Within-subject Measures Research Articles

Volume increase in the dentate gyrus after electroconvulsive therapy in depressed patients as measured with 7T.

Electroconvulsive therapy (ECT) is the most effective treatment for depression, yet its working mechanism remains unclear. In the animal analog of ECT, neurogenesis in the dentate gyrus (DG) of the hippocampus is observed. In humans, volume increase of the hippocampus has been reported, but accurately measuring the volume of subfields is limited with common MRI protocols. If the volume increase of the hippocampus in humans is attributable to neurogenesis, it is expected to be exclusively present in the DG, whereas other processes (angiogenesis, synaptogenesis) also affect other subfields. Therefore, we acquired an optimized MRI scan at 7-tesla field strength allowing sensitive investigation of hippocampal subfields. A further increase in sensitivity of the within-subjects measurements is gained by automatic placement of the field of view. Patients receive two MRI scans: at baseline and after ten bilateral ECT sessions (corresponding to a 5-week interval). Matched controls are also scanned twice, with a similar 5-week interval. A total of 31 participants (23 patients, 8 controls) completed the study. A large and significant increase in DG volume was observed after ECT (M = 75.44 mm3, std error = 9.65, p < 0.001), while other hippocampal subfields were unaffected. We note that possible type II errors may be present due to the small sample size. In controls no changes in volume were found. Furthermore, an increase in DG volume was related to a decrease in depression scores, and baseline DG volume predicted clinical response. These findings suggest that the volume change of the DG is related to the antidepressant properties of ECT, and may reflect neurogenesis.

Repeated Measures Regression in Laboratory, Clinical and Environmental Research: Common Misconceptions in the Matter of Different Within- and between-Subject Slopes.

When using repeated measures linear regression models to make causal inference in laboratory, clinical and environmental research, it is typically assumed that the within-subject association of differences (or changes) in predictor variable values across replicates is the same as the between-subject association of differences in those predictor variable values. However, this is often false. For example, with body weight as the predictor variable and blood cholesterol (which increases with higher body fat) as the outcome: (i) a 10-lb. weight increase in the same adult affects more greatly an increase in cholesterol in that adult than does (ii) one adult weighing 10 lbs. more than a second indicate higher cholesterol in the heavier adult. A 10-lb. weight gain in the first adult more likely reflects a build-up of body fat in that person, while a second person being 10 lbs. heavier than the first could be influenced by other factors, such as the second person being taller. Hence, to make causal inferences, different within- and between-subject slopes should be separately modeled. A related misconception commonly made using generalized estimation equations (GEE) and mixed models on repeated measures (i.e., for fitting cross-sectional regression) is that the working correlation structure only influences variance of the parameter estimates. However, only independence working correlation guarantees that the modeled parameters have interpretability. We illustrate this with an example where changing the working correlation from independence to equicorrelation qualitatively biases parameters of GEE models and show that this happens because within- and between-subject slopes for the outcomes regressed on the predictor variables differ. We then systematically describe several common mechanisms that cause within- and between-subject slopes to differ: change effects, lag/reverse-lag and spillover causality, shared within-subject measurement bias or confounding, and predictor variable measurement error. The misconceptions we describe should be better publicized. Repeated measures analyses should compare within- and between-subject slopes of predictors and when they do differ, investigate the causal reasons for this.

Detecting Lies via a Theme-Selection Strategy

Most of deception research has focused on past events that were either completely truthful or a complete fabrication. However, people often tell a mixture of truths and lies. This could enable investigators to make within-subjects comparisons between different themes discussed in one interview, which we examined in the current experiment. Seventy-three participants took part in the experiment and were asked to either tell the truth about two themes, or to tell the truth about one theme and lie about the second theme in a HUMINT setting. Results showed that examining the differences in the amount of detail provided by the interviewees for each theme- obtained through a Theme-Selection strategy (a within-subjects measure)- yielded stronger results than examining differences between truth tellers and liars based on the entire interview without accounting for themes (between-subjects measure). The present study therefore highlighted the effectiveness of within-subjects measurements to both discriminate truth tellers from liars and to discover which section of a statement is false.

How Representational Pictures Enhance Students’ Performance and Test-Taking Pleasure in Low-Stakes Assessment

Abstract. Pictures are often used in standardized educational large-scale assessment (LSA), but their impact on test parameters has received little attention up until now. Even less is known about pictures’ affective effects on students in testing (i.e., test-taking pleasure and motivation). However, such knowledge is crucial for a focused application of multiple representations in LSA. Therefore, this study investigated how adding representational pictures (RPs) to text-based item stems affects (1) item difficulty and (2) students’ test-taking pleasure. An experimental study with N = 305 schoolchildren was conducted, using 48 manipulated parallel science items (text-only vs. text-picture) in a rotated multimatrix design to realize within-subject measures. Students’ general cognitive abilities, reading abilities, and background variables were assessed to consider potential interactions between RPs’ effects and students’ performance. Students also rated their item-solving pleasure for each item. Results from item-response theory (IRT) model comparisons showed that RPs only reduced item difficulty when pictures visualized information mandatory for solving the task, while RPs substantially enhanced students’ test-taking pleasure even when they visualized optional context information. Overall, our findings suggest that RPs have a positive cognitive and affective influence on students’ performance in LSA (i.e., multimedia effect in testing) and should be considered more frequently.

One-Year Results for Patients with Unilateral Hearing Loss and Accompanying Severe Tinnitus and Hyperacusis Treated with a Cochlear Implant

Objective: To show that patients with unilateral hearing loss (UHL), with one ear fulfilling cochlear implant (CI) indication criteria, and an additional severe tinnitus handicap can be treated effectively with a CI. Method: A prospective multi-centre study was conducted in five Spanish centres. Sixteen adult patients with UHL and a mean Tinnitus Handicap Inventory (THI) score of at least 58 were implanted. The study design included repeated within-subject measures of quality of life (Health Utility Index Mark 3 [HUI3]), tinnitus (THI, Visual Analogue Scale [VAS] on tinnitus loudness), hearing (Speech, Spatial, and Qualities of Hearing Scale– [SSQ]), and hyperacusis (Test de Hipersensibilidad al Sonido [THS]) up to 12 months after the initial CI fitting. Results: Group data showed significant subjective benefit from CI treatment: the preoperative HUI3 total utility score of 0.45 went up to 0.57 at 6 months and 0.63 at 12 months; the preoperative THI total score of 75 decreased to 40 at 6 months and 35 at 12 months. The preoperative tinnitus loudness VAS score of 8.2 decreased to 2.4 at 6 months and 2.2 at 12 months with the implant “On” and to 6.7 at 6 months and 6.5 at 12 months with the implant “Off.” The preoperative THS total score of 26 decreased to 17 at 12 months. The preoperative SSQ total score of 4.2 increased to 5.1 at 6 months and 6.3 at 12 months. No unanticipated adverse events were reported during the study period. At 12 months after CI activation all subjects (except 1 subject who used the device 6 days a week) wore their devices all day and every day. The primary reason for CI use was split evenly between tinnitus suppression (n = 6) and both hearing and tinnitus (n = 6). Conclusion: A CI should be considered as a treatment option in patients with UHL and a concomitant severe tinnitus handicap. However, appropriate counselling of candidates on the anticipated risks, benefits, and limitations that are inherent to cochlear implantation is imperative.

