Non-invasive Brain Stimulation and Exercise Intervention for Patients With Motor Neuron Disease

Amyotrophic Lateral Sclerosis Functional rating scale - revised version (ALSFRS-R)

The Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) is a 12-item questionnaire used to assess functional ability in people with ALS across four domains: bulbar, fine motor, gross motor, and respiratory function. Each item is scored from 0 (unable) to 4 (normal), with a total score ranging from 0 to 48. It can be self-reported or clinician-administered in person, by phone, or online. Lower scores indicate greater disability. The ALSFRS-R is used to monitor disease progression and guide clinical care.

Muscle evoke potential (MEP)

Participants will be stimulated at the primary motor cortex by transcranial magnetic stimulation to measure cortical excitability, which sends the motor outputs to Tibialis Anterior (TA) and Abductor Pollicis Brevis (APB) muscles. The MEP will be used to assess muscle activity in these muscles during the stimulation. The MEP will be measured in mV.

Motor unit number estimation (MScan fit-MUNE)

For MScan fit-MUNE, CMAP is recorded at multiple stimulation intensities. The MScan fit-MUNE software then generates a curve representing the relationship between stimulation intensity and CMAP amplitude. A mathematical model is fitted to this curve to estimate the number of motor units contributing to the generation of the CMAP.

Motor unit number index (MUNIX)

For MUNIX (Motor Unit Number Index), the procedure begins with recording the CMAP. Then, the participant is asked to gently contract the muscle. During this contraction, the interference pattern of muscle electrical activity is recorded. The MUNIX value is calculated by analyzing the ratio between the CMAP amplitude and the amplitude of the interference pattern. This provides an estimate of motor unit function.

Muscle mass

We will used the bioelectrical impedance analysis (BIA), which is a method used for measuring body composition.Participants will be asked to step on to the BIA device, placing their feet on the foot electrodes. The muscle mass will be recored in kilograms.

Body mass index (BMI)

We will used the bioelectrical impedance analysis (BIA), which is a method used for measuring body composition.Participants will be asked to step on to the BIA device, placing their feet on the foot electrodes. The BMI will be recored in kg/m\^2.

Hand grip test

The Hand Grip Test is an objective measure of isometric grip strength, commonly used to assess overall muscle strength and functional status. The test is performed using a handheld dynamometer, which the participant squeezes with maximum effort, typically while seated with the elbow at a 90-degree angle. The test is usually repeated three times per hand, and the highest or average value measured in kilograms is recorded. Lower grip strength is associated with reduced physical function and is often used as an indicator of frailty, sarcopenia, or neuromuscular decline.

Pinch grip test

The Pinch Grip Test is used to assess the strength of the thumb muscles in individuals with motor neuron disease (MND). Participants are asked to hold a pinch grip dynamometer with their arm positioned at a 90-degree angle and squeeze as hard as possible for 3 to 5 seconds. Each set consists of 10 repetitions, and the test includes 5 sets in total, with a 1-minute rest between sets. The goal is to measure the maximum force generated during the test. Afterward, participants are instructed to maintain a pinch force at 50% ± 5% of their maximum strength for as long as possible. Results are recorded in kilograms (kg) and duration (seconds).