Faculty Bibliography
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483
Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop
BACKGROUND:Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities. OBJECTIVE:This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment. METHODS:The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs. RESULTS:Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them. CONCLUSIONS:These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders.
PMCID:5997279
PMID: 29398575
ISSN: 1876-4754
CID: 2947992
Acute Clinical Predictors of Symptom Recovery in Emergency Department Patients with Uncomplicated Mild Traumatic Brain Injury (mTBI) or Non-TBI Injuries
There is a subset of patients with mild traumatic brain injury (mTBI) that report persistent symptoms that impair their functioning and quality of life. Being able to predict which patients will experience prolonged symptom recovery would help clinicians target resources for clinical follow-up to those most in need and would facilitate research to develop precision medicine treatments for mTBI. The purpose of this study was to investigate the predictors of symptom recovery in a prospective sample of emergency department trauma patients with either mTBI or non-mTBI injuries. Subjects were examined at several time points from within 72 hours to 45 days post-injury. We quantified and compared the value of a variety of demographic, injury, and clinical assessment (symptom, neurocognitive) variables for predicting self-reported symptom duration in both mTBI (n = 89) and trauma control (n = 73) patients. Several injury-related and neuropsychological variables assessed acutely (< 72 hours) post-injury predicted symptom duration, particularly loss of consciousness (mTBI group), acute somatic symptom burden (both groups), and acute reaction time (both groups), with reasonably good model fit when including all of these variables (AUC = .76). Incorporating self-reported litigation involvement modestly increased prediction further (AUC = .80). The results highlight the multifactorial nature of mTBI recovery, and injury recovery more generally, and the need to incorporate a variety of variables to achieve adequate prediction. Further research to improve this model and validate it in new and more diverse trauma samples will be useful to build a neurobiopsychosocial model of recovery that informs treatment development.
PMCID:5784791
PMID: 29017409
ISSN: 1557-9042
CID: 2732252
Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: Results from a randomized, sham-controlled trial
BACKGROUND: Fatigue is a common and debilitating feature of multiple sclerosis (MS) that remains without reliably effective treatment. Transcranial direct current stimulation (tDCS) is a promising option for fatigue reduction. We developed a telerehabilitation protocol that delivers tDCS to participants at home using specially designed equipment and real-time supervision (remotely supervised transcranial direct current stimulation (RS-tDCS)). OBJECTIVE: To evaluate whether tDCS can reduce fatigue in individuals with MS. METHODS: Dorsolateral prefrontal cortex left anodal tDCS was administered using a RS-tDCS protocol, paired with 20 minutes of cognitive training. Here, two studies are considered. Study 1 delivered 10 open-label tDCS treatments (1.5 mA; n = 15) compared to a cognitive training only condition ( n = 20). Study 2 was a randomized trial of active (2.0 mA, n = 15) or sham ( n = 12) delivered for 20 sessions. Fatigue was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form. RESULTS AND CONCLUSION: In Study 1, there was modest fatigue reduction in the active group (-2.5 +/- 7.4 vs -0.2 +/- 5.3, p = 0.30, Cohen's d = -0.35). However, in Study 2 there was statistically significant reduction for the active group (-5.6 +/- 8.9 vs 0.9 +/- 1.9, p = 0.02, Cohen's d = -0.71). tDCS is a potential treatment for MS-related fatigue.
PMCID:5975187
PMID: 28937310
ISSN: 1477-0970
CID: 2708592
Toward generally accepted forensic assessment practices among clinical neuropsychologists: a survey of professional practice and common test use
OBJECTIVE: This study investigated professional practice and common test use among clinical neuropsychologists engaging in forensic assessment. METHOD: Doctorate-level psychologists active in the practice of neuropsychology and on the INS and NAN membership listings (n = 502) were surveyed about their demographics, professional practice, and common test use. Participants who reported engaging in forensic practice (n = 255) were further surveyed about their forensic practice. RESULTS: Forensic participants were more likely to be male and Caucasian, and reported higher ages, more years of professional experience, and a higher prevalence of board certification. While characteristics of their professional and forensic practice varied, forensic participants reported spending most of their professional time conducting neuropsychological assessments with adult clients in a private or group practice setting, focusing on civil referrals and civil legal questions involving older adult issues, developmental issues, head injury, and psychiatric issues. Common test use across neuropsychological assessment domains is presented for board-certified forensic participants (n = 77). An examination of these results reveals that the current pattern of test use is similar to the results of a more general survey of neuropsychological test use. CONCLUSIONS: The findings provide insight into the practice of forensic neuropsychological assessment, and further establish the admissibility of neuropsychological evidence in the United States legal system. Results will be useful for clinical neuropsychologists, field leaders, and legal professionals hoping to gain insight into the role of clinical neuropsychology in civil and criminal legal decision-making.
