Faculty Bibliography

Objective: To examine whether a history of childhood adversity (i.e. abuse, dysfunction) influence clinical features of multiple sclerosis (MS) in adult patients. maltreatment, and household Background: Multiple epidemiological studies have linked adverse childhood experiences to changes in brain structure and stress-responsive physiologic mechanisms. Such changes have been found to profoundly increase risk for chronic disease, poorer emotional and social functioning, and cognitive impairment in adulthood. However, the specific role of these experiences in MS remains unclear. Design/Methods: Participants with MS were recruited from a cohort that previously completed a larger cognitive remediation trial. Measures included the Adverse Childhood Experience (ACE) and Resilience Questionnaire (RQ) self-report inventories. ACE and RQ scores were compiled into a composite score to provide a more comprehensive measure of endured childhood adversity, and these measures were compared to individual disease features. Results: A total of 76 participants completed the study (mean age 49.8+/-12.5 and 80% female). ACE scores were significantly and inversely correlated with RQ scores (r = -0.46, p<0.001), suggesting that greater childhood adversity corresponds with poorer psychological resilience. ACE, but not RQ, significantly predicted age of onset (r= -0.31, p=0.03 and r= -1.91, p=0.18 respectively). Both ACE and RQ were linked to estimated premorbid cognitive functioning (r= -0.30, p=0.009 and r= -0.27, p=0.02). However, the composite score of both measures offered the strongest predictive value for the impact of childhood adversity on age of onset (r= -0.31, p=0.02) and premorbid cognitive functioning (r = -0.32, p=0.005). Neither ACE nor RQ were related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). Conclusions: Cumulative stress due to adverse childhood experiences and decreased psychological resilience may increase the likelihood of earlier MS onset and predict poorer premorbid cognitive functioning in adulthood

Objective: Speeded Saccadic Eye Movement Predicts Symbol Digit Modalities Test Performance in Multiple Sclerosis Background: Multiple sclerosis is an autoimmune demyelinating disease with estimates of cognitive impairment above 30% in pediatric and 50% in adult patients. The SDMT, a widely-used screening tool that measures speeded information processing, has been used to track cognitive decline in MS. The K-D test is a brief measure of saccadic eye movement speed using a timed number naming test, commonly used for the detection of mild traumatic brain injury. Here, we tested the sensitivity of the K-D test in MS and its association with performance on the SDMT. Design/Methods: Adult and pediatric patients with clinically-definite MS were consecutively recruited through the NYU Langone MS Comprehensive Care Center. All participants completed the SDMT and K-D at a single visit. Results: A total of 30 participants completed the assessments ranging in age from 13 to 72 years (mean 38 +/- 19 years), were 74% female, and with an EDSS range 0.0 to 6.5. Relative to age normative data, the K-D indicated greater impairment than the SDMT (74% vs. 48%, respectively). Controlling for age, both tests were significantly correlated (r=0.44, p =0.02), demonstrating a close contribution of oculomotor function to SDMT performance. Conclusions: The K-D test is sensitive to detecting impairment in MS across the lifespan. Performance on the SDMT is closely associated with oculomotor function in MS

Objective: To test whether home delivery of tDCS paired with cognitive training can improve cognitive outcomes in participants with multiple sclerosis (MS). Background: Cognitive impairment is a common debilitating MS symptom. Transcranial direct current stimulation (tDCS) paired with cognitive training presents itself as a possible option for those with cognitive impairment, but requires daily sessions, placing strain on patients. Here we explore the feasibility and efficacy of a remotely- supervised tDCS protocol (RS-tDCS) paired with cognitive training for patients with MS. Design/Methods: MS participants completed 10 sessions of tDCS paired with cognitive training (1.5 mA x 20 minutes, dorsolateral prefrontal cortex montage). RS-tDCS participants were compared to a control group of adults with MS who underwent ten 20-minute cognitive training sessions through the same remotely-supervised procedures. Cognitive outcomes were tested by composite scores measuring change in performance on standard measures (Brief International Cognitive Assessment in MS or BICAMS), basic attention (Attention Network Test-Interaction (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). Results: After ten sessions, the RS-tDCS group (n=25) compared to the control group (n=20) had significant improvements in complex attention (p = 0.01) and response variability (p = 0.01) composites. The groups did not differ in change of measures of basic attention (p = 0.95) or standard BICAMS cognitive measures (p = 0.99). Conclusions: RS-tDCS paired with cognitive training is effective for enhancing complex attention and reducing response variability. The benefit of telerehabilitation using RS-tDCS combined with cognitive training may be generalizable to other conditions

Objective: To evaluate whether tDCS improves fatigue in MS and the role of baseline affect in response, using a remotely-supervised telerehabilitation protocol. Background: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability through low amplitude currents. Previous work suggests tDCS as a method for symptomatic management in MS. However, these initial studies have been limited due to small sample sizes and few active treatment sessions. Design/Methods: Participants completed ten 20 minute sessions of tDCS (1.5 mA, dorsolateral prefrontal cortex, left anodal) paired with cognitive training. Sessions were completed from home using our RS-tDCS protocol. All participants completed baseline and follow-up mood and fatigue self-report measures including the Modified Fatigue Impact Scale (MFIS) and the Positive and Negative Affect Schedule (PANAS). Baseline positive affect (PA) and negative affect (NA) were z-transformed and averaged into a representative affect score. Results: Participants (n=25) aged 30 to 69 years with a range of impairment (Expanded Disability Status Scale (EDSS) scores of 1.0 to 8.0) and all subtypes were enrolled. RS-tDCS treatment led to clear improvements in both dimensions of affect (PA, Cohen's d = 0.32 and NA, d = -0.66) and fatigue (MFIS, d = -0.59). Participants' baseline affect score correlated with change in NA (r = 0.61, p < 0.01) and MFIS (r = 0.39, p = 0.06). Among participants who had a baseline affect z-score less than 0 (n=17) indicating affect disturbance, there was a greater magnitude of improvement and significant change from baseline (PA, d = 0.57, p=0.02; NA d = -1.07, p < 0.001; and MFIS d = -0.84, p<0.01). Conclusions: Telerehabilitation using RS-tDCS improves mood and fatigue in MS patients treated at home, with greater effects found in those with baseline features of mood or anxiety