Efficient estimation for time-varying coefficient longitudinal models

ABSTRACTFor estimation of time-varying coefficient longitudinal models, the widely used local least-squares (LS) or covariance-weighted local LS smoothing uses information from the local sample average. Motivated by the fact that a combination of multiple quantiles provides a more complete picture of the distribution, we investigate quantile regression-based methods to improve efficiency by optimally combining information across quantiles. Under the working independence scenario, the asymptotic variance of the proposed estimator approaches the Cramér–Rao lower bound. In the presence of dependence among within-subject measurements, we adopt a prewhitening technique to transform regression errors into independent innovations and show that the prewhitened optimally weighted quantile average estimator asymptotically achieves the Cramér–Rao bound for the independent innovations. Fully data-driven bandwidth selection and optimal weights estimation are implemented through a two-step procedure. Monte Carlo studies show that the proposed method delivers more robust and superior overall performance than that of the existing methods.

Controlling alpha for mixed effects models for repeated measures

ABSTRACTMixed Effects Models for Repeated Measures (MMRM) is often used in clinical trials with longitudinal data. However, there has not been an in-depth examination available on how investigators can implement interim analysis while also controlling the overall alpha for clinical trials under an MMRM analysis framework. Statistical independence among measurements, which is often assumed in group sequential testing (GST), is not valid under an MMRM framework due to the correlations induced by longitudinal within-subject measurements. Therefore, methods associated with GST derived under independence need to be adjusted accordingly. While these correlations can be estimated from the study data, regulatory agencies may not accept results based on these estimated correlations since there is no guarantee that the overall alpha is strongly controlled. In this article, we propose a new AC-Hybrid-approach for controlling the overall alpha. The AC-Hybrid-approach has two key attributes. First, we apply the MMRM analysis framework on all available data at every analysis timepoint. Second, we use complete-case information fractions to derive the group sequential stopping boundaries. We prove that the overall alpha is controlled regardless of the correlations among within-subject measurements. We also show the impact of this approach on the alpha and the power through examples.

Improvements in health-related quality of life, cardio-metabolic health, and fitness in postmenopausal women after a supervised, multicomponent, adapted exercise program in a suited health promotion intervention: a multigroup study.

This study explored the multidimensional outcomes that resulted from the adherence to regular exercise among previously sedentary postmenopausal women. The exercise was managed through a supervised, multicomponent, adapted approximately 20-week program in a suited health promotion intervention. A multigroup, mixed-design study with between-group (intervention, sedentary, and active women) and within-subject measures (baseline, postintervention, and 3- and 12-month follow-ups) was conducted using intention-to-treat methodology. The Cervantes Scale assessed health-related quality of life (HRQoL), and several indicators of cardio-metabolic status and fitness were also assessed. After the intervention, the participants experienced positive changes in short and long-term physical and mental health, with significant enhancements in several HRQoL dimensions, particularly mental well-being and menopause-related health and subdomains. Improvements were maintained or continued (eg, mental well-being) throughout the period, leading up to the 12-month follow-up. These outcomes were accompanied by significant improvements in cardio-metabolic status and fitness, including weight, body mass index, cardio-respiratory fitness, and flexibility. Our findings parallel previous empirical evidence showing the benefits associated with regular exercise, and add evidence to the association of positive outcomes in HRQoL with improvements in cardio-metabolic health and fitness status after the adoption of an active lifestyle.

EXAMINING LONGITUDINAL NEUROIMAGING PATTERNS IN AUTOSOMAL DOMINANT ALZHEIMER DISEASE: FINDINGS FROM THE DOMINANTLY INHERITED ALZHEIMER NETWORK

