Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial.

BACKGROUND: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings. METHODS: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task). RESULTS: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula. CONCLUSIONS: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements. TRIAL REGISTRATION NUMBER: NCT03679468.

Bypassing Striatal Learning Mechanisms Using Delayed Feedback to Circumvent Learning Deficits in Traumatic Brain Injury.

OBJECTIVE: Feedback facilitates learning by guiding and modifying behaviors through an action-outcome contingency. As the majority of existing studies have focused on the immediate presentation of feedback, the impact of delayed feedback on learning is understudied. Prior work demonstrated that learning from immediate and delayed feedback employed distinct brain regions in healthy individuals, and compared to healthy individuals, individuals with traumatic brain injury (TBI) are impaired in learning from immediate feedback. The goal of the current investigation was to assess the effects of delayed vs immediate feedback on learning in individuals with TBI and examine brain networks associated with delayed and immediate feedback processing. SETTING: Nonprofit research organization. PARTICIPANTS: Twenty-eight individuals with moderate-to-severe TBI. DESIGN: Participants completed a paired-associate word learning task while undergoing magnetic resonance imaging. During the task, feedback was presented either immediately, after a delay, or not at all (control condition). MAIN MEASURES: Learning performance accuracy, confidence ratings, post-task questionnaire, and blood oxygen level-dependent signal. RESULTS: Behavioral data showed that delayed feedback resulted in better learning performance than immediate feedback and no feedback. In addition, participants reported higher confidence in their performance during delayed feedback trials. During delayed vs immediate feedback processing, greater activation was observed in the superior parietal and angular gyrus. Activation in these areas has been previously associated with successful retrieval and greater memory confidence. CONCLUSION: The observed results might be explained by delayed feedback processing circumventing the striatal dopaminergic regions responsible for learning from immediate feedback that are impaired in TBI. In addition, delayed feedback evokes less of an affective reaction than immediate feedback, which likely benefited memory performance. Indeed, compared to delayed feedback, positive or negative immediate feedback was more likely to be rated as rewarding or punishing, respectively. The findings have significant implications for TBI rehabilitation and suggest that delaying feedback during rehabilitation might recruit brain regions that lead to better functional outcomes.

An Umbrella Review of Self-Management Interventions for Health Conditions With Symptom Overlap With Traumatic Brain Injury.

OBJECTIVE: To synthesize evidence for the effectiveness of self-management interventions for chronic health conditions that have symptom overlap with traumatic brain injury (TBI) in order to extract recommendations for self-management intervention in persons with TBI. DESIGN: An umbrella review of existing systematic reviews and/or meta-analyses of randomized controlled trials or nonrandomized studies targeting self-management of chronic conditions and specific outcomes relevant to persons with TBI. METHOD: A comprehensive literature search of 5 databases was conducted using PRISMA guidelines. Two independent reviewers conducted screening and data extraction using the Covidence web-based review platform. Quality assessment was conducted using criteria adapted from the Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2). RESULTS: A total of 26 reviews met the inclusion criteria, covering a range of chronic conditions and a range of outcomes. Seven reviews were of moderate or high quality and focused on self-management in persons with stroke, chronic pain, and psychiatric disorders with psychotic features. Self-management interventions were found to have positive effects on quality of life, self-efficacy, hope, reduction of disability, pain, relapse and rehospitalization rates, psychiatric symptoms, and occupational and social functioning. CONCLUSIONS: Findings are encouraging with regard to the effectiveness of self-management interventions in patients with symptoms similar to those of TBI. However, reviews did not address adaptation of self-management interventions for those with cognitive deficits or for populations with greater vulnerabilities, such as low education and older adults. Adaptations for TBI and its intersection with these special groups may be needed.

Slowing processing speed is associated with cognitive fatigue in newly diagnosed multiple sclerosis patients.

