Unloaded Minds - How Prolonged Unloading Shapes Human Performance in Lunar Gravity

Condition(s) studied

Investigational drug(s) / intervention(s)

Unilateral lower limb suspension: Unilateral Lower Limb Suspension (ULLS) is a validated spaceflight analog for the lower limbs, which mimics unloading specifically in the lower limbs 3. In ULLS, participants wear a shoe with \~100 mm elevated sole and use short-length crutches aided by a hand grip and forearm support distal to the elbow. This allows the contralateral lower limb to remain unloaded in a straight position and move passively at the hip. The ULLS model specifically targets skeletal muscle unloading in the lower limb with no or minor systemic deconditioning, and it imposes minimal restrictions on participants' daily activities. A key advantage of ULLS is that the contralateral, weight-bearing limb provides a valid inherent control accounting for individual factors such as nutrition, genetics, and lifestyle.

Study summary

During spaceflight and lunar missions, reduced gravitational loading causes the muscles and nervous system to decondition rapidly. While muscle wasting is well documented, much less is known about how the brain and spinal cord adapt to the absence of normal mechanical loading - and how these central changes interact with muscle deterioration to impair movement control.

This study investigates how two weeks of simulated lower limb unloading affects the brain's movement programs (motor engrams), the functional connection between nerves and muscles, and overall movement quality. Healthy participants undergo 14 days of Unilateral Lower Limb Suspension (ULLS), a model in which one leg is kept unloaded using a raised shoe and crutches while the other leg functions normally. After the unloading period, participants travel to Bordeaux, France, where they walk on a treadmill for the first time - in lunar gravity - during a parabolic flight.

Before and after the unloading period, participants are assessed with MRI (muscle size), force plate tests (jump performance and balance), nerve stimulation (number of functional motor units), and treadmill gait analysis combining brain activity (EEG), muscle activity (EMG), joint movement, and plantar pressure measurements. The same gait analysis is repeated during the parabolic flight under lunar gravity (0.16G).

The results will shed light on how the brain and muscles adapt to disuse and reactivate under partial gravity - with direct relevance to astronaut safety and rehabilitation, as well as clinical conditions involving prolonged limb immobilization.

Eligibility

Primary outcome measure(s)

• Muscle volume — Three days before the initiation of the ULLS intervention and at day 15 of unloading, for both thigh and calf muscles bilaterally.
  Three days before the initiation of the ULLS intervention, and at day 15 of unloading, all participants will undergo an MRI scan to assess thigh and calf muscle size. Muscle volume will be evaluated using cross-sectional T2-weighted images acquired on a 3-Tesla MR system. Anatomical landmarks and standardized procedures will ensure that the same segment is scanned at both time points. Participants will rest in a supine position for approximately 30 minutes prior to each scan to minimize measurement interference caused by fluid shift. Images will be analysed using manual segmentation to delineate individual muscle boundaries in each cross-sectional slice; muscle volume is then calculated by summing the cross-sectional areas of the target muscles across all slices and multiplying by slice thickness.

Trial sites (1)

More Karolinska Institutet trials in Sweden