Comparability between wearable inertial sensors and an electronic walkway for spatiotemporal and relative phase data in young children aged 6-11 years.

BACKGROUND: Approaches to gait analysis are evolving rapidly and now include a wide range of options: from e-patches to video platforms to wearable inertial measurement unit systems. Newer options for gait analysis are generally more inclusive for the assessment of children, more cost effective and easier to administer. However, there is limited data on the comparability of newer systems with more established traditional approaches in young children. RESEARCH QUESTION: To determine comparability between the Physilog®5 wearable inertial sensor and GAITRite® electronic walkway for spatiotemporal (stride length, time and velocity, cadence) and relative phase (double support time, stance, swing, loading, foot flat and push off) data in young children. METHODS: A total 34 typically developing participants (41% female) aged 6-11 years old median age 8.99 years old (interquartile range 2.83) were assessed walking at self-selected speed over the GAITRite® electronic walkway while concurrently wearing shoe-attached Physilog®5 IMU sensors. Level of agreement was analysed by Lin's concordance correlation coefficient (CCC), Bland-Altman plots and 95% limit of agreement. Systematic bias was assessed using 95% confidence interval of the mean difference. RESULTS: Excellent to almost perfect agreement was observed between systems for spatiotemporal metrics: cadence (CCC=0.996), stride length (CCC=0.993), stride time (CCC=0.996), stride velocity (CCC=0.988). The relative phase metrics adjusted for stride velocity showed improved comparability when compared to the unadjusted metrics: swing adjusted (adj) (CCC=0.635); stance adj (CCC: 0.879); loading adj: (CCC=0.626). SIGNIFICANCE: Spatiotemporal metrics are highly compatible across GAITRite® electronic walkway and Physilog®5 IMU systems in young children. Relative phase metrics were somewhat compatible between systems when adjusted for stride velocity.

Feasibility of wearable technology for 'real-world' gait analysis in children with Prader-Willi and Angelman syndromes.

BACKGROUND: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurodevelopmental disorders in need of innovative 'real-world' outcome measures to evaluate treatment effects. Instrumented gait analysis (IGA) using wearable technology offers a potentially feasible solution to measure "real-world' neurological and motor dysfunction in these groups. METHODS: Children (50% female; 6-16 years) diagnosed with PWS (n = 9) and AS (n = 5) completed 'real-world' IGA assessments using the Physilog®5 wearable. PWS participants completed a laboratory assessment and a 'real-world' long walk. The AS group completed 'real-world' caregiver-assisted assessments. Mean and variability results for stride time, cadence, stance percentage (%) and stride length were extracted and compared across three different data reduction protocols. RESULTS: The wearables approach was found to be feasible, with all participants able to complete at least one assessment. This study also demonstrated significant agreement, using Lin's concordance correlation coefficient (CCC), between laboratory and 'real-world' assessments in the PWS group for mean stride length, mean stance % and stance % CV (n = 7, CCC: 0.782-0.847, P = 0.011-0.009). CONCLUSION: 'Real-world' gait analysis using the Physilog®5 wearable was feasible to efficiently assess neurological and motor dysfunction in children affected with PWS and AS.

Validation of shoe-worn Gait Up Physilog®5 wearable inertial sensors in adolescents.

BACKGROUND: Gait Up Physilog® wearable inertial sensors are a powerful alternative to traditional laboratory-based gait assessment for children with gait impairment. To build clinician trust in these devices and ultimately facilitate their use outside confined spaces, studies have examined performance of previous versions of Physilog® wearable inertial sensors but predominant focus has been on older adults. Despite their different gait patterns and behavioural/cognitive profiles, there are limited studies in children. RESEARCH QUESTION: To determine whether key spatiotemporal gait parameters (stride length, time and velocity) collected by shoe-worn Physilog®5 sensors in a hallway assessment protocol are a valid method of gait assessment in typically developing adolescents aged 12-15 years. METHODS: A total 30 typically developing participants (50 % female) median age 13.7 (interquartile range 2.34) were assessed in an exploratory study whilst walking at self-selected speed over the GAITRite® electronic walkway, concurrently wearing Physilog®5 sensors. Concurrent validity was analysed by Lin's concordance correlation coefficient (CCC), Bland-Altman plots and 95 % limit of agreement. Systematic bias was assessed using 95 % confidence interval of the mean difference. RESULTS: Mean stride data demonstrated substantial agreement for stride length (CCC = 0.975) and stride velocity (CCC = 0.979) to almost perfect agreement for stride time (CCC > 0.996). Agreement between the technologies for individual stride-to-stride data remained high for stride time (CCC = 0.952); yet reduced for stride length (CCC = 0.868) and stride velocity (CCC = 0.877). Male/female differences in performance of the technology were observed for stride velocity, favouring females. SIGNIFICANCE: Physilog®5 inertial sensors accurately measure walking in adolescents, with stride time the most accurately detected parameter. This demonstrates that wearables can be used by researchers and clinicians working with adolescent groups as an alternative to fixed systems. These findings will ultimately pave the way to using wearables for assessments with children outside of the laboratory environment.