OBJECTIVE: To further investigate objective measures of cognitive fatigue (CF), defined as the inability to sustain performance over time, in newly diagnosed multiple sclerosis (MS) patients, by conducting a performance analysis on the Paced Auditory Serial Addition Test (PASAT) based on the type of errors (omissions vs. incorrect responses) committed. METHOD: Sixty-two newly diagnosed patients with MS (pwMS) and 41 healthy controls (HC) completed the PASAT. Analysis of the change in performance during the test was performed by comparing the number of correct responses, incorrect responses, and omissions in the 1st versus the 3rd tertile of the PASAT. RESULTS: A significant decline in accuracy over time was observed to be related to an increment in the number of omissions, significantly more pronounced in pwMS than in HC. No change in the number of incorrect responses throughout the PASAT was observed for either group. CONCLUSIONS: CF can be detected even in newly diagnosed pwMS and might objectively manifest as a progressive increase in omissions during a sustained highly demanding task (i.e., PASAT). This pattern may reflect slowed processing speed and increased fatigue in pwMS. Focusing on omissions on the PASAT instead of correct responses only may improve its specificity as an objective measure of CF.

The Efficacy of the Speed of Processing Training Program in Improving Functional Outcome: From Restoration to Generalization.

OBJECTIVE: To examine the efficacy of Speed of Processing Training (SOPT) in improving everyday functional outcomes in persons with multiple sclerosis (MS). DESIGN: Randomized controlled trial. SETTING: A nonprofit rehabilitation research institution and the community. PARTICIPANTS: In total, 60 participants with MS with impaired processing speed were randomly assigned to SOPT (n=33) or an active control group (n=27). INTERVENTION: SOPT, a restorative computerized cognitive intervention involving 10 treatment sessions consisting of visual tasks designed to improve speed and accuracy of information processing MAIN OUTCOME MEASURES: Outcomes included performance on the Timed Instrumental Activities of Daily Living (TIADL) and self-report of functional behavior, quality of life, and affect. RESULTS: The treatment group showed improvement in the total TIADL score and 2 subtests compared with the active control group. Participants in the treatment group who demonstrated improved cognitive performance after the intervention also showed improved performance on one TIADL subtest. Quality of life, affective symptomatology, and self-reported functional status were not changed after the intervention. CONCLUSIONS: Improvement in underlying cognitive or perceptual deficits is thought to promote recovery and everyday performance as per the restorative approach to cognitive rehabilitation. However, this study showed only selected improvements in everyday functional outcomes for persons with MS.

Depression, Anxiety, and Suicidality in Individuals With Chronic Traumatic Brain Injury Before and During the COVID-19 Pandemic: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To examine the prevalence, severity, and correlates of depression, anxiety, and suicidal ideation in people with traumatic brain injury (TBI) assessed before and during the COVID-19 pandemic. DESIGN: Retrospective cohort study using data collected through the Traumatic Brain Injury Model Systems (TBIMS) network at 1, 2, 5, 10, 15, 20, 25, or 30 years post TBI. SETTING: United States-based TBIMS rehabilitation centers with telephone assessment of community residing participants. PARTICIPANTS: Adults (72.4% male; mean age, 47.2 years) who enrolled in the TBIMS National Database and completed mental health questionnaires prepandemic (January 1, 2017 to February 29, 2020; n=5000) or during pandemic (April 1, 2022 to June 30, 2021; n=2009) (N=7009). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 questionnaire. RESULTS: Separate linear and logistic regressions were constructed with demographic, psychosocial, injury-related, and functional characteristics, along with a binary indicator of COVID-19 pandemic period (prepandemic vs during pandemic), as predictors of mental health outcomes. No meaningful differences in depression, anxiety, or suicidal ideation were observed before vs during the COVID-19 pandemic. Correlations between predictors and mental health outcomes were similar before and during the pandemic. CONCLUSIONS: Contrary to our predictions, the prevalence, severity, and correlates of mental health conditions were similar before and during the COVID-19 pandemic. Results may reflect generalized resilience and are consistent with the most recent findings from the general population that indicate only small, transient increases in psychological distress associated with the pandemic. While unworsened, depression, anxiety, and suicidal ideation remain prevalent and merit focused treatment and research efforts.

