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34 Severity of Traumatic Brain Injury Predicts Neurobehavioral Outcomes and White Matter Microstructure
- Julia Friedman, Kathryn Vannatta, William A Cunningham, Elisabeth A Wilde, Keith Owen Yates, Kristen R Hoskinson
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 142-143
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Objective:
Pediatric traumatic brain injury (TBI) is the leading cause of disability in children under the age of 15, often resulting in executive function deficits and poor behavioral outcomes. Damage to white matter tracts may be a driving force behind these difficulties. We examined if whether 1) greater TBI severity was associated with worse neurobehavioral outcome, 2) greater TBI severity was associated with tract-based white matter microstructure, and 3) worse neurobehavioral outcome was associated with white matter microstructure.
Participants and Methods:Twelve children with complicated-mild TBI (cmTBI; Mage=12.59, nmale=9), 17 with moderate-to-severe TBI (msTBI; Mage =11.50, nmale=11), and 21 with orthopedic injury (OI; Mage =11.60, nmale=16), 3.94 years post injury on average, were recruited from a large midwestern children’s hospital with a Level 1 Trauma Center. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Child Behavior Checklist (CBCL) while children completed 64-direction diffusion tensor imaging in a Siemens 3T scanner. White matter microstructure was quantified with FMRIB’s Diffusion Toolbox (FSLv6.0.4). Tract-Based Spatial Statistics computed fractional anisotropy (FA) and mean diffusivity (MD) for the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF), bilaterally.
Results:Group differences were assessed using one-way ANOVA. Children with msTBI were rated as having worse Sluggish Cognitive Tempo on the CBCL than children with cmTBI and OI (p=.02, eta2=.143); no other parent-rated differences reached significance. Group differences were found in left SLF FA (p=.031; msTBI<cmTBI=OI) and approached significance in left UF FA (p=.062, eta2=.114; msTBI<OI). Group differences were also found in right IFOF MD (p=.048; msTBI>OI) and left SLF MD (p=.013; msTBI>cmTBI=OI). Bivariate correlations assessed cross-domain associations. Higher left IFOF FA was associated with better BRIEF Metacognitive Skills (r=-.301, p=.030) and CBCL School Competence (r=.280; p=.049). Higher left SLF FA was associated with better BRIEF Behavioral Regulation and Metacognitive Skills (r=-.331, p=.017 and r=-.291, p=.036, respectively), and CBCL School Competence and Attention Problems (r=.398, p=.004 and r=-.435, p=.001, respectively). Similarly, higher right UF FA was broadly associated with better neurobehavioral outcomes, including Behavioral Regulation and Metacognitive Skills (r=-.324, p=.019 and r=-.359, p=.009, respectively), and School Competence, Attention Problems, and Sluggish Cognitive Tempo (r=.328, p=.020, r=-.398, p=.003, and r=-.356, p=.010, respectively). Higher right CB MD was associated with worse Behavioral Regulation (r=.327, p=.018) and more Attention Problems (r=.278, p=.046); higher left and right SLF MD was associated with Sluggish Cognitive Tempo (r=.363, p=.008, r=.408, p=.003, respectively).
Conclusions:Children with TBI, particularly msTBI, were rated as having cognitive slowing; while other anticipated group differences in neurobehavioral outcomes were not found, this appears driven by milder difficulties in cmTBI and OI groups. In fact, across CBCL and BRIEF subscales, children with msTBI were rated as approaching or exceeding a full standard deviation deficit based on normative data. TBI severity was also associated with white matter microstructure and cross-domain associations linked microstructure with observable neurobehavioral morbidities, suggesting a possible mechanism post-injury. Future longitudinal studies would be useful to examine the temporal evolution of deficits.
1 Social Brain Network Connectivity Relates to Social and Adaptive Outcomes Following Pediatric Traumatic Brain Injury
- Katherine A Billetdeaux, Whitney Mattson, Eric Nelson, Brianna Laney, Kathryn Vannatta, William A Cunningham, Elisabeth A Wilde, Keith Yeates, Kristen R Hoskinson
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 509-510
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Objective:
Traumatic brain injury (TBI) is a prevalent cause of long-term morbidity in children and adolescents and can lead to persistent difficulties with social and behavioral function. TBI may impact brain structures that support social cognition, social perception, and day-to-day social interactions—termed the social brain network (SBN). We examined differences in links among the SBN and regions of interest from other neural networks thought to support social outcomes, i.e., the default mode network (DMN) and salience network (SN). Furthermore, we examined how differences in co-activation among the SBN and these other key networks were associated with ratings of social and day-to-day adaptive outcomes.
