Neuroimaging has revealed that major depression is underpinned by dysfunctional brain networks, with symptom variability stemming from altered interactions within and between brain regions. While the effect of depression severity is well-studied, the effect of depression duration (chronicity) is relatively neglected, despite its clinical significance. This study examined how severity, chronicity, and their interaction affect brain network connectivity and grey matter volume. Forty-six patients (31 females, mean age 40.5) were assessed using whole-brain network modeling and voxel-based morphometry (VBM). Severity was measured via the Hamilton Depression Rating Scale, and chronicity was defined as an episode lasting over 24 months. The key finding was that chronicity moderated the impact of severity on functional connectivity between the Central Executive Network (CEN) and the precuneus (part of the Default Mode Network, DMN). Chronic versus non-chronic patients showed opposite patterns. Non-chronic patients showed stronger CEN-Default Mode Precuneus connectivity at low severity and weaker at high severity; chronic patients showed the reverse. This study reveals a novel impact of chronicity on CEN-DMN interactions, a neglected moderator of brain-symptom severity correlations in depression.

PURPOSE:Cerebral Palsy (CP) is the commonest cause of childhood motor disability. Transcranial direct current stimulation (tDCS) is a promising adjuvant therapy, but research targeting upper and lower limbs simultaneously is needed. We aimed to pilot tDCS with upper/lower limb motor training, estimate the potential effect on motor function, and investigate brain imaging correlates of function. MATERIALS AND METHODS:Participants (10-16 years) with CP affecting upper and/or lower limbs were randomised (online software) to 10 sessions of active (n = 14) or sham (n = 13) tDCS combined with motor training. The primary outcomes were upper and lower limb function assessed at 1-week post-intervention using the Jebson Taylor hand function (JTT) and Timed Up and Go (TUG) tests. Secondary, imaging outcomes included baseline tractography, grey matter volume, and resting state connectivity. RESULTS:Adherence was good: 74% completed all intervention sessions, 100% completed the primary outcome assessment. There were no between-group differences (1-week post-intervention, intention-to-treat; group-by-time JTT: F(1,25)=1.189,p = 0.286, partial-eta-squared = 0.05; TUG: F(1,25)=1.605,p = 0.217, partial-eta-squared = 0.06). Imaging showed subtle associations between better JTT at baseline and higher grey matter volume (caudate nucleus) and stronger sensorimotor resting state connectivity. CONCLUSIONS:The trial was well tolerated, but effect sizes were small. Larger studies are needed to further explore tDCS for CP.

Introduction The number of people living with dementia worldwide is growing. Devising and implementing preventive strategies that are globally applicable is of paramount importance. However, previous studies have largely been limited to cohorts that are geographically and culturally homogenous. It is not known whether the associations between demographics, vascular risk factors (VRFs), and cognitive changes are consistent across cohorts with cultural and geographical variations. Methods Data were analysed retrospectively from 6 community-dwelling cohorts (> 60 years old) with cultural and geographical variations (British = 536; Hong Kong Chinese = 494; Australian = 302; Singaporean Chinese = 108; German = 102; Swedish = 94). Clinical demographics, VRFs, longitudinal cognitive changes, and MRI data (including T1, FLAIR, and diffusion images) were analysed from all 6 cohorts. First, across all cohorts, a grand canonical correlation analysis (n=1636) was used to establish common modes of covariation between demographics and VRFs on one side, and cognitive changes on the other side. Second, separately for each cohort, mediation analysis was used to investigate the mediating role of normalised total grey matter volume, microstructural integrity, white matter hyperintensity, and hippocampal structural network in the association mentioned above. Then the mediation outputs will be used in the meta- analysis to assess the indirect effect estimates and variance of each significant brain mediator. Results We identified three modes of covariation between dementia risk and cognition across all cohorts (p< 0.01). The strongest mode linked younger age and higher levels of education with better cognition at baseline and follow-up (Figure 1). Meta-analysis showed that, across cohorts, normalised total grey matter volume (Indirect effect = 0.02, Z = 3.13, p < 0.001, I² = 0%) was a significant mediator between demographics, VRFs, and cognitive decline after Bonferroni correction (Figure 2). The hippocampal structural network did not survive Bonferroni correlation while other brain mediators were not significant in the meta-analyses. Discussion This study investigated the complex relationship between demographics, VRFs, brain health, and cognition. Cohorts with cultural and demographic variations shared a common relationship between age, education, and cognition. However, individual cohort differences are detected in the contribution of different neuroimaging metrics.

[This corrects the article DOI: 10.3389/fnins.2023.1187790.].

