Faculty Bibliography

Surface-based cortical thickness (CT) analyses are increasingly being used to investigate variations in brain morphology across the spectrum of brain health, from neurotypical to neuropathological. An outstanding question is whether individual differences in cortical morphology, such as regionally increased or decreased CT, are associated with domain-specific performance deficits in healthy adults. Since CT studies are correlational, they cannot establish causality between brain morphology and cognitive performance. A direct comparison with classic lesion methods is needed to determine whether the regional specificity of CT-cognition correlations is similar to that observed in patients with brain lesions. We address this question by comparing the neuroanatomical overlap of effects when 1) whole brain vertex-wise CT is tested as a correlate of performance variability on a commonly used neuropsychological test of executive function, Trailmaking Test Part B (TMT-B), in healthy adults and 2) voxel-based lesion-symptom mapping (VBLSM) is used to map lesion location to performance decrements on the same task in patients with frontal lobe lesions. We found that reduced performance on the TMT-B was associated with increased CT in bilateral prefrontal regions in healthy adults and that results spatially overlapped in the left dorsomedial prefrontal cortex with findings from the VBLSM analysis in patients with frontal brain lesions. Findings indicate that variations in the structural integrity of the left dorsomedial prefrontal lobe, ranging from individual CT differences in healthy adults to structural lesions in patients with neurological disorders, are associated with poor performance on the TMT-B. These converging results suggest that the left dorsomedial prefrontal region houses a critical region for the complex processing demands of TMT-B, which include visuomotor tracking, sequencing, and cognitive flexibility.

BACKGROUND: The Sport Concussion Assessment Tool-3 (SCAT3) facilitates sideline clinical assessments of concussed athletes. Yet, there is little published research on clinically relevant metrics for the SCAT3 as a whole. PURPOSE: We documented the psychometric properties of the major SCAT3 components (symptoms, cognition, balance) and derived clinical decision criteria (ie, reliable change score cutoffs and normative conversation tables) for clinicians to apply to cases with and without available preinjury baseline data. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: High school and collegiate athletes (N = 2018) completed preseason baseline evaluations including the SCAT3. Re-evaluations of 166 injured athletes and 164 noninjured controls were performed within 24 hours of injury and at 8, 15, and 45 days after injury. Analyses focused on predictors of baseline performance, test-retest reliability, and sensitivity and specificity of the SCAT3 using either single postinjury cutoffs or reliable change index (RCI) criteria derived from this sample. RESULTS: Athlete sex, level of competition, attention-deficit/hyperactivity disorder (ADHD), learning disability (LD), and estimated verbal intellectual ability (but not concussion history) were associated with baseline scores on >/=1 SCAT3 components (small to moderate effect sizes). Female sex, high school level of competition (vs college), and ADHD were associated with higher baseline symptom ratings (d = 0.25-0.32). Male sex, ADHD, and LD were associated with lower baseline Standardized Assessment of Concussion (SAC) scores (d = 0.28-0.68). Male sex, high school level of competition, ADHD, and LD were associated with poorer baseline Balance Error Scoring System (BESS) performance (d = 0.14-0.26). After injury, the symptom checklist manifested the largest effect size at the 24-hour assessment (d = 1.52), with group differences diminished but statistically significant at day 8 (d = 0.39) and nonsignificant at day 15. Effect sizes for the SAC and BESS were small to moderate at 24 hours (SAC: d = -0.36; modified BESS: d = 0.46; full BESS: d = 0.51) and became nonsignificant at day 8 (SAC) and day 15 (BESS). Receiver operating characteristic curve analyses demonstrated a stronger discrimination for symptoms (area under the curve [AUC] = 0.86) than cognitive and balance measures (AUCs = 0.58 and 0.62, respectively), with comparable discrimination of each SCAT3 component using postinjury scores alone versus baseline-adjusted scores (P = .71-.90). Normative conversion tables and RCI criteria were created to facilitate the use of the SCAT3 both with and without baseline test results. CONCLUSION: Individual predictors should be taken into account when interpreting the SCAT3. The normative conversion tables and RCIs presented can be used to help interpret concussed athletes' performance both with and without baseline data, given the comparability of the 2 interpretative approaches.

