Improved quality of life and psychological symptoms following mindfulness and cognitive rehabilitation in multiple sclerosis and their mediating role for cognition: a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) frequently gives rise to depressive and anxiety symptoms, but these are often undertreated. This study investigated the effect of mindfulness-based cognitive therapy (MBCT) and cognitive rehabilitation therapy (CRT) on psychological outcomes and quality of life (QoL), and whether they mediate treatment effects on MS-related cognitive problems. METHODS: This randomized controlled trial included MS patients with cognitive complaints (n = 99) and compared MBCT (n = 32) and CRT (n = 32) to enhanced treatment as usual (n = 35). Baseline, post-treatment and 6-months follow-up assessments included patient-reported outcome measures (PROMS) and cognitive outcomes (self-reported and neuropsychological assessment). PROMS concerned psychological symptoms, well-being, QoL, and daily life function. Linear mixed models indicated intervention effects on PROMS and mediation effects of PROMS on cognitive outcomes. RESULTS: MBCT positively affected depressive symptoms (Cohen's d (d) = -0.46), fatigue (d = -0.39), brooding (d = -0.34), mindfulness skills (d = 0.49), and mental QoL (d = -0.73) at post-treatment. Effects on mindfulness skills remained significant 6 months later (d = 0.42). CRT positively affected depressive symptoms (d = -0.46), mindfulness skills (d = 0.37), and mental QoL (d = -0.45) at post-treatment, but not at 6-month follow-up. No effects on anxiety, well-being, self-compassion, physical QoL, and daily life function were found. Treatment effects on self-reported, but not objective, cognition were mediated by psychological symptoms and mindfulness skills. CONCLUSIONS: MBCT and CRT reduced a wide array of psychological symptoms and improved mental QoL. These improvements seemed to impact self-reported cognitive problems after both treatments, whereas objective cognitive improvements after MBCT seemed independent of improvement in psychological symptoms. Future studies should investigate long-term sustainability of these beneficial effects. TRIAL REGISTRATION: The trial was prospectively registered in the Dutch Trial registry on 31 May 2017 (NL6285; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6459 ).

Neurophysiological brain function predicts response to cognitive rehabilitation and mindfulness in multiple sclerosis: a randomized trial.

BACKGROUND: Cognitive treatment response varies highly in people with multiple sclerosis (PwMS). Identification of mechanisms is essential for predicting response. OBJECTIVES: This study aimed to investigate whether brain network function predicts response to cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT). METHODS: PwMS with cognitive complaints completed CRT, MBCT, or enhanced treatment as usual (ETAU) and performed three measurements (baseline, post-treatment, 6-month follow-up). Baseline magnetoencephalography (MEG) measures were used to predict treatment effects on cognitive complaints, personalized cognitive goals, and information processing speed (IPS) using mixed models (secondary analysis REMIND-MS study). RESULTS: We included 105 PwMS (96 included in prediction analyses; 32 CRT, 31 MBCT, 33 ETAU), and 56 healthy controls with baseline MEG. MEG did not predict reductions in complaints. Higher connectivity predicted better goal achievement after MBCT (p = 0.010) and CRT (p = 0.018). Lower gamma power (p = 0.006) and higher connectivity (p = 0.020) predicted larger IPS benefits after MBCT. These MEG predictors indicated worse brain function compared to healthy controls (p < 0.05). CONCLUSIONS: Brain network function predicted better cognitive goal achievement after MBCT and CRT, and IPS improvements after MBCT. PwMS with neuronal slowing and hyperconnectivity were most prone to show treatment response, making network function a promising tool for personalized treatment recommendations. TRIAL REGISTRATION: The REMIND-MS study was prospectively registered in the Dutch Trial registry (NL6285; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6459 ).

Learning capacity in early-stage Alzheimer's disease: The role of feedback during learning on memory performance.