Participants and Methods:Participants included children and adolescents with moderate to severe TBI (msTBI; n=11, Mage=11.78, 6 male), complicated-mild TBI (cmTBI; n=12, Mage=12.59, 9 male), and orthopedic injury (OI; n=22, Mage=11.69, 15 male). Participants underwent resting-state functional MRI on a 3Tesla Siemens Prisma scanner. Parents rated their child’s social and adaptive function on the Child Behavior Checklist (CBCL) and Adaptive Behavior Assessment System-Third Edition (ABAS-3). Resting-state connectivity was assessed using the CONN Toolbox, including preprocessing, denoising, and alignment to the participants’ processed T1 MPRAGE sequence followed by seed-to-voxel analysis using a SBN mask and targeted regions of interest within the DMN and SN. Individual-level r-to-z correlations were extracted from resulting clusters of co-activation with the SBN mask and exported into SPSSv28.0 for integration with behavioral data.
Results:One-way ANOVAs used to examine group differences in social and adaptive outcome revealed significant group differences in CBCL Social Competence (F=4.49, p=.019) and all composite scores on the ABAS-3 (Fs=3.78 to 5.17, ps=.031 to .010). In each domain, children with msTBI were rated as having elevated difficulties relative to cmTBI or OI, whereas cmTBI and OI groups did not differ. Connectivity also differed significantly between groups, with children with OI demonstrating greater connectivity between the SBN and the anterior cingulate cortex of the SN (t=5.19, p(FDR)<.0001) and posterior cingulate cortex of the DMN (f=4.30, p(FDR)<.001) than children with msTBI. Children with cmTBI also showed greater connectivity between the SBN and left temporal pole of the DMN (t=7.45, p(FDR)<.000001) than children with msTBI. Degree of connectivity between the SBN and posterior cingulate was significantly positively correlated across all domains of adaptive function (rs=.451 to .504, ps=.010 to .003), whereas degree of connectivity between the SBN and left temporal pole was strongly positively related to Social Competence (a=.633, p=.006) and conceptual adaptive skills on the ABAS (A=.437, p=.037).
Conclusions:Our findings provide insights into the neural substrates of social and adaptive morbidity after pediatric TBI, particularly msTBI, by linking alterations in connectivity among the SBN, DMN, and SN with measures of social and adaptive outcome. While the posterior cingulate was broadly associated with adaptive outcome, the temporal pole was particularly strongly associated with social competence. This may reflect the diverse functions and high degree of interconnectivity of the posterior cingulate, which contributes to various cognitive and attentional processes, relative to the strong amygdala/limbic connections of the temporal pole.
16 Superior Verbal Learning and Memory in Pediatric Brain Tumor Survivors Treated with Proton Versus Photon Radiotherapy
- Lisa E. Mash, Lisa S. Kahalley, M. Fatih Okcu, David R. Grosshans, Arnold C. Paulino, Heather Stancel, Luz A. De Leon, Elisabeth A. Wilde, Nilesh Desai, Zili D. Chu, William E. Whitehead, Murali Chintagumpala, Kimberly P Raghubar
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 17-18
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Objective:
Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers less radiation to healthy brain tissue. PRT has been associated with improved long term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory outcomes.
Participants and Methods:Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing > 1 year following radiotherapy. XRT and PRT groups were similar with respect to sex, handedness, race, age at diagnosis, age at evaluation, tumor characteristics, and treatment history (i.e., craniospinal irradiation, craniotomy, shunting, chemotherapy, radiation dose). Verbal learning and memory were assessed using the age-appropriate version of the California Verbal Learning Test (CVLT-II/CVLT-C). Measures of intellectual functioning, executive functioning, attention and adaptive behavior were also collected. Performance on neuropsychological measures was compared between treatment groups (XRT vs. PRT) using analysis of covariance (ANCOVA). On the CVLT, each participant was classified as having an encoding deficit profile (i.e., impaired learning, recall, and recognition), retrieval deficit profile (i.e., impaired recall but intact recognition), intact profile, or other profile. Chi-squared tests of independence were used to compare the probability of each memory profile between treatment groups. Pearson correlation was used to examine associations between memory performance and strategy use, intellectual functioning, adaptive behavior, attention, and executive functioning.
Results:Overall, patients receiving PRT demonstrated superior verbal learning (CVLT Trials 1-5; t(76) = 2.61, p = .011), recall (CVLT Long Delay Free; t(76) = 3.57, p = .001) and strategy use (CVLT Semantic Clustering; t(76) = 2.29, p = .025) compared to those treated with XRT. Intact performance was more likely in the PRT group than the XRT group (71% PRT, 38% XRT; X2 = 8.14, p = .004). Encoding and retrieval deficits were both more common in the XRT group, with encoding problems being most prevalent (Encoding Deficits: 31% XRT, 12% PRT, X2 = 4.51, p = .034; Retrieval Deficits: 17% XRT, 4% PRT, X2 = 4.11, p = .043). Across all participants, semantic clustering predicted better encoding (r = .28, p = .011) and retrieval (r = .26, p = .022). Better encoding predicted higher intellectual (r = .56, p < .001) and adaptive functioning (r = .30, p = .011), and fewer parent-reported concerns about day-today attention (r = -.36, p = .002), and cognitive regulation (r = -.35, p = .002).