The developmental dynamics of gait maturation with a focus on spatiotemporal measures.

Gait analysis is recognised as a powerful clinical tool for studying relationships between motor control and brain function. By drawing on the literature investigating gait in individuals with neurological disorders, this review provides insight into the neural processes that contribute to and regulate specific spatiotemporal sub-components of gait and how they may mature across early to late childhood. This review also discusses the roles of changing anthropomorphic characteristics, and maturing sensory and higher-order cognitive processes in differentiating the developmental trajectories of the sub-components of gait. Importantly, although studies have shown that cognitive-gait interference is larger in children compared to adults, the contributing neurocognitive mechanisms may vary across age groups who have different types of attentional or cognitive vulnerabilities. These findings have implications for current models of gait maturation by highlighting the need for a dynamic model that focuses on the integration of various factors that contribute to gait though experience and practice. This is essential to elucidating why gait and other motor deficits are often contiguous with cognitive neurodevelopmental disorders.

Brain structure and intragenic DNA methylation are correlated, and predict executive dysfunction in fragile X premutation females.

DNA methylation of the Fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary has been associated with executive dysfunction in female carriers of a FMR1 premutation (PM: 55-199 CGG repeats), whereas neuroanatomical changes have been associated with executive dysfunction in PM males. To our knowledge, this study for the first time examined the inter-relationships between executive function, neuroanatomical structure and molecular measures (DNA methylation and FMR1 mRNA levels in blood) in PM and control (<44 CGG repeats) females. In the PM group, FMR1 intron 1 methylation was positively associated with executive function and cortical thickness in middle and superior frontal gyri, and left inferior parietal gyrus. By contrast, in the control group, FMR1 intron 1 methylation was negatively associated with cortical thickness of the left middle frontal gyrus and superior frontal gyri. No significant associations were revealed for either group between FMR1 mRNA and neuroanatomical structure or executive function. In the PM group, the lack of any significant association between FMR1 mRNA levels and phenotypic measures found in this study suggests that either FMR1 expression is not well conserved between tissues, or that FMR1 intron 1 methylation is linked to neuroanatomical and cognitive phenotype in PM females via a different mechanism.

ß-glucuronidase mRNA levels are correlated with gait and working memory in premutation females: understanding the role of FMR1 premutation alleles.

Fragile X tremor ataxia syndrome (FXTAS) is a late-onset disorder manifesting in a proportion of FMR1 premutation individuals (PM: 55-199 CGG triplet expansions). FXTAS is associated with elevated levels of FMR1 mRNA which are toxic. In this study, relationships between neurocognitive and intra-step gait variability measures with mRNA levels, measured in blood samples, were examined in 35 PM and 35 matched control females. The real-time PCR assays measured FMR1 mRNA, and previously used internal control genes: ß-Glucuronidase (GUS), Succinate Dehydrogenase 1 (SDHA) and Eukaryotic Translation Initiation Factor 4A (EI4A2). Although there was significant correlation of gait variability with FMR1 mRNA levels (p = 0.004) when normalized to GUS (FMR1/GUS), this was lost when FMR1 was normalized to SDHA and EI4A2 (2IC). In contrast, GUS mRNA level normalized to 2IC showed a strong correlation with gait variability measures (p < 0.007), working memory (p = 0.001) and verbal intelligence scores (p = 0.008). PM specific changes in GUS mRNA were not mediated by FMR1 mRNA. These results raise interest in the role of GUS in PM related disorders and emphasise the importance of using appropriate internal control genes, which have no significant association with PM phenotype, to normalize FMR1 mRNA levels.

Symbolic sequence learning is associated with cognitive-affective profiles in female FMR1 premutation carriers.

This study examines implicit sequence learning impairments that may indicate at-risk cerebellar profiles proposed to underlie some aspects of subtle cognitive and affective dysfunctions found among female fragile X mental retardation 1 (FMR1) premutation (PM)-carriers. A total of 34 female PM-carriers and 33 age- and intelligence-matched controls completed an implicit symbolically primed serial reaction time task (SRTT) previously shown to be sensitive to cerebellar involvement. Implicit learning scores indicated a preservation of learning in both groups; however, PM-carriers demonstrated poorer learning through significantly elevated response latencies overall and at each specific block within the symbolic SRTT. Group comparisons also revealed a core deficit in response inhibition, alongside elevated inattentive symptoms in female PM-carriers. Finally, strong and significant associations were observed between poor symbolic SRTT performance and executive, visuospatial and affective deficits in the PM-carrier group. These associations remained strong even after controlling motor speed, and were not observed in age- and intelligence quotient-matched participants. The findings implicate cerebellar non-motor networks subserving the implicit sequencing of responses in cognitive-affective phenotypes previously observed in female PM-carriers. We contend that symbolic SRTT performance may offer clinical utility in future pharmaceutical interventions in female PM-carriers.