TMS-induced silent periods: A review of methods and call for consistency.

Transcranial magnetic stimulation (TMS)-induced silent periods provide an in vivo measure of human motor cortical inhibitory function. Cortical silent periods (cSP, also sometimes referred to as contralateral silent periods) and ipsilateral silent periods (iSP) may change with advancing age and disease and can provide insight into cortical control of the motor system. The majority of past silent period work has implemented largely varying methodology, sometimes including subjective analyses and incomplete methods descriptions. This limits reproducibility of silent period work and hampers comparisons of silent period measures across studies. Here, we discuss methodological differences in past silent period work, highlighting how these choices affect silent period outcome measures. We also outline challenges and possible solutions for measuring silent periods in the unique case of the lower limbs. Finally, we provide comprehensive recommendations for collection, analysis, and reporting of future silent period studies.

Local dynamic stability during long-fatiguing walks in people with multiple sclerosis.

BACKGROUND: Altered balance/stability during walking is common in people with multiple sclerosis (PwMS). While dynamic gait stability has been related to falling and localized muscle fatigue, it has rarely been studied in MS. Specifically, the effects of walking-related fatigue on dynamic stability are unclear in PwMS. RESEARCH QUESTIONS: 1) Are temporal changes in dynamic stability during long-walks different among PwMS and healthy controls (HC)? 2) Is there a relationship between stability and walking performance changes in PwMS? METHODS: Twenty-five PwMS and ten HC participated in the six-minute walk test (6MWT) wearing six-wireless inertial sensors. Local dynamic stability (LDS) during gait was quantified by maximum-finite-time Lyapunov exponents (λS), where larger λS indicates less stable dynamics. Linear mixed models were fit to compare changes in LDS and walking performance over time among two groups. Additionally, the percent changes in λS and distance from minute 1 to 6 were recorded as Dynamic Stability Index (DSI6-1) and Distance-Walked Index (DWI6-1) respectively. Finally, Pearson correlation compared the association between DSI6-1 and DWI6-1. RESULTS: A significant group*time interaction was found for LDS. PwMS did not have different LDS than HC until minute-4 of walking, and differences persisted at minute-6. Further, PwMS walked significantly shorter distances and demonstrated a greater decline in walking performance (DWI6-1) during the 6MWT. Finally, DSI6-1 and DWI6-1 were significantly correlated in PwMS. Significance The dynamic stability differences among PwMS and HC were only apparent after 3-minutes of walking and ∼60% of PwMS became less stable over time, supporting the use of long walks in MS to capture stability changes during the motor task performance. A significant relationship between the decline in stability and poor walking performance over time during the 6MWT suggested a possible role of walking-related fatigue in the worsening of balance during long walks in PwMS.

Good agreement between smart device and inertial sensor-based gait parameters during a 6-min walk.

BACKGROUND: Traditional laboratory-based kinetic and kinematic gait analyses are expensive, time-intensive, and impractical for clinical settings. Inertial sensors have gained popularity in gait analysis research and more recently smart devices have been employed to provide quantification of gait. However, no study to date has investigated the agreement between smart device and inertial sensor-based gait parameters during prolonged walking. RESEARCH QUESTION: Compare spatiotemporal gait metrics measured with a smart device versus previously validated inertial sensors. METHODS: Twenty neurologically healthy young adults (7 women; age: 25.0 ±â€¯3.7 years; BMI: 23.4 ±â€¯2.9 kg/m2) performed a 6-min walk test (6MWT) wearing inertial sensors and smart devices to record stride duration, stride length, cadence, and gait speed. Pearson correlations were used to assess associations between spatiotemporal measures from the two devices and agreement between the two methods was assessed with Bland-Altman plots and limits of agreement. RESULTS: All spatiotemporal gait metrics (stride duration, cadence, stride length and gait speed) showed strong (r>0.9) associations and good agreement between the two devices. SIGNIFICANCE: Smart devices are capable of accurately reflecting many of the spatiotemporal gait metrics of inertial sensors. As the smart devices also accurately reflected individual leg output, future studies may apply this analytical strategy to clinical populations, to identify hallmarks of disability status and disease progression in a more ecologically valid environment.

Supraspinal control of automatic postural responses in people with multiple sclerosis.

The neural underpinnings of delayed automatic postural responses in people with multiple sclerosis (PwMS) are unclear. We assessed whether white matter pathways of two supraspinal regions (the cortical proprioceptive Broadman's Area-3; and the balance/locomotor-related pedunculopontine nucleus) were related to delayed postural muscle response latencies in response to external perturbations. 19 PwMS (48.8±11.4years; EDSS=3.5 (range: 2-4)) and 12 healthy adults (51.7±12.2years) underwent 20 discrete, backward translations of a support surface. Onset latency of agonist (medial-gastrocnemius) and antagonist (tibialis anterior) muscles were assessed. Diffusion tensor imaging assessed white-matter integrity (i.e. radial diffusivity) of cortical proprioceptive and balance/locomotor-related tracts. Latency of the tibialis anterior, but not medial gastrocnemius was larger in PwMS than control subjects (p=0.012 and 0.071, respectively). Radial diffusivity of balance/locomotor tracts was higher (worse) in PwMS than control subjects (p=0.004), and was significantly correlated with tibialis (p=0.002), but not gastrocnemius (p=0.06) onset latency. Diffusivity of cortical proprioceptive tracts was not correlated with muscle onset. Lesions in supraspinal structures including the pedunculopontine nucleus balance/locomotor network may contribute to delayed onset of postural muscle activity in PwMS, contributing to balance deficits in PwMS.

Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease: a randomized clinical trial.

BACKGROUND: There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. METHODS/DESIGN: This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. DISCUSSION: The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. TRIAL REGISTRATION: This trial is registered at clinical trials.gov (NCT02231073).

Fundamental differences in callosal structure, neurophysiologic function, and bimanual control in young and older adults.

Bimanual actions involve coordinated motion but often rely on the movements performed with each hand to be different. Older adults exhibit differentially greater variability for bimanual actions in which each hand has an independent movement goal. Such actions rely on interhemispheric communication via the corpus callosum, including both facilitatory and inhibitory interactions. Here, we investigated whether age differences in callosal structure and interhemispheric function contribute to this selective movement difficulty. Participants performed 3 force production tasks: 1) unimanual, 2) bimanual simultaneous, and 3) bimanual independent. Older adults had significantly greater interhemispheric facilitation during voluntary muscle activation. We also report a fundamental shift with age in the relationship between callosal tract microstructural integrity and interhemispheric inhibition (IHI). Specifically, older adults with relatively greater callosal tract microstructural integrity have less IHI. Furthermore, greater IHI was related to poorer bimanual performance (assessed by dominant hand force variability) in older adults on all tasks, whereas this relationship was only observed in young adults for the bimanual independent condition. These findings indicate changes in interhemispheric communication with advancing age such that older adults may rely on bilateral cortical cooperation to a greater extent than young adults for manual actions.