Models of Alzheimer pathology propose that amyloidosis, hypometabolism, and structural declines emerge not only over time, but also spatially in the brain. Autosomal dominant Alzheimer disease (ADAD) provides an elegant way to study the evolution of such pathology due to the ability to stage an individual relative to their years to expected symptom onset (EYO). Longitudinal neuroimaging data is a particularly powerful way to model such changes, as within-subject measures reduces between-subject variability caused by unobserved individual differences. We examined longitudinal PiB, FDG, and structural MRI data in a population of 400 individuals enrolled in the Dominantly Inherited Alzheimer's Network (DIAN). Data were processed examining 34 cortical and 7 subcortical regions. We utilized linear mixed effects models to explore changing pathology. Models were fit for each region included fixed effects for mutation status, time from baseline, baseline EYO, and all possible two and three-way interactions. To allow non-linearities, EYO was modeled as a restricted cubic spline. Analyses were run separately for each modality. The primary focus was on the first time point in the disease where biomarker change in that region differed between mutation carrier and non-carriers. Relative to non-carriers, rates of amyloid deposition were significantly higher in carriers at an average EYO across regions of -18.2, glucose metabolism began declining at an average EYO of -14.2, and MRI structural measures declined at an average EYO of -4.2. While this three-stage pattern was common across regions of the brain, it was not ubiquitous (Figure 1). Most prominently a subset of regions demonstrated elevated PiB PET accumulation and structural declines, but not abnormal glucose utilization. Further, the regional timing within a modality (e.g. PiB PET) was highly variable across brain regions (Figure 2).

Stability of infants' preference for prosocial others: Implications for research based on single-choice paradigms.

Some research suggests infants display a tendency to judge others’ prosocial behavior, and in particular, that infants show a strong preference for prosocial others. For example, data from one frequently cited and well-publicized study showed that, after watching a puppet show with three puppets, 74% of infants chose the puppet that “helped” rather than the puppet that “hindered” a third puppet from attaining its goal. The purpose of the current investigation was to replicate these methods and extend them by including a within-subject measure of infant puppet choice across repeated trials to assess the stability of infants’ choice. In the current study, 20 infants viewed a puppet show and chose between two puppets (i.e., helper or hinderer) immediately following the puppet show. Although results were similar to previously published work on the first-choice trial (65% of infants chose the helper puppet on the first trial), infants did not consistently choose the helper across trials; several infants demonstrated a side preference, with 9 infants almost exclusively choosing puppets presented on the right or left side. The current investigation addressed limitations of previous research by including a between-subjects (replication) as well as a within-subjects (extension) repeated measure of choice that allowed for the examination of the stability of the choice measure. Our results, particularly in light of other failed replications, raise questions regarding the robustness of infants’ preference for prosocial others and the reliability and validity of the single-choice paradigm.

Improvements in Health-Related Quality of Life, Cardio-Metabolic Health, and Fitness in Postmenopausal Women After an Exercise Plus Health Promotion Intervention: A Randomized Controlled Trial.

This study explored multidimensional outcomes that were derived from the adherence to regular exercise among previously sedentary postmenopausal 45 to 64 years old women who engaged in a ~20-week exercise program. A randomized controlled trial with between-group (intervention and control women) and within-subject measures (baseline, postintervention, and 3-month and 12-month follow-ups) was conducted. HRQoL and several indicators of cardio-metabolic status and fitness were assessed. After the intervention, the participants experienced a positive change in their short and long-term physical and mental health, with significant enhancements in several HRQoL dimensions, particularly mental well-being (23.3% of change) and menopause-related health and subdomains (17.0% of change) (P < .01). Improvements were maintained or continued (eg, mental well-being) overtime. These outcomes were accompanied by significant improvements in cardio-metabolic status and fitness, including weight, BMI, cardio-respiratory fitness and flexibility (up to 16.2% of change, P < .05). After the intervention, the intervention group exhibited better HRQoL than the control group at each of the measurement phases. Between-group differences were also observed for some indicators of cardiovascular health and flexibility. Our findings add evidence on the association of positive outcomes on HRQoL with improvements in cardio-metabolic health and fitness status after the adoption of an active lifestyle.

Asymmetry of the Modified Illinois Change of Direction Test Impacts Young Elite Soccer Players' Performance.