Societal Participation of People With Traumatic Brain Injury Before and During the COVID-19 Pandemic: A NIDILRR Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To examine the effect of the COVID-19 pandemic on societal participation in people with moderate-to-severe traumatic brain injury (TBI). DESIGN: Cross-sectional retrospective cohort. SETTING: National TBI Model Systems centers, United States. PARTICIPANTS: TBI Model Systems enrollees (N=7003), ages 16 and older and 1-30 years postinjury, interviewed either prepandemic (PP) or during the pandemic (DP). The sample was primarily male (72.4%) and White (69.5%), with motor vehicle collisions as the most common cause of injury (55.1%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The 3 subscales of the Participation Assessment with Recombined Tools-Objective: Out and About (community involvement), Productivity, and Social Relations. RESULTS: Out and About, but not Productivity or Social Relations, scores were appreciably lower among DP participants compared to PP participants (medium effect). Demographic and clinical characteristics showed similar patterns of association with participation domains across PP and DP. When their unique contributions were examined in regression models, age, self-identified race, education level, employment status, marital status, income level, disability severity, and life satisfaction were variably predictive of participation domains, though most effects were small or medium in size. Depression and anxiety symptom severities each showed small zero-order correlations with participation domains across PP and DP but had negligible effects in regression analyses. CONCLUSIONS: Consistent with the effect of COVID-19 on participation levels in the general population, people with TBI reported less community involvement during the pandemic, potentially compounding existing postinjury challenges to societal integration. The pandemic does not appear to have altered patterns of association between demographic/clinical characteristics and participation. Assessing and addressing barriers to community involvement should be a priority for TBI treatment providers. Longitudinal studies of TBI that consider pandemic-related effects on participation and other societally linked outcomes will help to elucidate the potential longer-term effect the pandemic has on behavioral health in this population.

The impact of personal protective factors on quality of life after traumatic brain injury.

PRIMARY OBJECTIVE: Examine the impact of four personal protective factors (self-awareness (SA), self-efficacy (SE), cognitive and emotional factors) on positive adaptation, or resiliency, in persons with traumatic brain injury (TBI). We hypothesized that people with better SA and cognitive skills, less depression and positive SE will report better quality of life (QOL). RESEARCH DESIGN: Correlational longitudinal design was used to explore relationships between outcome variables at initial evaluation and 6-months following initial evaluation. METHODS AND PROCEDURES: 38 community-dwelling adults at least 1 year after sustaining a moderate-to-severe TBI were administered the Self-Efficacy Scale, Awareness Questionnaire, Chicago Multiscale Depression Inventory, Symbol Digit Modalities Test, and SF-12. MAIN OUTCOME AND RESULTS: Higher rated SE and emotional functioning correlated with better QOL indicating SE and emotional functioning may be personal factors facilitating positive adaptation in persons with TBI. Interestingly, poorer cognitive functioning (i.e. processing speed) and lower SA correlated with better QOL. Additionally, cognitive and emotional functioning were significant predictors of QOL. CONCLUSION: Strengthening emotional functioning and SE may improve outcomes after TBI. However, it may be that self-reported QoL is a poor outcome for people with TBI and measurement in future studies and practice should focus on actual engagement of activities.

The influence of information processing speed on benefit from learning and memory rehabilitation in TBI: a sub-analysis of the TBI-MEM trial.