Conclusions:Results suggest that PRT is associated with superior verbal memory outcomes compared to XRT, which may be driven by encoding skills and use of learning strategies. Moreover, encoding ability predicted general intellectual ability and day-to-day functioning. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline following radiotherapy, which will better inform treatment approaches for survivors of pediatric brain tumor.
2 Cognitive Sparing in Proton Versus Photon Radiotherapy for Pediatric Brain Tumor Associated with White Matter Integrity
- Lisa E. Mash, Lisa S. Kahalley, Kimberly P. Raghubar, Naomi J. Goodrich-Hunsaker, Tracy J. Abildskov, Luz A. De Leon, Marianne MacLeod, Heather Stancel, Kelley Parsons, Brian Biekman, Elisabeth A. Wilde
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 312-313
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Objective:
Radiotherapy for pediatric brain tumor is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to conventional photon radiotherapy (XRT), presumably due to sparing of healthy brain tissue. This study examined long-term white matter change and neuropsychological performance in pediatric brain tumor survivors treated with XRT vs. PRT.
Participants and Methods:Pediatric brain tumor survivors treated with either XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging > 7 years following radiotherapy. A healthy control group (n = 23) was also recruited. Groups had similar demographic characteristics, except for handedness (p = .01), mean years of age at testing (XRT = 21.7, PRT = 16.9, Control = 15.5; p = .01), and mean years since radiation (XRT =14.7, PRT = 8.9, p < .001). Age and handedness were selected as covariates; analyses were not adjusted for time since radiation due to redundancy with treatment group (i.e., standard of care transitioned from XRT to PRT in 2007). Participants completed age-appropriate versions of the Weschler Intelligence Scales (WAISIV/WISC-IV/WISC-V) and the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI and Motor Coordination subtests). Tractography was conducted using automated fiber quantification (AFQ), and fractional anisotropy (FA) was extracted from 12 tracts of interest. Linear mixed models were used to summarize group differences in FA, with tracts nested within subjects. Neuropsychological performance and tract-level FA were compared between groups using analysis of covariance (ANCOVA). Pearson correlation was used to examine associations between cognitive functioning and tract-level FA.
Results:Across all tracts, FA was significantly lower in the XRT group than the PRT group (t(514) = -2.58, p = .01), but did not differ between PRT and Control groups (t(514) = .65, p = .51). For individual tracts, FA differed significantly between treatment groups (XRT < PRT) in the left inferior fronto-occipital fasciculus (IFOF), right IFOF, left inferior longitudinal fasciculus (ILF) and right uncinate (all t < -2.05, all p < .05). No significant differences in FA were found between PRT and Control participants for any tract. All neuropsychological scores were significantly lower for XRT than PRT patients (all p < .03), while PRT and Control groups performed similarly on these measures (all p >.19). Cognitive functioning was most consistently associated with FA of the corpus callosum major forceps (4/7 domains; all r > .33, all p < .04) and the left ILF (4/7 domains; all r > .37, all p <.02).
Conclusions:Both white matter integrity and neuropsychological performance were generally reduced in patients with a history of XRT, but not in those who received PRT. The PRT group was similar to healthy control participants with respect to both FA and cognitive scores, suggesting improved long-term outcomes compared to patients receiving XRT. This exploratory study is the first to provide direct support for white matter integrity as a mechanism of cognitive sparing in PRT. Future work with larger samples is necessary to replicate these findings.
57 Olfaction in Veterans with a History of Deployment-Related Mild Traumatic Brain Injury
- Maya Troyanskaya, Nicholas J Pastorek, Fariha Jamal, George R Jackson, Aliya I Sarwar, Elisabeth A Wilde, Randall S Scheibel
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 162-163
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Objective:
Olfaction is a critical sensory function and changes in the ability to detect smells could affect quality of life by diminishing appreciation of food, drink, and other aroma-based experiences, increase danger of hazardous exposures, and cause a loss of employment. Additionally, decrements in olfaction have been related to onset of some neurodegenerative conditions. Olfactory impairments in military populations are highly prevalent and often attributed to the long-term effects of mild traumatic brain injury (mTBI) and chronic psychiatric disorders. The main goal of this investigation was to examine olfactory function in a cohort of combat veterans using a quantitative smell test.
