Geschiktheid om de hersenen en cognitieve vaardigheden te helpen (Fit ABCS)

Web-based community-led, 12-week exercise program

Community based FTTs will use a web-based platform to deliver a 12-week exercise training program (120-minute group sessions of aerobic activity 3 times/week). Each session will include:

• Warm-up activities
• Aerobic activities and fitness training in a game-like fashion
• Organized sports/games
• Cool down activity
• Snack/reward time

Healthy control

In order to determine the feasibility of a 12 weeks of community-led exercise training for PBTS, there will be satisfactory patient recruitment. The goal is to recruit n=30 participants (≥25% probability)

Measure: The Bayesian probability statistic that 30 eligible patients will be recruited

In order to determine the feasibility of a 12 weeks of community-led exercise training for PBTS, there will be satisfactory participant attendance. The goal is for a participant to attend ≥60% of exercise training sessions (≥80% probability of participants).

Measure: The Bayesian probability statistic that participants will rate the therapeutic alliance between participant/instructor as cooperative and collaborative.

In order to determine the feasibility of a 12 weeks of community-led exercise training for PBTS, there will be satisfactory participant adherence to study procedures (neuroimaging, cognitive, health and quality of life (QOL), cardiovascular fitness and physical functioning assessments). The goal is for a recruited participant to complete all study procedures (≥80% probability).

Measure: The Bayesian probability statistic that a recruited participant will complete all study procedures

In order to determine the feasibility of a 12 weeks of community-led exercise training for PBTS, there will be satisfactory instructor adherence to deliver the program. The goal is for instructors to adhere to the web-based platform to deliver exercise training (≥80% probability).

Measure: The Bayesian probability statistic that instructors will adhere to the web-based platform to deliver exercise training

In order to determine the feasibility of a 12 weeks of community-led exercise training for PBTS, there will be satisfactory rating by the participant of the therapeutic alliance between participants and instructors. The goal is for participants to have a cooperative and collaborative relationship with the instructors, as rated by the Therapeutic Alliance Scales for Children-Revised questionnaire.

Measure: The Bayesian probability statistic that the therapeutic alliance between participant/instructor will be comparable across cohorts.

In order to determine the feasibility of a web-based platform to be used by community-based FTTs to deliver exercise training to PBTS, instructors will rate the platform as acceptable (e.g. would recommend to others, would continue to use). The goal is for instructors to rate the the platform as acceptable, indicating ease of use and satisfaction (≥80% probability).

Measure: The Bayesian probability statistic that instructors will rate the platform as acceptable

In order to determine the feasibility of a web-based platform to be used by community-based FTTs to deliver exercise training to PBTS, instructors will rate the platform as relevant (e.g. includes all necessary components to administer an exercise program, would choose to use such a tool to deliver an exercise program).The goal is for the instructors to rate the platform as relevant, indicating the presence of necessary information (≥80% probability).

Measure: The Bayesian probability statistic that instructors will rate the platform as relevant

In order to determine the feasibility of a web-based platform to be used by community-based FTTs to deliver exercise training to PBTS, instructors will rate the platform as efficient (e.g. is useful). The goal is for the instructors to rate the platform as efficient, indicating its usefulness (≥80% probability).

Measure: The Bayesian probability statistic that instructors will rate the platform as efficient

To compare community-led exercise training to historical data from a hospital-led exercise training for PBTS in terms of changes in hippocampal volume using MRI (magnetic resonance imaging).

Measures: Anatomical T1 weighted MRI will acquire estimates of hippocampal volume

To compare community-led exercise training to historical data from a hospital-led exercise training for PBTS in terms of changes in neural communication, as estimated by functional connectivity during magnetoencephalography (MEG) recording.

Measures: The weighted phase lag index (wPLI) will be used to measure functional connectivity during MEG recording as an estimate of neural communication

To compare community-led exercise training to historical data from a hospital-led exercise training program for PBTS in terms of changes in information processing speed.

Measure: Scores on the Rapid Visual Information Processing subtest of the Cambridge Neuropsychological Test Automated Battery

To compare community-led exercise training to historical data from a hospital-led exercise training program for PBTS in terms of changes in controlled attention.

Measure: Scores on the Match to Sample Visual Search Task subtest of the Cambridge Neuropsychological Test Automated Battery

To compare community-led exercise training to historical data from a hospital-led exercise training program for PBTS in terms of changes in declarative memory.

Measures: Scores on the Delayed Matching to Sample Task subtest of the Cambridge Neuropsychological Test Automated Battery

To compare community-led exercise training to historical data from a hospital-led exercise training program for PBTS in cardiovascular fitness, including heart rate, sub-maximal and and maximal work rates.

Measures: 6-Minute Walk Test and electrically braked cycle ergometer to measure heart rate, and sub-maximal and maximal pro-rated work rates

To compare community-led exercise training to historical data from a hospital-led exercise training program for PBTS in terms of changes in physical functioning, including bilateral coordination and balance (body coordination), and running speed/agility and strength (strength and agility).

Measure: Bilateral coordination and balance (body coordination), and running speed/agility and strength (strength and agility) using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Minimum points scored: 0, maximum points scored: 80; higher scores account for greater motor proficiency (better outcomes)

To investigate the impact of community-led exercise training in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in white matter microstructure using diffusion kurtosis imaging (DKI)

Measures: DKI will acquire kurtosis measures of water diffusion in the brain (mean, axial, radial kurtosis)

To investigate the impact of community-led exercise training in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes hippocampal volume using Anatomical T1 MRI

Measures: Hippocampal volume estimated using Anatomical T1 MRI

To investigate the impact of community-led exercise training in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in neural communication as estimated by functional connectivity during MEG recording.

Measures: The wPLI will be used to measure functional connectivity during MEG recording as an estimate of neural communication

To investigate the impact of community-led exercise training on the following outcomes in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in information processing speed.

Measures: Scores on the Pattern Comparison Processing Speed Test subtest of the National Institutes of Health Toolbox and Reaction Time Task subtest RTI subtest of the Cambridge Neuropsychological Test Automated Battery

To investigate the impact of community-led exercise training on the following outcomes in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in controlled attention

Measures: Scores on the Flanker Inhibitory Control & Attention Task subtest of the National Institutes of Health Toolbox, and the Stop Signal Task, Rapid Visual Information Processing, and Match to Sample Visual Search subtests of the of the Cambridge Neuropsychological Test Automated Battery

To investigate the impact of community-led exercise training on the following outcomes in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in declarative memory

Measures: Scores on the Children's Auditory Verbal and Learning Test-2 or Rey Auditory Verbal Learning Test (for participants who will be 18 years of age at the time of study completion) and Delayed Matching to Sample subtest of the Cambridge Neuropsychological Test Automated Battery

To investigate the impact of community-led exercise training on the following outcomes in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in full scale intelligence.

Measures: Scores on the Vocabulary and Matrix Reasoning subtests of the Wechsler Abbreviated Scale of Intelligence-Second Edition

To investigate the impact of community-led exercise training on the following outcomes in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in MEG behavioural measures.

Measures: Reaction time and accuracy scores on the Simple and Choice Visual-Motor Reaction Time Task, and Multi-Source Interference Task during MEG recording

To investigate the impact of community-led exercise training on the following outcomes in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in health and QOL

Measure: Scores on the Patient-Reported Outcomes Measurement Information System - Global health 7+2, Pediatric Quality of Life Scale generic core scale, physical activity preference questionnaire and Habitual Physical Activity Scale. All health and QOL measures are parent-proxy reports.

To investigate the impact of community-led exercise training on the following outcomes in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in cardiovascular fitness, including heart rate, sub-maximal and and maximal work rates.

Measures: 6-Minute Walk Test and electrically braked cycle ergometer to measure heart rate, and sub-maximal and maximal pro-rated work rates

To investigate the impact of community-led exercise training in PBTS to provide preliminary data for a subsequent adequately powered randomized controlled trial in terms of changes in physical functioning, including bilateral coordination and balance (body coordination), and running speed/agility and strength (strength and agility), and ataxia.

