0000000001228524
AUTHOR
Rossella Rizzo
A linear regression-based machine learning pipeline for the discovery of clinically relevant correlates of gait speed reserve from multiple physiological systems
Frailty in older adults is characterized by reduced physiological reserve. Gait speed reserve (GSR: maximum minus usual gait speed) could help identify frailty and act as a proxy for physiological reserve. Utilizing data from 2397 participants aged 50+ from wave 3 of The Irish Longitudinal Study on Ageing, we developed a stepwise linear regression-based machine learning pipeline to select the most important GSR predictors from 34 manually selected features across multiple domains. Variables were selected one at a time such that they maximized the mean adjusted r-squared score from a 5-fold cross-validation. A peak score of (0.16 +/- 0.03) was achieved with 14 variables (giving adjusted-r-sq…
Network Physiology of Cortico–Muscular Interactions
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 a…
Longitudinal Study on Sustained Attention to Response Task (SART): Clustering Approach for Mobility and Cognitive Decline
The Sustained Attention to Response Task (SART) is a computer-based go/no-go task to measure neurocognitive function in older adults. However, simplified average features of this complex dataset lead to loss of primary information and fail to express associations between test performance and clinically meaningful outcomes. Here, we combine a novel method to visualise individual trial (raw) information obtained from the SART test in a large population-based study of ageing in Ireland and an automatic clustering technique. We employed a thresholding method, based on the individual trial number of mistakes, to identify poorer SART performances and a fuzzy clusters algorithm to partition the da…
SART and Individual Trial Mistake Thresholds: Predictive Model for Mobility Decline
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 bin…
Inhibition of FTSJ1, a tryptophan tRNA-specific 2’-O-methyltransferase as possible mechanism to readthrough premature termination codons (UGAs) of the CFTR mRNA
Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10 % of the mutations affecting the CFTR gene are "stop" mutations, which generate a Premature Termination Codon (PTC), thus resulting in the synthesis of a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, that is the capacity of the ribosome to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough and for some of them the mechanism of action is still under debate. By in silico analysis as well as in vitro studies, we investigate a possible mechanism of action (MOA) by whic…
Mid-sagittal plane detection for advanced physiological measurements in brain scans
Objective The process of diagnosing many neurodegenerative diseases, such as Parkinson's and progressive supranuclear palsy, involves the study of brain magnetic resonance imaging (MRI) scans in order to identify and locate morphological markers that can highlight the health status of the subject. A fundamental step in the pre-processing and analysis of MRI scans is the identification of the mid-sagittal plane, which corresponds to the mid-brain and allows a coordinate reference system for the whole MRI scan set. Approach To improve the identification of the mid-sagittal plane we have developed an algorithm in Matlab® based on the k-means clustering function. The results have been compared …
Transitions in frailty phenotype states and components over 8 years: Evidence from The Irish Longitudinal Study on Ageing
Abstract Aim Fried's frailty phenotype (FP) is defined by exhaustion (EX), unexplained weight loss (WL), weakness (WK), slowness (SL) and low physical activity (LA). Three or more components define the frail state, and one or two the prefrail. We described longitudinal transitions of FP states and components in The Irish Longitudinal Study on Ageing (TILDA). Methods We included participants aged ≥50 years with FP information at TILDA wave 1 (2010), who were followed-up over four longitudinal waves (2012, 2014, 2016, 2018). Next-wave transition probabilities were estimated with multi-state Markov models. Results 5683 wave 1 participants were included (2612 men and 3071 women; mean age 63.1 y…
Dynamic networks of physiologic interactions of brain waves and rhythms in muscle activity.
The brain plays a central role in facilitating vital body functions and in regulating physiological and organ systems, including the skeleto-muscular and locomotor system. While neural control is essential to synchronize and coordinate activation of various muscle groups and muscle fibers within muscle groups in relation to body movements and distinct physiologic states, the dynamic networks of brain-muscle interactions have not been explored and the complex regulatory mechanism of brain-muscle control remains unknown. Here we present a first study of network interactions between brain waves at different cortical locations and peripheral muscle activity across key physiologic states - wake,…
Brain-predicted age difference score is related to specific cognitive functions: A multi-site replication analysis
Abstract Brain-predicted age difference scores are calculated by subtracting chronological age from ‘brain’ age. 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. 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: Dokuz Eylul University (n=175), the Cogni…
Universal spectral profile and dynamic evolution of muscle activation: A hallmark of muscle type and physiological state
The skeletal muscle is an integrated multicomponent system with complex dynamics of continuous myoelectrical activation of various muscle types across time scales to facilitate muscle coordination among units and adaptation to physiological states. To understand the multiscale dynamics of neuromuscular activity, we investigated spectral characteristics of different muscle types across time scales and their evolution with physiological states. We hypothesized that each muscle type is characterized by a specific spectral profile, reflecting muscle composition and function, that remains invariant over time scales and is universal across subjects. Furthermore, we hypothesized that the myoelectr…