Impact of Lockdown during COVID-19 Pandemic on Central Activation, Muscle Activity, Contractile Function, and Spasticity in People with Multiple Sclerosis

Background. People with multiple sclerosis (MS) suffer from symptoms related to neural control, such as reduced central activation, lower muscle activity, and accentuated spasticity. A forced 9-week home confinement related to COVID-19 in Spain may have worsened these symptoms. However, no study has demonstrated the impact of home confinement on neuromuscular mechanisms in the MS population. This study was aimed at analyzing the effects of a 9-week home confinement on central activation, muscle activity, contractile function, and spasticity in MS patients. Methods. Eighteen participants were enrolled in the study. Left and right knee extensor maximum voluntary isometric contraction (MVIC), maximal neural drive via peak surface electromyography (EMG) of the vastus lateralis, central activation ratio (CAR), and muscle contractile function via electrical stimulation of the knee extensor muscles, as well as spasticity using the pendulum test, were measured immediately before and after home confinement. Results. Seventeen participants completed the study. CAR significantly decreased after lockdown ( ES = 1.271 , p < 0.001 ). Regarding spasticity, there was a trend to decrease in the number of oscillations ( ES = 0.511 , p = 0.059 ) and a significant decrease in the duration of oscillations ( ES = 0.568 , p = 0.038 ). Furthermore, in the left leg, there was a significant decrease in the first swing excursion ( ES = 0.612 , p = 0.027 ) and in the relaxation index ( ES = 0.992 , p = 0.001 ). Muscle contractile properties, MVIC, and EMG variables were not modified after confinement. Conclusions. The results suggest that a home confinement period of 9 weeks may lead to an increase in lower limb spasticity and a greater deficit in voluntary activation of the knee extensors.

Central Activation of Alpha7 Nicotinic Signaling Attenuates LPS-Induced Neuroinflammation and Sickness Behavior in Adult but Not in Aged Animals

We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As α7 nAChRs are implicated in the “Cholinergic anti-inflammatory pathway”, we aimed to determine how α7 nAChR stimulation modulates microglial phenotype in an LPS-induced neuroinflammation model in adult and aged mice. For this, BALB/c mice were injected intraperitoneally with LPS (0.33 mg/kg) and treated with the α7 nAChR agonist PNU282987, using different administration protocols. LPS challenge reduced body weight and induced lethargy and social withdrawal in adult mice. Peripheral (intraperitoneal) co-administration of the α7 nAChR agonist PNU282987 with LPS, attenuated body weight loss and sickness behavior associated with LPS challenge in adult mice, and reduced microglial activation with suppression of IL-1β and TNFα mRNA levels. Furthermore, central (intracerebroventricular) administration of the α7 nAChR agonist, even 2 h after LPS injection, attenuated the decrease in social exploratory behavior and microglial activation induced by peripheral administration of LPS, although this recovery was not achieved if activation of α7 nAChRs was performed peripherally. Finally, we observed that the positive results of central activation of α7 nAChRs were lost in aged mice. In conclusion, we provide evidence that stimulation of α7 nAChR signaling reduces microglial activation in an in vivo LPS-based model, but this cholinergic-dependent regulation seems to be dysfunctional in microglia of aged mice.

Central activation deficits contribute to post stroke lingual weakness in a rat model

Lingual weakness frequently occurs after stroke and is associated with deficits in speaking and swallowing. Chronic weakness after stroke has been attributed to both impaired central activation of target muscles and reduced force generating capacity within muscles. How these factors contribute to lingual weakness is not known. We hypothesized that lingual weakness due to middle cerebral artery occlusion (MCAO) would manifest as reduced muscle force capacity and reduced muscle activation. Rats were randomized into MCAO or sham surgery groups. Maximum volitional tongue forces were quantified 8 weeks after surgery. Hypoglossal nerve stimulation was used to assess maximum stimulated force, muscle twitch properties, and force-frequency response. The central activation ratio was determined by maximum volitional/maximum stimulated force. Genioglossus muscle fiber type properties and neuromuscular junction innervation were assessed. Maximum volitional force and the central activation ratio were significantly reduced with MCAO. Maximum stimulated force was not significantly different. No significant differences were found for muscle twitch properties, unilateral contractile properties, muscle fiber type percentages, or fiber size. However, the twitch/tetanus ratio was significantly increased in the MCAO group relative to sham. A small but significant increase in denervated NMJs and fiber-type grouping occurred in the contralesional genioglossus. Results suggest the primary cause of chronic lingual weakness after stroke is impaired muscle activation rather than a deficit of force generating capacity in lingual muscles. Increased fiber type grouping and denervated NMJs in the contralesional genioglossus suggest partial reinnervation of muscle fibers may have preserved force generating capacity, but not optimal activation patterns.

