Dissecting the cognitive phenotype of post-stroke fatigue using computerized assessment and computational modeling of sustained attention.

Post-stroke fatigue (PSF) is prevalent among stroke patients, but its mechanisms are poorly understood. Many patients with PSF experience cognitive difficulties, but studies aiming to identify cognitive correlates of PSF have been largely inconclusive. With the aim of characterizing the relationship between subjective fatigue and attentional function, we collected behavioral data using the attention network test (ANT) and self-reported fatigue scores using the fatigue severity scale (FSS) from 53 stroke patients. In order to evaluate the utility and added value of computational modeling for delineating specific underpinnings of response time (RT) distributions, we fitted a hierarchical drift diffusion model (hDDM) to the ANT data. Results revealed a relationship between fatigue and RT distributions. Specifically, there was a positive interaction between FSS score and elapsed time on RT. Group analyses suggested that patients without PSF increased speed during the course of the session, while patients with PSF did not. In line with the conventional analyses based on observed RT, the best fitting hDD model identified an interaction between elapsed time and fatigue on non-decision time, suggesting an increase in time needed for stimulus encoding and response execution rather than cognitive information processing and evidence accumulation. These novel results demonstrate the significance of considering the sustained nature of effort when defining the cognitive phenotype of PSF, intuitively indicating that the cognitive phenotype of fatigue entails an increased vulnerability to sustained effort, and suggest that the use of computational approaches offers a further characterization of specific processes underlying behavioral differences.

Use It or Lose It? A 5-Year Follow-up Study of Goal Management Training in Patients with Acquired Brain Injury.

OBJECTIVES: To determine the perceived 5-year outcome of Goal Management Training (GMT) for individuals with chronic acquired brain injury and executive dysfunction, when compared to a nonspecific psychoeducational intervention (Brain Health Workshop, BHW). METHODS: Of the 67 subjects in the initial randomized controlled trial [Tornås et al. (2016). Journal of the International Neuropsychological Society, 1-17], 50 (GMT, n = 21; BHW, n = 29) subjects returned written consent and questionnaires (54% male, age 45.8 ± 10.9 years). The 5-year follow-up consisted of two questionnaires, including the Behavior Rating Inventory of Executive Function for daily life executive function (EF) and Quality of Life after Brain Injury to assess health-related quality of life (HRQoL). Changes related to daily life EF and HRQoL were assessed pre-treatment, post-treatment, 6-month follow-up, and 5-year follow-up. Data were analyzed using a 2 × 4 mixed-design ANOVA. RESULTS: The findings indicate that GMT is efficacious in improving EF and HRQoL 6-month post-treatment. However, these changes failed to remain significant at 5-year follow-up. CONCLUSIONS: Data from 50 participants receiving either GMT or BHW suggested that the significant GMT-related improvements on perceived EF and HRQoL observed at 6-month follow-up were no longer present at 5-year follow-up. These findings indicate a need to promote maintenance of interventions post-treatment.

Moderators, mediators and nonspecific predictors of outcome after cognitive rehabilitation of executive functions in a randomised controlled trial.

Moderators, mediators and nonspecific predictors of treatment after cognitive rehabilitation of executive functions in a randomised controlled trial Objective: To explore moderators, mediators and nonspecific predictors of executive functioning after cognitive rehabilitation in a randomised controlled trial, comparing Goal Management Training (GMT) with an active psycho-educative control-intervention, in patients with chronic acquired brain injury. METHODS: Seventy patients with executive dysfunction were randomly allocated to GMT (n = 33) or control (n = 37). Outcome measures were established by factor-analysis and included cognitive executive complaints, emotional dysregulation and psychological distress. RESULTS: Higher age and IQ emerged as nonspecific predictors. Verbal memory and planning ability at baseline moderated cognitive executive complaints, while planning ability at six-month follow-up mediated all three outcome measures. Inhibitory cognitive control emerged as a unique GMT specific mediator. A general pattern regardless of intervention was identified; higher levels of self-reported cognitive-and executive-symptoms of emotional dysregulation and psychological distress at six-month follow-up mediated less improvement across outcome factors. CONCLUSIONS: The majority of treatment effects were nonspecific to intervention, probably underscoring the variables' general contribution to outcome of cognitive rehabilitation interventions. Interventions targeting specific cognitive domains, such as attention or working memory, need to take into account the patients' overall cognitive and emotional self-perceived functioning. Future studies should investigate the identified predictors further, and also consider other predictor candidates.

