Multimodal Imaging Brain Markers in Early Adolescence Are Linked with a Physically Active Lifestyle.

The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7 d physical activity, body mass index, heart rate, and blood pressure. Using canonical correlation analysis, we unravel a latent mode of brain-physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater gray matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence.SIGNIFICANCE STATEMENT An active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents' level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging-derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain-body relationships in an effort to foster brain health at this crucial stage in development.

A critical evaluation of systematic reviews assessing the effect of chronic physical activity on academic achievement, cognition and the brain in children and adolescents: a systematic review.

BACKGROUND: International and national committees have started to evaluate the evidence for the effects of physical activity on neurocognitive health in childhood and adolescence to inform policy. Despite an increasing body of evidence, such reports have shown mixed conclusions. We aimed to critically evaluate and synthesise the evidence for the effects of chronic physical activity on academic achievement, cognitive performance and the brain in children and adolescents in order to guide future research and inform policy. METHODS: MedLine, Embase, PsycINFO, Cochrane Library, Web of Science, and ERIC electronic databases were searched from inception to February 6th, 2019. Articles were considered eligible for inclusion if they were systematic reviews with or without meta-analysis, published in peer-reviewed (English) journals. Reviews had to be on school-aged children and/or adolescents that reported on the effects of chronic physical activity or exercise interventions, with cognitive markers, academic achievement or brain markers as outcomes. Reviews were selected independently by two authors and data were extracted using a pre-designed data extraction template. The quality of reviews was assessed using AMSTAR-2 criteria. RESULTS: Of 908 retrieved, non-duplicated articles, 19 systematic reviews met inclusion criteria. One high-quality review reported inconsistent evidence for physical activity-related effects on cognitive- and academic performance in obese or overweight children and adolescents. Eighteen (critically) low-quality reviews presented mixed favourable and null effects, with meta-analyses showing small effect sizes (0.1-0.3) and high heterogeneity. Low-quality reviews suggested physical activity-related brain changes, but lacked an interpretation of these findings. Systematic reviews varied widely in their evidence synthesis, rarely took intervention characteristics (e.g. dose), intervention fidelity or study quality into account and suspected publication bias. Reviews consistently reported that there is a lack of high-quality studies, of studies that include brain imaging outcomes, and of studies that include adolescents or are conducted in South American and African countries. CONCLUSIONS: Inconsistent evidence exists for chronic physical activity-related effects on cognitive-, academic-, and brain outcomes. The field needs to refocus its efforts towards improving study quality, transparency of reporting and dissemination, and is urged to differentiate between intervention characteristics for its findings to have a meaningful impact on policy.

The importance of prototype similarity for physical activity: Cross-sectional and longitudinal associations in a large sample of young adolescents.

OBJECTIVES: Physical activity declines during adolescence. The Theory of Planned Behaviour (TPB) is a useful framework for investigating activity but leaves variance unexplained. We explored the utility of a dual-process approach using the TPB and the Prototype Willingness Model (PWM) to investigate correlates of physical activity, and 1-year change in physical activity, among a large sample of adolescents. DESIGN: A cross-sectional and longitudinal analysis of baseline and follow-up data from the Fit to Study cluster-randomized trial. METHODS: A total of 9,699 secondary school pupils at baseline and 4,632 at follow-up (mean age = 12.5 years) completed measures of past week physical activity and constructs from both behaviour-change models, at time-points 1 year apart. Cross-sectional analyses used multilevel, stepwise regression models to measure the strength of associations between model constructs and physical activity, and variance in behaviour explained by PWM over and above TPB. In longitudinal analyses, change scores were calculated by subtracting follow-up from baseline scores. Models controlling for trial treatment status measured the strength of associations between change scores, and variance explained. RESULTS: At baseline, after controlling for past behaviour, physically active prototype similarity had the strongest relationship with activity after the intention to be active. Change in prototype similarity had the strongest relationship with change in activity after the change in intention and attitudes. Prototype perceptions and willingness explained additional variance in behaviour. CONCLUSION: A dual-process model incorporating prototype perceptions could more usefully predict physical activity than models based on rational expectations alone. Behaviour-change interventions promoting an active self-image could be tested for effects on physical activity.

Hippocampal maintenance after a 12-month physical activity intervention in older adults: The REACT MRI study.

BACKGROUND: Physical activity interventions have had varying results on modifying hippocampal volume. METHODS: The Retirement in Action (REACT) study conducted a randomised-controlled trial of a 12-month physical activity and behaviour maintenance intervention in older adults at risk of mobility impairments. The physical activity sessions were delivered twice weekly for the first twelve weeks, and then reduced to once weekly, to groups of 15 participants. Activities included cardiovascular, strength, balance and flexibility exercises. A sub-sample of participants in the physical activity (N = 54) and control arms (N = 48) underwent a 3 T MRI brain scan and cognitive assessments at baseline, 6- and 12-months (mean age = 76.6 years, 6.8 SD). It was hypothesised that the intervention would lead to a reduced rate of decline in hippocampal volume. Group differences in changes in cognition were also examined. RESULTS: As hypothesised, we found a maintenance in left hippocampal volume in the intervention arm, in comparison with the control arm after 12 months (p = 0.027). In a secondary analysis, this effect was attenuated after including age, sex and education level as covariates (p = 0.057). There was no significant between-group difference in the right hippocampus (p = 0.405). Contrary to our hypothesis, we did not find a beneficial effect of the intervention on cognitive outcomes. CONCLUSIONS: Our findings suggest that a community-based physical activity intervention can significantly ward-off hippocampal atrophy in older adults. While the lack of effects on cognition may limit the interpretability of our results, our findings of hippocampal maintenance are promising given the potential clinical relevance of protecting the hippocampus from age-related decline.