OBJECTIVE: This study examined the influence of processing speed (PS) on benefit from treatment with the Kessler Foundation modified Story Memory Technique® (KF-mSMT®), a cognitive rehabilitation intervention shown to improve new learning and memory in traumatic brain injury (TBI). SETTING: Non-profit research center. PARTICIPANTS: 62 participants with moderate-to-severe TBI were included, 31 assigned to the treatment group and 31 to the placebo-control group. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. The present study represents a post-hoc analysis to examine the role of PS on treatment efficacy. MAIN MEASURES: Baseline and follow-up neuropsychological assessment including the California Verbal Learning Test, Second Edition (CVLT-II), Memory Assessment Scales - Prose Memory (MAS-PM) and the Symbol Digit Modalities Test (SDMT). RESULTS: A treatment effect was not observed on the CVLT-II learning slope in the treatment group relative to the placebo group post-treatment, after co-varying for education, baseline CVLT slope and PS performance. However, performance on a measure of PS, the SDMT, was a significant predictor of post-treatment change following KF-mSMT® treatment. PS was not a significant predictor of benefit from treatment as documented by the MAS-PM immediate or delayed recall score, both of which showed a significant treatment effect. CONCLUSION: Performance on measures of cognitive dysfunction aside from learning and memory impact the benefit from KF-mSMT® treatment. Implications for cognitive rehabilitation for individuals with TBI are discussed.

The relationship between processing speed and verbal and non-verbal new learning and memory in progressive multiple sclerosis.

OBJECTIVE: Processing speed (PS) deficits are the most common cognitive deficits in multiple sclerosis (MS), followed by learning and memory deficits, and are often an early cognitive problem. It has been argued that impaired PS is a primary consequence of MS, which in turn decreases learning. The current analysis examined the association between PS and learning in a large cohort of individuals with progressive MS. METHODS: Baseline data from a randomized clinical trial on rehabilitation taking place at 11 centers across North America and Europe were analyzed. Participants included 275 individuals with clinically definite progressive MS (primary, secondary) consented into the trial. RESULTS: Symbol Digit Modalities Test (SDMT) significantly correlated with California Verbal Learning Test-II (CVLT-II) (r = 0.21, p = 0.0003) and Brief Visuospatial Memory Test-Revised (BVMT-R) (r = 0.516, p < 0.0001). Receiver operating characteristic (ROC) analysis of the SDMT z score to distinguish between impaired and non-impaired CVLT-II performance demonstrated an area under the curve (AUC) of 0.61 (95% confidence interval (CI): 0.55-0.68) and a threshold of -1.62. ROC analysis between SDMT and BVMT-R resulted in an AUC of 0.77 (95% CI: 0.71-0.83) and threshold of -1.75 for the SDMT z score to predict impaired BVMT-R. CONCLUSION: Results indicate little ability beyond chance to predict CVLT-II from SDMT (61%), albeit statistically significant. In contrast, there was a 77% chance that the model could distinguish between impaired and non-impaired BVMT-R. Several potential explanations are discussed.

Cardiorespiratory fitness and free-living physical activity are not associated with cognition in persons with progressive multiple sclerosis: Baseline analyses from the CogEx study.

BACKGROUND: Aerobic exercise training (physical activity for improving cardiorespiratory fitness) represents a promising approach for managing cognitive impairment in multiple sclerosis (MS). However, there is limited evidence that levels of physical activity and fitness are associated with cognition in progressive MS. OBJECTIVE: We examined associations among cardiorespiratory fitness, moderate-to-vigorous physical activity (MVPA), and cognitive performance in a large, international progressive MS sample. METHODS: Two hundred forty European and North American persons with progressive MS underwent cardiorespiratory fitness measurement on a recumbent stepper, wore an ActiGraph GT3X + accelerometer for 7 days for measuring MVPA, and underwent the Brief International Cognitive Assessment in MS. RESULTS: Cardiorespiratory fitness was not significantly correlated with Symbol Digit Modalities Test (SDMT; r = -0.01; r = -0.04), California Verbal Learning Test-II (CVLT-II; r = 0.05; r = 0.05), or Brief Visuospatial Memory Test-Revised (BVMT-R; r = -0.14; r = -0.14) z-scores controlling for age, sex, and education. MVPA and SDMT (r = 0.05), CVLT-II (r = -0.07), and BVMT-R (r = 0.01) z-scores were not significantly correlated. CONCLUSION: Cardiorespiratory fitness and MVPA were not associated with cognition in this large progressive MS sample, yet these outcomes represent critical manipulation checks for documenting the success of the CogEx trial. This highlights the importance of examining other exercise-related mechanisms-of-action for improving cognition in progressive MS.

