PRO-FIT-CARE study: the feasibility assessment of a pilot online exercise intervention for persons living with obesity and female infertility.

Introduction: Moderate-to-high physical activity participation is associated with a reduced risk of infertility. Yet, exercise interventions that target cardiorespiratory fitness, independent of weight loss, are lacking in obesity and female fertility research. Purpose: The primary objective of the PRO-FIT-CARE (PROmoting FITness for CArdiometabolic & REproductive Health) study was to assess the feasibility of a moderate-to-high-intensity online exercise program for persons with obesity and female infertility. Methods: Feasibility, safety, acceptability, and efficacy were assessed by examining: (1) recruitment and consent rate, (2) study retention, (3) adverse events, (4) participant satisfaction, (5) adherence, and (6) cardiorespiratory fitness. Results: Eleven of thirty-two women contacted agreed to participate in the program (34.4% consent rate). Eight participants (72.7%) completed the study. One musculoskeletal injury was reported. There was a 30% adherence rate based on prescribed exercise intensity (60%-80% of heart rate maximum). One of eleven participants attended 80% of the exercise intervention. Based on a weekly satisfaction survey, the program had an overall high level of satisfaction. Compared to sex and age normative data, post-intervention, two of eight participants improved their cardiorespiratory fitness percentile rank. Conclusion: The study highlights challenges with adherence to an online exercise program. While the program was safe and participants reported high levels of program satisfaction, approaches to improve adherence must be incorporated.

The effects of five sessions of continuous theta burst stimulation over contralesional sensorimotor cortex paired with paretic skilled motor practice in people with chronic stroke.

BACKGROUND: In individuals with chronic stroke, impairment of the paretic arm may be exacerbated by increased contralesional transcallosal inhibition (TCI). Continuous theta burst stimulation (cTBS) can decrease primary motor cortex (M1) excitability and TCI. However, contralesional cTBS shows inconsistent effects after stroke. Variable effects of cTBS could stem from failure to pair stimulation with skilled motor practice or a focus of applying cTBS over M1. OBJECTIVE: Here, we investigated the effects of pairing cTBS with skilled practice on motor learning and arm function. We considered the differential effects of stimulation over two different brain regions: contralesional M1 (M1c) or contralesional primary somatosensory cortex (S1c). METHODS: 37 individuals with chronic stroke participated in five sessions of cTBS and paretic arm skilled practice of a serial targeting task (STT); participants received either cTBS over M1c or S1c or sham before STT practice. Changes in STT performance and Wolf Motor Function Test (WMFT) were assessed as primary outcomes. Assessment of bilateral corticospinal, intracortical excitability and TCI were secondary outcomes. RESULTS: cTBS over sensorimotor cortex did not improve STT performance and paretic WMFT-rate beyond sham cTBS. TCI was reduced bi-directionally following the intervention, regardless of stimulation group. In addition, we observed an association between STT performance change and paretic WMFT-rate change in the M1c stimulation group only. CONCLUSIONS: Multiple sessions of STT practice can improve paretic arm function and decrease TCI bilaterally, with no additional benefit of prior cTBS. Our results suggest that improvement in STT practice following M1c cTBS scaled with change in paretic arm function in some individuals. Our results highlight the need for a better understanding of the mechanisms of cTBS to effectively identify who may benefit from this form of brain stimulation.

White Matter Biomarkers Associated with Motor Change in Individuals with Stroke: A Continuous Theta Burst Stimulation Study.

Continuous theta burst stimulation (cTBS) is a form of noninvasive repetitive brain stimulation that, when delivered over the contralesional hemisphere, can influence the excitability of the ipsilesional hemisphere in individuals with stroke. cTBS applied prior to skilled motor practice interventions may augment motor learning; however, there is a high degree of variability in individual response to this intervention. The main objective of the present study was to assess white matter biomarkers of response to cTBS paired with skilled motor practice in individuals with chronic stroke. We tested the effects of stimulation of the contralesional hemisphere at the site of the primary motor cortex (M1c) or primary somatosensory cortex (S1c) and a third group who received sham stimulation. Within each stimulation group, individuals were categorized into responders or nonresponders based on their capacity for motor skill change. Baseline diffusion tensor imaging (DTI) indexed the underlying white matter microstructure of a previously known motor learning network, named the constrained motor connectome (CMC), as well as the corticospinal tract (CST) of lesioned and nonlesioned hemispheres. Across practice, there were no differential group effects. However, when categorized as responders vs. nonresponders using change in motor behaviour, we demonstrated a significant difference in CMC microstructural properties (as measured by fractional anisotropy (FA)) for individuals in M1c and S1c groups. There were no significant differences between responders and nonresponders in clinical baseline measures or microstructural properties (FA) in the CST. The present study identifies a white matter biomarker, which extends beyond the CST, advancing our understanding of the importance of white matter networks for motor after stroke.

Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis.

In individuals with multiple sclerosis (MS), transcranial magnetic stimulation (TMS) may be employed to assess the integrity of corticospinal system and provides a potential surrogate biomarker of disability. The purpose of this study was to provide a comprehensive examination of the relationship between multiple measures corticospinal excitability and clinical disability in MS (expanded disability status scale (EDSS)). Bilateral corticospinal excitability was assessed using motor evoked potential (MEP) input-output (IO) curves, cortical silent period (CSP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and transcallosal inhibition (TCI) in 26 individuals with MS and 11 healthy controls. Measures of corticospinal excitability were compared between individuals with MS and controls. We evaluated the relationship(s) between age and clinical demographics such as age at MS onset (AO), disease duration (DD) and clinical disability (EDSS) with measures of corticospinal excitability. Corticospinal excitability thresholds were higher, MEP latency and CSP onset delayed and MEP durations prolonged in individuals with MS compared to controls. Age, DD and EDSS correlated with corticospinal excitability thresholds. Also, TCI duration and the linear slope of the MEP amplitude IO curve correlated with EDSS. Hierarchical regression modeling demonstrated that combining multiple TMS-based measures of corticospinal excitability accounted for unique variance in clinical disability (EDSS) beyond that of clinical demographics (AO, DD). Our results indicate that multiple TMS-based measures of corticospinal and interhemispheric excitability provide insights into the potential neural mechanisms associated with clinical disability in MS. These findings may aid in the clinical evaluation, disease monitoring and prediction of disability in MS.

Comparing a diffusion tensor and non-tensor approach to white matter fiber tractography in chronic stroke.

Diffusion tensor imaging (DTI)-based tractography has been used to demonstrate functionally relevant differences in white matter pathway status after stroke. However, it is now known that the tensor model is insensitive to the complex fiber architectures found in the vast majority of voxels in the human brain. The inability to resolve intra-voxel fiber orientations may have important implications for the utility of standard DTI-based tract reconstruction methods. Intra-voxel fiber orientations can now be identified using novel, tensor-free approaches. Constrained spherical deconvolution (CSD) is one approach to characterize intra-voxel diffusion behavior. In the current study, we performed DTI- and CSD-based tract reconstruction of the corticospinal tract (CST) and corpus callosum (CC) to test the hypothesis that characterization of complex fiber orientations may improve the robustness of fiber tract reconstruction and increase the sensitivity to identify functionally relevant white matter abnormalities in individuals with chronic stroke. Diffusion weighted magnetic resonance imaging was performed in 27 chronic post-stroke participants and 12 healthy controls. Transcallosal pathways and the CST bilaterally were reconstructed using DTI- and CSD-based tractography. Mean fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were calculated across the tracts of interest. The total number and volume of reconstructed tracts was also determined. Diffusion measures were compared between groups (Stroke, Control) and methods (CSD, DTI). The relationship between post-stroke motor behavior and diffusion measures was evaluated. Overall, CSD methods identified more tracts than the DTI-based approach for both CC and CST pathways. Mean FA, ADC, and RD differed between DTI and CSD for CC-mediated tracts. In these tracts, we discovered a difference in FA for the CC between stroke and healthy control groups using CSD but not DTI. CSD identified ipsilesional CST pathways in 9 stroke participants who did not have tracts identified with DTI. Additionally, CSD differentiated between stroke ipsilesional and healthy control non-dominant CST for several measures (number of tracts, tract volume, FA, ADC, and RD) whereas DTI only detected group differences for number of tracts. In the stroke group, motor behavior correlated with fewer diffusion metrics derived from the DTI as compared to CSD-reconstructed ipsilesional CST and CC. CSD is superior to DTI-based tractography in detecting differences in diffusion characteristics between the nondominant healthy control and ipsilesional CST. CSD measures of microstructure tissue properties related to more motor outcomes than DTI measures did. Our results suggest the potential utility and functional relevance of characterizing complex fiber organization using tensor-free diffusion modeling approaches to investigate white matter pathways in the brain after stroke.