Health-related behaviours have been related to brain structural features. In developing settings, such as Latin America, high social inequality has been inversely associated with several health-related behaviours affecting brain development. Understanding the relationship between health behaviours and brain structure in such settings is particularly important during adolescence when critical habits are acquired and ingrained. In this cross-sectional study, we carry out a multimodal analysis identifying a brain region associated with health-related behaviours (i.e., adiposity, fitness, sleep problems and others) and cognitive/academic performance, independent of socioeconomic status in a large sample of Chilean adolescents. Our findings suggest that the relationship between health behaviours and cognitive/academic performance involves a particular brain phenotype that could play a mediator role. These findings fill a significant gap in the literature, which has largely focused on developed countries and raise the possibility of promoting healthy behaviours in adolescence as a means to influence brain structure and thereby cognitive/academic achievement, independently of socioeconomic factors. By highlighting the potential impact on brain structure and cognitive/academic achievement, policymakers could design interventions that are more effective in reducing health disparities in developing countries.

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience. The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

Developmental coordination disorder (DCD) is characterized by motor learning deficits that are poorly understood within whole-body activities context. Here we present results of one of the largest non-randomized interventional trials combining brain imaging and motion capture techniques to examine motor skill acquisition and its underpinning mechanisms in adolescents with and without DCD. A total of 86 adolescents with low fitness levels (including 48 with DCD) were trained on a novel stepping task for a duration of 7 weeks. Motor performance during the stepping task was assessed under single and dual-task conditions. Concurrent cortical activation in the prefrontal cortex (PFC) was measured using functional near-infrared spectroscopy (fNIRS). Additionally, structural and functional magnetic resonance imaging (MRI) was conducted during a similar stepping task at the beginning of the trial. The results indicate that adolescents with DCD performed similarly to their peers with lower levels of fitness in the novel stepping task and demonstrated the ability to learn and improve motor performance. Both groups showed significant improvements in both tasks and under single- and dual-task conditions at post-intervention and follow-up compared to baseline. While both groups initially made more errors in the Stroop task under dual-task conditions, at follow-up, a significant difference between single- and dual-task conditions was observed only in the DCD group. Notably, differences in prefrontal activation patterns between the groups emerged at different time points and task conditions. Adolescents with DCD exhibited distinct prefrontal activation responses during the learning and performance of a motor task, particularly when complexity was increased by concurrent cognitive tasks. Furthermore, a relationship was observed between MRI brain structure and function measures and initial performance in the novel stepping task. Overall, these findings suggest that strategies that address task and environmental complexities, while simultaneously enhancing brain activity through a range of tasks, offer opportunities to increase the participation of adolescents with low fitness in physical activity and sports.

ObjectivesPhysical 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.DesignA cross‐sectional and longitudinal analysis of baseline and follow‐up data from the Fit to Study cluster‐randomized trial.MethodsA 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.ResultsAt 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.ConclusionA 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.

Although we understand how serotonin receptors function at the single-cell level, what role different serotonin receptors play in regulating brain-wide activity and, in turn, human behavior, remains unknown. Here, we developed transcriptomic-neuroimaging mapping to characterize brain-wide functional signatures associated with specific serotonin receptors: serotonin receptor networks (SRNs). Probing SRNs with optogenetics-functional magnetic resonance imaging (MRI) and pharmacology in mice, we show that activation of dorsal raphe serotonin neurons differentially modulates the amplitude and functional connectivity of different SRNs, showing that receptors' spatial distributions can confer specificity not only at the local, but also at the brain-wide, network level. In humans, using resting-state functional MRI, SRNs replicate established divisions of serotonin effects on impulsivity and negative biases. These results provide compelling evidence that heterogeneous brain-wide distributions of different serotonin receptor types may underpin behaviorally distinct modes of serotonin regulation. This suggests that serotonin neurons may regulate multiple aspects of human behavior via modulation of large-scale receptor networks.

Myelination has been increasingly implicated in the function and dysfunction of the adult human brain. Although it is known that axon myelination shapes axon physiology in animal models, it is unclear whether a similar principle applies in the living human brain, and at the level of whole axon bundles in white matter tracts. Here, we hypothesised that in humans, cortico-cortical interactions between two brain areas may be shaped by the amount of myelin in the white matter tract connecting them. As a test bed for this hypothesis, we use a well-defined interhemispheric premotor-to-motor circuit. We combined TMS-derived physiological measures of cortico-cortical interactions during action reprogramming with multimodal myelin markers (MT, R1, R2* and FA), in a large cohort of healthy subjects. We found that physiological metrics of premotor-to-motor interaction are broadly associated with multiple myelin markers, suggesting interindividual differences in tract myelination may play a role in motor network physiology. Moreover, we also demonstrate that myelination metrics link indirectly to action switching by influencing local primary motor cortex dynamics. These findings suggest that myelination levels in white matter tracts may influence millisecond-level cortico-cortical interactions during tasks. They also unveil a link between the physiology of the motor network and the myelination of tracts connecting its components, and provide a putative mechanism mediating the relationship between brain myelination and human behaviour.

