Multimodal neuroimaging correlates of physical-cognitive covariation in Chilean adolescents. The Cogni-Action Project.

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.

Cost-effectiveness of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: an economic evaluation of the REACT (Retirement in Action) trial.

BACKGROUND: Mobility limitations in older populations have a substantial impact on health outcomes, quality of life, and social care costs. The Retirement in Action (REACT) randomised controlled trial assessed a 12-month community-based group physical activity and behaviour maintenance intervention to help prevent decline in physical functioning in older adults at increased risk of mobility limitation. We aimed to do an economic evaluation of the REACT trial to investigate whether the intervention is cost-effective. METHODS: In this health economic evaluation, we did cost-effectiveness and cost-utility analyses of the REACT programme versus standard care on the basis of resource use, primary outcome, and health-related quality-of-life data measured in the REACT trial. We also developed a decision analytic Markov model that forecasts the mobility of recipients beyond the 24-month follow-up of the trial and translated this into future costs and potential benefit to health-related quality of life using the National Health Service and Personal Social Services perspective. Participants completed questionnaire booklets at baseline, and at 6, 12, and 24 months after randomisation, which included a resource use questionnaire and the EQ-5D-5L and 36-item short-form survey (SF-36) health-related quality-of-life instruments. The cost of delivering the intervention was estimated by identifying key resources, such as REACT session leader time, time of an individual to coordinate the programme, and venue hire. EQ-5D-5L and SF-36 responses were converted to preference-based utility values, which were used to estimate quality-adjusted life-years (QALYs) over the 24-month trial follow-up using the area-under-the-curve method. We used generalised linear models to examine the effect of the REACT programme on costs and QALYs and adjust for baseline covariates. Costs and QALYs beyond 12 months were discounted at 3·5% per year. This is a pre-planned analysis of the REACT trial; the trial itself is registered with ISRCTN (ISRCTN45627165). FINDINGS: The 12-month REACT programme was estimated to cost £622 per recipient to deliver. The most substantial cost components are the REACT session leader time (£309 per participant), venue hire (£109), and the REACT coordinator time (£80). The base-case analysis of the trial-based economic evaluation showed that reductions in health and social care usage due to the REACT programme could offset the REACT delivery costs (£3943 in the intervention group vs £4043 in the control group; difference: -£103 [95% CI -£695 to £489]) with a health benefit of 0·04 QALYs (0·009-0·071; 1·354 QALYs in the intervention group vs 1·314 QALYs in the control group) within the 24-month timeframe of the trial. INTERPRETATION: The REACT programme could be considered a cost-effective approach for improving the health-related quality of life of older adults at risk of mobility limitations. FUNDING: National Institute for Health Research Public Health Research Programme.

Frequency modulation of entorhinal cortex neuronal activity drives distinct frequency-dependent states of brain-wide dynamics.

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.

A community-based physical activity intervention to prevent mobility-related disability for retired older people (REtirement in ACTion (REACT)): study protocol for a randomised controlled trial.

BACKGROUND: The REtirement in ACTion (REACT) study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial (RCT) with an internal pilot phase. It aims to test the effectiveness and cost-effectiveness of a community, group-based physical activity intervention for reducing, or reversing, the progression of functional limitations in older people who are at high risk of mobility-related disability. METHODS/DESIGN: A sample of 768 sedentary, community-dwelling, older people aged 65 years and over with functional limitations, but who are still ambulatory (scores between 4 and 9 out of 12 in the Short Physical Performance Battery test (SPPB)) will be randomised to receive either the REACT intervention, delivered over a period of 12 months by trained facilitators, or a minimal control intervention. The REACT study incorporates comprehensive process and economic evaluation and a nested sub-study which will test the hypothesis that the REACT intervention will slow the rate of brain atrophy and of decline in cognitive function assessed using magnetic resonance imaging (MRI). Outcome data will be collected at baseline, 6, 12 and 24 months for the main study, with MRI sub-study data collected at baseline, 6 and 12 months. The primary outcome analysis (SPPB score at 24 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals. DISCUSSION: REACT represents the first large-scale, pragmatic, community-based trial in the UK to target the non-disabled but high-risk segment of the older population with an intervention to reduce mobility-related disability. A programme that can successfully engage this population in sufficient activity to improve strength, aerobic capacity, coordination and balance would have a major impact on sustaining health and independence. REACT is also the first study of its kind to conduct a full economic and comprehensive process evaluation alongside the RCT. If effective and cost-effective, the REACT intervention has strong potential to be implemented widely in the UK and elsewhere. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN45627165 . Retrospectively registered on 13 June 2016. Trial sponsor: University of Bath. Protocol Version 1.5.