The Utility of the Patient Health Questionnaire (PHQ-9) Sleep Disturbance Item as a Screener for Insomnia in Individuals With Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: To examine the utility of the sleep disturbance item of the Patient Health Questionnaire-9 (PHQ-9) as a screening tool for insomnia among individuals with moderate to severe traumatic brain injury (TBI). SETTING: Telephone interview. PARTICIPANTS: A sample of 248 individuals with a history of moderate to severe TBI participated in an interview within 2 years of their injury. DESIGN: Observational, cross-sectional analysis. MAIN MEASURES: The PHQ-9 was administered along with the Insomnia Severity Index, Pittsburgh Sleep Quality Index, Sleep Hygiene Index, Epworth Sleepiness Scale, and the Insomnia Interview Schedule. RESULTS: Receiver operating characteristic curve analysis was conducted for the PHQ-9 sleep item rating against a set of insomnia criteria to determine an optimal cutoff score. A cutoff of 2 on the PHQ-9 sleep item maximized sensitivity (76%) and specificity (79%), with an area under the curve of 0.79 (95% CI, 0.70-0.88). The 2 groups formed using this cutoff differed significantly on all sleep measures except the Epworth Sleepiness Scale. CONCLUSIONS: The PHQ-9 sleep item may serve as a useful screener to allow for detection of potential sleep disturbance among individuals with moderate to severe TBI. Those who screen positive using this item included in a commonly used measure of depression can be prioritized for further and more comprehensive assessment of sleep disorders.

The preliminary effects of moderate aerobic training on cognitive function in people with TBI and significant memory impairment: a proof-of-concept randomized controlled trial.

This single-blinded RCT investigated cognitive effects of aerobic exercise in persons with TBI-related memory impairment. Five participants . were randomly assigned to 12-weeks of either supervised moderate intensity aerobic cycling or an active control. Outcome measures included neuropsychological assessments and structural neuroimaging (MRI,). The exercise group demonstrated greater improvements on auditory verbal learning (RAVLT; d=1.54) and processing speed (SDMT; d=1.58). The exercise group showed larger increases in volume of the left hippocampus (d=1.49) and right thalamus (d=1.44). These pilot data suggest that 12-weeks of moderate intensity aerobic cycling may improve memory and processing speed in those with TBI-related memory impairments.

Relationship Between Age and Cerebral Hemodynamic Response to Breath Holding: A Functional Near-Infrared Spectroscopy Study.

Cerebrovascular reactivity (CVR) is routinely measured as a predictor of stroke in people with a high risk of ischemic attack. Neuroimaging techniques such as emission tomography, magnetic resonance imaging, and transcranial doppler are frequently used to measure CVR even though each technique has its limitations. Functional near-infrared spectroscopy (fNIRS), also based on the principle of neurovascular coupling, is relatively inexpensive, portable, and allows for the quantification of oxy- and deoxy-hemoglobin concentration changes at a high temporal resolution. This study examines the relationship between age and CVR using fNIRS in 45 young healthy adult participants aged 18-41 years (6 females, 26.64 ± 5.49 years) performing a simple breath holding task. Eighteen of the 45 participants were scanned again after a week to evaluate the feasibility of fNIRS in reliably measuring CVR. Results indicate (a) a negative relationship between age and hemodynamic measures of breath holding task in the sensorimotor cortex of 45 individuals and (b) widespread positive coactivation within medial sensorimotor regions and between medial sensorimotor regions with supplementary motor area and prefrontal cortex during breath holding with increasing age. The intraclass correlation coefficient (ICC) indicated only a low to fair/good reliability of the breath hold hemodynamic measures from sensorimotor and prefrontal cortices. However, the average hemodynamic response to breath holding from the two sessions were found to be temporally and spatially in correspondence. Future improvements in the sensitivity and reliability of fNIRS metrics could facilitate fNIRS-based assessment of cerebrovascular function as a potential clinical tool.