Exploring activity levels in physical education lessons in the UK: a cross-sectional examination of activity types and fitness levels.

OBJECTIVES: To establish pupil fitness levels, and the relationship to global norms and physical education (PE) enjoyment. To measure and describe physical activity (PA) levels during secondary school PE lessons, in the context of recommended levels, and how levels vary with activity and lesson type. METHODS: A cross-sectional design; 10 697 pupils aged 12.5 (SD 0.30) years; pupils who completed a multistage fitness test and wore accelerometers to measure PA during PE lessons. Multilevel models estimated fitness and PE activity levels, accounting for school and class-level clustering. RESULTS: Cardiorespiratory fitness was higher in boys than girls (ß=-0.48; 95% CI -0.56 to -0.39, p<0.001), within absolute terms 51% of boys and 54% of girls above the 50th percentile of global norms. On average, pupils spent 23.8% of PE lessons in moderate-to-vigorous PA (MVPA), and 7.1% in vigorous PA (VPA). Fitness-focused lessons recorded most VPA in co-educational (ß=1.09; 95% CI 0.43 to 1.74) and boys-only lessons (ß=0.32; 95% CI -0.21 to 0.85). In girls-only lessons, track athletics recorded most VPA (ß=0.13; 95% CI -0.50 to 0.75) and net/wall/racket games (ß=0.97; 95% CI 0.12 to 1.82) the most MVPA. For all lesson types, field athletics was least active (ß=-0.85; 95% CI -1.33 to -0.36). There was a relationship of enjoyment of PE to fitness (ß=1.03; 95% CI 0.83 to 1.23), and this relationship did not vary with sex (ß=-0.14 to 0.23; 95% CI -0.16 to 0.60). CONCLUSIONS: PE lessons were inactive compared with current guidelines. We propose that if we are to continue to develop a range of sporting skills in schools at the same time as increasing levels of fitness and PA, there is a need to introduce additional sessions of PE activity focused on increasing physical activity. TRIAL REGISTRATION NUMBER: NCT03286725.

Fit to Study: Reflections on designing and implementing a large-scale randomized controlled trial in secondary schools.

BACKGROUND: The randomised controlled trial (RCT) design is increasingly common among studies seeking good-quality evidence to advance educational neuroscience, but conducting RCTs in schools is challenging. Fit to Study, one of six such trials funded by the Education Endowment Foundation and Wellcome Trust, tested an intervention to increase vigorous physical activity during PE lessons on maths attainment among pupils aged 12-13. This review of designing and conducting an RCT in 104 schools is intended as a resource on which researchers might draw for future studies. METHOD: We consider intervention design and delivery; recruitment, retention, trial management, data collection and analysis including ethical considerations and working with evaluators. RESULTS: Teacher training, intervention delivery and data collection during large-scale RCTs require a flexible approach appropriate to educational settings, which in turn entails planning and resources. CONCLUSION: Simple interventions, with few outcome measures and minimal missing data, are preferable to more complex designs.

Associations between fitness, physical activity and mental health in a community sample of young British adolescents: baseline data from the Fit to Study trial.

OBJECTIVES: To examine relationships between fitness, physical activity and psychosocial problems among English secondary school pupils and to explore how components of physically active lifestyles are associated with mental health and well-being. METHODS: A total of 7385 participants aged 11-13 took a fitness test and completed self-reported measures of physical activity, attitudes to activity, psychosocial problems and self-esteem during the Fit to Study trial. Multilevel regression, which modelled school-level cluster effects, estimated relationships between activity, fitness and psychosocial problems; canonical correlation analysis (CCA) explored modes of covariation between active lifestyle and mental health variables. Models were adjusted for covariates of sex, free school meal status, age, and time and location of assessments. RESULTS: Higher fitness was linked with fewer internalising problems (ß=-0.23; 95% CI -0.26 to -0.21; p<0.001). More activity was also related to fewer internalising symptoms (ß=-0.24; 95% CI -0.27 to -0.20; p<0.001); the relationship between activity and internalising problems was significantly stronger for boys than for girls. Fitness and activity were also favourably related to externalising symptoms, with smaller effect sizes. One significant CCA mode, with a canonical correlation of 0.52 (p=0.001), was characterised high cross-loadings for positive attitudes to activity (0.46) and habitual activity (0.42) among lifestyle variables; and for physical and global self-esteem (0.47 and 0.42) among mental health variables. CONCLUSION: Model-based and data-driven analysis methods indicate fitness as well as physical activity are linked to adolescent mental health. If effect direction is established, fitness monitoring could complement physical activity measurement when tracking public health.

