Reduced Use and Immobilization: Neuromuscular and Cortical Adaptations

Overview of Reduced Use and Immobilization

This study guide focuses on the detrimental effects of immobilization and reduced use on the brain and neuromuscular systems. It evaluates how these systems adapt to periods of inactivity and lists specific interventions used to mitigate these negative consequences. There is currently no single reference source that summarizes this entire topic; however, specific areas are covered in the following materials:

• Cortical Adaptations: Refer to the collection of individual references provided throughout the presentation.

• Spinal and Muscular Adaptations: Consult the textbook written by Gardner and Anoka.

Learning Objectives

1. Examine the various experimental models used to induce immobilization.

2. Understand the physiological and neurological adaptations occurring at every level of the neuromuscular system.

3. Identify methods and countermeasures designed to alleviate the negative impacts of immobilization on nervous tissues and muscle fibers.

Experimental Models of Immobilization

Researchers use several different models to study reduced use, falling into three primary categories. It is important to note that the mechanisms of these models often overlap; for example, hind limb suspension prevents weight-bearing but also results in a reduction of electromyographic (EMG) activity and muscle contraction.

Primary Methodologies

1. Removal of Load Bearing: An example of this is hind limb suspension.

2. Reduction of Muscle Activity: This is achieved through techniques such as spinal cord isolation or the administration of local anesthesia.

3. Limb Immobilization: The physical restriction of a limb's movement.

Limitations in Human Models

In humans, the most common models are limb immobilization (via casting) and bed rest. However, these are often less effective in healthy populations than expected.

• Example Comparison: A subject's arm was placed in a full cast to restrict movement for a duration of $24$ hours. EMG data showed only a small reduction in muscle activity.

• Reasoning: Because the procedure is painless, subjects continue to perform frequent isometric contractions throughout the day.

• Demographics: Empirical data indicates that the amount of EMG activity recorded before and during immobilization differs significantly between men and women.

Cortical Adaptations to Immobilization

Substantial changes in the brain can occur very rapidly during periods of reduced use, with some effects visible after only a few hours. These effects compound over longer durations.

Observations via Brain Stimulation

Using brain stimulation techniques (such as Transcranial Magnetic Stimulation or TMS), the following observations have been documented:

• Cortical Area Shrinkage: The specific region of the motor cortex devoted to controlling the immobilized muscle decreases in size.

• Excitability Shifts: There is a decrease in excitability within the cortical area responsible for the immobilized muscle.

• Interhemispheric Changes: Alterations occur in the inhibitory signals sent between the two cortical hemispheres.

Cortical Representation and Mapping

TMS mapping (stimulating the scalp in a grid-like pattern to identify where a Motor Evoked Potential or MEP is produced) demonstrates the "use it or lose it" principle of brain plasticity.

• Tibialis Anterior Study: Patients underwent ankle joint immobilization for $16$ weeks. On average, the motor cortical area for the tibialis anterior muscle decreased by $39\%$.

• Duration Correlation: The reduction in cortical area is highly correlated with the duration of immobilization. In the most severe cases, the cortical area for the affected side shrank to approximately $20\%$ of the size of the unaffected side.

• Reversibility: These changes are not permanent and can be reversed rapidly through rehabilitation involving voluntary muscle contractions.

Short-term Impact

Short durations of immobilization also produce significant deficits.

• In one study, after only $12$ hours of arm immobilization, MEP amplitude declined by more than $50\%$.

• This was linked to a $43\%$ decrease in performance during a multi-joint coordination reaching task, highlighting the immediate negative impact of disuse on motor performance.

Interhemispheric Inhibition (IHI)

Connections between the left and right motor cortices are vital for managing unimanual and bimanual hand movements. The balance of this connection is sensitive to the activity of both limbs.

The Study of Right Arm Immobilization

In a study involving healthy subjects, the right arm was immobilized for $10$ hours. Researchers divided subjects based on the activity of the non-immobilized (left) arm:

1. Group G1 (Free Movement): The left arm moved freely. This resulted in:

   • Decreased excitability in the immobilized hemisphere.

   • Increased excitability in the freely moving (left-arm control) hemisphere.

   • Increased IHI directed toward the immobilized hemisphere and decreased inhibition toward the moving side.

2. Group G2 (Restricted Movement): The left arm was also restricted. This resulted in no increase in interhemispheric inhibition toward the immobilized side.

Conclusion: The inhibitory balance between the left and right motor areas is strongly dictated by specific muscle use patterns.

Non-Physical Countermeasures for Cortical Decline

Recent research suggests it is possible to block cortical changes during immobilization without requiring actual muscle activation.

Action Observation vs. Mental Imagery

Using TMS to examine changes after $10$ hours of right arm immobilization, subjects were placed into three groups:

• Control: Watched a nature documentary on a computer.

• Mental Imagery: Imagined reaching to grab an apple with the immobilized limb.