Functional Strength Training and Movement Performance Therapy for Upper Limb Recovery Early Poststroke-Efficacy, Neural Correlates, Predictive Markers, and Cost-Effectiveness: FAST-INdiCATE Trial.

BACKGROUND: Variation in physiological deficits underlying upper limb paresis after stroke could influence how people recover and to which physical therapy they best respond. OBJECTIVES: To determine whether functional strength training (FST) improves upper limb recovery more than movement performance therapy (MPT). To identify: (a) neural correlates of response and (b) whether pre-intervention neural characteristics predict response. DESIGN: Explanatory investigations within a randomised, controlled, observer-blind, and multicentre trial. Randomisation was computer-generated and concealed by an independent facility until baseline measures were completed. Primary time point was outcome, after the 6-week intervention phase. Follow-up was at 6 months after stroke. PARTICIPANTS: With some voluntary muscle contraction in the paretic upper limb, not full dexterity, when recruited up to 60 days after an anterior cerebral circulation territory stroke. INTERVENTIONS: Conventional physical therapy (CPT) plus either MPT or FST for up to 90 min-a-day, 5 days-a-week for 6 weeks. FST was "hands-off" progressive resistive exercise cemented into functional task training. MPT was "hands-on" sensory/facilitation techniques for smooth and accurate movement. OUTCOMES: The primary efficacy measure was the Action Research Arm Test (ARAT). Neural measures: fractional anisotropy (FA) corpus callosum midline; asymmetry of corticospinal tracts FA; and resting motor threshold (RMT) of motor-evoked potentials. ANALYSIS: Covariance models tested ARAT change from baseline. At outcome: correlation coefficients assessed relationship between change in ARAT and neural measures; an interaction term assessed whether baseline neural characteristics predicted response. RESULTS: 288 Participants had: mean age of 72.2 (SD 12.5) years and mean ARAT 25.5 (18.2). For 240 participants with ARAT at baseline and outcome the mean change was 9.70 (11.72) for FST + CPT and 7.90 (9.18) for MPT + CPT, which did not differ statistically (p = 0.298). Correlations between ARAT change scores and baseline neural values were between 0.199, p = 0.320 for MPT + CPT RMT (n = 27) and -0.147, p = 0.385 for asymmetry of corticospinal tracts FA (n = 37). Interaction effects between neural values and ARAT change between baseline and outcome were not statistically significant. CONCLUSIONS: There was no significant difference in upper limb improvement between FST and MPT. Baseline neural measures did not correlate with upper limb recovery or predict therapy response. TRIAL REGISTRATION: Current Controlled Trials: ISRCT 19090862, http://www.controlled-trials.com.

A common brain network links development, aging, and vulnerability to disease.

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

The future of functionally-related structural change assessment.

The brain is continually changing its function and structure in response to changing environmental demands. Magnetic resonance imaging (MRI) methods can be used to repeatedly scan the same individuals over time and in this way have provided powerful tools for assessing such brain change. Functional MRI has provided important insights into changes that occur with learning or recovery but this review will focus on the complementary information that can be provided by structural MRI methods. Structural methods have been powerful in indicating when and where changes occur in both gray and white matter with learning and recovery. However, the measures that we derive from structural MRI are typically ambiguous in biological terms. An important future challenge is to develop methods that will allow us to determine precisely what has changed.