with higher overall compliance in large city school districts compared to county districts. However, there was low compliance for several critical items. We found no statistically significant relationship between compliance and demographics. CONCLUSIONS: School districts need to increase compliance with concussion legislation to ensure the adequate implementation necessary for the law to impact health and educational outcomes. The results provide important information to individuals charged with the responsibility of implementation and ultimately reducing the negative outcomes associated with brain injuries in schools.

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

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.

The Relationship Between Traumatic Brain Injury and Criminality in Juvenile Offenders.

OBJECTIVE: To examine the relationship between traumatic brain injury (TBI) and criminal behavior in youth who are incarcerated or on probation in Texas. SETTING: Seven juvenile justice facilities. PARTICIPANTS: Juvenile offenders in state or county correctional facilities or on probation. DESIGN: Screening for TBI was conducted among adolescents at 7 juvenile justice centers. MAIN MEASURES: Participants were administered the Brain Injury Screening Questionnaire, and results were linked to participants' offense history and psychiatric diagnoses. RESULTS: One in 4 juvenile offenders met criteria for TBI, and the majority of injuries occurred prior to the adolescents' criminal offenses. A history of TBI was related to more violent crimes, as well as more mental health diagnoses and symptoms. CONCLUSION: The high rates of TBI and levels of distress found in juvenile offenders suggest a need for preventive actions, interventions to compensate for challenges related to TBI, and programs to assist individuals' transitions into the community.

Possible Medication-Resistant Deficits in Adult ADHD.

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.