Alzheimer's disease is characterized by a decline in episodic memory and executive functioning, hampering learning ability. Insight into outcome-based learning capacity may be relevant for optimizing the learning potential of these patients. To date, mixed results have been found in studies in which cognitively impaired participants have to learn based on positive and negative outcomes. In this study, we investigated the role of negative and positive feedback on memory performance and participants' ability to adjust their behaviour accordingly in a sample of 23 early-stage AD patients and 23 matched healthy controls. We administered a novel computerized object-location memory task, in which participants were instructed to learn and memorize the locations of different everyday objects following errorless learning (EL) and trial-and-error learning (TEL). A separate probabilistic TEL task was employed in which participants had to learn how to adjust their behaviour based on positive and negative feedback. EL had a beneficial general effect on memory performance for object locations. However, this effect was not larger in early-stage AD patients compared to controls and error frequency during acquisition of object locations was unrelated to later recall performance. No group differences were found on the probabilistic learning task with respect to learning performance over time and based on positive and negative feedback. Although the error monitoring system seems intact in patients with early-stage AD, errors during learning are likely acting as a source of interference causing difficulty in storage or retrieval of object locations.

Game-supported cognitive strategy training for slowed information processing speed after acquired brain injury: study protocol for a randomised controlled trial.

INTRODUCTION: Many individuals with acquired brain injury tend to experience problems with slowed information processing speed (IPS). A potentially beneficial and cost-effective supplement for cognitive rehabilitation of impaired IPS may be the implementation of serious gaming that focuses on compensatory learning as part of cognitive training. However, most digital platforms used during cognitive rehabilitation focus on restoring cognitive function and evidence for skill transfer from digital practice to everyday life is lacking. This study aims to investigate the efficacy of a game-supported cognitive strategy training. The training combines a well-validated time pressure management cognitive strategy training, targeting slowed IPS, with a novel game and a mobile application. The game-supported training focuses on the generalisation of strategy-use to untrained tasks in everyday life. METHODS AND ANALYSIS: The study is designed as a randomised controlled trial in which the experimental group (Karman Line - Tempo module: an 8-week game-supported cognitive strategy training) will be compared with an active control group (CogniPlus training: an 8-week computerised cognitive function training). Data from 60 individuals with acquired brain injury (30 per group, ages between 16 and 75) will be collected at baseline (T0), post-treatment (T1) and at 3-month follow-up (T2). The primary outcome measure is an objective assessment of compensatory strategy use in an untrained experimental task. The secondary outcome is the attainment of trained and untrained treatment goals assessed by goal attainment scaling. Pre-training and post-training data will be analysed using a 2×2 repeated measure analysis of variance. ETHICS AND DISSEMINATION: This study has been approved by the medical review ethics committee CMO Region Arnhem and Nijmegen (NL74818.091.20) and is registered in the Netherlands Trial Register. Research findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NL9437; The Netherlands Trial Register.

A short add-on sleep intervention in the rehabilitation of individuals with acquired brain injury: A randomized controlled trial.

BACKGROUND: Sleep disturbances are common after acquired brain injury (ABI) and have a negative impact on functioning. OBJECTIVE: This study examines whether a short add-on therapy for sleep disturbances in individuals with ABI is effective in addition to rehabilitation treatment as usual. METHODS: In the randomized-controlled study, 54 adults with ABI and self-reported sleep disturbances receiving outpatient rehabilitation services were randomized in two groups: one receiving a sleep intervention (based on cognitive behavioural therapy for insomnia (CBT-I)) in addition to their rehabilitation treatment (CBT-I + TAU group) and one receiving treatment as usual (TAU). The primary outcome was sleep quality, measured with the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes included measures of anxiety, depression, fatigue and dysfunctional beliefs and attitudes about sleep. RESULTS: The short add-on sleep therapy resulted in improvements in sleep quality in the CBT-I + TAU group as compared to the TAU group (ES = 0.924). Furthermore, the CBT-I + TAU group reported less dysfunctional beliefs and attitudes about sleep and were better able to cope with fatigue compared to the TAU group. CONCLUSIONS: The application of this short add-on sleep intervention could be implemented in neuropsychological rehabilitation settings.

Cognitive rehabilitation and mindfulness reduce cognitive complaints in multiple sclerosis (REMIND-MS): A randomized controlled trial.

BACKGROUND: Cognitive problems, both complaints and objective impairments, are frequent and disabling in patients with multiple sclerosis (MS) and profoundly affect daily living. However, intervention studies that focus on cognitive problems that patients experience in their daily lives are limited. This study therefore aimed to investigate the effectiveness of cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT) on patient-reported cognitive complaints in MS. METHODS: In this randomized-controlled trial, MS patients with cognitive complaints completed questionnaires and underwent neuropsychological assessments at baseline, post-treatment and 6-month follow-up. Patient-reported cognitive complaints were primarily investigated. Secondary outcomes included personalized cognitive goals and objective cognitive function. CRT and MBCT were compared to enhanced treatment as usual (ETAU) using linear mixed models. RESULTS: Patients were randomized into CRT (n = 37), MBCT (n = 36) or ETAU (n = 37), of whom 100 completed the study. Both CRT and MBCT positively affected patient-reported cognitive complaints compared to ETAU at post-treatment (p<.05), but not 6 months later. At 6-month follow-up, CRT had a positive effect on personalized cognitive goals (p=.028) and MBCT on processing speed (p=.027). Patients with less cognitive complaints at baseline benefited more from CRT on the Cognitive Failures Questionnaire (i.e. primary outcome measuring cognitive complaints) at post-treatment (p=.012-.040), and those with better processing speed at baseline benefited more from MBCT (p=.016). CONCLUSION: Both CRT and MBCT alleviated cognitive complaints in MS patients immediately after treatment completion, but these benefits did not persist. In the long term, CRT showed benefits on personalized cognitive goals and MBCT on processing speed. These results thereby provide insight in the specific contributions of available cognitive treatments for MS patients.

Pain education and pain management skills in virtual reality in the treatment of chronic low back pain: A multiple baseline single-case experimental design.

Chronic lower back pain is a major health problem and current treatments do not always lead to adequate pain control. Virtual reality (VR) is an upcoming technology that has shown to be effective in reducing acute pain. However, the value of VR in reducing chronic pain is still unknown. Therefore, the current study focuses on the effects of a recently developed VR application 'Reducept' using a multiple baseline single-case experimental design in 8 patients (N = 8). Reducept is a VR-training program aiming to improve pain management skills and providing pain education in patients with (chronic lower) back pain. Results based on visual and statistical analyses indicated that Reducept has the potential to reduce chronic lower back pain, although its clinical relevance was small. This study is one of the first that focuses on the possible effects of Reducept using sophisticated visual and statistical analyses. Our study shows a detailed overview of individual changes in pain intensity over time. Further research is necessary to investigate the working mechanism of Reducept and its impact on chronic pain conditions.

Errorless and trial-and-error learning of object locations in patients with executive deficits after brain injury.

Studies investigating the efficacy of errorless learning (EL), a rehabilitation method in which the occurrence of errors during learning are eliminated, have predominantly involved patients with memory impairment. However, the most recent perspective on the underlying mechanism of EL explicitly takes executive processes into account. The aim of this study was to investigate whether EL of object locations is beneficial for memory performance compared to trial-and-error learning (TEL) in patients with acquired brain injury (ABI) experiencing executive deficits (N = 15) and matched healthy controls (N = 15). Participants completed an EL and TEL condition of a computerized spatial learning task, in which the location of everyday objects had to be memorized. The number of errors made during learning was predetermined, varying from 0 (EL condition) to 1, 2, 3, 4 or 5 errors (TEL condition). Results showed a beneficial effect of EL on memory performance in both ABI patients and controls (p < .001), but this advantage was not larger in ABI patients compared to controls and was not moderated by the amount of errors made during learning.

Treatments for sleep disturbances in individuals with acquired brain injury: A systematic review.

OBJECTIVE: To systematically review the evidence on the treatments of sleep disturbances in individuals with acquired brain injury. DATA SOURCES: PubMed, Embase, Web of Science, and PsycINFO were searched from inception to January 2021. REVIEW METHOD: Eligibility criteria were (1) participants with mild to severe acquired brain injury from traumatic brain injury and stroke (⩾three months post-injury), (2) individuals aged 16 years and older, (3) participants with self-reported sleep disturbances, (4) controlled group studies and single case (experimental) studies, and (5) interventions aimed at treatment of sleep disturbances. Two researchers independently identified relevant studies and assessed their study quality using the revised Cochrane assessment of bias tool (RoB 2.0) and the risk-of-bias in N-of-1 trials (RoBiNT) scale. RESULTS: The search yielded 655 records; 11 studies met the inclusion criteria and were included, with a total of 227 participants (207 individuals with traumatic brain injury, 20 stroke patients). Two studies included pharmacological therapy, six studies examined the effects of cognitive behavioral therapy and three studies investigated alternative interventions such as acupuncture. CONCLUSION: Although there was heterogeneity in the study quality of the included studies, their outcomes suggest that cognitive behavioral therapy is recommended as treatment of choice for improving sleep in individuals with acquired brain injury, especially for patients with mild to severe traumatic brain injury. Future research should examine the effects of cognitive behavioral therapy in more high-quality randomized controlled designs.

Functional brain network organization measured with magnetoencephalography predicts cognitive decline in multiple sclerosis.

BACKGROUND: Cognitive decline remains difficult to predict as structural brain damage cannot fully explain the extensive heterogeneity found between MS patients. OBJECTIVE: To investigate whether functional brain network organization measured with magnetoencephalography (MEG) predicts cognitive decline in MS patients after 5 years and to explore its value beyond structural pathology. METHODS: Resting-state MEG recordings, structural MRI, and neuropsychological assessments were analyzed of 146 MS patients, and 100 patients had a 5-year follow-up neuropsychological assessment. Network properties of the minimum spanning tree (i.e. backbone of the functional brain network) indicating network integration and overload were related to baseline and longitudinal cognition, correcting for structural damage. RESULTS: A more integrated beta band network (i.e. smaller diameter) and a less integrated delta band network (i.e. lower leaf fraction) predicted cognitive decline after 5 years (Radj2=15%), independent of structural damage. Cross-sectional analyses showed that a less integrated network (e.g. lower tree hierarchy) related to worse cognition, independent of frequency band. CONCLUSIONS: The level of functional brain network integration was an independent predictive marker of cognitive decline, in addition to the severity of structural damage. This work thereby indicates the promise of MEG-derived network measures in predicting disease progression in MS.

Neurobehavioral Initiation and Motivation Problems After Acquired Brain Injury.

Motivation is a primary and permanent source of human behavior and adaptation. Motivational deficits, along with deficiencies in initiation, frequently occur in individuals with acquired brain injury (ABI). These neurobehavioral problems are associated with consequences at the participation level: patients are reluctant to engage in rehabilitation, and their subsequent social reintegration is often at risk. The same problems may also become a heavy burden for the families of individuals with ABI. In the present paper, we will critically review both the current definitions and the instruments used to measure motivational disorders following ABI. We will also describe the neural system underlying motivation and its impairments. What emerges is the need to develop specific rehabilitative treatments, still absent at the moment, with the ultimate aim of ensuring a better quality of life for both the patients and their proxies.

The impact of error frequency on errorless and errorful learning of object locations using a novel paradigm.

Errorless learning (EL) is an approach in which errors are eliminated or reduced as much as possible while learning of new information or skills. In contrast, during trial-and-error - or errorful - learning (TEL) errors are not reduced and are often even promoted. There is a complex and conflicting pattern of evidence whether EL or TEL may result in better memory performance. One major confound in the extant literature is that most EL studies have not controlled for the number of errors made during TEL, resulting in a large variability in the amount of errors committed. This variability likely explains why studies on the cognitive underpinnings of EL and TEL have produced mixed findings. In this study, a novel object-location learning task was employed to examine EL and TEL in 30 healthy young adults. The number of errors was systematically manipulated, allowing us to investigate the impact of frequency of errors on learning outcome. The results showed that recall from memory was significantly better during EL. However, the number of errors made during TEL did not influence the performance in young adults. Altogether, our novel paradigm is promising for measuring EL and TEL, allowing for more accurate analyses to understand the impact of error frequency on a person's learning ability and style.

Transfer effects of errorless Goal Management Training on cognitive function and quality of life in brain-injured persons.

BACKGROUND: Previous findings had shown that the addition of errorless learning to traditional Goal Management Training (GMT) resulted in superior results when training everyday tasks in persons with executive deficits after brain injury. OBJECTIVE: To investigate the additional effects of an errorless GMT on cognitive function and quality of life after acquired brain injury. METHODS: This is a supplementary analysis of findings from an RCT in which 67 patients with executive impairments after acquired brain injury were randomly allocated to an experimental errorless GMT (n = 33) or conventional GMT (n = 34) to train two individually chosen everyday tasks. Objective cognitive function using neuropsychological tests, subjective cognitive complaints and quality of life using questionnaires were assessed before and after training. RESULTS: No significant interaction effects between these three types of outcome measures and the two forms of GMT were found. Irrespective of treatment, performance on two executive tests (Modified Six Elements Test; p = 0.006, Zoo Map test; p = 0.001) improved and daily executive function problems as reported by the participants (EFI; p = 0.001) and proxies (DEX; p = 0.01) diminished. CONCLUSIONS: Besides the previously found superiority of errorless GMT when training everyday tasks, additional improvements in cognition and quality of life did not differ between the two treatments.

Moderators, Mediators, and Nonspecific Predictors of Treatment Outcome in an Intervention for Everyday Task Improvement in Persons With Executive Deficits After Brain Injury.

OBJECTIVE: To identify moderators, mediators, and predictors of everyday task performance after an experimental combination of errorless learning and goal management training. DESIGN: Predictor analysis of a randomized controlled intervention trial. SETTING: Outpatient rehabilitation centers. PARTICIPANTS: Patients (N=60) with acquired brain injury of nonprogressive nature with a minimal postonset time of 3 months. INTERVENTIONS: Participants were randomly allocated to 8 sessions of errorless or conventional goal management training. MAIN OUTCOME MEASURE: Everyday task performance, assessed at baseline and after treatment by evaluating correct, ineffective, and missing task steps. RESULTS: Demographic variables, neuropsychological test performance, subjective cognitive function, and quality of life were selected as candidate predictors. The results showed that age (P=.03) and estimated intelligence quotient (IQ) (P=.02) emerged as moderators. Higher age was associated with better everyday task performance after conventional goal management training, whereas higher IQ was associated with better performance after errorless goal management training. Higher executive function scores after training predicted improved everyday task performance across the 2 treatment conditions (P=.04). CONCLUSIONS: The identified predictors may contribute to a more tailored cognitive rehabilitation approach in which treatments and patients are better matched when clinicians decide to train everyday tasks.

Reliability of an Adapted Version of the Modified Six Elements Test as a Measure of Executive Function.

The Modified Six Elements Test (MSET) is used to examine executive deficits-more specifically, planning deficits. This study investigates the reliability of an adapted version of the MSET and proposes a novel scoring method. Two parallel versions of the adapted MSET were administered in 60 healthy participants in a counterbalanced order. Test-retest and parallel-form reliability were examined using intraclass correlation coefficients, Bland-Altman analyses, standard errors of measurement, and smallest real differences, representing clinically relevant changes over time. Moreover, the ecological validity of the adapted MSET was evaluated using the Executive Function Index, a self-rating questionnaire measuring everyday executive performance. No systematic differences between the test occasions were present, and the adapted MSET including the proposed scoring method was capable of detecting real clinical changes. Intraclass correlations for the test-retest and parallel-form reliability were modest, and the variability between the test scores was high. The nonsignificant correlations with the Executive Function Index did not confirm the previously established ecological validity of the MSET. We show that both parallel versions of the test are clinically equivalent and can be used to measure executive function over the course of time without task-specific learning effects.

Do Old Errors Always Lead to New Truths? A Randomized Controlled Trial of Errorless Goal Management Training in Brain-Injured Patients.

Both errorless learning (EL) and Goal Management Training (GMT) have been shown effective cognitive rehabilitation methods aimed at optimizing the performance on everyday skills after brain injury. We examine whether a combination of EL and GMT is superior to traditional GMT for training complex daily tasks in brain-injured patients with executive dysfunction. This was an assessor-blinded randomized controlled trial conducted in 67 patients with executive impairments due to brain injury of non-progressive nature (minimal post-onset time: 3 months), referred for outpatient rehabilitation. Individually selected everyday tasks were trained using 8 sessions of an experimental combination of EL and GMT or via conventional GMT, which follows a trial-and-error approach. Primary outcome measure was everyday task performance assessed after treatment compared to baseline. Goal attainment scaling, rated by both trainers and patients, was used as secondary outcome measure. EL-GMT improved everyday task performance significantly more than conventional GMT (adjusted difference 15.43, 95% confidence interval [CI] [4.52, 26.35]; Cohen's d=0.74). Goal attainment, as scored by the trainers, was significantly higher after EL-GMT compared to conventional GMT (mean difference 7.34, 95% CI [2.99, 11.68]; Cohen's d=0.87). The patients' goal attainment scores did not differ between the two treatment arms (mean difference 3.51, 95% CI [-1.41, 8.44]). Our study is the first to show that preventing the occurrence of errors during executive strategy training enhances the acquisition of everyday activities. A combined EL-GMT intervention is a valuable contribution to cognitive rehabilitation in clinical practice.

Validity of an adapted scoring method for a Modified Six Elements Test in individuals with brain injury.

The Modified Six Elements Test (MSET) assesses several executive functions. We examined whether an adapted scoring method is appropriate for discriminating between brain-injured persons with and without executive deficits. A MSET was administered to 70 participants with acquired brain injury in the chronic phase. The group was divided into individuals with and without executive impairments based on several other executive tests. The discriminative value for both the conventional raw score and the adapted scoring method was evaluated using receiver operating characteristic analyses. Both scoring methods discriminated significantly between persons with impaired and unimpaired executive functions (raw score: area under the curve, AUC = 0.703, p = .004; adapted score: AUC = 0.780, p = .000). Only the adapted scoring method proved sensitive (81%) and specific (67%) within a clinically useful range. Within this range, an acceptable cut-off score could be determined. Altogether, the proposed MSET scoring index is a potentially clinically useful contribution to the measurement of executive functions.

Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study.

BACKGROUND: Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI). METHODS: Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing. RESULTS: No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks. CONCLUSIONS: Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01246843.

A randomized controlled trial on errorless learning in goal management training: study rationale and protocol.

BACKGROUND: Many brain-injured patients referred for outpatient rehabilitation have executive deficits, notably difficulties with planning, problem-solving and goal directed behaviour. Goal Management Training (GMT) has proven to be an efficacious cognitive treatment for these problems. GMT entails learning and applying an algorithm, in which daily tasks are subdivided into multiple steps. Main aim of the present study is to examine whether using an errorless learning approach (preventing the occurrence of errors during the acquisition phase of learning) contributes to the efficacy of Goal Management Training in the performance of complex daily tasks. METHODS/DESIGN: The study is a double blind randomized controlled trial, in which the efficacy of Goal Management Training with an errorless learning approach will be compared with conventional Goal Management Training, based on trial and error learning. In both conditions 32 patients with acquired brain injury of mixed etiology will be examined. Main outcome measure will be the performance on two individually chosen everyday-tasks before and after treatment, using a standardized observation scale and goal attainment scaling. DISCUSSION: This is the first study that introduces errorless learning in Goal Management Training. It is expected that the GMT-errorless learning approach will improve the execution of complex daily tasks in brain-injured patients with executive deficits. The study can contribute to a better treatment of executive deficits in cognitive rehabilitation. TRIAL REGISTRATION: (Dutch Trial Register): NTR3567.