Gluteal Central Activation in Females With Patellofemoral Pain: A Preliminary Study

Context: Lesser hip muscle strength is commonly observed in females with patellofemoral pain (PFP) compared with females without PFP and is associated with poor subjective function and single-leg squat (SLS) biomechanics. Hip muscle weakness is theorized to be related to PFP, suggesting centrally mediated muscle inhibition may influence the observed weakness. The central activation ratio (CAR) is a common metric used to quantify muscle inhibition via burst superimposition. However, gluteal inhibition has yet to be evaluated using this approach in females with PFP. The study objectives are to (1) describe gluteal activation in the context of subjective function, hip strength, and squatting biomechanics and (2) examine the relationship of gluteal activation with subjective function and squatting biomechanics in females with PFP. Design: Cross-sectional. Methods: Seven females with PFP (age = 22.8 [3.6] y; mass = 69.4 [18.0] kg; height = 1.67 [0.05] m, duration of pain = 6–96 mo) completed this study. Subjective function was assessed with the Anterior Knee Pain Scale, while fear-avoidance beliefs were assessed with the Fear-Avoidance Belief Questionnaire physical activity and work subscales. Biomechanical function was assessed with peak hip and knee angles and moments in the sagittal and frontal planes during SLS. Gluteus medius (GMed) and gluteus maximus (GMax) activation were assessed with the CAR. Descriptive statistics were calculated, and relationships between variables were assessed with Spearman rho correlations. Results: The CAR of GMed and GMax was 90.5% (8.1%) and 84.0% (6.3%), respectively. Lesser GMed CAR was strongly associated with greater hip adduction during SLS (ρ = −.775, P = .02) and greater fear-avoidance beliefs—physical activity subscale (ρ = −.764, P = .018). Conclusion: We found a wide range in GMed and GMax activation across females with PFP. Lesser GMed activation was associated with greater hip adduction during SLS and fear of physical activity, suggesting that gluteal inhibition should be assessed in patients with PFP.

Effect of verbal encouragement on quadriceps and knee joint function during three sets of knee extension exercise

BACKGROUND: Although the common practice of verbal encouragement is scientifically supported, its effect on the maintenance of force output in fatiguing exertions is unknown. OBJECTIVE: To examine the effects of verbal encouragement on exercise-induced quadriceps and knee joint function during three sets of knee extension exercise. METHODS: Sixty-five healthy males (23.3 years, 175.8 cm, 75.3 kg) underwent testing using the administration of verbal encouragement (n= 32) or not (n= 33) during assessment of quadriceps and knee joint function. Assessments were performed at baseline and times 1, 2, and 3. The knee concentric isokinetic extension at 60∘/s, was performed between the time points. For quadriceps function, maximal isometric strength and activation (central activation ratio) were recorded. Absolute error values on knee flexion replications at 15∘ or 45∘ were recorded for knee joint function. RESULTS: There was no verbal encouragement effect over three sets of exercise in quadriceps strength (condition × time: F3,189= 1.71, p= 0.17) and knee flexion replication (condition × time for 15∘: F3,189= 0.11, p= 0.96; 45∘: F3,189= 0.63, p= 0.6). However, subjects who had received verbal encouragement maintained quadriceps activation (condition × time: F3,189= 5.49, p= 0.001). Specifically, quadriceps activation in the verbal condition was 3.0% higher at time 2 (p= 0.01) and 4.7% higher at time 3 (p= 0.0003) versus in the non-verbal condition. CONCLUSIONS: Verbal encouragement appears to be effective in maintaining central activation, but is insufficient for promoting strength. This supports the idea that peripheral contributing factors play a larger role in force production when performing multiple sets of exercises.