Cognitive-Communication Predictors of Employment Outcomes 1 and 5 Years Posttraumatic Brain Injury.

OBJECTIVE: To examine changes in functional memory, problem solving, comprehension, expression, and social communication over the first 2 years posttraumatic brain injury (TBI) and the ability of each to predict return to work (RTW) outcomes at 1 year and 5 years postinjury. DESIGN: Secondary analysis of data from a multicenter longitudinal cohort study. SETTING: Acute inpatient rehabilitation facilities and community follow-up. PARTICIPANTS: A total of 3543 individuals between 16 and 60 years of age who were competitively employed at the time of TBI and had completed year 1, year 2, and year 5 postinjury follow-ups. MAIN OUTCOME MEASURES: Year 1 and year 5 RTW status (± competitively employed) at the time of study completion. RESULTS: Greater function across each of the 5 cognitive-communication abilities was associated with RTW success at 1 year and 5 years post-TBI. At discharge, these 5 abilities showed comparable odds of predicting later employment. At year 1 and year 2 follow-ups, independence with problem solving was the most predictive of employment 5 years post-TBI, followed by social interaction, memory, expression, and comprehension. CONCLUSIONS: An increased rehabilitation focus on functional memory, problem solving, comprehension, expression, and social interaction post-TBI has the potential to improve RTW outcomes.

The application of Strategy-based Training to Enhance Memory (STEM) in multiple sclerosis: A pilot RCT.

New learning and memory (NLM) impairments are common in multiple sclerosis (MS), negatively impacting daily life. Few studies seek to remediate these deficits to improve everyday functioning. Self-generation, spaced learning and retrieval practice have been shown to improve NLM in healthy persons and have been incorporated into an 8-session treatment protocol, Strategy-based Training to Enhance Memory (STEM). STEM teaches participants about each of the techniques, how to apply them in daily life and provides practice. Participants are taught to restructure a memory-demanding situation to optimize self-generation, spaced learning and retrieval practice. This pilot double-blind, placebo-controlled, randomized clinical trial (RCT) tested the efficacy of STEM in 20 learning-impaired participants with clinically definite MS (9 treatment, 11 control). Significant treatment effects were noted on self-report measures of daily functioning (primary outcome). Objective neuropsychological testing approached significance, showing a medium-large effect on verbal NLM. Results suggest that STEM may improve everyday functioning in individuals with MS. A full-scale RCT is warranted to validate findings in a larger sample so that findings may be generalized to the broader MS community.

The efficacy of the modified Story Memory Technique in progressive MS.

BACKGROUND: Impairments in new learning and memory are common in individuals with multiple sclerosis (MS), negatively impacting everyday life, including occupational and social functioning. OBJECTIVE: This study examined the efficacy of the modified Story Memory Technique (mSMT) in a progressive multiple sclerosis (PMS) sample through a double-blind, placebo-controlled, randomized clinical trial (RCT). METHODS: Thirty (30) individuals with PMS, naïve to the mSMT, were randomized to the treatment or placebo control group. The Treatment Group completed mSMT training twice per week for 5 weeks while the Placebo Group met with the therapist at the same frequency, engaging in non-training-oriented tasks to control for professional contact and disease alterations. RESULTS: The treatment group showed significant improvements in learning compared with the placebo control group, evident on both objective evaluation of new learning and self-report of functioning in daily life. Increased awareness of cognitive deficits was also noted post-treatment. CONCLUSION: These data provide Class I evidence supporting the efficacy of the mSMT in PMS. A behavioral intervention, targeted to specifically strengthen new learning, can significantly improve memory performance in PMS, and this improvement in memory performance is maintained 3 months later.

