Harvey S. Levin - US grants

DESCRIPTION (provided by applicant) Executive functions (EFs) are cognitive control processes that include flexibility in problem solving, planning, allocation of attention, maintenance and manipulation of information over time, and self-regulation. EFs, which deploy specific cognitive skills such as declarative memory and other domains such as perceptuomotor skills, are mediated by prefrontal cortex and its circuitry. EFs are frequently impaired after traumatic brain injury (TBI), thus contributing to disability and reduced quality of life. Working memory and inhibition are fundamental processes of EFs which have been associated with prefrontal cortex and its network. Although the prefrontal region is vulnerable to injury by acceleration/deceleration and blunt trauma, structural brain imaging is limited in understanding the neurobiology of EF deficits after TBI. Using functional magnetic resonance imaging (fMRI), the Aims 9 of this 3 center project are to (1) Investigate whether the extent of cortical activation during working memory (N-back for faces) and inhibition (left-right incompatibility of arrows) tasks in adults 3 months following moderate to severe TBI differs from that of adults who have sustained extracranial injury; (2) Examine longitudinal changes in activation of prefrontal and related cortical regions during performance of working memory and inhibition tasks in TBI patients reimaged at I year postinjury; (3) Investigate the relationship between patterns of brain activation during working memory and inhibition tasks at 3 months and 1 year postinjury and performance on laboratory, clinical, and everyday measures of EF; (4) In an ongoing study of a separate cohort of moderate to severe TBI patients, evaluate the effects of methylphenidate (MPH) taken for 1 month on prefrontal activation during performance of working memory and inhibition tasks and the associated changes in performance on EF measures. Moderate to severe TBI patients (total n= 180) and general trauma patients (total n=60) will be recruited from the neurosurgery and surgery services at 3 centers. Aims 1-3 will be addressed by fMRI and EF assessment at 3 months and 1 year postinjury. Aim 4 will involve fMRI and EF assessment of TBI patients with working memory deficit who are treated for 28 days with MPH 15 in- bid beginning between 3 and 12 months postinjury. Patients studied for Aim 4 will undergo fMRI and EF assessment before beginning MPH and 1 hour after their final dose of MPH. Laboratory EF measures include dual task performance, subject ordered pointing, N-back letters task, selective learning, and risk taking; the revised Neurobehavioral Rating Scale provides clinical ratings of EFs; and assessment of EFs in everyday activities will include measures of dysexecutive functioning and planning. Analyses will test TBI-related alterations in brain activation at 3 months postinjury, changes on reimaging at 1 year, relationship to EFs, and MPH effects.

DESCRIPTION (provided by applicant): The goal of the proposed program is to provide postdoctoral fellows with mentored research training to prepare them for careers as independent investigators in medical rehabilitation research. Three postdoctoral fellows, including two Ph.D.s and one M.D., will begin training in year 1 over a two-year period in this multidisciplinary program designed to produce academicians who are capable of competing for Federal grants and mentoring the next generation of investigators in rehabilitation research. A training faculty representing externally funded basic science and clinical investigators drawn from various departments at Baylor College of Medicine, the University of Texas Health Science Center at Houston, and Rice University, would mentor the research of fellows in hypothesis-driven projects in two areas of concentration, including (1) neuroplasticity and neuroimaging, and (2) medical rehabilitation and clinical trials. The program reflects (a) current models of illness, disablement, and rehabilitation and health;(b) trends in research emphasizing neuroplasticity as a mediator of recovery and response to therapy;(c) interaction of the person with disability and the environment;and (d) the development and evaluation of innovative interventions to mitigate complications of injury and improve health-related quality of life. The core of the training program includes courses in Rehabilitation Research and the Ethical Conduct of Research with elective coursework in the trainee's selected area of concentration and other didactic activities. One-to-one mentoring will be emphasized in the trainee's acquisition of skills in methodology, project management, preparation of manuscripts, communication skills, good citizenship in science, and developing competitive grant applications. Trainees will be selected from all professional areas of medical rehabilitation and Ph.D.s who are trained in fields such as bioengineering, neuropsychology, neuroscience, and health services research. Oversight of the program and methods for evaluation of the trainees and the mentors are proposed. The Department of Physical Medicine and Rehabilitation at Baylor College of Medicine has established procedures for recruitment of qualified candidates who are underrepresented minorities and/or persons with disabilities. The PIs believe that the proposed training-faculty, curriculum, and institutional environment will produce productive and ethical investigators who will advance medical rehabilitation research.