OBJECTIVE: To determine the degree to which preinjury and acute postinjury psychosocial and injury-related variables predict symptom duration following sport-related concussion. METHODS: A total of 2,055 high school and collegiate athletes completed preseason evaluations. Concussed athletes (n = 127) repeated assessments serially (<24 hours and days 8, 15, and 45) postinjury. Cox proportional hazard modeling was used to predict concussive symptom duration (in days). Predictors considered included demographic and history variables; baseline psychological, neurocognitive, and balance functioning; acute injury characteristics; and postinjury clinical measures. RESULTS: Preinjury somatic symptom score (Brief Symptom Inventory-18 somatization scale) was the strongest premorbid predictor of symptom duration. Acute (24-hour) postconcussive symptom burden (Sport Concussion Assessment Tool-3 symptom severity) was the best injury-related predictor of recovery. These 2 predictors were moderately correlated (r = 0.51). Path analyses indicated that the relationship between preinjury somatization symptoms and symptom recovery was mediated by postinjury concussive symptoms. CONCLUSIONS: Preinjury somatization symptoms contribute to reported postconcussive symptom recovery via their influence on acute postconcussive symptoms. The findings highlight the relevance of premorbid psychological factors in postconcussive recovery, even in a healthy athlete sample relatively free of psychopathology or medical comorbidities. Future research should elucidate the neurobiopsychosocial mechanisms that explain the role of this individual difference variable in outcome following concussive injury.

As a 10-year follow up to our original study (Rabin, Barr, & Burton, 2005), we surveyed the test usage patterns of clinical neuropsychologists in the U.S and Canada. We expanded the original questionnaire to include additional cognitive and functional domains and to address current practice-related issues. Participants were randomly selected from the combined membership lists of the National Academy of Neuropsychology and the International Neuropsychological Society. Respondents were 512 doctorate-level members (25% usable response rate; 54% women) who had been practicing neuropsychology for 15 years on average. The Wechsler Adult Intelligence Scales, followed by the Wechsler Memory Scales, Trail Making Test, California Verbal Learning Test, and Wechsler Intelligence Scale for Children, were the most commonly used tests. These top five responses were identical and in the same order as those from 10 years ago. Participants respectively identified a lack of ecological validity and difficulty comparing the meaning of standardized scores across tests as the greatest challenges associated with the selection of neuropsychological instruments and interpretation of test data. Overall, we found great consistency in assessment practices over the 10-year period. We compare results to those of previous studies and discuss challenges and implications for neuropsychology.

OBJECTIVE: We evaluated how attention deficit-hyperactivity disorder (ADHD) and learning disability (LD) are associated with concussion history and performance on standard concussion assessment measures. Based on previous reports that developmental disorders are associated with increased injury proneness and poorer cognitive performance, we anticipated that ADHD and LD would be associated with increased history of concussion and poorer baseline performance on assessment measures. DESIGN: Cross-sectional study. SETTING: Clinical research center. PARTICIPANTS: The study sample aggregated data from two separate projects: the National Collegiate Athletic Association Concussion Study and Project Sideline. INTERVENTIONS: We analyzed preseason baseline data from 8056 high school and collegiate athletes (predominantly male football players) enrolled in prior studies of sport-related concussion. MAIN OUTCOME MEASURES: Measures included demographic/health history, symptoms, and cognitive performance. RESULTS: Attention deficit-hyperactivity disorder and LD were associated with 2.93 and 2.08 times the prevalence, respectively, of 3+ historical concussions (for comorbid ADHD/LD the prevalence ratio was 3.38). In players without histories of concussion, individuals with ADHD reported more baseline symptoms, and ADHD and LD were associated with poorer performance on baseline cognitive tests. Interactive effects were present between ADHD/LD status and concussion history for self-reported symptoms. CONCLUSIONS: Neurodevelopmental disorders and concussion history should be jointly considered in evaluating concussed players. CLINICAL RELEVANCE: Clinical judgments of self-reported symptoms and cognitive performance should be adjusted based on athletes' individual preinjury baselines or comparison with appropriate normative samples.

