Implanted vagus nerve stimulation (VNS) delivered concurrently with upper limb rehabilitation has been shown to improve arm function after stroke. Transcutaneous auricular VNS (taVNS) offers a non-invasive alternative to implanted VNS and may provide similar therapeutic benefit. There is much discussion about the optimal approach for combining VNS and physical therapy, as such we sought to determine whether taVNS administered during robotic training, specifically delivered during the premotor planning stage for arm extension movements, would confer additional motor improvement in patients with chronic stroke. Thirty-six patients with chronic, moderate-severe upper limb hemiparesis (>6 months; mean Upper Extremity Fugl-Meyer score = 25 ± 2, range 13–48), were randomized to receive 9 sessions (1 h in length, 3x/week for 3 weeks) of active (N = 18) or sham (N = 18) taVNS (500 ms bursts, frequency 30 Hz, pulse width 0.3 ms, max intensity 5 mA, ∼250 stimulated movements per session) delivered during robotic training. taVNS was triggered by the onset of a visual cue prior to center-out arm extension movements. Clinical assessments and surface electromyography (sEMG) measures of the biceps and triceps brachii were collected during separate test sessions. Significant motor improvements were measured for both the active and sham taVNS groups, and these improvements were robust at 3 month follow-up. Compared to the sham group, the active taVNS group showed a significant reduction in spasticity of the wrist and hand at discharge (Modified Tardieu Scale; taVNS = –8.94% vs. sham = + 2.97%, p < 0.05). The EMG results also demonstrated significantly increased variance for the bicep peak sEMG amplitude during extension for the active taVNS group compared to the sham group at discharge (active = 26.29% MVC ± 3.89, sham = 10.63% MVC ± 3.10, mean absolute change admission to discharge, p < 0.01), and at 3-month follow-up, the bicep peak sEMG amplitude was significantly reduced in the active taVNS group (P < 0.05). Thus, robot training improved the motor capacity of both groups, and taVNS, decreased spasticity. taVNS administered during premotor planning of movement may play a role in improving coordinated activation of the agonist-antagonist upper arm muscle groups by mitigating spasticity and increasing motor control following stroke.Clinical Trial Registration:www.ClinicalTrials.gov, identifier (NCT03592745).
Background: Muscle spasticity is a common impediment to motor recovery in patients with chronic stroke. Standard-of-care treatments such as botulinum toxin injections can temporarily relieve muscle stiffness and pain associated with spasticity, but often at the expense of increased muscle weakness. Recent preclinical investigations of a non-invasive treatment that pairs trans-spinal direct current stimulation and peripheral nerve direct current stimulation (tsDCS+pDCS) provided promising data for a novel approach based on bioelectronic medicine for the treatment of patients with post-stroke spasticity. Methods: Twenty-six patients with upper limb hemiparesis and wrist spasticity at least 6 months after their initial stroke participated in this single-blind crossover design study to test whether tsDCS+pDCS reduces chronic upperextremity spasticity. Subjects received five consecutive daily sessions (20 min of stimulation or sham) of anodal tsDCS+pDCS, separated by a one-week washout period. The sham condition always preceded the active condition. Clinical and objective measures of spasticity and motor function were collected before and after each condition, and for five weeks after the completion of the active intervention. Results: Subjects treated with active tsDCS+pDCS demonstrated significant reductions in both Modified Tardieu Scale scores (summed across the upper limb, P < 0.05), and in objective torque measures (Nm) of the spastic catch response at the wrist flexor (P < 0.05), compared to the sham condition. Motor function also improved significantly (measured by the Fugl-Meyer and Wolf Motor Function Test; P < 0.05 for both tests) after active treatment. Conclusions: tsDCS+pDCS intervention alone significantly reduced upper limb spasticity in participants with stroke. Decreased spasticity was persistent for five weeks after treatment, and was accompanied by improved motor function even though patients were unsupervised and there was no prescribed activity or training during that interval.
Background Women are disproportionately afflicted with dementias, though the exact risk factors explaining why are yet to be determined. Additionally, perimenopausal women experience deficits in verbal memory during menopause compared to their pre‐ and postmenopausal state. Because sleep debt also leads to verbal memory deficits, we explored whether one of the hallmark symptoms of menopause, hot flushes, cause an increase of sleep disturbances. Methods N = 63 perimenopausal and postmenopausal women (mean age of 53.1 ± 1.1 years old) with hot flushes were recorded using actigraphy for sleep/wake activity and skin conductance for objective hot flushes over one night. The two time series were compared to each other using Granger causality to establish statistical causality. The number of objective hot flushes, determined by skin conductance, and amount of time spent awake were compared with linear regression. Results Of the 63 women, 76.2% were found to have skin conductance which granger‐caused more awake activity at night. Additionally, we have reinforced that a greater number of nightly objective hot flushes is associated with greater time spent awake (b = 28 minutes/hot flush, p < .001). Conclusion Those women who have hot flush granger‐caused awakenings may be at a higher risk of sleep disturbances during and following menopause. The relationship between hot flushes and lower sleep quality has previously been shown, but here we show that there may be a causal link of hot flushes causing night‐time awakenings. These hot flush granger‐caused awakenings may represent a female‐specific risk factor for cognitive impairment.
Introduction RAR disruptions are more common among individuals with dementia than healthy individuals. In healthy older women, RAR disruption predicted future diagnosis of Mild Cognitive Impairment (MCI). With no cure for Alzheimer’s Disease, it is crucial to identify modifiable risk-factors for early prevention of cognitive decline. Here we aim to determine whether RAR disruption was associated with cognitive status and cognitive performance in early post-menopausal women, thereby representing a modifiable risk factor for dementia. Methods The sample drawn from MsBrain study, included 229 cognitively unimpaired women and 42 women with MCI/dementia, based on score on Montreal Cognitive Assessment (MOCA) adjusted for age and race. Participants completed a 72-hour wrist actigraphy monitoring and neuropsychological assessment including: California Verbal Learning Test (CVLT), Letter Number Sequencing (LNS), Card Rotation Test, Symbol Digit Modalities Test (SDMT). Latent profile analysis (LPA) was performed using five nonparametric RAR variables (intra-daily variability (IV), inter-daily stability (IS), relative amplitude (RA), alpha and F-statistic). The association between RAR clusters and cognitive performance and the relationship between RAR clusters, cognitive status and race/ethnicity were assessed using linear regression models, controlling for age, race/ethnicity, education and body mass index (BMI); and using chi-square test respectively. Results LPA revealed three clusters: Robust with high F-Stat, RA and IS and low IV; Normal;Weak with low RA and high alpha. The proportion of subjects with MCI/dementia did not differ between clusters however there was a significant association between race and RAR clusters, X2 (2, N = 271)=14.18, p<0[P1] .001, with non-white women more likely than white women to belong in the Weak group (p < .01). In an adjusted analysis of healthy women, the Weak group performed worse than the Robust group in LNS control (p<.050 ). In the unadjusted model, the Weak group performed worse than Robust group in CVLT Total Learning and Long Delay Recall and SDMT (p=.0074, p=.011and p= .0041, respectively). Conclusion Non-white women had weaker RAR than their white counterparts. Weaker RARs related to poorer working memory as measured by LNS; and poorer verbal memory and processing speed, measured by CVLT and SDMT however these effects were largely influenced by covariates, particularly race/ethnicity and education. Support (If Any)
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