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce StandardRat , a consensus rat functional MRI acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired in rats from 46 centers. We developed a reproducible pipeline for the analysis of rat data acquired with diverse protocols and determined experimental and processing parameters associated with a more robust functional connectivity detection. We show that the standardized protocol enhances biologically plausible functional connectivity patterns, relative to pre-existing acquisitions. The protocol and processing pipeline described here are openly shared with the neuroimaging community to promote interoperability and cooperation towards tackling the most important challenges in neuroscience.

Synaptic plasticity is required for learning and follows Hebb’s Rule, the com-putational principle underpinning associative learning. In recent years, a complementary type of brain plasticity has been identified in myelinated axons, which make up the majority of brain’s white matter. Like synaptic plasticity, myelin plasticity is required for learning, but it is unclear whether it is Hebbian or whether it follows different rules. Here, we provide evidence that white matter plasticity operates following Hebb’s Rule in humans. Across two experiments, we find that co-stimulating cortical areas to induce Hebbian plasticity leads to relative increases in cortical excitability and associated increases in a myelin marker within the stimulated fiber bundle. We conclude that Hebbian plasticity extends beyond synaptic changes, and can be observed in human white matter fibers.

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.

Objective: To test the extent to which initial walking speed influences dual-task performance after walking intervention, hypothesising that slow walking speed affects automatic gait control, limiting executive resource availability. Design: A secondary analysis of a trial of dual-task (DT) and single-task (ST) walking interventions comparing those with good (walking speed ⩾0.8 m s−1, n = 21) and limited (walking speed <0.79 m s−1, n = 24) capacity at baseline. Setting: Community. Subjects: Adults six-months post stroke with walking impairment. Interventions: Twenty sessions of 30 minutes treadmill walking over 10 weeks with (DT) or without (ST) cognitive distraction. Good and limited groups were formed regardless of intervention received. Main measures: A two-minute walk with (DT) and without (ST) a cognitive distraction assessed walking. fNIRS measured prefrontal cortex activation during treadmill walking with (DT) and without (ST) Stroop and planning tasks and an fMRI sub-study used ankle-dorsiflexion to simulate walking. Results: ST walking improved in both groups (∆baseline: Good = 8.9 ± 13.4 m, limited = 5.3±8.9 m, Group × time = P < 0.151) but only the good walkers improved DT walking (∆baseline: Good = 10.4 ± 13.9 m, limited = 1.3 ± 7.7 m, Group × time = P < 0.025). fNIRS indicated increased ispilesional prefrontal cortex activation during DT walking following intervention ( P = 0.021). fMRI revealed greater DT cost activation for limited walkers, and increased resting state connectivity of contralesional M1 with cortical areas associated with conscious gait control at baseline. After the intervention, resting state connectivity between ipsilesional M1 and bilateral superior parietal lobe, involved in integrating sensory and motor signals, increased in the good walkers compared with limited walkers. Conclusion: In individual who walk slowly it may be difficult to improve dual-task walking ability. Registration: ISRCTN50586966

Human neuroimaging studies have shown that, during cognitive processing, the brain undergoes dynamic transitions between multiple, frequency-tuned states of activity. Although different states may emerge from distinct sources of neural activity, it remains unclear whether single-area neuronal spiking can also drive multiple dynamic states. In mice, we ask whether frequency modulation of the entorhinal cortex activity causes dynamic states to emerge and whether these states respond to distinct stimulation frequencies. Using hidden Markov modeling, we perform unsupervised detection of transient states in mouse brain-wide fMRI fluctuations induced via optogenetic frequency modulation of excitatory neurons. We unveil the existence of multiple, frequency-dependent dynamic states, invisible through standard static fMRI analyses. These states are linked to different anatomical circuits and disrupted in a frequency-dependent fashion in a transgenic model of cognitive disease directly related to entorhinal cortex dysfunction. These findings provide cross-scale insight into basic neuronal mechanisms that may underpin flexibility in brain-wide dynamics.

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2*). Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone. To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40 to 200 may be required to detect such joint multimodal effects, depending on the task being considered. These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WM’s relationship with behaviour, suggesting that variable biological effects may be shaping their interaction. Highlights Pre-registered testing of microstructural imaging across modalities (FA, MT, R1, R2*) to test WM-behaviour relationships. Partial support for FA-behaviour relationships hypothesised based on previous literature. Multimodal approaches can help detect WM-behaviour relationships that are not detected with FA alone. Sample sizes of 40 to 200 may be needed to detect myelin-behaviour relationships in joint multimodal analyses. Variable biological effects may be shaping WM-behaviour relationships.