CONTEXT: Younger age has been hypothesized to be a risk factor for prolonged recovery after sport-related concussion, yet few studies have directly evaluated age differences in acute recovery. OBJECTIVE: To compare clinical recovery patterns for high school and collegiate athletes. DESIGN: Prospective cohort study. SETTING: Large, multicenter prospective sample collected from 1999-2003 in a sports medicine setting. SUBJECTS: Concussed athletes (n = 621; 545 males and 76 females) and uninjured controls (n = 150) participating in high school and collegiate contact and collision sports (79% in football, 15.7% in soccer, and the remainder in lacrosse or ice hockey). MAIN OUTCOME MEASURE(S): Participants underwent evaluation of symptoms (Graded Symptom Checklist), cognition (Standardized Assessment of Concussion, paper-and-pencil neuropsychological tests), and postural stability (Balance Error Scoring System). Athletes were evaluated preinjury and followed serially at several time points after concussive injury: immediately, 3 hours postinjury, and at days 1, 2, 3, 5, 7, and 45 or 90 (with neuropsychological measures administered at baseline and 3 postinjury time points). RESULTS: Comparisons of concussed high school and collegiate athletes with uninjured controls suggested that high school athletes took 1 to 2 days longer to recover on a cognitive (Standardized Assessment of Concussion) measure. Comparisons with the control group on other measures (symptoms, balance) as well as direct comparisons between concussed high school and collegiate samples revealed no differences in the recovery courses between the high school and collegiate groups on any measure. Group-level recovery occurred at or before 7 days postinjury on all assessment metrics. CONCLUSIONS: The findings suggest no clinically significant age differences exist in recovery after sport-related concussion, and therefore, separate injury-management protocols are not needed for high school and collegiate athletes.

INTRODUCTION: Depression and memory dysfunction significantly impact the quality of life of patients with epilepsy. Current therapies for these cognitive and psychiatric comorbidities are limited. We explored the efficacy and safety of transcranial direct current stimulation (TDCS) for treating depression and memory dysfunction in patients with temporal lobe epilepsy (TLE). METHODS: Thirty-seven (37) adults with well-controlled TLE were enrolled in a double-blinded, sham-controlled, randomized, parallel-group study of 5days of fixed-dose (2mA, 20min) TDCS. Subjects were randomized to receive either real or sham TDCS, both delivered over the left dorsolateral prefrontal cortex. Patients received neuropsychological testing and a 20-minute scalp EEG at baseline immediately after the TDCS course and at 2- and 4-week follow-up. RESULTS: There was improvement in depression scores immediately after real TDCS, but not sham TDCS, as measured by changes in the Beck Depression Inventory (BDI change: -1.68 vs. 1.27, p<0.05) and NDDI-E (-0.83 vs. 0.9091, p=0.05). There was no difference between the groups at the 2- or 4-week follow-up. There was no effect on delayed or working memory performance. Transcranial direct current stimulation was well-tolerated and did not increase seizure frequency or interictal discharge frequency. Transcranial direct current stimulation induced an increase in delta frequency band power over the frontal region and delta, alpha, and theta band power in the occipital region after real stimulation compared to sham stimulation, although the difference did not reach statistical significance. DISCUSSION: This study provides evidence for the use of TDCS as a safe and well-tolerated nonpharmacologic approach to improving depressive symptoms in patients with well-controlled TLE. However, there were no changes in memory function immediately following or persisting after a stimulation course. Further studies may determine optimal stimulation parameters for maximal mood benefit.