BackgroundThe modified Illinois change of direction test (MICODT) is an asymmetrical test because the numbers of changes of direction performed to the right and to the left are unequal. Therefore, it is possible that the asymmetry of this test may influence agility performance testing.ObjectivesThe aim of this study was to compare two opposite/mirrored versions of the modified Illinois change of direction test.Patients and MethodsForty-six right-footed soccer players (17.2 ± 1.6 years-old) participated in the study. Players performed a modified Illinois change of direction test and a mirrored version of this test “inverted modified Illinois change of direction test” (I/MICODT) in a randomized and counter-balanced order. Paired t-test was used to determine whether significant differences existed between time performances of the tests as a within-subjects measure. Players were thereafter stratified into MICODT group or I/MICODT group according to their best performance and independent t-tests were used to determine differences between groups.ResultsThe analysis revealed no significant difference in time performance between the two versions of test as a within-subjects measure (P > 0.05, ES = 0.05). However, significant better time performances among inverted modified Illinois change of direction group (52% of players) were found when compared to the modified Illinois change of direction group (48% of players) (P < 0.04, ES = 0.66).ConclusionsThe modified Illinois change of direction test must be considered as an asymmetrical test because it underestimates more than half of the players’ agility performances. Therefore, fitness coaches should take these results into account when using this test.

Validating the Rett Syndrome Gross Motor Scale.

Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale was developed to measure gross motor abilities in this population. The current study investigated the validity and reliability of the Rett Syndrome Gross Motor Scale. Video data showing gross motor abilities supplemented with parent report data was collected for 255 girls and women registered with the Australian Rett Syndrome Database, and the factor structure and relationships between motor scores, age and genotype were investigated. Clinical assessment scores for 38 girls and women with Rett syndrome who attended the Danish Center for Rett Syndrome were used to assess consistency of measurement. Principal components analysis enabled the calculation of three factor scores: Sitting, Standing and Walking, and Challenge. Motor scores were poorer with increasing age and those with the p.Arg133Cys, p.Arg294* or p.Arg306Cys mutation achieved higher scores than those with a large deletion. The repeatability of clinical assessment was excellent (intraclass correlation coefficient for total score 0.99, 95% CI 0.93–0.98). The standard error of measurement for the total score was 2 points and we would be 95% confident that a change 4 points in the 45-point scale would be greater than within-subject measurement error. The Rett Syndrome Gross Motor Scale could be an appropriate measure of gross motor skills in clinical practice and clinical trials.

A Measure of the Auditory-perceptual Quality of Strain from Electroglottographic Analysis of Continuous Dysphonic Speech: Application to Adductor Spasmodic Dysphonia

(1) To develop an automated algorithm to analyze electroglottographic (EGG) signal in continuous dysphonic speech, and (2) to identify EGG waveform parameters that correlate with the auditory-perceptual quality of strain in the speech of patients with adductor spasmodic dysphonia (ADSD). Software development with application in a prospective controlled study. EGG was recorded from 12 normal speakers and 12 subjects with ADSD reading excerpts from the Rainbow Passage. Data were processed by a new algorithm developed with the specific goal of analyzing continuous dysphonic speech. The contact quotient, pulse width, a new parameter peak skew, and various contact closing slope quotient and contact opening slope quotient measures were extracted. EGG parameters were compared between normal and ADSD speech. Within the ADSD group, intra-subject comparison was also made between perceptually strained syllables and unstrained syllables. The opening slope quotient SO7525 distinguished strained syllables from unstrained syllables in continuous speech within individual subjects with ADSD. The standard deviations, but not the means, of contact quotient, EGGW50, peak skew, and SO7525 were different between normal and ADSD speakers. The strain-stress pattern in continuous speech can be visualized as color gradients based on the variation of EGG parameter values. EGG parameters may provide a within-subject measure of vocal strain and serve as a marker for treatment response. The addition of EGG to multidimensional assessment may lead to improved characterization of the voice disturbance in ADSD.

Modulation of instrumental responding by a conditioned threat stimulus requires lateral and central amygdala.