0-11 years old; 21+ years old; Acceleration; Active Follow-up; Acute; Adolescent; Adolescent Youth; Adult; Age; Amnesia; Amnesia-Memory Loss; Anxiety; Area; Attention; Biologic Marker; Biological Markers; Blood Sample; Blood Serum; Blood specimen; Brain; Brain imaging; Brain region; CRISP; Categories; Cell Communication and Signaling; Cell Signaling; Cerebrum; Child; Child Youth; Children (0-21); Cognitive; Cognitive Manifestations; Cognitive Symptoms; Complex; Computer Retrieval of Information on Scientific Projects Database; Consciousness, Loss of; Corpus Callosum; Corpus Callosums; DAI; Data; Data Collection; Depression; Diffuse Axonal Injury; Diffusion MRI; Diffusion Magnetic Resonance Imaging; Diffusion Weighted MRI; Distress; Emotional; Emotional Depression; Encephalon; Encephalons; Environment; Episodic memory; Episodic memory, function; Exhibits; Extremities; Family; Funding; Genu of the Corpus Callosum; Glasgow Coma Scale; Grant; Gray; Gray unit of radiation dose; Human, Adult; Human, Child; Image; Injury; Institution; Internal Capsule; Interview; Intracellular Communication and Signaling; Investigation; Investigators; Lateral; Learning; Limb structure; Limbs; MR Imaging; MR Tomography; MRI; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Manuals; Measures; Medial; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Memory; Memory, Immediate; Memory, Short-Term; Memory, Shortterm; Mental Depression; Modeling; Molecular Marker; Motor; NIH; NMR Imaging; NMR Tomography; National Institutes of Health; National Institutes of Health (U.S.); Nervous; Nervous System, Brain; Neurobehavioral Manifestations; Non-Trunk; Nuclear Magnetic Resonance Imaging; Orthopedic; Orthopedic Surgical Profession; Orthopedics; Outcome; Patient Self-Report; Patients; Pilot Projects; Post-Concussion Symptoms; Post-Concussion Syndrome; Post-Concussive Symptoms; Post-Concussive Syndrome; Prefrontal Cortex; Proteins; Rate; Recovery; Relative; Relative (related person); Research; Research Personnel; Research Resources; Researchers; Resources; Rewards; Sample Size; Schools; Score; Self-Report; Sensitivity and Specificity; Serum; Short-Term Memory; Signal Transduction; Signal Transduction Systems; Signaling; Signature Molecule; Signs and Symptoms, Neurobehavioral; Source; Speed; Speed (motion); Stress; Structure; Structure of genu of corpus callosum; Superior temporal gyrus; Symptoms; Symptoms of depression; Trauma; Trauma, Brain; Traumatic Brain Injury; Traumatic encephalopathy; Unconscious; Unconscious State; Unconsciousness; United States National Institutes of Health; Week; Work; Zeugmatography; abstracting; adult human (21+); adult youth; base; biological signal transduction; biomarker; brain visualization; children; cognitive control; cognitive recovery; depressive; depressive symptoms; diffusion tensor imaging; executive control; executive function; follow-up; functional outcomes; gene product; gray matter; imaging; interest; juvenile; juvenile human; nerve injury; neural; neural injury; neurobehavioral; pilot study; processing speed; relating to nervous system; response; social; socioeconomic; socioeconomically; socioeconomics; stressor; substantia alba; substantia grisea; traumatic brain damage; white matter; working memory; young adult; youngster

DESCRIPTION (provided by applicant): This prospective, observational study addresses the overarching hypothesis that brain dysfunction and structural injury are present at one month post- sports concussion (SC) in asymptomatic high school athletes who have been cleared by a licensed health provider (LHP) for return to play (RTP). We hypothesize that a biomarker measured from serum on the day of recruitment is prognostic of recovery by one month post-SC. High school athletes will be recruited within three days post-SC (n=24) from consecutive referrals to Memorial Hermann Sports Medicine Clinic in Houston. A comparison group of 24 high school athletes with orthopedic injury (OI) will also be recruited. Weekly assessment via telephone of post-concussion symptoms will identify athletes who are asymptomatic by one month and cleared for RTP. At one month post-injury both groups will return to clinic for neurobehavioral assessment, magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and resting state functional magnetic resonance imaging to measure functional connectivity (FC) of brain regions. Data analysis will test between-group differences in integrity of white matter tracts (DTI) and FC of brain regions. Biomarker levels will be analyzed in relation to brain imaging and neurobehavioral recovery at one month in SC group.