Sutton B. Richmond

In this study, we investigated the effects of elevated CO ₂ on delayed signal enhancement in brain MRI following gadolinium contrast injection. We found CO ₂ effects on brain white matter and vitreous chamber of the eye, with higher tissue enhancement at 90 min relative to when participants breathed ambient air. These findings suggest delayed glymphatic clearance with elevated CO ₂ .

Multiple sclerosis (MS) often leads to mobility impairments, yet the neural mechanisms underlying these deficits remain poorly understood. This study examined whether resting-state functional connectivity (rs-FC) differs between people with MS (PwMS) and healthy controls in relation to spatiotemporal mobility performance. We hypothesized that group differences within the default mode (DMN), frontoparietal (FPN), somatomotor (SN), and visual (VIS) networks would be associated with gait and turning metrics. Twenty-nine PwMS and 28 matched controls completed a two-minute walk test, 180° walking turns, and 360° in-place turns at natural and fast speeds. fMRI data were analyzed using multivariate pattern analysis (MVPA) and post-hoc seed-to-voxel analyses for gait speed, cadence, double support time, stride length, turn duration, peak velocity, and turn angle. PwMS exhibited slower gait speed, shorter stride length, and impaired 360° turning, but no group differences in cadence, double support, or 180° turn metrics. MVPA revealed rs-FC differences across DMN, FPN, SN, and VIS networks. While rs-FC differences were evident for walking metrics, within-group associations were not significant. In contrast, 360° turn angle showed distinct within-group rs-FC associations, particularly involving VAN and DAN networks. These findings highlight turning as a sensitive task for capturing functional neural differences in MS.

Introduction: Assessing an individual’s physical capacity to move independently and safely to perform activities of daily living (i.e., functional mobility) can be approached through various modalities, including performance-based physiological tests, observational assessments, and self-report questionnaires. The purpose of this study was to establish a patient-reported outcome measure (PROM), termed PROWalk ^TM , based on the PROMIS Item Bank 2.0 – Physical Function, to assess perceived mobility challenges, specifically related to gait and balance function, and evaluate its performance in comparison to the Patient-Specific Functional Scale (PSFS) within a population of individuals with sensory peripheral neuropathy. Methods: The PROWalk PROM was developed with expert clinician input as a custom short form composed of selected items from the Item Bank. Participants with lower extremity peripheral neuropathy who had been prescribed a wearable sensory prosthesis were administered the PROWalk and the PSFS, a perceived functional mobility assessment via telecommunications at baseline and six weeks after wearing the sensory prosthesis. Results: Both measures displayed significant increases (i.e., improvements) over time with large effect sizes and upward linear trends for each instrument between baseline and six weeks. When normalized, the measures showed no bias, large limits of agreement, and no normalized change between the instruments. Discussion: The PROWalk PROM detected significant improvements in perceived functional mobility over time and showed strong temporal stability and suitability for standardized group-level comparisons, which were similar to the PSFS. Overall, the PROWalk appears to be a valid PROM for capturing improvements in self-reported functional mobility related to gait and balance function.

Declines in walking function commonly occur in people with multiple sclerosis (MS). Walking is a continuous movement and a complex motor task that requires precise timing and scaling of activation across many muscles. The objectives of this study were to identify kinematic gait characteristics during a 2-minute walk test that are associated with disease duration in individuals with relapsing-remitting MS (n=45). Participants were instrumented with inertial measurement units from APDM (APDM Inc, Portland, OR, USA) and performed the 2-minute walk test twice: once at their self-selected speed and another at their fastest, safe speed. Gait speed was not associated with MS disease duration (Self-selected: p= 0.180; Fast: p=0.167). Canonical correlation analysis showed that disease progression was strongly associated with lateral step width variability and ankle pitch at toe-off, which was also reflected in the multiple linear regression models. Both self-selected and fast-speed kinematics were associated with disease duration (Self-selected: p=0.007; Fast: p=0.004). Thus, we identified a multivariate model that is associated with disease duration in highly ambulatory MS individuals. Our study highlights the importance of considering individual differences in specific gait kinematics (such as lateral step width variability and ankle pitch at toe-off) when assessing disease progression in MS. This approach may provide more personalized insights into the impact of MS on mobility and help tailor interventions to improve gait and overall function in affected individuals. Future research should continue exploring these kinematic parameters to better understand their role in MS progression and develop targeted therapeutic strategies.

Background: Increased sway within a stationary base of support (BoS) is often interpreted as worse postural control. However, larger persons may have larger feet, facilitating broader sway patterns within their wider/longer base. Time to boundary (TtB) incorporates foot placement dimensions into the calculation and, thus, may not be confounded by dissimilar anthropometric features. Methods: Ninety-seven healthy adults stood quietly on a force platform for 150 s with their feet together while barefoot. BoS characteristics, center of pressure motion, and TtB were calculated and correlated with body height for eyes open and closed conditions. Results: BoS width, length, and total area positively correlated with body height. Path length and sway area were positively correlated with height for both vision conditions, with stronger correlations observed with eyes closed. At the same time, TtB was not correlated with height in either visual condition. Consequently, the tallest 20 individuals in the sample displayed greater path length and sway areas but equal TtB as the shortest 20 persons. Conclusion: Observed differences in position-based center of pressure measures could be an artifact of body size inequality not postural (in)stability. Meanwhile, TtB is normalized to BoS and is, therefore, not confounded by anthropometric differences.

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO₂). These environments mimic the headward fluid shifts, body unloading, and elevated CO₂observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO₂(30 days with elevated ambient CO₂). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO₂campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

The glymphatic system is a brain‐wide network of perivascular pathways along which cerebrospinal fluid and interstitial fluid rapidly exchange, facilitating solute and waste clearance from the brain parenchyma. The characterization of this exchange process in humans has relied primarily upon serial magnetic resonance imaging following intrathecal gadolinium‐based contrast agent injection. However, less invasive approaches are needed. Here, we administered a gadolinium‐based contrast agent intravenously in eight healthy participants and acquired magnetic resonance imaging scans prior to and 30, 90, 180, and 360 min post contrast injection. Using a region‐of‐interest approach, we observed that peripheral tissues and blood vessels exhibited high enhancement at 30 min after contrast administration, likely reflecting vascular and peripheral interstitial distribution of the gadolinium‐based contrast agent. Ventricular, grey matter and white matter enhancement peaked at 90 min, declining thereafter. Using k‐means clustering, we identify distinct distribution volumes reflecting the leptomeningeal perivascular network, superficial grey matter and deep grey/white matter that exhibit a sequential enhancement pattern consistent with parenchymal contrast enhancement via the subarachnoid cerebrospinal fluid compartment. We also outline the importance of correcting for (otherwise automatic) autoscaling of signal intensities, which could potentially lead to misinterpretation of gadolinium‐based contrast agent distribution kinetics. In summary, we visualize and quantify delayed tissue enhancement following intravenous administration of gadolinium‐based contrast agent in healthy human participants.