Participants and Methods:Participants underwent a neurological examination using a revised version of the Neurological Outcome Scale for Traumatic Brain Injury. Olfactory function was examined using a set of essential oil vials with common odors. Based on the number of correctly identified odors, the following grading system was employed: no deficit; mild; moderate; severe deficit; and absence of smell detection. All study assessments were performed prior to March of 2020 (onset of COVID-19 pandemic). In addition, participants completed performance validity testing (PVT) and screening for ongoing substance misuse using the Alcohol Use Disorders Identification Test and Drug Abuse Screening Test-10. Lifetime history of brain injury, combat-related extracranial injuries, and deployment characteristics were assessed using structured interview. All available medical records were reviewed.
Results:Participants were 38 veterans with a deployment-related mTBI who passed the PVT and did not have ongoing substance misuse issues. Olfactory examination revealed normosmia in 20 participants and various degrees of deficit in 18 (11= mild; 4=moderate; and 3=severe). The groups did not differ in demographics, post-injury interval, or current clinical (non-psychiatric) conditions. Participants with hyposmia frequently reported being exposed to a higher number of blasts and being positioned closer to the nearest primary blast, and more often endorsed a period of loss of consciousness after the most serious mTBI. In addition, they more often reported tympanic membrane perforation, extracranial injuries, and histories of both blast and blunt force mTBI. Comorbid diagnoses of posttraumatic stress disorder (PTSD), depression, chronic headaches, and pain were more common among these participants as well.
Conclusions:Several blast exposure and specific injury-related characteristics increase the likelihood of long-term olfactory impairments, comorbid psychiatric conditions, and chronic pain among veterans with a history of deployment-related mTBI. Notably, none of the participants with hyposmia had a clinical diagnosis of olfactory dysfunction or were receiving service-connected disability for a loss of sense of smell at the time of their assessment. Multidisciplinary rehabilitation care provided to combat veterans with history of mTBI and/or PTSD should include olfactory examination using both quantitative and qualitative smell tests, education regarding the adversities related to loss of smell, management of current psychiatric symptoms, and follow-up assessments. The lack of a comparison group without a history of mTBI and the small sample size were the main limitations of this investigation.
61 Neurocognitive functioning improves in former athletes with sport-related concussion and repetitive head hits following transcranial photobiomodulation treatment
- Spencer W Liebel, Paula K Johnson, Hannah M Lindsey, Michael J Larson, Carrie Esopenko, Elizabeth S Hovenden, Hilary A Russell, Carmen Velez, Christine M Mullen, Lawrence S Carr, Elisabeth A Wilde, David F Tate
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 166-167
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Objective:
Significant advances in the research of sport-related concussion (SRC) and repetitive head impacts (RHI) over the previous decade have translated to improved injury identification, diagnosis, and management. However, an objective gold standard for SRC/RHI treatment has remained elusive. SRC often result in heterogenous clinical outcomes, and the accumulation of RHI over time is associated with long-term declines in neurocognitive functioning. Medical management typically entails an amalgamation of outpatient medical treatment and psychiatric and/or behavioral interventions for specific symptoms rather than treatment of the underlying functional and/or structural brain injury. Transcranial photobiomodulation (tPBM), a form of light therapy, has been proposed as a non-invasive treatment for individuals with traumatic brain injuries (TBI), possibly including SRC/RHI. With the present proof-of-concept pilot study, we sought to address important gaps in the neurorehabilitation of former athletes with a history of SRC and RHI by examining the effects of tPBM on neurocognitive functioning.
Participants and Methods:The current study included 49 participants (45 male) with a history of SRC and/or RHI. Study inclusion criteria included: age 18-65 years and a self-reported history of SRC and/or RHI. Exclusion criteria included: a history of neurologic disease a history of psychiatric disorder, and MRI contraindication. We utilized a non-randomized proof-of-concept design of active treatment over the course of 8-10 weeks, and neurocognitive functioning was assessed at pre- and post-treatment. A Vielight Neuro Gamma at-home brain tPBM device was distributed to each participant following baseline assessment.
Participants completed standardized measures of neurocognitive functioning, including the California Verbal Learning Test (CVLT-3), Delis Kaplan Executive Function System (D-KEFS), Continuous Performance Test (CPT-3), and The NIH Toolbox Cognition Battery. Neurocognitive assessments were collected prior to and following tPBM treatment. Paired t-tests and Wilcoxon’s signed-rank tests were used to evaluate change in performance on measures of neurocognitive functioning for normal and nonnormal variables, respectively, and estimates of effect size were obtained.
