Cast immobilization increases long-interval intracortical inhibition

Abstract

Immobilization reduces muscle performance, and despite these performance losses being associated with neural impairments little is known regarding adaptations in cortical properties. We utilized transcranial magnetic stimulation to assess changes in flexor carpi radialis (FCR) intracortical facilitation (ICF), and short- and long-interval intracortical inhibition (SICI and LICI) in healthy humans undergoing 3 weeks of immobilization. Measurements were obtained at rest and during contraction (15% intensity). Central activation and the Hoffman reflex (H-reflex) were also assessed. Strength decreased 43.2% +/- 6.1% following immobilization, and central activation also decreased (97.5% +/- 2.4% to 73.2% +/- 8.3%). No changes in ICF, SICI, or LICI were observed at rest; however, LICI was increased during contraction (67.5% +/- 6.9% to 53.1% +/- 6.7% of unconditioned response). The increase in LICI correlated with the loss of strength (r = -0.63). The H-reflex increased following immobilization. These findings suggest that immobilization increases intracortical inhibition during contraction, and this increase is primarily mediated by GABA(B) receptors.

FIGURE 1

The change of MEP sizes obtained with paired pulse TMS. (A) Measurement of SICI and ICF. The intensity of the conditioning pulse (CP) was set 5% below active motor threshold, and the test pulse (TP) was set to evoke MEPs between 0.5–1 mV. At short interstimulus intervals (e.g., 3 ms) the CP inhibits the MEP in comparison to the TP only (SICI), whereas at longer interstimulus intervals (e.g., 15 ms) it facilitates the MEP (ICF). (B) Measurement of LICI. To quantify LICI, two pulses of the same size were delivered at an interstimulus interval of 100 ms. This results in the second MEP being inhibited in comparison to the first MEP.

FIGURE 2

The experimental setup for recording mechanical forces and electrical signals from the wrist flexor muscles. EMG was recorded from the flexor carpi radialis muscle, and torque was recorded from the wrist flexors. Paired-pulse TMS was performed to evaluate intracortical properties, and electrical stimulation of the median nerve was performed to evaluate central activation.

FIGURE 3

Immobilization decreased muscle strength (closed circles; left axis) and central activation (open circles; right axis). Wrist flexion muscle strength decreased ~43% following immobilization, and strength remained ~15% below baseline levels after 1 week of recovery. No changes in muscle strength or central activation were observed in the control group. Central activation decreased from ~98% of maximum before immobilization to ~73% following immobilization. After 1 week of recovery, central activation was ~94% of maximum, but this was still less than was observed at baseline. *Significantly different from preimmobilization (baseline) value (P ≤ 0.05).

FIGURE 4

Immobilization increased LICI. (A) ICF recorded under resting conditions and during a 15% MVC contraction did not change with immobilization. (B) SICI recorded under resting conditions and during a 15% MVC contraction did not change with immobilization. (C) LICI recorded under resting conditions did not change with immobilization. However, LICI recorded during a 15% MVC contraction increased following immobilization, and remained elevated after 1 week of recovery (note: a smaller value indicates the first pulse exerts a greater inhibitory effect on the second pulse; thus, the interpretation is an increase in LICI). *Significantly different from preimmobilization (baseline) value (P ≤ 0.05).

FIGURE 5

The immobilization-induced increase in LICI explained 39% of the between-subject variability in the loss of muscle strength (A) and 35% of the between-subject variability in the impairment in central activation (B). *P ≤ 0.05.

FIGURE 6

Change in LICI in the flexor carpi radialis muscle at different contraction intensities. A control experiment was conducted to examine the relationship between the change in LICI and contraction intensity. LICI was graded with contraction intensity, but this difference was only significant above 25% MVC. *Significantly different from 15% MVC (P ≤ 0.05).