Human gravity-gradient noise in interferometric gravitational-wave detectors

Among all forms of routine human activity, the one which produces the strongest gravity-gradient noise in interferometric gravitational-wave detectors (e.g. LIGO) is the beginning and end of weight transfer from one foot to the other during walking. The beginning and end of weight transfer entail sharp changes (time scale τ∼20 msec) in the horizontal jerk (first time derivative of acceleration) of a person’s center of mass. These jerk pairs, occurring about twice per second, will produce gravity-gradient noise in LIGO in the frequency band 2.5 Hz≲f≲1/(2τ)≃25 Hz with the form sqrt[Sh(f)]∼0.6×10-23 Hz-1/2(f/10 Hz)-6[∑i(ri/10 m)-6]1/2. Here the sum is over all the walking people, ri is the distance of the i’th person from the nearest interferometer test mass, and we estimate this formula to be accurate to within a factor 3. To ensure that this noise is negligible in advanced LIGO interferometers, people should be prevented from coming nearer to the test masses than r≃10 m. A r≃10 m exclusion zone will also reduce to an acceptable level gravity gradient noise from the slamming of a door and the striking of a fist against a wall. The dominant gravity-gradient noise from automobiles and other vehicles is probably that from decelerating to rest. To keep this below the sensitivity of advanced LIGO interferometers will require keeping vehicles at least 30 m from all test masses

Lost in Translation: Simple Steps in Experimental Design of Neurorehabilitation-based Research Interventions to Promote Motor Recovery Post-Stroke

Stroke continues to be a leading cause of disability. Basic neurorehabilitation research is necessary to inform the neuropathophysiology of impaired motor control, and to develop targeted interventions with potential to remediate disability post-stroke. Despite knowledge gained from basic research studies, the effectiveness of researchbased interventions for reducing motor impairment has been no greater than standard of practice interventions. In this perspective, we offer suggestions for overcoming translational barriers integral to experimental design, to augment traditional protocols, and re-route the rehabilitation trajectory toward recovery and away from compensation. First, we suggest that researchers consider modifying task practice schedules to focus on key aspects of movement quality, while minimizing the appearance of compensatory behaviors. Second, we suggest that researchers supplement primary outcome measures with secondary measures that capture emerging maladaptive compensations at other segments or joints. Third, we offer suggestions about how to maximize participant engagement, self-direction, and motivation, by embedding the task into a meaningful context, a strategy more likely to enable goal-action coupling, associated with improved neuro-motor control and learning. Finally, we remind the reader that motor impairment post-stroke is a multidimensional problem that involves central and peripheral sensorimotor systems, likely influenced by chronicity of stroke. Thus, stroke chronicity should be given special consideration for both participant recruitment and subsequent data analyses. We hope that future research endeavors will consider these suggestions in the design of the next generation of intervention studies in neurorehabilitation, to improve translation of research advances to improved participation and quality of life for stroke survivors

Use It and Improve It or Lose It: Interactions between Arm Function and Use in Humans Post-stroke

“Use it and improve it, or lose it” is one of the axioms of motor therapy after stroke. There is, however, little understanding of the interactions between arm function and use in humans post-stroke. Here, we explored putative non-linear interactions between upper extremity function and use by developing a first-order dynamical model of stroke recovery with longitudinal data from participants receiving constraint induced movement therapy (CIMT) in the EXCITE clinical trial. Using a Bayesian regression framework, we systematically compared this model with competitive models that included, or not, interactions between function and use. Model comparisons showed that the model with the predicted interactions between arm function and use was the best fitting model. Furthermore, by comparing the model parameters before and after CIMT intervention in participants receiving the intervention one year after randomization, we found that therapy increased the parameter that controls the effect of arm function on arm use. Increase in this parameter, which can be thought of as the confidence to use the arm for a given level of function, lead to increase in spontaneous use after therapy compared to before therapy

Epidural Electrical Stimulation for Stroke Rehabilitation: Results of the Prospective, Multicenter, Randomized, Single-Blinded Everest Trial.

BackgroundThis prospective, single-blinded, multicenter study assessed the safety and efficacy of electrical epidural motor cortex stimulation (EECS) in improving upper limb motor function of ischemic stroke patients with moderate to moderately severe hemiparesis.MethodsPatients ≥ 4 months poststroke were randomized 2:1 to an investigational (n = 104) or control (n = 60) group, respectively. Investigational patients were implanted (n = 94) with an epidural 6-contact lead perpendicular to the primary motor cortex and a pulse generator. Both groups underwent 6 weeks of rehabilitation, but EECS was delivered to investigational patients during rehabilitation. The primary efficacy endpoint (PE) was defined as attaining a minimum improvement of 4.5 points in the upper extremity Fugl-Meyer (UEFM) scale as well as 0.21 points in the Arm Motor Ability Test (AMAT) 4 weeks postrehabilitation. Follow-up assessments were performed 1, 4, 12, and 24 weeks postrehabilitation. Safety was evaluated by monitoring adverse events (AEs) that occurred between enrollment and the end of rehabilitation.ResultsPrimary intent-to-treat analysis showed no group differences at 4 weeks, with PE being met by 32% and 29% of investigational and control patients, respectively (P = .36). Repeated-measures secondary analyses revealed no significant treatment group differences in mean UEFM or AMAT scores. However, post hoc comparisons showed that a greater proportion of investigational (39%) than control (15%) patients maintained or achieved PE (P = .003) at 24 weeks postrehabilitation. Investigational group mean AMAT scores also improved significantly (P < .05) when compared to the control group at 24 weeks postrehabilitation. Post hoc analyses also showed that 69% (n = 9/13) of the investigational patients who elicited movement thresholds during stimulation testing met PE at 4 weeks, and mean UEFM and AMAT scores was also significantly higher (P < .05) in this subgroup at the 4-, 12-, and 24-week assessments when compared to the control group. Headache (19%), pain (13%), swelling (7%), and infection (7%) were the most commonly observed implant procedure-related AEs. Overall, there were 11 serious AEs in 9 investigational group patients (7 procedure related, 4 anesthesia related).ConclusionsThe primary analysis pertaining to efficacy of EECS during upper limb motor rehabilitation in chronic stroke patients was negative at 4 weeks postrehabilitation. A better treatment response was observed in a subset of patients eliciting stimulation induced upper limb movements during motor threshold assessments performed prior to each rehabilitation session. Post hoc comparisons indicated treatment effect differences at 24 weeks, with the control group showing significant decline in the combined primary outcome measure relative to the investigational group. These results have the potential to inform future chronic stroke rehabilitation trial design