PMID: 28675974
ISSN: 1744-4144
CID: 2617272
The Use of an Electrophysiological Brain Function Index in the Evaluation of Concussed Athletes
OBJECTIVE: To evaluate the effectiveness of the electroencephalographic (EEG) Brain Function Index (BFI) for characterizing sports-related concussive injury and recovery. PARTICIPANTS: Three hundred fifty-four (354) male contact sport high school and college athletes were prospectively recruited from multiple locations over 6 academic years of play (244 control baseline athletes and 110 athletes with a concussion). METHODS: Using 5 to 10 minutes of eyes closed resting EEG collected from frontal and frontotemporal regions, a BFI was computed for all subjects and sessions. Group comparisons were performed to test for the significance of the difference in the BFI score between the controls at baseline and athletes with a concussion at several time points. RESULTS: There was no significant difference in BFI between athletes with a concussion at baseline (ie, prior to injury) and controls at baseline (P = .4634). Athletes with a concussion, tested within 72 hours of injury, exhibited significant differences in BFI compared with controls (P = .0036). The significant differences in BFI were no longer observed at 45 days following injury (P = .19). CONCLUSION: Controls and athletes with a concussion exhibited equivalent BFI scores at preseason baseline. The concussive injury (measured within 72 hours) significantly affected brain function reflected in the BFI in the athletes with a concussion. The BFI of the athletes with a concussion returned to levels seen in controls by day 45, suggesting recovery. The BFI may provide an important objective marker of concussive injury and recovery.
PMID: 28520677
ISSN: 1550-509x
CID: 2562952
Cognitive impairment in pediatric-onset multiple sclerosis is detected by the Brief International Cognitive Assessment for Multiple Sclerosis and computerized cognitive testing
BACKGROUND: Cognitive impairment is a common and troubling feature of pediatric-onset multiple sclerosis (POMS). Brief cognitive assessment in the outpatient setting can identify and longitudinally monitor cognitive involvement so that early intervention is possible. OBJECTIVES: The goal of this study was to measure the sensitivity of two cognitive assessment approaches that are brief, repeatable, and suitable for clinical practice and for multicenter investigation. METHODS: Participants with POMS ( n = 69) were consecutively evaluated as part of outpatient neurologic visits and compared to healthy control participants (HC, n = 66) using the Brief International Cognitive Assessment for MS (BICAMS) approach and timed information processing measures from Cogstate, a computer-based assessment. RESULTS: There was strong agreement in the detection rate of impairment between both assessments, with 26% for the BICAMS and 27% for Cogstate. Two of the Cogstate tasks were the most sensitive individual measures. CONCLUSION: Both the BICAMS and Cogstate timed processing measures offer practical, sensitive, and standardized approaches for cognitive screening assessment in POMS.
PMID: 28322606
ISSN: 1477-0970
CID: 2499402
Remotely Supervised Transcranial Direct Current Stimulation Increases the Benefit of At-Home Cognitive Training in Multiple Sclerosis
OBJECTIVE: To explore the efficacy of remotely-supervised transcranial direct current stimulation (RS-tDCS) paired with cognitive training (CT) exercise in participants with multiple sclerosis (MS). METHODS: In a feasibility study of RS-tDCS in MS, participants completed ten sessions of tDCS paired with CT (1.5 mA x 20 min, dorsolateral prefrontal cortex montage). RS-tDCS participants were compared to a control group of adults with MS who underwent ten 20-min CT sessions through the same remotely supervised procedures. Cognitive outcomes were tested by composite scores measuring change in performance on standard tests (Brief International Cognitive Assessment in MS or BICAMS), basic attention (ANT-I Orienting and Attention Networks, Cogstate Detection), complex attention (ANT-I Executive Network, Cogstate Identification and One-Back), and intra-individual response variability (ANT-I and Cogstate identification; sensitive markers of disease status). RESULTS: After ten sessions, the tDCS group (n = 25) compared to the CT only group (n = 20) had significantly greater improvement in complex attention (p = 0.01) and response variability (p = 0.01) composites. The groups did not differ in measures of basic attention (p = 0.95) or standard cognitive measures (p = 0.99). CONCLUSIONS: These initial findings indicate benefit for RS-tDCS paired with CT in MS. Exploratory analyses indicate that the earliest tDCS cognitive benefit is seen in complex attention and response variability. Telerehabilitation using RS-tDCS combined with CT may lead to improved outcomes in MS.