Results:Study participants’ ability for adapting to novel stimuli and task requirements (i.e., fluid cognition; t=5.96; p<.001; d=.90), verbal learning/encoding (t=3.20; p=.003; d=.48) and delayed recall (z=3.32; p=.002; d=.50), processing speed (t=3.13; p=.003; d=.47), sustained attention (t=-4.39; p<.001; d=-.71), working memory (t=3.61; p=.001; d=.54), and aspects of executive functioning improved significantly following tPBM treatment. No significant improvements in phonemic and semantic verbal fluencies, reading ability, and vocabulary were shown following tPBM treatment.
Conclusions:The results of this pilot study demonstrate that following 8-10 weeks of active tPBM treatment, retired athletes with a history of SRC and/or RHI experienced significant improvements in fluid cognition, learning and memory, processing speed, attention, working memory, and aspects of executive functioning. Importantly, the majority of effect sizes ranged from moderate to large, suggesting that tPBM has clinically meaningful improvements on neurocognitive functioning across various cognitive domains. These results offer support for future research employing more rigorous study designs on the potential neurorehabilitative effects of tPBM in athletes with SRC/RHI.
Invited Symposium 1: Traumatic Brain Injury: Highlighting the Contributions of Dr. Harvey S. Levin Ph.D., ABPP-CN, FACSM 1946 - 2022
- Maya Troyanskaya, Randall Scott Scheibel, Felicia C. Goldstein, Linda Ewing-Cobbs, Erin D. Bigler, Elisabeth A. Wilde
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 399-400
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Harvey S. Levin obtained his Bachelor’s degree from City College of New York, in New York city, Ph.D. in Clinical Psychology from the University of Iowa, in Iowa City, completed his internships in Clinical Neuropsychology and Pediatric Psychology at the University of Iowa Hospitals in Iowa City and Clinical Psychology, Psychiatry and Pediatrics at the Illinois Masonic Medical Center in Chicago, and his fellowship in Neuropsychology at University of Iowa Hospitals in Iowa City.
Dr. Levin started his career in 1972 as Instructor with the Department of Psychology at the University of Iowa and transitioned to The University of Texas Medical Branch (UTMB) in Galveston, Texas, in 1974, where he began an internationally renowned career in clinical work, teaching, and, most of all, pioneering research on traumatic brain injury (TBI). He ultimately became the Chela and Jimmy Storm Distinguished Professor in Surgical Research, Division of Neurosurgery, Department of Surgery in 1987. After leaving Texas for two years to take a position with the University of Maryland Medical System and Shock Trauma Institute in Baltimore, he moved back to Houston Texas in 1995 and established the Cognitive Neuroscience Laboratory (CNL) within the Department of Physical Medicine & Rehabilitation at Baylor College of Medicine, which was supported by federal grants, including funding from the National Institutes of Health, Department of Defense, Department of Veterans Affairs, and Centers for Disease Control and Prevention, and numerous private foundations. The CNL integrated rehabilitation and neuroplasticity research with multimodality brain imaging, clinical and neuropsychological assessment, and fluid biomarkers. Dr. Levin was Professor with the Departments of Physical Medicine and Rehabilitation where he served as Director of Research (1995-2014), Pediatrics, and Neurosurgery at Baylor College of Medicine. He was also a Research Scientist and the Director of the Center of Excellence for Traumatic Brain Injury at the Michael E. DeBakey Veterans Affairs Medical Center (2008-2013), and Adjunct Professor with the Department of Psychology at Rice University in Houston, Texas.
Dr. Levin’s research focused on investigating both acute and long-term outcomes of mild to severe TBI in civilian and military populations, including cognitive and behavioral sequelae in relation to neuropathology using advanced brain imaging modalities. He began prospective, longitudinal studies of adults and children who had sustained TBI associated with closed head trauma upon joining UTMB and developed, in collaboration with Drs O’Donnell and Grossman, the Galveston Orientation and Amnesia Test (GOAT). The GOAT was the first measure to assess post-traumatic amnesia and orientation following moderate to severe TBI, is still most widely used by the clinicians and researchers, and it has been translated to 16 languages. The original publication, “Levin HS, O’Donnell VM, Grossman RG. The Galveston Orientation and Amnesia Test. A practical scale to assess cognition after head injury. J Nerv Ment Dis. 1979 Nov;167(11):675-84. doi: 10.1097/00005053-197911000-00004. PMID: 501342”, has over 1200 citations. This work continued with participation in the NINDS Traumatic Coma Data Bank and the organization of outcome assessments for NINDS-funded clinical trials of hypothermia to treat severe TBI. To monitor the quality of outcome data across performing sites, Dr. Levin and colleagues developed a code for the reliability of data collected and implemented the role of an outcome monitor who evaluated adherence to protocol across sites. Following establishment of the CNL, he pursued investigation of TBI outcomes across the lifespan using multimodality brain imaging and biomarkers, errorless learning, translational studies in collaboration with neuroscientists using animal models, and clinical trials of methylphenidate, progesterone, CDP-choline. Dr. Levin spent over 30 years researching neurobehavioral outcomes of head injury in children, starting with a small pilot study funded by the Shriners Hospital in 1991 and continuing with several cycles of a multicenter R01 grant funded by the National Institute of Health. In later years, he used his expertise as a member of several large consortiums, including the Long-term Impact of Military-Relevant Brain Injury Consortium \ Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) funded by the VA and DoD and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) funded by the NINDS.
