Clinical trial The goal of this clinical trial is to learn how muscle weakness and atrophy develop during short periods of arm immobilization and whether a type of exercise called cross-education can help reduce these effects in women at midlife. The main questions it aims to answer are: What changes happen in the nervous system that lead to weakness when a wrist is immobilized? Can training the opposite arm help maintain muscle strength, muscle size, and nervous system function in the immobilized arm? Researchers will compare women who have their wrist immobilized with or without opposite-arm resistance training. Participants will: Wear a wrist cast on one arm for 7 days Complete strength training with the opposite arm or no training, depending on their group Attend study visits for strength and nervous system testing Have non-invasive tests (like magnetic brain stimulation, muscle recordings, and muscle imaging) to measure how the nervous system and muscle responds
This clinical trial employs a two-phase, parallel-group randomized controlled design targeting midlife women (ages 40-65), stratified by menopausal status. Participants will be randomized to either a cross-education training group (TRAIN) or a standard care control group (CONTROL). Phase 1 (Immobilization and Cross-Education Intervention): To induce rapid declines in neuromuscular function, participants will undergo unilateral wrist immobilization of the non-dominant arm using a hard cast for 7 days. During this period, the TRAIN group will complete three supervised resistance training sessions with the non-immobilized arm, while the CONTROL group will remain inactive. The intervention protocol emphasizes eccentric-biased resistance exercise, as prior data indicate that eccentric contractions optimize neural adaptation and mechanical loading. The protocol was developed from prior laboratory work and proof-of-concept interventions, with the goal of maximizing the cross-education response. Phase 2 (Rehabilitation and Recovery): Following cast removal, both groups will complete a 2-week standardized rehabilitation program (3 sessions per week) designed to restore wrist strength and function in the previously immobilized arm. Rehabilitation training is supervised and includes progressive resistance exercise to target recovery of neuromuscular performance.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
20
The wrist immobilization will use a medical device (wrist cast) to immobilize the left, non-dominant wrist for 7 days.
The cross-education intervention will consist of resistance training on the dominant, right hand.
The resistance training rehabilitation will occur for the non-dominant, left hand following the immobilization phase for all participants.
Neuromuscular Physiology Laboratory
Manhattan, Kansas, United States
Handgrip Strength
Maximal handgrip strength (Kg) using an isometric handgrip dynamometer.
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
Wrist Extension Strength
Peak torque (Nm) of the wrist extensor muscles measured using isokinetic dynamometry
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
Wrist Flexion Strength
Peak torque (Nm) of the wrist flexor muscles measured using isokinetic dynamometry.
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
Wrist Muscle Cross-Sectional Area and Volume (CT Imaging)
Muscle cross-sectional area (cm²) and volume (cm³) of the wrist extensors and flexors, assessed using computed tomography (CT). Scans will be obtained at standardized anatomical landmarks of the forearm. Cross-sectional images will be segmented and analyzed with imaging software to quantify muscle size. The primary outcome is mean muscle cross-sectional area, with muscle volume derived from consecutive slices. These measures provide indices of muscle size and atrophy/hypertrophy over time.
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
Motor Evoked Potential (MEP) Amplitude
Amplitude (mV) of motor-evoked potentials elicited by single-pulse TMS applied over the primary motor cortex of the left wrist and recorded from the extensor carpi radialis muscle. Larger amplitudes reflect greater corticospinal excitability.
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
Short-Interval Intracortical Inhibition (SICI)
Short-interval intracortical inhibition assessed by paired-pulse TMS with a subthreshold conditioning stimulus followed by a suprathreshold test stimulus at an interstimulus interval of 2-5 ms. Outcome is the percent suppression of MEP amplitude relative to unconditioned trials.
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
Long-Interval Intracortical Inhibition (LICI)
Assessed using paired-pulse TMS with a suprathreshold conditioning stimulus followed by a suprathreshold test stimulus at an interstimulus interval of 50-200 ms. LICI is quantified as the percent suppression of conditioned motor-evoked potential (MEP) amplitude relative to unconditioned MEPs.
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
Intracortical Facilitation (ICF)
Assessed using paired-pulse TMS with a subthreshold conditioning stimulus followed by a suprathreshold test stimulus at an interstimulus interval of 8-20 ms. ICF is quantified as the percent increase of conditioned MEP amplitude relative to unconditioned MEPs.
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
Active Motor Threshold (AMT)
Defined as the lowest TMS stimulus intensity (expressed as a percentage of maximum stimulator output) required to evoke MEPs ≥200 μV in at least 5 out of 10 consecutive trials during voluntary contraction of the target muscle at 10% of maximal effort. AMT reflects corticospinal excitability during an active state.
Time frame: Baseline, immediately post-immobilization at 1 week, and post-rehabilitation at 3 weeks.
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