Cerebral Responses During Exercise in Hypoxia (CERVOX)

Evaluation of the Cerebral Responses to Exercise in Hypoxia

While the exercise responses are classically described at the cardiorespiratory and muscle levels, recent data suggest that the brain is also significantly stressed by exercise and may even participate to performance limitation. In hypoxia in particular, cerebral responses to exercise may be altered and promote performance reduction during endurance exercise. In the present study, the investigators used innovative approaches to assess cerebral perturbations associated with exercise in hypoxia.

Study Overview

• Status: Completed
• Conditions: Hypoxia; Brain Hypoxia
• Intervention / Treatment: Other: Hypoxic exposure

Detailed Description

In the classical paradigm of exercise physiology, cardio-respiratory capacity and muscle fatigue are though to set the limit of exercise tolerance. However, there are experimental situations where it is not possible to explain exercise performance limitation using this classical paradigm, and it is therefore necessary to look for an alternative. Recent investigations highlight changes associated with exercise in the brain, e.g. changes in cerebral perfusion, cerebral oxygenation and neuron excitability. Also, several results suggest that in some conditions, the central nervous system fails to drive the motoneurons adequately, i.e. the so called central fatigue. However, the phenomenon of central limitation to exercise and its underlying neurophysiological mechanisms are still to clarify. Cerebral metabolism and neurohumoral responses during fatiguing exercise are therefore to investigate in order to propose a new paradigm able to explain exercise limitation. Among the conditions where the classical paradigm of exercise performance limitation does not appear to suit the actual observations, exercise under hypoxic environment appears to be particularly challenging. Some data suggest indeed that the cerebral response to exercise may be substantially modified in hypoxia compared to normoxia.

Hence, in the present project, the investigators aim to evaluate the effect of hypoxia on brain adaptation to exercise in healthy human. In particular, the objective is to assess the brain neurophysiological response to a fatiguing exercise, including cerebral perfusion and oxygenation, cerebral activation, cortical excitability as well as the resultant motor command while inhaling normoxic or hypoxic gas mixtures. To fulfil these objectives, complementary methodological approaches will be used during exercise both normoxic and hypoxic conditions: functional magnetic resonance imaging (fMRI) will be used to evaluate cerebral activation, the perfusion imaging arterial spin labelling (ASL) nuclear magnetic resonance method will assess regional cerebral perfusion, near infrared spectroscopy (NIRS) will allow measurement of cerebral oxygenation, measurement of motor evoked potential in response to transcranial magnetic stimulation (TMS) will assess the cortical excitability, measurement of the level of central activation (assessed by TMS) and the electromyographic (EMG) signals will evaluate the motor command. Moreover, to account for the effect of the muscle mass involved during exercise and the duration of hypoxic exposure, brain adaptation to exercise in hypoxia will be assessed for motor task involving small (thumb adduction) or large (knee extension, cycle ergometry) muscle groups as well as for acute (<1 hour) or prolonged hypoxic exposure (several hours: 6 hours). This multi-technical approach will be possible through this collaborative project between three partners experts in brain function investigation and exercise physiology (Institut Fédératif de Recherche 'RMN Biomédical et Neurosciences' Joseph Fourier University and University Hospital, Grenoble; 'Exercise Physiology' Laboratory, University Hospital, St Etienne; 'Motor Efficiency and Deficiency Laboratory', Montpellier I University, Montpellier).

The investigators hypothesise that hypoxia would enhance the cerebral perturbation associated with a given fatiguing exercise, i.e. would induce greater reduction in cerebral blood and cerebral oxygenation, greater reduction in cortical excitability and central activation as well as larger reduction in central command, and this particularly when a large muscle mass is involved as well as when hypoxic exposure is prolonged.

This project aims to renew our vision of the limitation of human exercise performance as well as our understanding of exercise tolerance under hypoxemic conditions. The later is relevant for sport and altitude medicine dealing with exercise and altitude tolerance, as well as for diseases characterised by hypoxemia and exercise intolerance such as respiratory diseases like chronic obstructive pulmonary diseases for example.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38042
    • Grenoble University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• 18-50 yrs
• No cardiovascular, respiratory or neuromuscular disorders

Exclusion Criteria:

• Cardiovascular, respiratory or neuromuscular diseases
• Contraindication for TMS and MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sportsmen; One single group of active healthy subjects was investigated	Other: Hypoxic exposure; Subjects breath either normoxic or hypoxic (FiO2 = 12%) gas mixture; Other Names: Hypoxia (FiO2 = 12%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in voluntary activation	Maximum voluntary activation level measured using TMS	Baseline and after 4h of exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in tissue oxygenation	Muscle and cerebral oxygenation measured with NIRS and fMRI	Baseline and after 4 hours of exercise

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: June 4, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Estimate): June 7, 2012
• Last Update Submitted That Met QC Criteria: June 4, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Exercise; Performance; Oxygenation; Cerebral
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia; Hypoxia, Brain
• Other Study ID Numbers: 1002; 2010-A00121-38 (Registry Identifier: ID RCB)