During his career, Dr. Levin authored and coauthored more than 400 articles in scientific journals and over 100 books, with one of them, “Levin, H. S., Benton, A. L., & Grossman, R. G. (1982). Neurobehavioral consequences of closed head injury. Oxford University Press, USA”, having over 1100 citation, as well as book chapters that advanced knowledge of TBI, epilepsy, neurodegenerative diseases, and other illnesses that affect brain functioning. He was also very active as a reviewer on federal grant panels and as an editor and reviewer for the Journal of Neurotrauma, Journal of Clinical and Experimental Neuropsychology, Archives of Physical Medicine & Rehabilitation, Neuropsychology, Journal of the International Neuropsychological Society, Lancet, JAMA, Pediatrics, and other top-cited journals. He served as president of the International Neuropsychological Society in 1989-1990. Dr. Levin was a recipient of numerous prestigious awards, including the Javits Neuroscience Investigator Award, the Jennett-Plum Award for Research on Traumatic Brain Injury, the Distinguished Career Award by the International Neuropsychological Society, the American Congress of Rehabilitation Gold Key Award, the Distinguished Lifetime Contribution to Neuropsychology Award from the National Academy of Neuropsychology, as well as awards from other head injury and psychological organizations, including the International Brain Injury Association, the National Head Injury Foundation, the North American Brain Injury Society, Texas Psychological Association, and the Defense and Veterans Brain Injury Center. In addition to his stellar scientific accomplishments, Dr. Levin trained, mentored, and provided supervision to interns, fellows, postdocs, residents, medical and psychology students. He was the Director of an NCMRR/NIH T32 Postdoctoral Research Program, and training supervisor in neuropsychology for Baylor College of Medicine and for the Memorial Hermann TIRR Neuropsychology Postdoctoral Fellowship Programs. A passionate educator, he taught classes at Baylor College of Medicine, the University of Houston, and the National and Kapodistrian University of Athens Medical School in Greece and served as an evaluator for the American Board of Clinical Neuropsychology/American Board of Professional Psychology. He was often invited as a lecturer at numerous scientific organizations.
The main objective of this symposium is to provide an overview of the current state of research in TBI while highlighting Dr. Levin’s contributions to this field. The symposium will start with a brief overview of Dr. Levin’s career (Dr. Randall S. Scheibel), followed by presentations focused on the assessment of adult TBI, including posttraumatic amnesia (Dr. Felicia C. Goldstein), the current state of pediatric TBI (Dr. L. Ewing-Cobbs), and novel imaging in TBI (Dr. Erin D. Bigler). There will be a brief discussion session at the end lead by Dr. Elisabeth A. Wilde.
21 - How Should One Measure “Outcome” of Concussion?: An Introduction to the Common Data Elements for Mild TBI and Concussion
- from Part III - Diagnosis and Management of Concussion
- Edited by Jeff Victoroff, Erin D. Bigler, Brigham Young University, Utah
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- Concussion and Traumatic Encephalopathy
- Published online:
- 22 February 2019
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- 28 February 2019, pp 694-715
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Summary
More than a decade before the publication of this text, leaders at the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) in Bethesda, Maryland, judged that research might be better coordinated, and efforts of different teams of investigators far better synthesized, if scholars used a common toolbox of outcome measures. The importance of that judgment is apparent to anyone who has undertaken a meta-analysis only to find that 100 experiments seeking to test the same scientific hypothesis were all done in unique and incomparable ways. The initiative to rectify this problem by strongly recommending specific instruments was christened the Common Data Elements (CDE) project. The authors of the present chapter have been intimately engaged in this progressive initiative. Here, they expertly summarize the first major product released by that team: the CDEs for traumatic brain injury. This is half the battle toward capitalizing on the collective efforts of researchers around the nation and the world, all working to understand CBI. The other half of the battle, of course, is to define CBI biologically.