PMCID:5975186
PMID: 28225155
ISSN: 1525-1403
CID: 2460232
Assessment of acute head injury in an emergency department population using sport concussion assessment tool - 3rd edition
Sport Concussion Assessment Tool version 3 (SCAT-3) is one of the most widely researched concussion assessment tools in athletes. Here normative data for SCAT3 in nonathletes are presented. The SCAT3 was administered to 98 nonathlete healthy controls, as well as 118 participants with head-injury and 46 participants with other body trauma (OI) presenting to the ED. Reference values were derived and classifier functions were built to assess the accuracy of SCAT3. The control population had a mean of 2.30 (SD = 3.62) symptoms, 4.38 (SD = 8.73) symptom severity score (SSS), and 26.02 (SD = 2.52) standardized assessment of concussion score (SAC). Participants were more likely to be diagnosed with a concussion (from among healthy controls) if the SSS > 7; or SSS 7 and headache or pressure in head present, or SSS 7 and headache or pressure in head, or SSS
PMID: 27854143
ISSN: 2327-9109
CID: 2310982
Spectrum of CFTR gene mutations in Ecuadorian cystic fibrosis patients: the second report of the p.H609R mutation
BACKGROUND:High heterogeneity in the CFTR gene mutations disturbs the molecular diagnosis of cystic fibrosis (CF). In order to improve the diagnosis of CF in our country, the present study aims to define a panel of common CFTR gene mutations by sequencing 27 exons of the gene in Ecuadorian Cystic Fibrosis patients. METHODS:Forty-eight Ecuadorian individuals with suspected/confirmed CF diagnosis were included. Twenty-seven exons of CFTR gene were sequenced to find sequence variations. Prevalence of pathogenic variations were determined and compared with other countries' data. RESULTS:We found 70 sequence variations. Eight of these are CF-causing mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K. Also this study is the second report of p.H609R in Ecuadorian population. Mutation prevalence differences between Ecuadorian population and other Latin America countries were found. CONCLUSION:The panel of mutations suggested as an initial screening for the Ecuadorian population with cystic fibrosis should contain the mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K.
PMID: 29178639
ISSN: 2324-9269
CID: 3317412
Remotely supervised transcranial direct current stimulation (RS-tDCS) improves fatigue in multiple sclerosis [Meeting Abstract]
Background: Fatigue is known for being one of the most debilitating and common symptoms of multiple sclerosis (MS). Despite its prevalence, though, reliable treatment options are lacking. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation treatment that uses low amperage (2.0 mA) electric current to stimulate cortical regions. tDCS has been shown to improve fatigue in MS following consecutive daily treatment sessions. We have recently developed and shown the feasibility of a remotely supervised tDCS (RS-tDCS) protocol to ease the burden of daily sessions and allow patients to complete the treatment at home. We aim to evaluate the efficacy of RS-tDCS in fatigue management for patients with MS. Methods: We enrolled n = 31 patients with MS (all subtypes) into a randomly controlled, double-blind trial; n = 27 patients provided data for analysis with n = 15 randomized to the active group and n = 12 in the placebo or "sham" group. Participants came to the clinic for baseline and follow-up measures including self-report forms on fatigue. At baseline they were also trained in operating the tDCS headset. Participants then took the device home where they complete 20 sessions of tDCS (20 minutes, 2.0 mA, dorsolateral prefrontal cortex montage, left anodal) paired with cognitive training. Results: Our primary outcome measure was the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue scale. When comparing change in PROMIS Fatigue between the active and sham tDCS groups we found that active tDCS participants had significantly greater reductions in fatigue (mean change in Active =-5.6 +/- 8.9 vs. Sham = 0.9 +/- 1.9, p = 0.02 conditions). We analyzed the within-subject effect tDCS had and found a significant, beneficial effect in the active group (pre-treatment mean = 26.6 +/- 9.2, post-treatment mean = 21.0 +/- 6.4, p = 0.04) and no such effect in the sham group (pre-treatment mean = 22.9 +/- 7.9, post-treatment mean = 23.8 +/- 8.4, p = 0.15). Finally, we calculated Cohen's d effect size (Active d =-0.71, Sham d = 0.11). Conclusions: These data suggest that RS-tDCS provides significant reduction in MS-related fatigue
EMBASE:619358784
ISSN: 1477-0970
CID: 2871622
