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.

Supporting young people with pediatric multiple sclerosis can be challenging for families and health care providers. Adolescents may be more resilient than adults in reaction to the diagnosis but can have more difficulty planning for their futures. Appropriate, sensitive, and focused health provision should include consideration of the perspective of both the patient and parents. Multidisciplinary management strategies are often effective, as are referrals to programs that enhance individual and family coping and strengthen a sense of community.

In comparison with the large body of evidence on cognitive functioning in adults with multiple sclerosis (MS), there is limited information on cognition in pediatric-onset MS (POMS). Unique vulnerabilities in POMS can derive from having a disease that occurs during key periods of age-expected brain growth, active myelination in the CNS, and maturation of neural networks during the learning curve and key formative years in the academic career of the patient. Therefore, the consequences of MS on developing cognitive faculties can be assessed only in the pediatric population and cannot be simply extrapolated from studies carried on in the adult population. Until the last decade, research in the pediatric population was mainly represented by small clinical series, often limited by the narrow scope of neuropsychological assessment and lack of adequate control groups. Over the last decade, however, cognitive functioning and mood-related difficulties have become an increasing concern as awareness of this population has grown. A few specialized MS centers have begun performing more systematic research in the field in order to assess the prevalence of cognitive impairments and mood-related difficulties in patients with POMS, to better characterize the neuropsychological pattern and determine the functional consequences of these problems. This chapter summarizes our current understanding of cognitive and mood-related difficulties in POMS and highlights perceived gaps in knowledge and priorities for future research.

Depression, common in chronic medical conditions, and hepatic encephalopathy (HE), a reversible neuropsychiatric syndrome due to liver dysfunction, are associated with impaired health-related quality of life (HRQOL) in cirrhosis and hepatitis C (HCV). This study investigated the impact of depression and HE on HRQOL in cirrhotic patients with HCV. A convenience sample of 43 ambulatory patients, with varying degrees of cirrhosis secondary to HCV, was prospectively enrolled in this study. Participants were assessed for any current depressive, fatigue, and daytime sleepiness symptoms and underwent a psychometric evaluation to determine the presence of HE symptoms. Participants reported current HRQOL on general health and liver disease-specific questionnaires. Diagnosis and current health status were confirmed via medical records. The associations between disease severity, depressive symptoms, HE, fatigue, and daytime sleepiness were measured. Predictors of HRQOL in this sample were determined. Depressive symptoms (70 %) and HE (77 %) were highly prevalent in this sample, with 58 % actively experiencing both conditions at the time of study participation. A significant positive association was found between depressive symptoms and HE severity (P = .05). Depressive symptoms were significantly associated with fatigue (P < .001), daytime sleepiness (P < .001), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). HE was significantly associated with fatigue (P = .02), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). Depressive symptoms and HE were significant predictors of reduced HRQOL (P < .001), with depressive symptoms alone accounting for 58.8 % of the variance. Depressive symptoms and HE accounted for 68.0 % of the variance. Findings suggest a possible pathophysiological link between depression and HE in cirrhosis, and potentially a wider-reaching benefit of treating minimal and overt HE than previously appreciated.

This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (