Acquired Brain Injury
Conditions
Keywords
Traumatic Brain Injury, Stroke, executive dysfunction
Brief summary
There is a pressing need to develop more effective interventions to remediate cognitive deficits in highly prevalent disabling conditions such as stroke, head injury and other forms of acquired brain injury (ABI). Neuropsychological rehabilitation interventions developed in a clinical setting have shown some beneficial effects, but the effectiveness of clinical interventions have potential to be enhanced if informed by findings from cognitive neuroscience. Research into cognitive training using methods such as functional magnetic resonance imaging (fMRI) has contributed to an understanding of factors that promote changes in brain function, but this approach seldom includes individuals with brain damage or cognitive deficits. Its potential for application with clinical populations is therefore uncertain, meaning that people who may benefit do not have access to interventions that may improve their health and wellbeing. The proposed research brings together methods from neuropsychological rehabilitation and cognitive neuroscience to investigate 1) the feasibility of, and effect sizes arising from, combining an existing clinical intervention targeting mental strategies with an adaptive training programme targeting core cognitive processes, and 2) whether the novel treatment combination promotes changes in brain function that are detectable using fMRI. This project will develop and evaluate a training intervention that aims to improve outcomes from a strategy-based rehabilitation intervention, Goal Management Training (GMT), by adding process-based cognitive training with adaptive difficulty to enhance the executive function of working memory updating (WMU). People with ABI (n=32) will complete 9 sessions of GMT, a recommended treatment for deficits in frontal-lobe executive functions, with the addition of 8 WMU training sessions with or without adaptive training. Measures of feasibility, acceptability, and fidelity will be taken, and effect sizes of differences in pre- to post-training changes on neural, cognitive, and functional measurements will be determined by comparing two experimental groups in which difficulty of the WMU training tasks either adaptively increases in response to performance or is fixed.
Detailed description
Globally, stroke and head injury are leading causes of disability. Deficits in cognitive functions are common in these conditions, including impairment in frontal-lobe 'executive' functions such as working memory and the ability to solve problems, plan, and regulate actions in order to achieve intended goals. These deficits affect individuals' ability to live independently, work, and maintain social relationships. We propose that improving outcomes for people with acquired brain injury (ABI) requires an interdisciplinary approach in which neuropsychological rehabilitation and cognitive neuroscience complement one another. In neuropsychological rehabilitation, interventions are classified as 'restorative' (restoration of underlying core cognitive processes including executive functions) or 'compensatory' (compensation of function through the use of external aids or learned strategies). Clinical guidelines recommend the use of 'meta-cognitive strategy training' for the treatment of deficits in frontal-lobe executive functions. Goal Management Training (GMT) is one such validated meta-cognitive strategy. GMT trains compensatory mental strategies to manage attention during multi-step tasks. GMT has been evaluated behaviourally in randomised controlled trials with positive, albeit modest, outcomes in individuals with ABI. In cognitive neuroscience, an emerging research area concerns experience-induced neural changes referred to as neural plasticity. These may involve neural changes in: 1) task-based functional activation patterns, i.e. activity increases, decreases, or reorganisation, 2) brain structure, i.e., grey matter and white matter volume changes and 3) functional connectivity, i.e. changes in connectivity between brain regions that are recruited for a mental procedure as well as changes in the strength and magnitude. Neuroimaging studies have demonstrated that programmes to train core cognitive processes including working memory (WM) executive functions can drive changes both in behavioural and neural measures. Performance gains after process-based training have been observed by several authors employing different training tasks and including both younger and older populations. In addition, generalisation to broad cognitive abilities such as reasoning, episodic memory, after process-based training, has been observed in both young and older adults although this area is under debate. This work has primarily involved healthy adults and whether the same findings apply to those with ABI needs to be investigated. This research study aims to develop and evaluate a novel treatment intervention for people with ABI that combines a process-based cognitive training with a strategy-based GMT rehabilitation intervention, and to acquire functional magnetic resonance imaging (fMRI) data before and after the intervention to measure patterns of brain activity associated with a task requiring executive functions. We propose that outcomes from GMT might be improved by an adaptive, process-based intervention aimed at enhancing working memory processes. Adaptive task difficulty involves dynamic adjustment of training task demands so that the individual remains within an optimal range of performance. i. Aims The primary aim of the study is to investigate whether it is feasible and acceptable to deliver a novel intervention combining GMT with WMU training, within a randomised controlled trial (RCT) context in a sample of ABI individuals. A further aim is to examine the behavioural and neural changes related to the novel intervention as well as the effect sizes. ii. Research Question This project will combine methods from neuropsychological rehabilitation and cognitive neuroscience to answer the following: 1) Is it feasible to combine an existing treatment for executive dysfunction, GMT, with an adaptive WMU training and how much benefit is gained? 2) Does the novel treatment combination promote neural plasticity that is detectable using fMRI? iii. Outcomes Primary outcomes will be measures of feasibility, acceptability, and fidelity. Secondary outcomes will be pre- to post-training change in behavioural data (i.e., neuro-psychological assessment battery, measures of cognitive task performance and everyday functioning) and fMRI data (i.e., task-related brain activity), analysed by training condition. In addition, exploratory analyses of individual differences in responsiveness to WMU training will be performed, by calculating correlations between amount of adaptive training task improvement and pre- to post-training change on neural, cognitive, and functional measurements. iv. Design Randomised controlled trial methodology; specifically stratified randomisation in conjunction with permuted block random allocation, using an active control group will compare two conditions: (1) GMT combined with adaptive training \[AT\]; (2) GMT combined with non-adaptive \[NA\] training. Thirty-two adults with non-progressive ABI sustained in adulthood will be recruited from the NHS.. Participants will complete a combination of standard GMT (9 sessions) and 8 WMU (AT or NA) training sessions, delivered in small groups. Neuropsychological and functional assessments will be performed before and after the intervention. In addition, fMRI scanning sessions will be conducted pre- and post-training
Interventions
BEHAVIORALGMT combined with WMU Training
GMT teaches the use of mental strategies to support sustained attention during complex (multi-step) task performance following an interactive programme. GMT is structured into nine modules, with interactive discussions and homework assignments. It will be conducted on a group basis. WMU training consists of computerised working memory updating tasks in which trial accuracy and response time are recorded. Two tasks will be trained: 1. a visuo-spatial Matrix Updating (MU) and 2. a verbal Keep Track (KT). For both training tasks, level of difficulty can be modulated by increasing or decreasing the update level, i.e., the number of updates on each trial.
Sponsors
University of Glasgow
NHS Greater Glasgow and Clyde
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Only those able to give informed consent and able to comply with the training protocol will be included. * ≥ 6 months post-ABI at time of recruitment (expression of interest to participate either verbally or in writing) * Adults over the age of 18. * English language fluency (speaking) * a combination of self/relative/friend/carer reports of everyday organisation/memory problems
Exclusion criteria
* Individuals with contra-indications to MRI (e.g. heart pacemaker) * Comorbid progressive neurological disorder or neurodegenerative condition (e.g. dementia) * Major psychiatric disorder considered likely to prevent engagement in the intervention programme (pre-ABI history of mood disorder or stable antidepressant medication will not lead to exclusion) * History of major substance abuse problems likely to prevent engagement in the intervention programme * Unable to give informed consent * Unable to cooperate with the study protocol (e.g. severe impairment of hearing, vision or language)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Recruitment Process. | From pre-intervention (Week 1) to post-intervention (Week 12). | Number of people referred from NHS eligible for screening and those entering the intervention. This will be continuously monitored throughout the study period. |
| Participants' Drop-out Rates | From pre-intervention (Week 1) to post-intervention (Week 12). | Number of people completing the intervention to assess drop-out rates. This will be continuously monitored throughout the study period. |
| Participants' Coherence and Adherence to the Intervention. | From pre-intervention (Week 1) to post-intervention (Week 12). | Mean percentage of working memory training sessions completed (a total of eight) were calculated across participants. |
| Feedback Questionnaire | Post-intervention session (Week 12) | Participant evaluation of the intervention using a study-specific questionnaire including eight 5-point Likert-scale agreement questions (scores of 1 to 5 with 1 being positive and 5 being negative). Mean feedback score was calculated across participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Spatial Planning and Problem Solving Using the Stockings of Cambridge Test Variant From CANTAB Connect Research Web-testing. | Pre-intervention (Week 1) and post-intervention (Week 12) | Number of assessed problems that the participant successfully completed in the minimum possible number of moves. Calculated over all assessed trials. Higher score indicates a better outcome. Mean percentage change between pre and post intervention scores was calculated across participants. |
| Changes in Spatial Working Memory Using the Spatial Working Memory Test Variant From CANTAB Connect Research Web-testing. | Pre-intervention (Week 1) and post-intervention (Week 12) | The number of times the subject incorrectly revisits a box in which a token has previously been found. Calculated across all assessed four, six and eight token trials. Higher score indicates a worse outcome. Mean percentage change between pre and post intervention scores was calculated across participants. |
| Visuospatial Working Memory Using the Visuospatial Matrix Updating fMRI Task | Post-intervention session (week 12) | Performance in visuospatial working memory using the visuospatial Matrix Updating fMRI task. Accuracy is calculated as the proportion of correct responses at low and high difficulty task trials. Post-intervention session was used to calculate this measure. |
| Changes in Visuospatial Working Memory Using the Spatial Span Reverse Test Variant From CANTAB Connect Research Web-testing. | Pre-intervention (Week 1) and Post-intervention (Week 12) | The Spatial Span reverse test variant from CANTAB connect research web-testing was used calculated by the longest sequence of boxes successfully recalled. Higher score indicates a better outcome. Mean percentage change between pre and post intervention scores was calculated across participants. |
| Changes in Visuospatial Working Memory Using the Spatial Span Forward Test Variant From CANTAB Connect Research Web-testing. | Pre-intervention (Week 1) and post-intervention (Week 12) | The Spatial Span forward test variant from CANTAB connect research web-testing was used calculated by the longest sequence of boxes successfully recalled by the participant. Higher score indicates a better outcome. Mean percentage change between pre and post intervention scores was calculated across participants. |
| Visuospatial Working Memory fMRI Task Accuracy Using the Spatial N-back fMRI Task | Post-intervention session (Week 12) | Performance on spatial working memory using the spatial n-back fMRI task as calculated by proportion of correct responses at low and high difficulty n-back task trials. Post-intervention session was used to calculate this measure. |
| Episodic Visual Memory Accuracy Using the Object-location Association fMRI Task. | Post-intervention session (Week 12) | Performance on visual episodic memory using the Object-location association fMRI task calculated by the proportion of correct responses at low and high difficulty level task trials. Post-intervention session was used to calculate this measure. |
| Changes in Shifting Attention Using the Intra-Extra Dimensional Set Shift Test Variant From CANTAB Connect Research Web-testing. | Pre-intervention (Week 1) and post-intervention (Week 12) | Number of trials for which the outcome was an incorrect response (subject pressed the incorrect button within the response window), calculated across all assessed trials. Higher score indicates a worse outcome. Mean percentage change between pre and post intervention scores was calculated across participants. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adaptive Training (AT) Participants in this group receive a combination of Goal Management Training (GMT) and computerised Working Memory Updating (WMU). For participants in the AT group, difficulty of the WMU training tasks is progressively increased in response to task performance. | 14 |
| Non-Adaptive Training (NA) Participants in this group receive a combination of Goal Management Training (GMT) and computerised Working Memory Updating (WMU). For participants in the NA group, difficulty of the WMU training tasks remains at a relatively low level throughout the training period. | 0 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | Total | Adaptive Training (AT) |
|---|---|---|
| Age, Continuous | 53.14 years STANDARD_DEVIATION 10.49 | 53.14 years STANDARD_DEVIATION 10.49 |
| Race and Ethnicity Not Collected | 0 Participants | — |
| Region of Enrollment United Kingdom | 14 Participants | 14 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 0 |
| other Total, other adverse events | 0 / 14 | 0 / 0 |
| serious Total, serious adverse events | 0 / 14 | 0 / 0 |
Outcome results
Primary
Feasibility of Recruitment Process.
Number of people referred from NHS eligible for screening and those entering the intervention. This will be continuously monitored throughout the study period.
Time frame: From pre-intervention (Week 1) to post-intervention (Week 12).
Population: In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adaptive Training (AT) | Feasibility of Recruitment Process. | 33.33 % participants entered the intervention |
Primary
Feedback Questionnaire
Participant evaluation of the intervention using a study-specific questionnaire including eight 5-point Likert-scale agreement questions (scores of 1 to 5 with 1 being positive and 5 being negative). Mean feedback score was calculated across participants.
Time frame: Post-intervention session (Week 12)
Population: From the N=14 people entering the AT group, a total of N=5 dropped out and therefore we analysed data from the remaining N=9 individuals. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Feedback Questionnaire | 1.25 Average feedback score | Standard Deviation 0.31 |
Primary
Participants' Coherence and Adherence to the Intervention.
Mean percentage of working memory training sessions completed (a total of eight) were calculated across participants.
Time frame: From pre-intervention (Week 1) to post-intervention (Week 12).
Population: From the N=14 people entering the AT group, N=5 dropped out and therefore we analysed data from the remaining N=9 individuals. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Participants' Coherence and Adherence to the Intervention. | 73.61 % of working memory sessions completed | Standard Deviation 19.2 |
Primary
Participants' Drop-out Rates
Number of people completing the intervention to assess drop-out rates. This will be continuously monitored throughout the study period.
Time frame: From pre-intervention (Week 1) to post-intervention (Week 12).
Population: In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adaptive Training (AT) | Participants' Drop-out Rates | 35.7 % of participants who dropped out |
Secondary
Changes in Shifting Attention Using the Intra-Extra Dimensional Set Shift Test Variant From CANTAB Connect Research Web-testing.
Number of trials for which the outcome was an incorrect response (subject pressed the incorrect button within the response window), calculated across all assessed trials. Higher score indicates a worse outcome. Mean percentage change between pre and post intervention scores was calculated across participants.
Time frame: Pre-intervention (Week 1) and post-intervention (Week 12)
Population: From the N=14 people entering the AT group, a total of N=5 dropped out and therefore we analysed data from the remaining N=9 individuals. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Changes in Shifting Attention Using the Intra-Extra Dimensional Set Shift Test Variant From CANTAB Connect Research Web-testing. | 10.11 % change between pre and post scores | Standard Deviation 80 |
Secondary
Changes in Spatial Planning and Problem Solving Using the Stockings of Cambridge Test Variant From CANTAB Connect Research Web-testing.
Number of assessed problems that the participant successfully completed in the minimum possible number of moves. Calculated over all assessed trials. Higher score indicates a better outcome. Mean percentage change between pre and post intervention scores was calculated across participants.
Time frame: Pre-intervention (Week 1) and post-intervention (Week 12)
Population: From the N=14 people entering the AT group, a total of N=5 dropped out and therefore we analysed data from the remaining N=9 individuals. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Changes in Spatial Planning and Problem Solving Using the Stockings of Cambridge Test Variant From CANTAB Connect Research Web-testing. | 6.33 % change between pre and post scores | Standard Deviation 30.75 |
Secondary
Changes in Spatial Working Memory Using the Spatial Working Memory Test Variant From CANTAB Connect Research Web-testing.
The number of times the subject incorrectly revisits a box in which a token has previously been found. Calculated across all assessed four, six and eight token trials. Higher score indicates a worse outcome. Mean percentage change between pre and post intervention scores was calculated across participants.
Time frame: Pre-intervention (Week 1) and post-intervention (Week 12)
Population: From the N=14 people entering the AT group, a total of N=5 dropped out and therefore we analysed data from the remaining N=9 individuals. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Changes in Spatial Working Memory Using the Spatial Working Memory Test Variant From CANTAB Connect Research Web-testing. | 19.72 % change between pre and post scores | Standard Deviation 48.64 |
Secondary
Changes in Visuospatial Working Memory Using the Spatial Span Forward Test Variant From CANTAB Connect Research Web-testing.
The Spatial Span forward test variant from CANTAB connect research web-testing was used calculated by the longest sequence of boxes successfully recalled by the participant. Higher score indicates a better outcome. Mean percentage change between pre and post intervention scores was calculated across participants.
Time frame: Pre-intervention (Week 1) and post-intervention (Week 12)
Population: From the N=14 people entering the AT group, a total of N=5 dropped out and therefore we analysed data from the remaining N=9 individuals. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Changes in Visuospatial Working Memory Using the Spatial Span Forward Test Variant From CANTAB Connect Research Web-testing. | 3.70 % change between pre and post scores | Standard Deviation 18.22 |
Secondary
Changes in Visuospatial Working Memory Using the Spatial Span Reverse Test Variant From CANTAB Connect Research Web-testing.
The Spatial Span reverse test variant from CANTAB connect research web-testing was used calculated by the longest sequence of boxes successfully recalled. Higher score indicates a better outcome. Mean percentage change between pre and post intervention scores was calculated across participants.
Time frame: Pre-intervention (Week 1) and Post-intervention (Week 12)
Population: From the N=14 people entering the AT group, a total of N=5 dropped out and therefore we analysed data from the remaining N=9 individuals. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Changes in Visuospatial Working Memory Using the Spatial Span Reverse Test Variant From CANTAB Connect Research Web-testing. | 14.89 % change between pre and post scores | Standard Deviation 37.12 |
Secondary
Episodic Visual Memory Accuracy Using the Object-location Association fMRI Task.
Performance on visual episodic memory using the Object-location association fMRI task calculated by the proportion of correct responses at low and high difficulty level task trials. Post-intervention session was used to calculate this measure.
Time frame: Post-intervention session (Week 12)
Population: From the N=14 people entering the AT group, a total of N=7 people took part in the fMRI session. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Episodic Visual Memory Accuracy Using the Object-location Association fMRI Task. | 0.58 proportion of correct responses | Standard Deviation 0.15 |
Secondary
Visuospatial Working Memory fMRI Task Accuracy Using the Spatial N-back fMRI Task
Performance on spatial working memory using the spatial n-back fMRI task as calculated by proportion of correct responses at low and high difficulty n-back task trials. Post-intervention session was used to calculate this measure.
Time frame: Post-intervention session (Week 12)
Population: From the N=14 people entering the AT group, a total of N=7 people took part in the fMRI session. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Visuospatial Working Memory fMRI Task Accuracy Using the Spatial N-back fMRI Task | 0.78 proportion of correct responses | Standard Deviation 0.14 |
Secondary
Visuospatial Working Memory Using the Visuospatial Matrix Updating fMRI Task
Performance in visuospatial working memory using the visuospatial Matrix Updating fMRI task. Accuracy is calculated as the proportion of correct responses at low and high difficulty task trials. Post-intervention session was used to calculate this measure.
Time frame: Post-intervention session (week 12)
Population: From the N=14 people entering the AT group, a total of N=7 people took part in the fMRI session. In the context of disruptions associated with COVID-19, a decision was made to focus on testing the feasibility of running the experimental condition (Adaptive training) initially and therefore no participant was assigned in the control group (Non-Adaptive training).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adaptive Training (AT) | Visuospatial Working Memory Using the Visuospatial Matrix Updating fMRI Task | 0.69 proportion of correct responses | Standard Deviation 0.25 |