Reduced Upper Limb Recovery in Subcortical Stroke Patients With Small Prior Radiographic Stroke

Background: Research imaging costs limit lesion-based analyses in already expensive large stroke rehabilitation trials. Despite the belief that lesion characteristics influence recovery and treatment response, prior studies have not sufficiently addressed whether lesion features are an important consideration in motor rehabilitation trial design.Objective: Using clinically-obtained neuroimaging, evaluate how lesion characteristics relate to upper extremity (UE) recovery and response to therapy in a large UE rehabilitation trial.Methods: We reviewed lesions from 297 participants with mild-moderate motor impairment in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study and their association with motor recovery, measured by the UE Fugl-Meyer (UE-FM). Significant lesion features identified on correlational and bivariate analysis were further analyzed for associations with recovery and therapy response using longitudinal mixed models.Results: Prior radiographic stroke was associated with less recovery on UE-FM in participants with motor impairment from subsequent subcortical stroke (−5.8 points) and in the overall sample (−3.6 points), but not in participants with cortical or mixed lesions. Lesion volume was also associated with less recovery, particularly after subcortical stroke. Every decade increase in age was associated with 1 less point of recovery on UE-FM. Response to specific treatment regimens varied based on lesion characteristics. Subcortical stroke patients experienced slightly less recovery with higher doses of upper extremity task-oriented training. Participants with cortical or mixed lesions experienced more recovery with higher doses of usual and customary therapy. Other imaging features (leukoaraiosis, ischemic vs. hemorrhagic stroke) were not significant.Conclusions: ICARE clinical imaging revealed information useful for UE motor trial design: stratification of persons with and without prior radiographic stroke may be required in participants with subcortical stroke, the majority of motor rehabilitation trial participants. Most of the prior radiographic strokes were small and cortically-based, suggesting even minor prior brain injury remote to the acute stroke lesion may limit spontaneous and therapy-related recovery. Lesion location may be associated with response to different therapy regimens, but the effects are variable and of unclear significance

Measuring Habitual Arm Use Post-stroke With a Bilateral Time-Constrained Reaching Task

Background: Spontaneous use of the more-affected arm is a meaningful indicator of stroke recovery. The Bilateral Arm Reaching Test (BART) was previously developed to quantify arm use by measuring arm choice to targets projected over a horizontal hemi-workspace. In order to improve clinical validity, we constrained the available movement time, thereby promoting more spontaneous decision making when selecting between the more-affected and less affected arm during the BART.Methods: Twenty-two individuals with mild to moderate hemiparesis were tested with the time-based BART in three time-constraint conditions: no-time constraint, medium, and fast conditions. Arm use was measured across three sessions with a 2-week interval in a spontaneous choice block, in which participants were instructed to use either the more-affected or the less-affected arm to reach targets. We tested the effect of time-constraint condition on the more-affected arm use, external validity of the BART with the Actual Amount of Use Test (AAUT), and test-retest reliability across the three test sessions.Results: The fast condition in the time-based BART showed reduced use of the more-affected arm compared to the no-time constraint condition P < 0.0001) and the medium condition P = 0.0006; Tukey post hoc analysis after mixed-effect linear regression). In addition, the fast condition showed strong correlation with the AAUT r = 0.829, P < 0.001), and excellent test-retest reliability (ICC = 0.960, P < 0.0001).Conclusion: The revised BART with a time-restricted fast condition provides an objective, accurate, and repeatable measure of spontaneous arm use in individuals with chronic stroke hemiparesis

Interrater Reliability of the Wolf Motor Function Test–Functional Ability Scale: Why It Matters

Background. One important objective for clinical trialists in rehabilitation is determining efficacy of interventions to enhance motor behavior. In part, limitation in the precision of measurement presents a challenge. The few valid, low-cost observational tools available to assess motor behavior cannot escape the variability inherent in test administration and scoring. This is especially true when there are multiple evaluators and raters, as in the case of multisite randomized controlled trials (RCTs). One way to enhance reliability and reduce variability is to implement rigorous quality control (QC) procedures. Objective. This article describes a systematic QC process used to refine the administration and scoring procedures for the Wolf Motor Function Test (WMFT)–Functional Ability Scale (FAS). Methods. The QC process, a systematic focus-group collaboration, was developed and used for a phase III RCT, which enlisted multiple evaluators and an experienced WMFT-FAS rater panel. Results. After 3 staged refinements to the administration and scoring instructions, we achieved a sufficiently high interrater reliability (weighted κ = 0.8). Conclusions and Implications. A systematic focus-group process was shown to be an effective method to improve reliability of observational assessment tools for motor behavior in neurorehabilitation. A reduction in noise-related variability in performance assessments will increase power and potentially lower the number needed to treat. Improved precision of measurement can lead to more cost-effective and efficient clinical trials. Finally, we suggest that improved precision in measures of motor behavior may provide more insight into recovery mechanisms than a single measure of movement time alone