Two studies explored the role of the amygdala in response modulation by an aversive conditioned stimulus (CS) in rats. Experiment 1 investigated the role of amygdala circuitry in conditioned suppression using a paradigm in which licking for sucrose was inhibited by a tone CS that had been previously paired with footshock. Electrolytic lesions of the lateral amygdala (LA) impaired suppression relative to sham-operated animals, and produced the same pattern of results when applied to central amygdala. In addition, disconnection of the lateral and central amygdala, by unilateral lesion of each on opposite sides of the brain, also impaired suppression relative to control subjects that received lesions of both areas on the same side. In each case, lesions were placed following Pavlovian conditioning and instrumental training, but before testing. This procedure produced within-subjects measures of the effects of lesion on freezing and between-group comparisons for the effects on suppression. Experiment 2 extended this analysis to a task where an aversive CS suppressed shuttling responses that had been previously food reinforced and also found effects of bilateral lesions of the central amygdala in a pre-post design. Together, these studies demonstrate that connections between the lateral and central amygdala constitute a serial circuit involved in processing aversive Pavlovian stimuli, and add to a growing body of findings implicating central amygdala in the modulation of instrumental behavior.

Within-subject and between-subject conceptions of metacomprehension accuracy

This study examines two conceptualizations of metacomprehension accuracy, which is recognized as an important feature of individual differences in learning. Within-subject accuracy requires students to judge their learning of parts of a lesson, and take tests for each part. Within-subject accuracy is computed by correlating judgments with performance on all parts for each student. A second conceptualization, between-subject accuracy, is computed by correlating each student's average judgment with average performance across all students. This measure corresponds to how well students judge their learning of the entire lesson compared to other students, and does not require multiple isolated lessons and tests for each learner. In Experiment 1, participants watched multimedia science lessons, completed a summarizing task for each lesson, made a learning judgment, and took transfer and retention tests. In Experiment 2, practice questions replaced the summaries. The study tasks did not consistently improve either type of metacomprehension accuracy. Overall, students generally displayed a statistically significant level of metacomprehension accuracy both on within-subject and between-subject measures of metacomprehension accuracy, yielding support for adding between-subject measures as a complement to the more commonly used within-subject measures.

Cochlear Implants as a Treatment Option for Unilateral Hearing Loss, Severe Tinnitus and Hyperacusis

Tinnitus is an incapacitating condition commonly affecting cochlear implant (CI) candidates. The aim of this clinical study is to assess the long-term effects of CI treatment in patients with severe-to-profound, sensorineural, unilateral hearing loss (UHL) and incapacitating tinnitus. We performed a prospective Cochlear™ company-sponsored multicentre study in five Spanish centres. Sixteen patients with UHL and incapacitating tinnitus, which was indicated by a Tinnitus Handicap Inventory (THI) score >58%, received a Nucleus® CI in their deaf ear. The study design includes repeated within-subject measures on hearing, tinnitus, hyperacusis and quality of life up to 12 months after initial CI fitting. In addition to hearing loss and tinnitus, all patients suffered from hyperacusis. Most patients had a sudden hearing loss and received a CI within 2 years after their hearing loss. Preliminary 6-month, post-CI activation data of 13 subjects showed that the majority of patients perceived a subjective benefit from CI treatment, which was assessed using the THI, a Visual Analogue Scale of tinnitus loudness/annoyance and the Speech, Spatial and Qualities of Hearing Scale. Preliminary 12-month data of 7 subjects showed that most patients also perceived a degree of relief from their hyperacusis. One patient showed no improvements in any of the applied scales, which could be explained by partial insertion of the electrode due to obstruction of the cochlea by otosclerosis. In conclusion, CI can successfully be used in the treatment of UHL patients with accompanying severe tinnitus and hyperacusis. Implantation resulted in hearing benefits and a durable relief from tinnitus and hyperacusis in the majority of patients. These findings support the hypothesis that pathophysiological mechanisms after peripheral sensorineural hearing loss are at least partly reversible when hearing is restored with a CI.

