Faculty Bibliography

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.

MOTIVATION:Boolean networks (BNs) are commonly used to model genetic regulatory networks (GRNs). Due to the sensibility of the dynamical behavior to changes in the updating scheme (order in which the nodes of a network update their state values), it is increasingly common to use different updating rules in the modeling of GRNs to better capture an observed biological phenomenon and thus to obtain more realistic models.In Aracena et al. equivalence classes of deterministic update schedules in BNs, that yield exactly the same dynamical behavior of the network, were defined according to a certain label function on the arcs of the interaction digraph defined for each scheme. Thus, the interaction digraph so labeled (update digraphs) encode the non-equivalent schemes. RESULTS:We address the problem of enumerating all non-equivalent deterministic update schedules of a given BN. First, we show that it is an intractable problem in general. To solve it, we first construct an algorithm that determines the set of update digraphs of a BN. For that, we use divide and conquer methodology based on the structural characteristics of the interaction digraph. Next, for each update digraph we determine a scheme associated. This algorithm also works in the case where there is a partial knowledge about the relative order of the updating of the states of the nodes. We exhibit some examples of how the algorithm works on some GRNs published in the literature. AVAILABILITY AND IMPLEMENTATION:An executable file of the UpdateLabel algorithm made in Java and the files with the outputs of the algorithms used with the GRNs are available at: www.inf.udec.cl/ ∼lilian/UDE/ CONTACT: lilisalinas@udec.cl SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

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.

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.

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.

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).

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access. Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.