Study protocol: improving cognition in people with progressive multiple sclerosis: a multi-arm, randomized, blinded, sham-controlled trial of cognitive rehabilitation and aerobic exercise (COGEx).

BACKGROUND: Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, in particular processing speed (PS) deficits, and that a combination of these two treatments is more effective than each individual treatment given alone. We further hypothesize that improvements in PS will be associated with modifications of functional and/or structural plasticity within specific brain networks/regions involved in PS measured with advanced MRI techniques. METHODS: This study is a multisite, randomized, double-blinded, sham controlled clinical trial of CR and aerobic exercise. Three hundred and sixty subjects from 11 sites will be randomly assigned into one of four groups: CR plus aerobic exercise; CR plus sham exercise; CR sham plus aerobic exercise and CR sham plus sham exercise. Subjects will participate in the assigned treatments for 12 weeks, twice a week. All subjects will have a cognitive and physical assessment at baseline, 12 weeks and 24 weeks. In an embedded sub-study, approximately 30% of subjects will undergo structural and functional MRI to investigate the neural mechanisms underlying the behavioral response. The primary outcome is the Symbol Digit Modalities Test (SDMT) measuring PS. Secondary outcome measures include: indices of verbal and non-verbal memory, depression, walking speed and a dual cognitive-motor task and MRI. DISCUSSION: The study is being undertaken in 6 countries (11 centres) in multiple languages (English, Italian, Danish, Dutch); with testing material validated and standardized in these languages. The rationale for this approach is to obtain a robustly powered sample size and to demonstrate that these two interventions can be given effectively in multiple countries and in different languages. TRIAL REGISTRATION: The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468. Registration was performed before recruitment was initiated.

The Neural Mechanisms Underlying Processing Speed Deficits in Individuals Who Have Sustained a Spinal Cord Injury: A Pilot Study.

Our objective was to determine differences in brain activation during a processing-speed task in individuals with SCI compared to a group of age-matched healthy controls and to a group of older healthy controls. Ten individuals with cervical SCI (C3-C5), 10 age-matched healthy controls and 10 older healthy controls participated in a cross-sectional study in which performance on neuropsychological tests of processing speed and brain activation were the main outcome measures. The brain areas used by the individuals with SCI during the processing-speed task differed significantly from the age-matched healthy controls, but were similar to the older control cohort, and included activation in frontal, parietal and hippocampal areas. This suggests that individuals with SCI may compensate for processing-speed deficits by relying on brain regions that classically support control cognitive processes such as executive control and memory.

Development and Psychometric Characteristics of the TBI-QOL Independence Item Bank and Short Form and the TBI-QOL Asking for Help Scale.

OBJECTIVE: To develop an item response theory (IRT)-calibrated, patient-reported outcome measure of subjective independence for individuals with traumatic brain injury (TBI). DESIGN: Large-scale item calibration field testing; confirmatory factor analysis (CFA) and graded response model IRT analyses. SETTING: Five TBI Model System centers across the United States. PARTICIPANTS: Adults with complicated mild, moderate, or severe TBI (N=556). OUTCOME MEASURES: Traumatic Brain Injury-Quality of Life (TBI-QOL) Independence item bank and the TBI-QOL Asking for Help scale. RESULTS: A total of 556 individuals completed 44 items in the Independence item pool. Initial factor analyses indicated that items related to the idea of "asking for help" were measuring a different construct from other items in the pool. These 9 items were set aside. Twenty-two other items were removed because of bimodal distributions and/or low item-total correlations. CFA supported unidimensionality of the remaining Independence items. Graded response model IRT analysis was used to estimate slopes and thresholds for the final 13 Independence items. An 8-item fixed-length short form was also developed. The 9 Asking for Help items were analyzed separately. One misfitting item was deleted, and the final 8 items became a fixed-length IRT-calibrated scale. Reliability was high for both measures. CONCLUSIONS: The IRT-calibrated TBI-QOL Independence item bank and short form and TBI-QOL Asking for Help scale may be used to measure important issues for individuals with TBI in research and clinical applications.