Rehabilitation of Executive Functions in Patients with Chronic Acquired Brain Injury with Goal Management Training, External Cuing, and Emotional Regulation: A Randomized Controlled Trial.

Executive dysfunction is a common consequence of acquired brain injury (ABI), causing significant disability in daily life. This randomized controlled trial investigated the efficacy of Goal Management Training (GMT) in improving executive functioning in patients with chronic ABI. Seventy patients with a verified ABI and executive dysfunction were randomly allocated to GMT (n=33) or a psycho-educative active control condition, Brain Health Workshop (BHW) (n=37). In addition, all participants received external cueing by text messages. Neuropsychological tests and self-reported questionnaires of executive functioning were administered pre-intervention, immediately after intervention, and at 6 months follow-up. Assessors were blinded to group allocation. Questionnaire measures indicated significant improvement of everyday executive functioning in the GMT group, with effects lasting at least 6 months post-treatment. Both groups improved on the majority of the applied neuropsychological tests. However, improved performance on tests demanding executive attention was most prominent in the GMT group. The results indicate that GMT combined with external cueing is an effective metacognitive strategy training method, ameliorating executive dysfunction in daily life for patients with chronic ABI. The strongest effects were seen on self-report measures of executive functions 6 months post-treatment, suggesting that strategies learned in GMT were applied and consolidated in everyday life after the end of training. Furthermore, these findings show that executive dysfunction can be improved years after the ABI.

Goal Management Training Combined With External Cuing as a Means to Improve Emotional Regulation, Psychological Functioning, and Quality of Life in Patients With Acquired Brain Injury: A Randomized Controlled Trial.

OBJECTIVE: To investigate whether goal management training (GMT) expanded to include external cuing and an emotional regulation module is associated with improved emotional regulation, psychological functioning, and quality of life (QOL) after chronic acquired brain injury (ABI). DESIGN: Randomized controlled trial with blinded outcome assessment at baseline, posttraining, and 6-month follow-up. SETTING: Outpatient. PARTICIPANTS: Persons with ABI and executive dysfunction (N=70; 64% traumatic brain injury; 52% men; mean age ± SD, 43±13y; mean time since injury ± SD, 8.1±9.4y). INTERVENTION: Eight sessions of GMT in groups, including a new module addressing emotional regulation, and external cuing. A psychoeducative control condition (Brain Health Workshop) was matched on amount of training, therapist contact, and homework. MAIN OUTCOME MEASURES: Emotional regulation was assessed with the Brain Injury Rehabilitation Trust Regulation of Emotions Questionnaire, the Emotional Control subscale and the Emotion Regulation factor (Behavior Rating Inventory of Executive Function-Adult Version), and the Positive and Negative Affect subscales from the Dysexecutive Questionnaire. Secondary outcome measures included psychological distress (Hopkins Symptom Checklist-25) and QOL (Quality of Life After Brain Injury Scale). RESULTS: Findings indicated beneficial effects of GMT on emotional regulation skills in everyday life and in QOL 6 months posttreatment. No intervention effects on measures of psychological distress were registered. CONCLUSIONS: GMT is a promising intervention for improving emotional regulation after ABI, even in the chronic phase. More research using objective measures of emotional regulation is needed to investigate the efficacy of this type of training.

Regional brain volume prior to treatment is linked to outcome after cognitive rehabilitation in traumatic brain injury.

