Physiopathology of Lower Cortical Activation in COPD Patients: Contribution of Cortical Neuromodulation

Study Overview
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Brief Summary
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Patients with COPD have lower cortical activation and higher cortical inhibitory levels. The purpose of this study is to test the reversibility the lower cortical activation by counterbalancing the increased cortical inhibitory levels with neuro-modulation.

Detailed Description
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Chronic obstructive pulmonary disease (COPD) patients exhibit not only respiratory symptoms but also a peripheral muscular weakness. This weakness is characterized by a loss in strength, harmful for the patients' life quality and vital prognostic. Even if many papers have enlightened damages at a peripheral level, the muscular atrophy itself cannot totally explain the loss in force. Furthermore, the contractile properties of COPD muscles fibres are preserved. Consequently, it seems that the peripheral muscle weakness cannot only be explained by peripheral factors and central structures may be involved. A recent work showed that during quadriceps voluntary contraction, cortical activation in COPD patients was significantly lower than in healthy subjects, contributing in the loss in strength. However, the pathophysiology underlying this loss of strength is still unclear and two hypotheses can be advanced: 1) the influence of anatomical lesions in the brain of COPD patients and 2) the particular metabolism of this population. Indeed, COPD patients show a reduced oxidative activity and an increased glycolytic contribution (decreased type I fibres and increased type II fibres, increased glycolytic enzymes activity, increased metabolites production). This specific metabolic may lead to an over-activation of type III-IV afferents, projecting onto somatosensory cortex sensitive to metabolites at a peripheral level, and produce inhibitory activity on the primary motor cortex, seat of the motor control. What is reported in the literature so far, is that COPD patients display increased cortical inhibitory values than healthy subjects. Therefore, beyond understanding better the nervous mechanisms involved in the COPD's peripheral muscle weakness, the aim of this study is to counterbalance this increased cortical inhibitory level. We hypothesize that modulating inhibitory processes at a cortical level would induced a reduction of inhibitions in patients with COPD and an increase in the force produced. In case this hypothesis would be verified, we will be able to confirm that this increased cortical level in COPD patients is reversible and may be a target for rehabilitation.

Official Title
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Physiopathology of Lower Cortical Activation in COPD Patients: Contribution of Cortical Neuromodulation

Conditions
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Physiology

Intervention / Treatment
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* Device: Anodal transcranial direct-current-stimulation
* Device: Sham transcranial direct-current-stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Health insurance Patients : COPD Gold II-IV Patients : No rehabilitation since at least 1 yrs Control : sedentary (< 9 Voorips) Exclusion Criteria: Pregnant women Seizures Unable to give written consent Metalic object above shoulders Dermatological issue concerning surface electrodes Drugs influencing central nervous system Caffeine consumption > 4 coffee / day Neurological disorders Patients : recent exacerbation (< 4 weeks)

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COPD patients<br>COPD patients group | Device: Anodal transcranial direct-current-stimulation<br>* 2mA / 20min Anodal and Sham tDCS over dominant M1. Anodal tDCS consists of 30s of ramp up followed by 20min of stimulation and 30s of ramp down.<br>Device: Sham transcranial direct-current-stimulation<br>* Sham tDCS consists of only 30s of ramp up followed by 30s of ramp down and no further stimulation. Participants therefore have the same feeling for both modalities : slight itching due to the induced current at the beginning of the protocol (during around 30s) allowing no differentiation by the participant between the anodal or sham sessions.<br>|
| Active Comparator: Healthy subjects<br>Healthy subject group, matched with COPD patients group on age, weight and BMI | Device: Anodal transcranial direct-current-stimulation<br>* 2mA / 20min Anodal and Sham tDCS over dominant M1. Anodal tDCS consists of 30s of ramp up followed by 20min of stimulation and 30s of ramp down.<br>Device: Sham transcranial direct-current-stimulation<br>* Sham tDCS consists of only 30s of ramp up followed by 30s of ramp down and no further stimulation. Participants therefore have the same feeling for both modalities : slight itching due to the induced current at the beginning of the protocol (during around 30s) allowing no differentiation by the participant between the anodal or sham sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in motor-evoked potentials | Cortical excitability | Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in short-interval intracortical inhibition | Cortical inhibition level | Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention) | 
| Change in cortical silent period | Cortical inhibition level | Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention) | 
| Change in cortical voluntary activation | Motor command | Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention) | 
| Change in strength | Functional output | Baseline (pre-intervention) ; Post-Stim (immediately post-intervention) ; Post-30 (30min post-intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Transcranial direct-current stimulation, Transcranial magnetic stimulation, Motor-evoked potentials, Inhibition, Muscle weakness