Age-dependent modulation of motor network connectivity for skill acquisition, consolidation and interlimb transfer after motor practice

Objective: Age-related differences in neural strategies for motor learning are not fully understood. We determined the effects of age on the relationship between motor network connectivity and motor skill acquisition, consolidation, and interlimb transfer using dynamic imaging of coherent sources. Methods: Healthy younger (n = 24, 18-24 y) and older (n = 24, 65-87 y) adults unilaterally practiced a visuomotor task and resting-state electroencephalographic data was acquired before and after practice as well as at retention. Results: The results showed that right-hand skill acquisition and consolidation did not differ between age groups. However, age affected the ability to transfer the newly acquired motor skill to the non-practiced limb. Moreover, strengthened left- and right-primary motor cortex-related beta conectivity was negatively and positively associated with right-hand skill acquisition and left-hand skill consolidation in older adults, respectively. Conclusion: Age-dependent modulations of bilateral resting-state motor network connectivity indicate age-specific strategies for the acquisition, consolidation, and interlimb transfer of novel motor tasks. Significance: The present results provide insights into the mechanisms underlying motor learning that are important for the development of interventions for patients with unilateral injuries. (C) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved

Knee joint neuromuscular activation performance during muscle damage and superimposed fatigue

This study examined the concurrent effects of exercise-induced muscle damage and superimposed acute fatigue on the neuromuscular activation performance of the knee flexors of nine males (age: 26.7 ± 6.1yrs; height 1.81 ± 0.05m; body mass 81.2 ± 11.7kg [mean ± SD]). Measures were obtained during three experimental conditions: (i) FAT-EEVID, involving acute fatiguing exercise performed on each assessment occasion plus a single episode of eccentric exercise performed on the first occasion and after the fatigue trial; (ii) FAT, involving the fatiguing exercise only and; (iii) CON consisting of no exercise. Assessments were performed prior to (pre) and at lh, 24h, 48h, 72h, and 168h relative to the eccentric exercise. Repeated-measures ANOVAs showed that muscle damage within the FAT-EEVID condition elicited reductions of up to 38%, 24%) and 65%> in volitional peak force, electromechanical delay and rate of force development compared to baseline and controls, respectively (F[io, 80] = 2.3 to 4.6; p to 30.7%>) following acute fatigue (Fp; i6] = 4.3 to 9.1; p ; Fp, iq = 3.9; p <0.05). The safeguarding of evoked muscle activation capability despite compromised volitional performance might reveal aspects of capabilities for emergency and protective responses during episodes of fatigue and antecedent muscle damaging exercise

Adaptive Control of Dynamic Balance across the Adult Lifespan

Introduction The ability to adapt dynamic balance to perturbations during gait deteriorates with age. To prevent age-related decline in adaptive control of dynamic balance, we must first understand how adaptive control of dynamic balance changes across the adult lifespan. We examined how adaptive control of the margin of stability (MoS) changes across the lifespan during perturbed and unperturbed walking on the split-belt treadmill. Methods Seventy-five healthy adults (age range, 18-80 yr) walked on an instrumented split-belt treadmill with and without split-belts. Linear regression analyses were performed for the mediolateral (ML) and anteroposterior (AP) MoS, step length, single support time, step width, double support time, and cadence during unperturbed and perturbed walking (split-belt perturbation), with age as predictor. Results Age did not significantly affect dynamic balance during unperturbed walking. However, during perturbed walking, the ML MoS of the leg on the slow belt increased across the lifespan due to a decrease in bilateral single support time. The AP MoS did not change with aging despite a decrease in step length. Double support time decreased and cadence increased across the lifespan when adapting to split-belt walking. Age did not affect step width. Conclusions Aging affects the adaptive control of dynamic balance during perturbed but not unperturbed treadmill walking with controlled walking speed. The ML MoS increased across the lifespan, whereas bilateral single support times decreased. The lack of aging effects on unperturbed walking suggests that participants' balance should be challenged to assess aging effects during gait. The decrease in double support time and increase in cadence suggests that older adults use the increased cadence as a balance control strategy during challenging locomotor tasks

Do gait and muscle activation patterns change at middle-age during split-belt adaptation?

Advancing age affects gait adaptability, but it is unclear if such adaptations to split-belt perturbations are already affected at middle-age. Changes in neuromuscular control, that already start at middle-age, may underlie the age-related changes in gait adaptation. Thus, we examined the effects of age on adaptations in gait and muscle activation patterns during split-belt walking in healthy young and middle-aged adults. Young (23.3±3.13 years) and middle-aged adults (55.3±2.91 years) walked on an instrumented split-belt treadmill. Both age groups adapted similarly by reducing asymmetry in step length and double support time. Surface EMG was recorded from eight leg muscles bilaterally. Principal Component Analysis (PCA) was applied to the EMG data of all subjects, for the fast and slow leg separately, to identify muscle activation patterns. The principal components consisted of i.e. temporal projections that were analyzed with Statistical Parametric Mapping (SPM). The functional muscle groups, identified by PCA, increased activation during early adaptation and post-adaptation, and decreased activation over time similarly in both age groups. Extra activation peaks of the plantar- and dorsiflexors suggest a role in gait modulation during split-belt walking. Both young and middle-aged adults re-established gait symmetry and showed adaptation effects in the muscle activation patterns. Since the adaptation of muscle activation patterns parallels adaptation of gait symmetry, changes in muscle activation likely underlie the changes in step parameters during split-belt adaptation. In conclusion, split-belt adaptation, in terms of gait and muscle activation patterns, is still preserved at middle-age, suggesting that age-related differences occur later in the lifespan

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655

Effect of cross exercise on quadriceps acceleration reaction time and subjective scores (Lysholm questionnaire) following anterior cruciate ligament reconstruction

Abstract Background Anterior cruciate ligament (ACL) injury or reconstruction can cause knee impairments and disability. Knee impairments are related to quadriceps performance – accelerated reaction time (ART) – and disability to performance of daily living activities which is assessed by questionnaires such as the Lysholm knee score. The purposes of this study were to investigate the effect of cross exercise, as supplementary rehabilitation to the early phase of ACL reconstruction: a) on quadriceps ART at the angles 45°, 60° and 90° of knee flexion and, b) on the subjective scores of disability in ACL reconstructed patients. Methods 42 patients who underwent ACL reconstruction were randomly divided into 3 groups, two experimental and one control. All groups followed the same rehabilitation program. The experimental groups followed 8 weeks of cross eccentric exercise (CEE) on the uninjured knee; 3 d/w, and 5 d/w respectively. Quadriceps ART was measured at 45°, 60° and 90° of knee flexion pre and nine weeks post-operatively using an isokinetic dynamometer. Patients also completed pre and post operatively the Lysholm questionnaire whereby subjective scores were recorded. Results Two factor ANOVA showed significant differences in ART at 90° among the groups (F = 4.29, p = 0.02, p Significant differences were also found in the Lysholm score among the groups (F = 4.75, p = 0.01, p Conclusion CEE showed improvements on quadriceps ART at 90° at a sequence of 3 d/w and in the Lysholm score at a sequence of 3 d/w and 5 d/w respectively on ACL reconstructed patients.</p

Contralateral Effects of Unilateral Strength and Skill Training:Modified Delphi Consensus to Establish Key Aspects of Cross-Education

Background Cross-education refers to increased motor output (i.e., force generation, skill) of the opposite, untrained limb following a period of unilateral exercise training. Despite extensive research, several aspects of the transfer phenomenon remain controversial. Methods A modified two-round Delphi online survey was conducted among international experts to reach consensus on terminology, methodology, mechanisms of action, and translational potential of cross-education, and to provide a framework for future research. Results Through purposive sampling of the literature, we identified 56 noted experts in the field, of whom 32 completed the survey, and reached consensus (75% threshold) on 17 out of 27 items. Conclusion Our consensus-based recommendations for future studies are that (1) the term 'cross-education' should be adopted to refer to the transfer phenomenon, also specifying if transfer of strength or skill is meant; (2) functional magnetic resonance imaging, short-interval intracortical inhibition and interhemispheric inhibition appear to be promising tools to study the mechanisms of transfer; (3) strategies which maximize cross-education, such as high-intensity training, eccentric contractions, and mirror illusion, seem worth being included in the intervention plan; (4) study protocols should be designed to include at least 13-18 sessions or 4-6 weeks to produce functionally meaningful transfer of strength, and (5) cross-education could be considered as an adjuvant treatment particularly for unilateral orthopedic conditions and sports injuries. Additionally, a clear gap in views emerged between the research field and the purely clinical field. The present consensus statement clarifies relevant aspects of cross-education including neurophysiological, neuroanatomical, and methodological characteristics of the transfer phenomenon, and provides guidance on how to improve the quality and usability of future cross-education studies