Cognitive rehabilitation is useful for many after traumatic brain injury (TBI), but we lack critical knowledge about which patients benefit the most from different approaches. Advanced neuroimaging techniques have provided important insight into brain pathology and systems plasticity after TBI, and have potential to inform new practices in cognitive rehabilitation. In this study, we aimed to identify candidate structural brain measures with relevance for rehabilitation of cognitive control (executive) function after TBI. Twenty-eight patients (9 female, mean age 40.5 (SD = 13.04) years) with TBI (>21 months since injury) that participated in a randomized controlled cognitive rehabilitation trial (NCT02692352) were included in the analyses. Regional brain volume was extracted from T1-weighted MRI scans before treatment using tensor-based morphometry. Both positive and negative associations between treatment outcome (everyday cognitive control function) and regional brain volume were observed. The most robust associations between regional brain volume and improvement in function were observed in midline fronto-parietal regions, including the anterior and posterior cingulate cortices. The study provides proof of concept and valuable insight for planning future studies focusing on neuroimaging in cognitive rehabilitation after TBI.

No add-on effect of tDCS on fatigue and depression in chronic stroke patients: A randomized sham-controlled trial combining tDCS with computerized cognitive training.

BACKGROUND: Fatigue and emotional distress rank high among self-reported unmet needs in life after stroke. Transcranial direct current stimulation (tDCS) may have the potential to alleviate these symptoms for some patients, but the acceptability and effects for chronic stroke survivors need to be explored in randomized controlled trials. METHODS: Using a randomized sham-controlled parallel design, we evaluated whether six sessions of 1 mA tDCS (anodal over F3, cathodal over O2) combined with computerized cognitive training reduced self-reported symptoms of fatigue and depression. Among the 74 chronic stroke patients enrolled at baseline, 54 patients completed the intervention. Measures of fatigue and depression were collected at five time points spanning a 2 months period. RESULTS: While symptoms of fatigue and depression were reduced during the course of the intervention, Bayesian analyses provided evidence for no added beneficial effect of tDCS. Less severe baseline symptoms were associated with higher performance improvement in select cognitive tasks, and study withdrawal was higher in patients with more fatigue and younger age. Time-resolved symptom analyses by a network approach suggested higher centrality of fatigue items (except item 1 and 2) than depression items. CONCLUSION: The results reveal no add-on effect of tDCS on fatigue or depression but support the notion of fatigue as a relevant clinical symptom with possible implications for treatment adherence and response.

Structural brain disconnectivity mapping of post-stroke fatigue.

Stroke patients commonly suffer from post stroke fatigue (PSF). Despite a general consensus that brain perturbations constitute a precipitating event in the multifactorial etiology of PSF, the specific predictive value of conventional lesion characteristics such as size and localization remains unclear. The current study represents a novel approach to assess the neural correlates of PSF in chronic stroke patients. While previous research has focused primarily on lesion location or size, with mixed or inconclusive results, we targeted the extended structural network implicated by the lesion, and evaluated the added explanatory value of a structural disconnectivity approach with regards to the brain correlates of PSF. To this end, we estimated individual structural brain disconnectome maps in 84 S survivors in the chronic phase (≥3 months post stroke) using information about lesion location and normative white matter pathways obtained from 170 healthy individuals. PSF was measured by the Fatigue Severity Scale (FSS). Voxel wise analyses using non-parametric permutation-based inference were conducted on disconnectome maps to estimate regional effects of disconnectivity. Associations between PSF and global disconnectivity and clinical lesion characteristics were tested by linear models, and we estimated Bayes factor to quantify the evidence for the null and alternative hypotheses, respectively. The results revealed no significant associations between PSF and disconnectome measures or lesion characteristics, with moderate evidence in favor of the null hypothesis. These results suggest that symptoms of post-stroke fatigue among chronic stroke patients are not simply explained by lesion characteristics or the extent and distribution of structural brain disconnectome, and are discussed in light of methodological considerations.

Emotional Regulation Following Acquired Brain Injury: Associations With Executive Functioning in Daily Life and Symptoms of Anxiety and Depression.