Objective: To explore the feasibility and safety of remotely supervised transcranial direct current stimulation RS-tDCS) paired with computerized cognitive training exercises in participants with Parkinson's disease (PD). Background: tDCS is a recent therapeutic development with potential to ameliorate symptoms of PD including motor, sensory, mood, and cognition.. However, multiple treatment sessions are necessary for a cumulative benefit. The requirement to travel to the clinic for daily clinic treatment sessions has limited the design of clinical trials in PD to date. Here, we used a RS-tDCS protocol validated for use in patients with multiple sclerosis (MS), a condition that shares with PD significant impairment in mobility, cognition, and high prevalence of fatigue. Design/Methods: Each participant completed 10 tDCS sessions (20-minute each, 1.5-2.0-mA, dorsolateral prefrontal cortex montage) using the remotely-supervised protocol. Feasibility of the approach was assessed based on a series of checkpoints, addressing attendance and tolerability and safety of the 40 sessions paired with simultaneous CT. Results: A total of 40 sessions were completed with 100% compliance. All participants were able to quickly learn self-administration and the set up time decreased through the 10 sessions for those who struggled with set up in the beginning. No serious adverse events were reported. Most commonly reported side effects were skin tingling and burning sensation. The most intense side effect was burning sensation at intensity of 4, which qualifies as "mild" on scale from 1 [minimal] to 10 [severe]. Time that these side effects were noticed by participants throughout the duration of the study also tended to decrease. RS-tDCS range of 1.5-2.0mA was tolerable for all participants Conclusions: RS-tDCS was feasible and safe in PD participants and can be paired with tele-rehabilitation. This study encourages using this innovative protocol for larger studies and clinical trials in PD patients

OBJECTIVES: The aim of this study was to evaluate the reliability and validity of three computerized neurocognitive assessment tools (CNTs; i.e., ANAM, DANA, and ImPACT) for assessing mild traumatic brain injury (mTBI) in patients recruited through a level I trauma center emergency department (ED). METHODS: mTBI (n=94) and matched trauma control (n=80) subjects recruited from a level I trauma center emergency department completed symptom and neurocognitive assessments within 72 hr of injury and at 15 and 45 days post-injury. Concussion symptoms were also assessed via phone at 8 days post-injury. RESULTS: CNTs did not differentiate between groups at any time point (e.g., M 72-hr Cohen's d=-.16, .02, and .00 for ANAM, DANA, and ImPACT, respectively; negative values reflect greater impairment in the mTBI group). Roughly a quarter of stability coefficients were over .70 across measures and test-retest intervals in controls. In contrast, concussion symptom score differentiated mTBI vs. control groups acutely), with this effect size diminished over time (72-hr and day 8, 15, and 45 Cohen's d=-.78, -.60, -.49, and -.35, respectively). CONCLUSIONS: The CNTs evaluated, developed and widely used to assess sport-related concussion, did not yield significant differences between patients with mTBI versus other injuries. Symptom scores better differentiated groups than CNTs, with effect sizes weaker than those reported in sport-related concussion studies. Nonspecific injury factors, and other characteristics common in ED settings, likely affect CNT performance across trauma patients as a whole and thereby diminish the validity of CNTs for assessing mTBI in this patient population. (JINS, 2017, 23, 293-303).

Objective: To test whether the Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) predicts real-world functioning as measured by timed instrumental activities of daily living (ADLs). Background: The BICAMS is a cognitive screen that is widely-used in clinical practice and research to assess cognitive impairment in persons with multiple sclerosis (MS). It is important for cognitive measures to predict daily functioning. We compared performance on the BICAMS to a test consisting of ten timed instrumental activities of daily living, called the Test of Everyday Cognitive Ability or TECA. Design/Methods: All participants were administered the TECA along with three BICAMS measures: Symbol Digit Modalities Test (SDMT), the Brief Visuospatial Memory Test-Revised (BVMT-R), and either the Rey Auditory Verbal Learning Test (RAVLT) or substituted with the Selective Reminding Test (SRT). The TECA items were scored according to time and errors and averaged for one representative score, with higher scores indicating greater impairment. BICAMS measures were transformed to age-normative z scores for comparison, with scores of <-1.5 considered impaired, and one or more impaired scores indicating overall BICAMS impairment. Results: A total of n=177 MS patients (mean age 45+/- 14 years, 73% female) with a median EDSS=3.0 (range of 0.0 to 8.0) completed the study. Overall, 37% met BICAMS impairment criteria. Each of the individual BICAMS measures significantly predicted performance on the TECA: SDMT, r=-.53, p<.001, BVMT-R r= -0.32, p <0.001, and Verbal Learning r= -.34, p <0.001. Worse TECA scores were associated with poorer performance on the BICAMS. Conclusions: The TECA is a measure of timed instrumental activities of daily living that is valid for use in a diverse MS population. BICAMS significantly predicts performance on the TECA, indicating that it is a useful indicator of real-world functioning

BACKGROUND: Adverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood. OBJECTIVE: To investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS). METHODS: Sixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation. RESULTS: Adverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset (r = -0.30, p = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) (r = -0.25, p = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). CONCLUSION: Childhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS.