Physical activity has shown beneficial effects for cognitive and brain health, suggesting it may provide a highly scalable intervention to improve academic achievement. This project is part of a large-scale randomised controlled trial called Fit to Study (ClinicalTrials.gov ID: NCT03286725). The main Fit to Study trial aims to test the effect of a school-based physical activity intervention on academic performance (as well as cognition and physical measures) across Year 8 pupils in 100 secondary schools. The current study - the Fit to Study - Brain imaging sub-study - will target a sub-sample of participants in the large-scale trial, in order to test pre- to post intervention changes in hippocampal volume, as well as cognitive performance, mental health and brain organisation. We hypothesise that the intervention will change anterior hippocampal volume of Year-8 pupils, as well as mental health, cognitive performance, and more generally, brain structure and function. We further hypothesise that changes in brain organisation (e.g. hippocampal volume) may mediate changes in cognitive performance and mental health.

Physical activity has shown beneficial effects for cognitive and brain health. In particular, studies have shown that physical activity has the potential to increase the volume of the anterior portion of the hippocampus, a brain structure involved in learning and memory. The Fit to Study - Brain imaging sub-study is being conducted to understand better the effects of a physical activity intervention delivered during school PE lessons on anterior hippocampal volume, as well as cognition, mental health, and brain organisation.

The Fit to Study main trial aims to test the effect of a school-based physical activity intervention on academic performance (as well as cognition and physical measures) across Year 8 pupils in 100 secondary schools. A full description of the Fit to study main trail, including its outcome measures, has been provided as part of its registration at ClinicalTrials.gov (NCT03286725).

The Fit to Study - Brain imaging sub-study will target a sub-sample of participants of the large-scale trial, in order to test pre to post intervention changes in anterior hippocampal volume, as well as cognitive performance, mental health and brain organisation. The assessments will take place pre-intervention, immediately post-intervention and 12-months post-intervention, and will comprise structural and functional magnetic resonance imaging (MRI) scans.

Fit to Study main trial participants are considered eligible for brain imaging sub-study. The brain imaging sub-study consists of two sub-samples, recruited at different times during the trial:

1. The first cohort of 60 participants completed assessments pre-intervention, will complete identical assessments post-intervention to investigate pre-to-post intervention changes, and will be invited to take part in follow-up assessments.
2. A second cohort of ~50 participants will be recruited for post-intervention assessments that are similar, but not identical, to the assessments of the first group, as well as 1-year follow-up assessments. This cohort will enable cross-sectional analysis of between-group (intervention-control) differences in a larger sample.

The assessments are similar, but not identical for the two cohorts. The key assessments are listed here and details are provided in the 'outcome measures' section.

1. Cohort 1

   • Magnetic resonance imaging (at pre- and post intervention)
   • Computer-based cognitive tasks (at pre-, and post intervention and follow-up)
   • Mental health questionnaires (at pre-, and post intervention and follow-up)
   • Physical activity assessments (at pre-, and post intervention, and follow-up)
   • Fitness assessments (at pre-, and post intervention)
   • Gait assessments (at pre- and post intervention)

2. Cohort 2

   • Magnetic resonance imaging (at post intervention only)
   • Computer-based cognitive tasks (at post intervention and follow-up)
   • Mental health questionnaires (at post intervention and follow-up)
   • Physical activity assessments (at post intervention and follow-up)
   • Gait assessments (at post-intervention only)

The primary aims of the study are:

1. To examine cross-sectional relations between anterior hippocampal volume and physical activity and fitness at baseline (cohort 1)
2. To examine whether changes in anterior hippocampal volume are greater in the intervention group compared to the control group (i.e. group by time interaction tested in cohort 1)

Secondary aims are:

1. To examine cross-sectional relations between brain structure and function, and physical activity and fitness at baseline (cohort 1)
2. To examine whether changes in brain organisation, mental health, cognitive performance and fitness are greater in the intervention group compared to the control group (i.e. group by time interaction tested in cohort 1)
3. To examine whether brain organisation, mental health, cognitive performance and fitness is different in the intervention group compared to the control group post intervention
4. To identify MRI markers predisposing the PA intervention effect

1. Cohort 1:

   School level:

   Inclusion criteria

   • Enrolled in the the Fit to Study Main trial
   • Within a 75 miles radius from Oxford
   • Lower lower socio-economic background, as indicated by percentage of free school meal (FSM)-eligible pupils or postcode-derived index of multiple deprivation

   Pupil level:

   Inclusion criteria

   • Enrolled in the Fit to Study Main Trial
   • English speaking

   Exclusion criteria

   • Contraindication to MRI
   • Contraindication to VO2max fitness test

2. Cohort 2

School level:

Inclusion criteria

• High completion rates of baseline cognitive, questionnaire and fitness data relative to other schools
• Responsive to messages from the Fit to Study research team
• Lower socio-economic background, as indicated by the percentage of FSM or postcode-derived index of multiple deprivation
• For intervention schools only: adherence to the intervention.

From those schools that met criteria, a sub-sample of 10 schools is chosen by the trial manager.

Pupil level:

Inclusion criteria

• Low fitness compared to other pupils of their school who expressed an interest, based on their baseline fitness assessment (part of Fit to Study Main Trial)
• Enrolled in the Fit to Study Main Trial
• English speaking

Exclusion criteria

- Contraindication to MRI

If selected schools are not interested in the brain-imaging sub-study, these schools are replaced by other schools from the Fit to Study sample that are within reasonable travel distance (max 1.5h) from the brain imaging centre.

The datasets generated during and/or analysed as part of the brain imaging sub-study are available from the principal investigator upon reasonable request.