The effects of an aerobic training intervention on cognition, grey matter volumes and white matter microstructure.

While there is strong evidence from observational studies that physical activity is associated with reduced risk of cognitive decline and dementia, the extent to which aerobic training interventions impact on cognitive health and brain structure remains subject to debate. In a pilot study of 46 healthy older adults (66.6 years ± 5.2 years, 63% female), we compared the effects of a twelve-week aerobic training programme to a waitlist control condition on cardiorespiratory fitness, cognition and magnetic resonance imaging (MRI) outcomes. Cardiorespiratory fitness was assessed by VO2 max testing. Cognitive assessments spanned executive function, memory and processing speed. Structural MRI analysis included examination of hippocampal volume, and voxel-wise assessment of grey matter volumes using voxel-based morphometry. Diffusion tensor imaging analysis of fractional anisotropy, axial diffusivity and radial diffusivity was performed using tract-based spatial statistics. While the intervention successfully increased cardiorespiratory fitness, there was no evidence that the aerobic training programme led to changes in cognitive functioning or measures of brain structure in older adults. Interventions that are longer lasting, multi-factorial, or targeted at specific high-risk populations, may yield more encouraging results.

Associations between modifiable risk factors and white matter of the aging brain: insights from diffusion tensor imaging studies.

There is increasing interest in factors that may modulate white matter (WM) breakdown and, consequentially, age-related cognitive and behavioral deficits. Recent diffusion tensor imaging studies have examined the relationship of such factors with WM microstructure. This review summarizes the evidence regarding the relationship between WM microstructure and recognized modifiable factors, including hearing loss, hypertension, diabetes, obesity, smoking, depressive symptoms, physical (in) activity, and social isolation, as well as sleep disturbances, diet, cognitive training, and meditation. Current cross-sectional evidence suggests a clear link between loss of WM integrity (lower fractional anisotropy and higher mean diffusivity) and hypertension, obesity, diabetes, and smoking; a relationship that seems to hold for hearing loss, social isolation, depressive symptoms, and sleep disturbances. Physical activity, cognitive training, diet, and meditation, on the other hand, may protect WM with aging. Preliminary evidence from cross-sectional studies of treated risk factors suggests that modification of factors could slow down negative effects on WM microstructure. Careful intervention studies are needed for this literature to contribute to public health initiatives going forward.

Increased default-mode network centrality in cognitively impaired multiple sclerosis patients.

OBJECTIVE: To investigate how changes in functional network hierarchy determine cognitive impairment in multiple sclerosis (MS). METHODS: A cohort consisting of 332 patients with MS (age 48.1 ± 11.0 years, symptom duration 14.6 ± 8.4 years) and 96 healthy controls (HCs; age 45.9 ± 10.4 years) underwent structural MRI, fMRI, and extensive neuropsychological testing. Patients were divided into 3 groups: cognitively impaired (CI; n = 87), mildly cognitively impaired (MCI; n = 65), and cognitively preserved (CP; n = 180). The functional importance of brain regions was quantified with degree centrality, the average strength of the functional connections of a brain region with the rest of the brain, and eigenvector centrality, which adds to this concept by adding additional weight to connections with brain hubs because these are known to be especially important. Centrality values were calculated for each gray matter voxel based on resting-state fMRI data, registered to standard space. Group differences were assessed with a cluster-wise permutation-based method corrected for age, sex, and education. RESULTS: CI patients demonstrated widespread centrality increases compared to both HCs and CP patients, mainly in regions making up the default-mode network. Centrality decreases were similar in all patient groups compared to HCs, mainly in occipital and sensorimotor areas. Results were robust across centrality measures. CONCLUSIONS: Patients with MS with cognitive impairment show hallmark alterations in functional network hierarchy with increased relative importance (centrality) of the default-mode network.

Damaged fiber tracts of the nucleus basalis of Meynert in Parkinson's disease patients with visual hallucinations.

Damage to fiber tracts connecting the nucleus basalis of Meynert (NBM) to the cerebral cortex may underlie the development of visual hallucinations (VH) in Parkinson's disease (PD), possibly due to a loss of cholinergic innervation. This was investigated by comparing structural connectivity of the NBM using diffusion tensor imaging in 15 PD patients with VH (PD + VH), 40 PD patients without VH (PD - VH), and 15 age- and gender-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) of pathways connecting the NBM to the whole cerebral cortex and of regional NBM fiber tracts were compared between groups. In PD + VH patients, compared to controls, higher MD values were observed in the pathways connecting the NBM to the cerebral cortex, while FA values were normal. Regional analysis demonstrated a higher MD of parietal (p = 0.011) and occipital tracts (p = 0.027) in PD + VH, compared to PD - VH patients. We suggest that loss of structural connectivity between the NBM and posterior brain regions may contribute to the etiology of VH in PD. Future studies are needed to determine whether these findings could represent a sensitive marker for the hypothesized cholinergic deficit in PD + VH patients.