Search

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1–3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443.

Deep brain stimulation (DBS) for pain has largely been implemented in an uncontrolled manner to target the somatosensory component of pain, with research leading to mixed results. We have previously shown that patients with poststroke pain syndrome who were treated with DBS targeting the ventral striatum/anterior limb of the internal capsule (VS/ALIC) demonstrated a significant improvement in measures related to the affective sphere of pain. In this study, we sought to determine how DBS targeting the VS/ALIC modifies brain activation in response to pain. Five patients with poststroke pain syndrome who were blinded to DBS status (ON/OFF) and six age‐ and sex‐matched healthy controls underwent functional magnetic resonance imaging (fMRI) measuring blood oxygen level‐dependent activation in a block design. In this design, each participant received heat stimuli to the affected or unaffected wrist area. Statistical comparisons were performed using fMRI z‐maps. In response to pain, patients in the DBS OFF state showed significant activation (p< 0.001) in the same regions as healthy controls (thalamus, insula, and operculum) and in additional regions (orbitofrontal and superior convexity cortical areas). DBS significantly reduced activation of these additional regions and introduced foci of significant inhibitory activation (p< 0.001) in the hippocampi when painful stimulation was applied to the affected side. These findings suggest that DBS of the VS/ALIC modulates affective neural networks.

Resting-state peak alpha frequency (PAF) between 8–12 Hz has been found to be suppressed and slowed in chronic pain conditions suggesting its role as a potential biomarker. However, the cortical regions exhibiting PAF suppression and slowing, and their relationship with baseline pain levels are currently unknown. To address this question, we collected resting-state magnetoencephalography (MEG) from twenty-three complex regional pain syndrome (CRPS) patients (15F, 20-75 years) and pain-free controls (8F, 19-50 years). Min-norm source localization was performed on the preprocessed MEG data followed by power spectral density estimation at each source. To identify cortical sources exhibiting significant alpha power difference between patients and controls (P<0.05), we performed a nonparametric spatio-spectral cluster permutation t-test (cluster-defining threshold P<0.001). We parcellated the brain using a standard atlas to identify anatomical regions underlying significant clusters. Overall, both alpha power and PAF were significantly lower in CRPS patients compared to controls. The difference was most pronounced over bilateral paracentral, postcentral, precentral, precuneus, superior parietal and medial temporal areas. In CRPS patients, higher baseline pain level (measured using visual analog scale) was associated with 1. lower PAF power in frontal regions, 2. slower PAF in inferior frontal gyrus and 3. faster PAF in the temporal-parietal regions. Though greatest difference in alpha power between groups was observed over the sensorimotor areas, suppression and slowing of PAF in the frontal regions were associated with baseline pain level. These findings inform us about novel targets for neuromodulatory interventions that can alleviate pain in chronic pain populations. Funding: NIH K01DA050804.

Introduction: Decrements in muscular strength during long-duration missions in space could be mission-critical during construction and exploration activities. The purpose of this study was to quantify changes in muscle volume, strength, and endurance of crewmembers on the International Space Station (ISS) in the context of new measurements of loading during exercise countermeasures. Methods: Strength and muscle volumes were measured from four male ISS crewmembers (49.5 ± 4.7 yr. 179.3 ± 7.1 cm, 85.2 ± 10.4 kg) before and after long-duration spaceflight (181 ± 15 d). Preflight and in-flight measurements of forces between foot and shoe allowed comparisons of loading from 1-g exercise and exercise countermeasures on SS. Results: Muscle volume change was greater in the calf (-10 to 16%) than the thigh (-4% to -7%), but there was no change in the upper arm (+0.4 to -0.8%). Isometric and isokinetic strength changes at the knee (range -10.4 to -24.1%,), ankle (range -4 to -22.3%), and elbow (range -7.5 to -16.7%) were observed. Although there was an overall postflight decline in total work (-14%) during the endurance test, an increase in postflight resistance to fatigue was observed. The peak in-shoe forces during running and cycling on ISS were approximately 46% and 50% lower compared to 1 -g values. Discussion: Muscle volume and strength were decreased in the lower extremities of crewmembers during longduration spaceflight on ISS despite the use of exercise countermeasures. In-flight countermeasures were insufficient to replicate the daily mechanical loading experienced by the crewmembers before flight. Future exercise protocols need careful assessment both in terms of intensity and duration to maximize the "dose" of exercise and to increase loads compared to the measured levels. [ABSTRACT FROM AUTHOR]

Introduction: Loss in bone mineral density and muscle strength in astronauts following long-duration spaceflight have been well documented, but the altered force and movement environments in microgravity which may contribute to these changes have not been well characterized. This paper describes the instrumentation, software, and data collection procedures developed for the "Foot" experiment that was conducted on the International Space Station (ISS) to provide insight into the biomechanics of daily activity in a microgravity environment. Methods: The instrumentation used for data collection included the Ambulatory Data Acquisition System (ADAS), ADAS electromyography (EMG) modules, the Joint Excursion System, and the Total Force-Foot Ground Interface system, which were all integrated into a specially designed Lower Extremity Monitoring Suit. There were 14 total channels of data that were collected at sampling rates between 8 Hz and 1024 Hz, including 7 channels of EMG, 4 channels of joint angle data, 2 channels of in-shoe ground reaction force, and a marker channel for event recording. Data were typically collected for between 6.5 and 11.8 h of activity during 4 d on Earth and 4-7 d in flight. Results: Exemplar data sets collected preflight on astronauts in 1 g to validate the instrumentation are presented. Discussion: We conclude that the system provides valid and useful biomechanical information on long-term activity. The analysis of data collected on-orbit using the system described here will be presented in a series of future papers characterizing the biomechanics of astronaut activity during complete working days on the Earth and on the ISS. [ABSTRACT FROM AUTHOR]