Measure: Bilateral coordination and balance (body coordination), and running speed/agility and strength (strength and agility) using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Minimum points scored: 0, maximum points scored: 80; higher scores account for greater motor proficiency (better outcomes), strength assessment conducted by a registered Physiotherapist and the Scale for the Assessment and Rating of Ataxia. Minimum points scored: 0, maximum points scored: 40; higher scores indicate increased severity of ataxia (worse outcome)

To investigate the impact of community-let exercise training in PBTS to improve physical functioning in the participant's daily life, as reported by their parent.

Measure: Parent report the ease of physical (and cognitive) activities in their child's daily life.

To investigate whether PBTS participants more closely resemble their healthy peers in brain structure following exercise training and at 3-month follow up compared to before exercise training.

Measures: brain structure (MRI) as assessed through white matter microstructure as estimated by kurtosis (mean, axial, and radial).

To investigate whether PBTS participants more closely resemble their healthy peers in brain function following exercise training and at 3-month follow up compared to before exercise training.

Measures: Hippocampal volume and functional connectivity (MEG) as estimated by the weighted Phase Lag Index (wPLI)

To investigate whether PBTS participants more closely resemble their healthy peers in cognition following exercise training and at 3-month follow up compared to before exercise training

Measures: Pattern Comparison Processing Speed Test, Reaction Time (RTI) (reaction time for simple and 5-choice conditions= measured in milliseconds, shorter reaction time is better)

To investigate whether PBTS participants more closely resemble their healthy peers in cognition following exercise training and at 3-month follow up compared to before exercise training

Measures: Flanker Inhibitory Control & attention Task, SST, RVP, and MTS)

SST: Stop Signal Task (stop signal reaction time = milliseconds, lower is better)

RVP: Rapid Visual information Processing (A prime = range 0-1, higher is better)

MTS: Match To Sample visual search (correct trials (all trials) = %, higher is better)

To investigate whether PBTS participants more closely resemble their healthy peers in cognition following exercise training and at 3-month follow up compared to before exercise training

Measures: CAVLT-2 or RAVLT, DMS

CAVLT-2: Children's Auditory Verbal Learning Test 2 (standard scores range from <60 to >140, higher is better)

RAVLT: Rey Auditory Verbal Learning Test (T scores range from < 20 to >80, higher is better)

DMS: Delayed Matching to Sample (correct trials (all trials) = %, higher is better)

To investigate whether PBTS participants more closely resemble their healthy peers in cognition following exercise training and at 3-month follow up compared to before exercise training

Measures: 2 subtests (Vocabulary, Matrix Reasoning) where T-scores are computed (20-80 range) with a higher value denoting a better score.

To investigate whether PBTS participants more closely resemble their healthy peers in cognition following exercise training and at 3-month follow up compared to before exercise training

Measures: Go/No-Go task, MSIT

MSIT: Multi Source Interference Task (reaction time= milliseconds, lower is better; accuracy = /1, higher is better; this also applies to Go/No-Go)

To investigate whether PBTS participants more closely resemble their healthy peers in health and quality of life following exercise training and at 3-month follow- up compared to before exercise training.

Measure: PROMIS parent proxy scale- Global health 7+2, PedsQL generic core parent-proxy report

PROMIS: Patient-Reported Outcomes Measurement Information System (T-scores range 14.7-68.78, higher is better)

PedsQL: Pediatric Quality of Life scale (range 0-100, higher score is better QoL)

To investigate whether PBTS participants more closely resemble their healthy peers in health and quality of life following exercise training and at 3-month follow- up compared to before exercise training.

Measure: HAES parent-proxy report, and PEDI-CAT

HAES: Habitual Activity Estimation Scale (active hours = higher is better, inactive hours= lower is better)

PEDI-CAT: pediatric evaluation of disability inventory computer adaptive test (scaled scores range 20-80, higher is better)