Central Activation Ratio Is a Reliable Measure for Gluteal Neuromuscular Function

Context: Central activation ratio (CAR) is a common outcome measure used to quantify gross neuromuscular function of the quadriceps using the superimposed burst technique, yet this outcome measure has not been validated in the gluteal musculature. Objective: To quantify gluteus medius (GMed) and gluteus maximus (GMax) CAR in a healthy population and evaluate its validity and reliability over a 1-week period. Design: Descriptive. Setting: Laboratory. Patients or Other Participants: A total of 20 healthy participants (9 males and 11 females; age 22.2 [1.4] y, height 173.4 [11.1] cm, mass 84.8 [25.8] kg) were enrolled in this study. Interventions: Participants were assessed at 2 sessions, separated by 1 week. Progressive electrical stimuli (25%, 50%, 75%, and 100%) were delivered to the GMed and GMax at rest, and 100% stimuli were delivered during progressive hip abduction and extension contractions (25%, 50%, 75%, and 100% maximal voluntary isometric contraction). Main Outcome Measures: GMed and GMax CAR, and hip abduction and hip extension maximal voluntary isometric contraction torque. Line of best fit and coefficient of determination (r2) were used to assess the relationship between torque output and CAR at varying levels of stimuli. Intraclass correlation coefficients, ICCs(3,k), were used to assess the between-session reliability. Results: GMed CAR was 96.1% (3.4%) and 96.6% (3.2%), on visits 1 and 2, respectively, whereas GMax CAR was 86.5% (7.5%) and 87.2% (10.7%) over the 2 sessions. A third-order polynomial demonstrated the best line of fit between varying superimposed burst intensities at rest for both GMed (r2 = .156) and GMax (r2 = .602). Linear relationships were observed in the CAR during progressive contractions with a maximal superimposed burst, GMed (r2 = .409) and GMax (r2 = .639). Between-session reliability was excellent for GMed CAR, ICC(3,k) = .911, and moderate for GMax CAR, ICC(3,k) = .704. Conclusion: CAR appears to be an acceptable measure of GMed and GMax neuromuscular function in healthy individuals. Gluteal CAR measurements are reliable measures over a 1-week test period.

Inhibition of central activation of the diaphragm: a mechanism of weaning failure

Research into pathophysiology of failure to wean from mechanical ventilation has excluded several factors, including contractile fatigue, but the precise mechanism remains unknown. We recorded transdiaphragmatic pressure and diaphragmatic electrical activity in patients undergoing a T-tube trial. Diaphragmatic recruitment was submaximal at the end of a failed trial despite concurrent respiratory distress, signifying that inhibition of central neural output to the diaphragm is an important mechanism of weaning failure.

Fatigue, effort perception and central activation failure in chronic stroke survivors: a TMS and fMRI investigation

Fatigue is commonly seen in stroke survivors and the most common manifestation of fatigue is the requirement of high effort for activities of daily life. In this study we set out to identify the neural correlates of perceived effort and central activation failure, a neurophysiological measure correlated with perceived effort. Methods: Twelve chronic stroke survivors participated in this study. Fatigue levels were quantified using the Fatigue Severity Scale -7, perceived effort was quantified using a 1-10 numerical rating scale while performing an isometric biceps hold task, Central Activation Failure was quantified using the modified twitch interpolation technique using Transcranial Magnetic Stimulation and functional Magnetic Resonance Imaging was used to measure blood-oxygen-level dependent signal (BOLD) from the brain while the participant performed a hand grip task. Analysis: Following standard pre-processing procedures for fMRI data using SPM software, co-variance of BOLD signal with perceived effort levels and central activation failure was evaluated. Correlation analysis was performed between measures of fatigue and effort. Results: The main findings of this study were 1) high fatigue was associated with high perceived effort 2) higher perceived effort was associated with greater increase in BOLD fMRI activity in pre-SMA and the ipsilateral inferior frontal gyrus with increasing force 3) greater Central Activation Failure was associated with higher increase in BOLD fMRI activity in bilateral caudate, contralateral superior frontal gyrus and pre-motor cortices with increasing force.