Chronic Effects of Blast-Related TBI on Subcortical Functional Connectivity in Veterans – Erratum
- Mary R. Newsome, Andrew R. Mayer, Xiaodi Lin, Maya Troyanskaya, George R. Jackson, Randall S. Scheibel, Annette Walder, Ajithraj Sathiyaraj, Elisabeth A. Wilde, Shalini Mukhi, Brian A. Taylor, Harvey S. Levin
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- Journal of the International Neuropsychological Society / Volume 22 / Issue 7 / August 2016
- Published online by Cambridge University Press:
- 26 July 2016, pp. 790-792
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Chronic Effects of Blast-Related TBI on Subcortical Functional Connectivity in Veterans
- Mary R. Newsome, Andrew R. Mayer, Xiaodi Lin, Maya Troyanskaya, George R. Jackson, Randall S. Scheibel, Annette Walder, Ajithraj Sathiyaraj, Elisabeth A. Wilde, Shalini Mukhi, Brian A. Taylor, Harvey S. Levin
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- Journal of the International Neuropsychological Society / Volume 22 / Issue 6 / July 2016
- Published online by Cambridge University Press:
- 06 June 2016, pp. 631-642
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Objectives: Blast explosions are the most frequent mechanism of traumatic brain injury (TBI) in recent wars, but little is known about their long-term effects. Methods: Functional connectivity (FC) was measured in 17 veterans an average of 5.46 years after their most serious blast related TBI, and in 15 demographically similar veterans without TBI or blast exposure. Subcortical FC was measured in bilateral caudate, putamen, and globus pallidus. The default mode and fronto-parietal networks were also investigated. Results: In subcortical regions, between-groups t tests revealed altered FC from the right putamen and right globus pallidus. However, following analysis of covariance (ANCOVA) with age, depression (Center for Epidemiologic Studies Depression Scale), and posttraumatic stress disorder symptom (PTSD Checklist – Civilian version) measures, significant findings remained only for the right globus pallidus with anticorrelation in bilateral temporal occipital fusiform cortex, occipital fusiform gyrus, lingual gyrus, and cerebellum, as well as the right occipital pole. No group differences were found for the default mode network. Although reduced FC was found in the fronto-parietal network in the TBI group, between-group differences were nonsignificant after the ANCOVA. Conclusions: FC of the globus pallidus is altered years after exposure to blast related TBI. Future studies are necessary to explore the trajectory of changes in FC in subcortical regions after blast TBI, the effects of isolated versus repetitive blast-related TBI, and the relation to long-term outcomes in veterans. (JINS, 2016, 22, 631–642)
How Functional Connectivity between Emotion Regulation Structures Can Be Disrupted: Preliminary Evidence from Adolescents with Moderate to Severe Traumatic Brain Injury
- Mary R. Newsome, Randall S. Scheibel, Andrew R. Mayer, Zili D. Chu, Elisabeth A. Wilde, Gerri Hanten, Joel L. Steinberg, Xiaodi Lin, Xiaoqi Li, Tricia L. Merkley, Jill V. Hunter, Ana C. Vasquez, Lori Cook, Hanzhang Lu, Kami Vinton, Harvey S. Levin
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- Journal:
- Journal of the International Neuropsychological Society / Volume 19 / Issue 8 / September 2013
- Published online by Cambridge University Press:
- 28 August 2013, pp. 911-924
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Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD) control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent (BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development. (JINS, 2013, 19, 1–14)
Effects of Moderate to Severe Traumatic Brain Injury on Anticipating Consequences of Actions in Adolescents: A Preliminary Study
- Lori G. Cook, Gerri Hanten, Kimberley D. Orsten, Sandra B. Chapman, Xiaoqi Li, Elisabeth A. Wilde, Kathleen P. Schnelle, Harvey S. Levin
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- Journal of the International Neuropsychological Society / Volume 19 / Issue 5 / May 2013
- Published online by Cambridge University Press:
- 14 January 2013, pp. 508-517
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For this pilot study, we compared performance of 15 adolescents with moderate–severe traumatic brain injury (TBI) to that of 13 typically developing (TD) adolescents in predicting social actions and consequences for avatars in a virtual microworld environment faced with dilemmas involving legal or moral infractions. Performance was analyzed in relation to cortical thickness in brain regions implicated in social cognition. Groups did not differ in number of actions predicted nor in reasons cited for predictions when presented only the conflict situation. After viewing the entire scenario, including the choice made by the avatar, TD and TBI adolescents provided similar numbers of short-term consequences. However, TD adolescents provided significantly more long-term consequences (p = .010). Additionally, for the Overall qualitative score, TD adolescents’ responses were more likely to reflect the long-term impact of the decision made (p = .053). Groups differed in relation of the Overall measure to thickness of right medial prefrontal cortex/frontal pole and precuneus, with stronger relations for the TD group (p < .01). For long-term consequences, the relations to the posterior cingulate, superior medial frontal, and precentral regions, and to a lesser extent, the middle temporal region, were stronger for the TBI group (p < .01). (JINS, 2013, 19, 1–10.)
