Specific motor cortex hypoexcitability and hypoactivation in COPD patients with peripheral muscle weakness

Abstract

Background: Peripheral muscle weakness can be caused by both peripheral muscle and neural alterations. Although peripheral alterations cannot totally explain peripheral muscle weakness in COPD, the existence of an activation deficit remains controversial. The heterogeneity of muscle weakness (between 32 and 57% of COPD patients) is generally not controlled in studies and could explain this discrepancy. This study aimed to specifically compare voluntary and stimulated activation levels in COPD patients with and without muscle weakness.

Methods: Twenty-two patients with quadriceps weakness (COPD_MW), 18 patients with preserved quadriceps strength (COPD_NoMW) and 20 controls were recruited. Voluntary activation was measured through peripheral nerve (VA_peripheral) and transcranial magnetic (VA_cortical) stimulation. Corticospinal and spinal excitability (MEP/Mmax and Hmax/Mmax) and corticospinal inhibition (silent period duration) were assessed during maximal voluntary quadriceps contractions.

Results: COPD_MW exhibited lower VA_cortical and lower MEP/Mmax compared with COPD_NoMW (p < 0.05). Hmax/Mmax was not significantly different between groups (p = 0.25). Silent period duration was longer in the two groups of COPD patients compared with controls (p < 0.01). Interestingly, there were no significant differences between all COPD patients taken together and controls regarding VA_cortical and MEP/Mmax.

Conclusions: COPD patients with muscle weakness have reduced voluntary activation without altered spinal excitability. Corticospinal inhibition is higher in COPD regardless of muscle weakness. Therefore, reduced cortical excitability and a voluntary activation deficit from the motor cortex are the most likely cortical mechanisms implicated in COPD muscle weakness. The mechanisms responsible for cortical impairment and possible therapeutic interventions need to be addressed.

Keywords: Chronic obstructive pulmonary disease; Corticospinal excitability; Motor cortex; Peripheral muscle weakness.

Fig. 1

Flow diagram of the study

Fig. 2

Experimental design. QMVC: Quadriceps voluntary contractions at maximal (100% of QMVC) or submaximal (50 and 30% of QMVC) intensity. Superimposed and control doublets, maximal M-waves (Mmax), and maximal H-waves (Hmax) were delivered via electrical stimulation over the femoral nerve. Motor evoked potentials (MEP) were delivered over the motor cortex via transcranial magnetic stimulation

Fig. 3

a Quadriceps maximal voluntary torque (QMVC), b quadriceps maximal peak twitch (QPt), c voluntary activation estimated with motor cortex transcranial magnetic stimulation during maximal voluntary contractions [VA_cortical (%)], and d voluntary activation estimated with twitch interpolation during maximal voluntary contractions [VA_peripheral (%)], in healthy controls, patients with COPD and preserved muscle strength (COPD_NoMW), and patients with COPD and muscle weakness (COPD_MW). *, **, ***: p < 0.05, p < 0.01 and p < 0.001 respectively. Vertical bars represent SE

Fig. 4

Slopes and y-intercepts of linear relationship between maximal voluntary quadriceps torque (QMVC) and quadriceps maximal peak twitch (QPt) in healthy controls (gray squares and gray line), COPD patients without muscle weakness (COPD_NoMW) (empty circles and dotted line), and COPD patients with muscle weakness (COPD_MW) (dark circles and dark line)