• Action Observation: Observed a visual of another hand reaching to grab an apple.

Results:

• The Control and Mental Imagery groups showed the expected reduction in motor cortex excitability.

• The Action Observation group showed no change in cortical excitability.

• Interpretation: There is a specific link between action observation and motor execution that supports cortical plasticity; notably, this benefit was restricted to observation and was not induced by mental simulation (imagery).

Muscle Vibration/Sensory Feedback

A study investigated whether cortical changes were due to reduced muscle activity or reduced sensory feedback by applying vibration to immobilized muscles:

• $80\,Hz$ Vibration: Stimulates muscle afferents (muscle spindles).

• $30\,Hz$ Vibration: Stimulates tactile/skin afferents.

• No Vibration: Control.

Findings: Changes (decreased excitability and increased IHI) occurred in the No Vibration and $30\,Hz$ groups. However, the $80\,Hz$ stimulation group showed no changes in excitability. This suggests that activating muscle spindles can prevent the brain changes typically caused by short-term disuse.

Clinical Application: Constraint-Induced Movement Therapy (CIMT)

Immobilization can be used as a therapeutic tool for recovery following neurological damage, such as a stroke.

• Mechanism: The healthy hand is placed in a splint (immobilized) to force the patient to use the affected hand.

• Mapping Results: After $2$ weeks of CIMT, TMS mapping showed an increase in cortical representation in the damaged hemisphere for the target muscles.

• Outcome: This neural change was accompanied by improved motor function on the affected side and a decrease in the representation of the unaffected side, creating a more even balance of activity between the two hemispheres.

Training vs. Immobilization in Nearby Representations

Researchers explored what happens to adjacent muscles (e.g., the FDI muscle for the index finger and the ADM muscle for the little finger) when one is trained and the other is immobilized.

Individual Effects

• Training ($1$ week): Led to increased cortical representation of the trained finger, increased spatial overlap between adjacent finger representations, decreased intracortical inhibition, and improved performance in both the trained and untrained fingers.

• Immobilization ($1$ week): Resulted in decreased excitability, increased intracortical inhibition, and reduced performance, but these effects were muscle-specific and restricted to the immobilized finger.

Combined Training and Immobilization

When training one finger while immobilizing the adjacent finger on the same hand:

• The trained muscle showed increased representation and excitability.

• The detrimental effects were prevented in the immobilized muscle: its cortical representation and motor performance were maintained.

• There was no increased overlap of the representations, suggesting concurrent training of adjacent parts protects immobilized muscles from degradation.

Spinal and Motor Unit Adaptations

Immobilization results in significant changes at the spinal cord level, specifically regarding how the nervous system activates muscles.

Motor Unit Activity (6-8 Weeks)

• Twitch Force: There is a decrease in the amplitude of motor unit twitch forces.

• Recruitment: An increased number of motor units are recruited at higher force levels.

• Firing Rates: There is a clear decrease in the range of motor unit discharge rate modulation (lower difference between minimum and maximum firing rates).

Force Production and Twitch Interpolation

Twitch Interpolation measures the extra force produced by external stimulation during a maximal voluntary contraction to assess the level of neural drive.

• Bed Rest Study ($5$ weeks): Resulted in a $43\%$ decrease in maximal strength.

• Mechanism: While some loss was due to muscle fiber atrophy, the majority was due to the reduced ability of the nervous system to activate the muscle. This was evidenced by decreased EMG activity and an increased twitch interpolated force.

Muscular Adaptations: Fiber Type Shifts

Immobilization changes both the size and the composition of muscle fibers.

Fiber Type Contribution

Animal studies (e.g., spinally isolated cats) show a Slow-to-Fast shift in muscle fiber types:

• Slow-twitch fibers ($S$): Relative contribution to whole muscle force decreases.

• Fast-twitch fibers ($F$): Relative contribution increases.

Muscle Specificity

Muscles with high proportions of slow-twitch fibers are more susceptible to immobilization effects than fast-twitch muscles.

• Extensor Digitorum Longus (EDL - Fast): Shows no significant change in contraction time or fusion frequency with spinal isolation.

• Soleus (Slow): Shows a slower contraction time and a faster fusion frequency with spinal isolation.

• Significance: The muscles most used in daily activities (slow-twitch) are the ones that suffer the greatest changes when immobilized.

Countermeasures for Muscle Loss

Various strategies have been tested to minimize the loss of muscle mass:

• Weight Support: The most effective countermeasure is short periods (a few hours per day) of weight support.

• Enhanced Modalities: Weight support is even more effective when combined with treadmill support or eccentric contractions.

• Electrical Stimulation: Provides only a small benefit.

• Conclusion: A key component of recovery/prevention is likely related to weight-bearing itself, rather than just muscle activity. These countermeasures are most effective in muscles with high proportions of slow-twitch fibers, though they also benefit fast-twitch muscles.