Brain-predicted age difference scores are calculated by subtracting chronological age from 'brain' age, which is estimated using neuroimaging data. Positive scores reflect accelerated ageing and are associated with increased mortality risk and poorer physical function. To date, however, the relationship between brain-predicted age difference scores and specific cognitive functions has not been systematically examined using appropriate statistical methods. First, applying machine learning to 1,359 T1-weighted MRI scans, we predicted the relationship between chronological age and voxel-wise grey matter data. This model was then applied to MRI data from three independent datasets, significantly predicting chronological age in each dataset: Dokuz Eylül University (n=175), the Cognitive Reserve/Reference Ability Neural Network study (n=380), and The Irish Longitudinal Study on Ageing (n=487). Each independent dataset had rich neuropsychological data. Brain-predicted age difference scores were significantly negatively correlated with performance on measures of general cognitive status (two datasets); processing speed, visual attention, and cognitive flexibility (three datasets); visual attention and cognitive flexibility (two datasets); and semantic verbal fluency (two datasets). As such, there is firm evidence of correlations between increased brainpredicted age differences and reduced cognitive function in some domains that are implicated in cognitive ageing.

Skeletal muscle activity is continuously modulated across physiologic states to provide coordination, flexibility and responsiveness to body tasks and external inputs. Despite the central role the muscular system plays in facilitating vital body functions, the network of brain-muscle interactions required to control hundreds of muscles and synchronize their activation in relation to distinct physiologic states has not been investigated. Recent approaches have focused on general associations between individual brain rhythms and muscle activation during movement tasks. However, the specific forms of coupling, the functional network of cortico-muscular coordination, and how network structure and dynamics are modulated by autonomic regulation across physiologic states remains unknown. To identify and quantify the cortico-muscular interaction network and uncover basic features of neuro-autonomic control of muscle function, we investigate the coupling between synchronous bursts in cortical rhythms and peripheral muscle activation during sleep and wake. Utilizing the concept of time delay stability and a novel network physiology approach, we find that the brain-muscle network exhibits complex dynamic patterns of communication involving multiple brain rhythms across cortical locations and different electromyographic frequency bands. Moreover, our results show that during each physiologic state the cortico-muscular network is characterized by a specific profile of network links strength, where particular brain rhythms play role of main mediators of interaction and control. Further, we discover a hierarchical reorganization in network structure across physiologic states, with high connectivity and network link strength during wake, intermediate during REM and light sleep, and low during deep sleep, a sleep-stage stratification that demonstrates a unique association between physiologic states and cortico-muscular network structure. The reported empirical observations are consistent across individual subjects, indicating universal behavior in network structure and dynamics, and high sensitivity of cortico-muscular control to changes in autonomic regulation, even at low levels of physical activity and muscle tone during sleep. Our findings demonstrate previously unrecognized basic principles of brain-muscle network communication and control, and provide new perspectives on the regulatory mechanisms of brain dynamics and locomotor activation, with potential clinical implications for neurodegenerative, movement and sleep disorders, and for developing efficient treatment strategies.

The Sustained Attention to Response Task (SART) has been used to measure neurocognitive functions in older adults. However, simplified average features of this complex dataset may result in loss of primary information and fail to express associations between test performance and clinically meaningful outcomes. Here, we describe a new method to visualise individual trial (raw) information obtained from the SART test, vis-à-vis age, and groups based on mobility status in a large population-based study of ageing in Ireland. A thresholding method, based on the individual trial number of mistakes, was employed to better visualise poorer SART performances, and was statistically validated with binary logistic regression models to predict mobility and cognitive decline after 4 years. Raw SART data were available for 4864 participants aged 50 years and over at baseline. The novel visualisation-derived feature bad performance, indicating the number of SART trials with at least 4 mistakes, was the most significant predictor of mobility decline expressed by the transition from Timed Up-and-Go (TUG) < 12 to TUG ≥ 12 s (OR = 1.29; 95% CI 1.14–1.46; p < 0.001), and the only significant predictor of new falls (OR = 1.11; 95% CI 1.03–1.21; p = 0.011), in models adjusted for multiple covariates. However, no SART-related variables resulted significant for the risk of cognitive decline, expressed by a decrease of ≥ 2 points in the Mini-Mental State Examination (MMSE) score. This novel multimodal visualisation could help clinicians easily develop clinical hypotheses. A threshold approach to the evaluation of SART performance in older adults may better identify subjects at higher risk of future mobility decline.

Purpose. The skeletal muscle is an integrated multi-component system with complex dynamics of continuous myoelectrical activation of various muscle types across timescales to facilitate muscle coordination among units and adaptation to physiological states. To understand the multi-scale dynamics of neuromuscular activity, we investigate spectral characteristics of different muscle types across timescales and their evolution with physiological states. We hypothesize that each muscle type is characterized by specific spectral profile, reflecting muscle function and composition, that remains invariant over timescales and is universal across subjects. Further, we hypothesize that the myoelectrical activation and corresponding spectral profile during certain movement exhibit an evolution path in time that is unique for each muscle type, and reflects response in muscle dynamics to exercise, fatigue, and aging. Methods. To probe the multi-scale mechanism of neuromuscular regulation, we develop a novel protocol of repeated squat exercise segments, each performed until exhaustion, and we analyze differentiated spectral power response in frequency bands for leg and back muscle in young and old subjects. Results. We find that leg and back muscle activation is characterized by muscle-specific spectral profiles, with differentiated frequency bands contribution, and muscle-specific evolution path in response to fatigue and aging. Conclusion. The uncovered universality among subjects in the spectral profile of each muscle at a given physiological state, as well as the robustness in the evolution of these profiles over a range of timescales and states, reveals a previously unrecognized multi-scale mechanism underlying the differentiated response of distinct muscle types to exercise-induced fatigue and aging.