Objective: To examine whether a questionnaire measuring emotional regulation after acquired brain injury adds clinical information beyond what can be obtained with a comprehensive executive function questionnaire and an anxiety and depression measure. Method: Seventy adult persons (age 19-66 years, Mage = 43, SDage = 13) with acquired brain injury in the chronic phase and executive function complaints. All were recruited to participate in a randomized controlled trial (NCT02692352) evaluating the effects of cognitive rehabilitation. Traumatic brain injury was the dominant cause of injury (64%), and mean time since injury was 8 years. Emotional regulation was assessed with the Brain Injury Trust Regulation of Emotions Questionnaire (BREQ). Executive function was assessed with the Behavior Rating Inventory of Executive Function Adult Version (BRIEF-A). The Hopkins Symptom Checklist 25 (HCSL-25) was employed to measure anxiety and depression symptoms. Results: Overall, significant correlations were found between reports of emotional regulation (BREQ) and executive function in daily life (BRIEF-A). Furthermore, our analyses revealed a significant relationship between self-reported scores of emotional regulation (BREQ) and symptoms of anxiety and depression (HSCL-25). Conclusion: The significant associations between the BREQ and most of the other clinical measures indicate that, for patients with acquired brain injury, the BREQ does not add substantial information beyond what can be assessed with the BRIEF-A and the HSCL-25.

A Mindfulness-Based Stress Reduction Program via Group Video Conferencing for Adults With Cerebral Palsy - A Pilot Study.

Purpose: Adults with cerebral palsy experience challenges related to lifelong disability, such as stress, fatigue, pain and emotional issues. E-health services can be delivered regardless of residence and level of functioning. The aim of this pilot study was to explore the potential benefits and feasibility of a mindfulness-based program delivered to adults with cerebral palsy via group video conferencing. Methods: Six adults with cerebral palsy received an 8 week mindfulness group-based program via video conferencing. A multiple single-case study design was applied, including quantitative and qualitative elements. Pain was assessed 16 times through the study period. Questionnaires were administered to gather data on pain catastrophizing, stress, fatigue, emotional distress, positive and negative affect, and quality of life. A focus group interview addressed experiences with the intervention and the mode of delivery. Results: The participants' pain levels showed varied trajectories. Pain catastrophizing and negative affect were statistically significant decreased. Qualitative data indicated benefits from mindfulness in coping and stress management. The video conferencing delivery was evaluated as feasible, with no major adverse effects. Conclusion: Since the pilot study had a small sample size, potential treatment benefits should be interpreted with caution. However, this pilot study provides important information in the planning of future larger and controlled studies on mindfulness-based interventions programs via video conferencing for adults with cerebral palsy and other persons living with long-term disability.

A description of cognitive rehabilitation at Sunnaas Rehabilitation Hospital--balancing comprehensive holistic rehabilitation and retraining of specific functional domains.

BACKGROUND: Measures of cognitive rehabilitation should include comprehensive holistic rehabilitation as well as interventions targeting specific cognitive functions; it is however not clear how this knowledge should be put into practice. OBJECTIVE: To describe services provided at the cognitive rehabilitation unit at Sunnaas Rehabilitation Hospital (SRH), a regional rehabilitation centre in Norway. METHODS: Cognitive rehabilitation programs offered at SRH are described. For all patients served in 2011 and 2012, epidemiological and hospitalization related data were retrieved. Results from a patient satisfaction survey are presented. RESULTS: The services include individual holistic cognitive rehabilitation as well as group programs. 307 individual patients were served in 355 hospitalizations; 68.1% were male; age ranged from 18 to 78 years. The largest patient groups were stroke (46.6%) and traumatic brain injury (33.0%). Mean length of stay was 36.9 days. Median time post injury was 0.8 years (range 16 days - 14 years). More than 90% of the patients were satisfied with the services they received to a large or very large extent. CONCLUSIONS: Providing cognitive rehabilitation that encompasses both a holistic approach and targets specific cognitive functions is challenging. More research is warranted to illuminate further how cognitive rehabilitation services should be designed and conducted in practice.

Bridging the gap between clinical neuroscience and cognitive rehabilitation: the role of cognitive training, models of neuroplasticity and advanced neuroimaging in future brain injury rehabilitation.