Limited data exist comparing the performance of computerized neurocognitive tests (CNTs) for assessing sport-related concussion. We evaluated the reliability and validity of three CNTs-ANAM, Axon Sports/Cogstate Sport, and ImPACT-in a common sample. High school and collegiate athletes completed two CNTs each at baseline. Concussed (n=165) and matched non-injured control (n=166) subjects repeated testing within 24 hr and at 8, 15, and 45 days post-injury. Roughly a quarter of each CNT's indices had stability coefficients (M=198 day interval) over .70. Group differences in performance were mostly moderate to large at 24 hr and small by day 8. The sensitivity of reliable change indices (RCIs) was best at 24 hr (67.8%, 60.3%, and 47.6% with one or more significant RCIs for ImPACT, Axon, and ANAM, respectively) but diminished to near the false positive rates thereafter. Across time, the CNTs' sensitivities were highest in those athletes who became asymptomatic within 1 day before neurocognitive testing but was similar to the tests' false positive rates when including athletes who became asymptomatic several days earlier. Test-retest reliability was similar among these three CNTs and below optimal standards for clinical use on many subtests. Analyses of group effect sizes, discrimination, and sensitivity and specificity suggested that the CNTs may add incrementally (beyond symptom scores) to the identification of clinical impairment within 24 hr of injury or within a short time period after symptom resolution but do not add significant value over symptom assessment later. The rapid clinical recovery course from concussion and modest stability probably jointly contribute to limited signal detection capabilities of neurocognitive tests outside a brief post-injury window. (JINS, 2016, 22, 24-37).

Focal cortical dysplasia (FCD) is a malformation of cortical development that is associated with high rates of cognitive morbidity. However, the degree to which specific irregularities of dysplastic tissue directly impact cognition remains unknown. This study investigates the relationship between blurring of the cortical gray and white matter boundary on magnetic resonance imaging (MRI) and global cognitive abilities in FCD. Gray-white blurring (GWB) is quantified by sampling the non-normalized T1 image intensity contrast above and below the gray and white matter interface along the cortical mantle. Spherical averaging is used to compare resulting GWB for patients with histopathologically verified FCD with matched controls. Whole-brain correlational analyses are used to investigate the relationship between blurring and general cognitive abilities, controlling for epilepsy duration. Results show that cognitive performance is reduced in patients with FCD relative to controls. Patients show increased GWB in bilateral temporal, parietal, and frontal regions. Furthermore, increased GWB in these regions is linearly related to decreased cognition and mediates group differences in cognitive performance. These findings demonstrate that GWB is a marker of reduced cognitive efficiency in FCD that can potentially be used to probe general and domain-specific cognitive functions in other neurological disorders.

The International League Against Epilepsy (ILAE) Diagnostic Methods Commission charged the Neuropsychology Task Force with the job of developing a set of recommendations to address the following questions: (1) What is the role of a neuropsychological assessment? (2) Who should do a neuropsychological assessment? (3) When should people with epilepsy be referred for a neuropsychological assessment? and (4) What should be expected from a neuropsychological assessment? The recommendations have been broadly written for health care clinicians in established epilepsy settings as well as those setting up new services. They are based on a detailed survey of neuropsychological assessment practices across international epilepsy centers, and formal ranking of specific recommendations for advancing clinical epilepsy care generated by specialist epilepsy neuropsychologists from around the world. They also incorporate the latest research findings to establish minimum standards for training and practice, reflecting the many roles of neuropsychological assessment in the routine care of children and adults with epilepsy. The recommendations endorse routine screening of cognition, mood, and behavior in new-onset epilepsy, and describe the range of situations when more detailed, formal neuropsychological assessment is indicated. They identify a core set of cognitive and psychological domains that should be assessed to provide an objective account of an individual's cognitive, emotional, and psychosocial functioning, including factors likely contributing to deficits identified on qualitative and quantitative examination. The recommendations also endorse routine provision of feedback to patients, families, and clinicians about the implications of the assessment results, including specific clinical recommendations of what can be done to improve a patient's cognitive or psychosocial functioning and alleviate the distress of any difficulties identified. By canvassing the breadth and depth of scope of neuropsychological assessment, this report demonstrates the pivotal role played by this noninvasive and minimally resource intensive investigation in the care of people with epilepsy.