Clinical decision rules for the use of liquor diagnostics in hospitalized neurology patients reduced costs without affecting clinical outcomes
- Elisabeth Haschke-Becher, Uwe Totzke, Shahrzad Afazel, Tim Johansson, Markus Schwarz, Gunther Ladurner, Claudia Wild
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- Journal:
- International Journal of Technology Assessment in Health Care / Volume 25 / Issue 2 / April 2009
- Published online by Cambridge University Press:
- 31 March 2009, pp. 208-213
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Objectives: Excessive use of laboratory diagnostics has been common. This study aimed to evaluate whether clinical decision rules for the use of liquor diagnostics would enable cost containment without affecting medical care.
Methods: This was a single-center, retrospective, cost-minimization study based on the records of all 16,319 patients hospitalized and discharged at a Neurology Clinic in Austria between 2004 and 2006. Cost of liquor diagnostics, discharge diagnosis, duration of hospital stay, and mortality were compared along the line before, during, and after implementation of decision rules in mid-2005.
Results: There were no significant changes in patient characteristics over time, not in the diagnoses at discharge, nor in the percentage of patients undergoing liquor diagnostics. The average number of tests per patient significantly decreased. Standard tests largely replaced serological tests for infections, regardless of diagnosis. Annual costs for liquor diagnostics decreased by 32.9 percent. Overall, the duration of hospital stay and mortality significantly decreased as well; however, differences were not significant for any single diagnosis-related group.
Conclusions: Diagnostic algorithms may allow cost containment without affecting medical care.
WMS–III performance in patients with temporal lobe epilepsy: Group differences and individual classification
- NANCY WILDE, ESTHER STRAUSS, GORDON J. CHELUNE, DAVID W. LORING, ROY C. MARTIN, BRUCE P. HERMANN, ELISABETH M.S. SHERMAN, MICHAEL HUNTER
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- Journal:
- Journal of the International Neuropsychological Society / Volume 7 / Issue 7 / November 2001
- Published online by Cambridge University Press:
- 11 January 2002, pp. 881-891
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The utility of the WMS–III in detecting lateralized impairment was examined in a large sample of patients with temporal lobe epilepsy. Methods of analysis included evaluation of group means on the various indexes and subtest scores, the use of ROC curves, and an examination of Auditory–Visual Index discrepancy scores. In addition, performance on immediate and delayed indexes in the auditory and the visual modality was compared within each group. Of the WMS–III scores, the Auditory–Visual Delayed Index difference score appeared most sensitive to side of temporal dysfunction, although patient classification rates were not within an acceptable range to have clinical utility. The ability to predict laterality based on statistically significant index score differences was particularly weak for those with left temporal dysfunction. The use of unusually large discrepancies led to improved prediction, however, the rarity of such scores in this population limits their usefulness. Although the utility of the WMS–III in detecting laterality may be limited in preoperative cases, the WMS–III may still hold considerable promise as a measure of memory in documenting baseline performance and in detecting those that may be at risk following surgery. (JINS, 2001, 7, 881–891.)
New Chronological Frame for the Young Neolithic Baden Culture in Central Europe (4th Millennium BC)
- Eva Maria Wild, Peter Stadler, Mária Bondár, Susanne Draxler, Herwig Friesinger, Walter Kutschera, Alfred Priller, Werner Rom, Elisabeth Ruttkay, Peter Steier
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- Journal:
- Radiocarbon / Volume 43 / Issue 2B / 2001
- Published online by Cambridge University Press:
- 18 July 2016, pp. 1057-1064
- Print publication:
- 2001
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The Baden Culture is a widely spread culture of the Young Neolithics in east-central Europe. In southeast Europe, several parallel cultures are found at different places. The main innovations in east-central Europe associated with the Baden Culture were traditionally thought to originate in southeast Europe, Anatolia, and the Levant. However, in recent years, doubt about this theory has arisen among archaeologists.
Here, we try to contribute to this question by increasing the radiocarbon data set available for the Baden Culture. Thirty-two age determinations of samples from different sites assigned to the Baden Culture were performed by accelerator mass spectrometry (AMS) 14C dating. The new data were combined with previously published 14C dates. Data from the individual cultural phases of the entire Baden period and the parallel cultures in southeast Europe (Sitagroi, Cernavoda, and Ezero) were analyzed by sum calibration. Comparison of the results indicates that the southeastern cultures cannot be synchronized with the Boleráz period, the early phase of the Baden Culture. It seems that these cultures were parallel to the Baden Classical period. This finding, which has to be verified by more data from the southeastern cultures, contradicts the theory of the east-west spreading of these cultures.