BACKGROUND: Magnetic resonance imaging (MRI) has brought about advances in the fields of brain plasticity and lifespan brain change, that might be of special interest for cognitive rehabilitation research and, eventually, in clinical practice. Parallel, intensive cognitive training studies show promising results for the prospect of retraining some of the impaired functioning following acquired brain injury. OBJECTIVES: However, cognitive training research is largely performed without concurrent assessments of brain structural change and reorganization, which could have addressed possible mechanisms of training-related neuroplasticity. METHODS: Criticism of cognitive training studies is often focused on lack of ecologically valid, daily-living assessments of treatment effect, and on whether the applied cognitive measures overlap too much with the training exercises. Yet, the present paper takes another point of view, where the relevance of recent MRI research of brain plasticity to the field of cognitive rehabilitation is examined. RESULTS: Arguably, treatment ought to be measured at the same level of the International Classification of Functioning, Disability and Health model, as it is targeting. In the case of cognitive training that will be the "body structure" and "body function" levels. CONCLUSIONS: MRI has shown promise to detect macro- and microstructural activity-related changes in the brain following intensive training.

Cost-effectiveness analysis of an early-initiated, continuous chain of rehabilitation after severe traumatic brain injury.

The aim of this study is to estimate the long-term cost-effectiveness of two different rehabilitation trajectories after severe traumatic brain injury (sTBI). A decision tree model compared hospitalization costs, health effects, and incremental cost-effectiveness ratios (ICER) of a continuous chain versus a broken chain of rehabilitation. The expected costs were estimated by the reimbursement system using diagnosis-related group and based on point estimates of the Disability Rating Scale (DRS); the health effects were measured by means of area under the curve (AUC). The incremental health benefit was estimated as the difference in the AUCs between the chains. Lower values on the DRS scale indicate better health; thus, smaller AUCs were preferred. The modeled population was a cohort of 59 patients with sTBI (30 in continuous chain; 29 in broken chain) with 6-weeks, 1-year, and 5-year post-injury follow-ups. Regarding the DRS estimates, 5-year AUCs were 19.40 (continuous chain) and 23.46 (broken chain). Across 5 years, the continuous chain of rehabilitation had lower costs and better health effects. By replacing the broken chain with the continuous chain, NOK 37.000 could be saved and 4.06 DRS points gained. By means of probabilistic sensitivity analysis, the majority of ICER estimates (67% of the Monte Carlo simulations) indicated that a continuous chain of rehabilitation was less costly and more effective. These findings indicate that the trajectory of continuous rehabilitation represents a dominant strategy in that it reduces costs and improves outcomes after sTBI under reasonable assumptions.

Does an early onset and continuous chain of rehabilitation improve the long-term functional outcome of patients with severe traumatic brain injury?

There are currently no international guidelines regarding treatment in the early rehabilitation phase for persons with severe traumatic brain injury (TBI), and only a few studies have investigated the effect of integrating rehabilitation into acute TBI care. The aim of the study was to evaluate whether a continuous chain of rehabilitation that begins with the acute phase could improve the functional outcome of severe TBI patients, compared to a broken chain of rehabilitation that starts in the sub-acute phase of TBI. A total of 61 surviving patients with severe TBI were included in a quasi-experimental study conducted at the Level I trauma center in Eastern Norway. In the study, 31 patients were in the early rehabilitation group (Group A) and 30 patients were in the delayed rehabilitation group (Group B). The functional outcomes were assessed 12 months post-injury with the Glasgow Outcome Scale Extended (GOSE) and the Disability Rating Scale (DRS). A favorable outcome (GOSE 6-8) occurred in 71% of the patients from Group A versus 37% in Group B (p=0.007). The DRS score was significantly better in Group A (p=0.03). The ordinal logistic regression analysis was used to quantify the relationship between the type of rehabilitation chain and the GOSE. A better GOSE outcome was found in patients from Group A (unadjusted OR 3.25 and adjusted OR 2.78, respectively). These results support the hypothesis that better functional outcome occurs in patients who receive early onset and a continuous chain of rehabilitation.