Semiparametric Bayesian inference on skew-normal joint modeling of multivariate longitudinal and survival data.

We propose a semiparametric multivariate skew-normal joint model for multivariate longitudinal and multivariate survival data. One main feature of the posited model is that we relax the commonly used normality assumption for random effects and within-subject error by using a centered Dirichlet process prior to specify the random effects distribution and using a multivariate skew-normal distribution to specify the within-subject error distribution and model trajectory functions of longitudinal responses semiparametrically. A Bayesian approach is proposed to simultaneously obtain Bayesian estimates of unknown parameters, random effects and nonparametric functions by combining the Gibbs sampler and the Metropolis-Hastings algorithm. Particularly, a Bayesian local influence approach is developed to assess the effect of minor perturbations to within-subject measurement error and random effects. Several simulation studies and an example are presented to illustrate the proposed methodologies.

Rett syndrome: establishing a novel outcome measure for walking activity in an era of clinical trials for rare disorders

Background: Rett syndrome is a pervasive neurological disorder with impaired gait as one criterion. This study investigated the capacity of three accelerometer-type devices to measure walking activity in Rett syndrome. Methods: Twenty-six participants (mean 18 years, SD 8) wore an Actigraph, ActivPAL and StepWatch Activity Monitor (SAM) during a video-taped session of activities. Agreement was determined between step-counts derived from each accelerometer and observation. Repeatability of SAM-derived step counts was determined using pairs of one-minute epochs during which the same participant was observed to walk with the same cadence. Results: The mean difference (limit of agreement) for the Actigraph, ActivPAL and SAM were −41 (SD 33), −16 (SD 21) and −1 (SD 16) steps/min, respectively. Agreement was influenced by a device/cadence interaction (p < 0.001) with greater under-recording at higher cadences. For SAM data, repeatability of step-count pairs was excellent (intraclass correlation coefficient 0.91, 95% CI 0.79–0.96). The standard error of measurement was 6 steps/min and we would be 95% confident that a change ≥17 steps/min would be greater than within-subject measurement error. Conclusions: The capacity of the SAM to measure physical activity in Rett syndrome allows focus on participation-based activities in clinical practice and clinical trials.Implications for RehabilitationMany girls and women with Rett syndrome are able to walk on their own or with assistance but with altered movement patterns.Validated measures of physical activity, such as step counts, have potential to monitor function during daily life.Compared with other forms of accelerometer-type devices, such as ActiGraph and ActivPAL, the StepWatch Activity Monitor (SAM) measured step counts with good accuracy and repeatability.The capacity of the SAM to measure physical activity in Rett syndrome allows focus on participation-based activities in clinical practice and clinical trials.

RELICA: A method for estimating the reliability of independent components

Independent Component Analysis (ICA) is a widely applied data-driven method for parsing brain and non-brain EEG source signals, mixed by volume conduction to the scalp electrodes, into a set of maximally temporally and often functionally independent components (ICs). Many ICs may be identified with a precise physiological or non-physiological origin. However, this process is hindered by partial instability in ICA results that can arise from noise in the data. Here we propose RELICA (RELiable ICA), a novel method to characterize IC reliability within subjects. RELICA first computes IC “dipolarity” a measure of physiological plausibility, plus a measure of IC consistency across multiple decompositions of bootstrap versions of the input data. RELICA then uses these two measures to visualize and cluster the separated ICs, providing a within-subject measure of IC reliability that does not involve checking for its occurrence across subjects. We demonstrate the use of RELICA on EEG data recorded from 14 subjects performing a working memory experiment and show that many brain and ocular artifact ICs are correctly classified as “stable” (highly repeatable across decompositions of bootstrapped versions of the input data). Many stable ICs appear to originate in the brain, while other stable ICs account for identifiable non-brain processes such as line noise. RELICA might be used with any linear blind source separation algorithm to reduce the risk of basing conclusions on unstable or physiologically un-interpretable component processes.