Background Physical activity (PA) may positively stimulate the brain, cognition and mental health during adolescence, a period of dynamic neurobiological development. High-intensity interval training (HIIT) or vigorous PA interventions are time-efficient, scalable and can be easily implemented in existing school curricula, yet their effects on cognitive, academic and mental health outcomes are unclear. The primary aim of the Fit to Study trial was to investigate whether a pragmatic and scalable HIIT-style VPA intervention delivered during school physical education (PE) could improve attainment in maths. The primary outcome has previously been reported and was null. Here, we report the effect of the intervention on prespecified secondary outcomes, including cardiorespiratory fitness, cognitive performance, and mental health in young adolescents. Methods The Fit to Study cluster randomised controlled trial included Year 8 pupils ( n = 18,261, aged 12–13) from 104 secondary state schools in South/Mid-England. Schools were randomised into an intervention condition ( n = 52), in which PE teachers delivered an additional 10 min of VPA per PE lesson for one academic year (2017–2018), or into a “PE as usual” control condition. Secondary outcomes included assessments of cardiorespiratory fitness (20-m shuttle run), cognitive performance (executive functions, relational memory and processing speed) and mental health (Strength and Difficulties Questionnaire and self-esteem measures). The primary intention-to-treat (ITT) analysis used linear models and structural equation models with cluster-robust standard errors to test for intervention effects. A complier-average causal effect (CACE) was estimated using a two-stage least squares procedure. Results The HIIT-style VPA intervention did not significantly improve cardiorespiratory fitness, cognitive performance (executive functions, relational memory or processed speed), or mental health (all p > 0.05). Subgroup analyses showed no significant moderation of intervention effects by sex, socioeconomic status or baseline fitness levels. Changes in cardiorespiratory fitness were not significantly related to changes in cognitive or mental health outcomes. The trial was marked by high drop-out and low intervention compliance. Findings from the CACE analysis were in line with those from the ITT analysis. Conclusion The one-academic year HIIT-style VPA intervention delivered during regular school PE did not significantly improve fitness, cognitive performance or mental health, but these findings should be interpreted with caution given low implementation fidelity and high drop-out. Well-controlled, large-scale, school-based trials that examine the effectiveness of HIIT-style interventions to enhance cognitive and mental health outcomes are warranted. Trial registration ISRCTN registry, 15,730,512 . Trial protocol and analysis plan for primary outcome prospectively registered on 30th March 2017. ClinicalTrials.gov , NCT03286725 . Secondary measures (focus of current manuscript) retrospectively registered on 18 September 2017.

The triple-network model of psychopathology is a framework to explain the functional and structural neuroimaging phenotypes of psychiatric and neurological disorders. It describes the interactions within and between three distributed networks: the salience, default-mode, and central executive networks. These have been associated with brain disorder traits in patients. Homologous networks have been proposed in animal models, but their integration into a triple-network organization has not yet been determined. Using resting-state datasets, we demonstrate conserved spatio-temporal properties between triple-network elements in human, macaque, and mouse. The model predictions were also shown to apply in a mouse model for depression. To validate spatial homologies, we developed a data-driven approach to convert mouse brain maps into human standard coordinates. Finally, using high-resolution viral tracers in the mouse, we refined an anatomical model for these networks and validated this using optogenetics in mice and tractography in humans. Unexpectedly, we find serotonin involvement within the salience rather than the default-mode network. Our results support the existence of a triple-network system in the mouse that shares properties with that of humans along several dimensions, including a disease condition. Finally, we demonstrate a method to humanize mouse brain networks that opens doors to fully data-driven trans-species comparisons.

An important question in neuroscience is how local activity can be flexibly and selectively routed across the brain network. A proposed mechanism to flexibly route information is frequency division multiplexing: selective readout can be achieved by segregating the signal into non-overlapping frequency bands. Here, in wild-type mice and in a transgenic model (3xTgAD) of Alzheimer’s Disease (AD), we use optogenetic activation of the entorhinal cortex, concurrent whole-brain fMRI, and hidden Markov modeling. We demonstrate how inducing neuronal spiking with different theta frequencies causes spatially distinct states of brain network dynamics to emerge and to preferentially respond to one frequency, showing how selective information streams can arise from a single neuronal source of activity. This theta modulation mechanism, however, is impaired in the AD model. This work demonstrates that neuronal multiplexing is a sufficient mechanism to enable flexible brain network communication, and provides insight into the aberrant mechanisms underlying cognitive decline. ### Competing Interest Statement The authors have declared no competing interest.

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 (β=−0.23; 95% CI −0.26 to −0.21; p<0.001). More activity was also related to fewer internalising symptoms (β=−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.