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WASHINGTON -- For almost one hundred years the brain's “central command” system ? whose charge includes controlling the body's cardiorespiratory response to exercise ? has been pursued. Animal experiments and functional imaging studies have provided clues to the location of this system, but the underlying electrophysiological activity has never been measured. Oxford University researchers recently examined several deep brain nuclei during exercise and have concluded that the periaqueductal grey area (PAG), the small-celled gray matter adjoining or surrounding the cerebral aqueduct and the third ventricle in the midbrain, contains the greatest number of neural changes in connection with anticipation of exercise. The findings provide direct evidence implicating the PAG as a key area of the brain's circuitry's affecting cardiorespiratory response to exercise.
The study, Identifying Cardiorespiratory Neurocircuitry Involved in Central Command During Exercise in Humans, was conducted by Alexander L. Green, Shouyan Wang, Sarah Purvis, Sarah L. F. Owen, John F. Stein, Abe Guz, Tipu Z. Aziz, and David Paterson, all affiliated with the Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford; and Peter G. Bain, with the Division of Neurosciences and Mental Health, Imperial College London, Charing Cross Campus, London, all in the United Kingdom. Dr. Paterson will discuss the team's findings in detail during the 120th annual meeting of the American Physiological Society (APS; www.the-APS.org), part of the Experimental Biology (EB '07) conference. More than 12,000 scientific investigators are attending the conference, being held April 28-May 2, 2007 at the Washington, DC Convention Center.
The Study: Methodology
The researchers set out to test the hypothesis that neural activity in subcortical structures recorded from humans who have deep brain stimulating electrodes chronically implanted is directly related to changes in heart rate (HR), arterial blood pressure (ABP) and pulmonary ventilation (VE) when they are altered by anticipation of exercise and actual exercise. They sought to establish whether the subcortical structures provide neural circuitry that is involved in the anticipatory cardiorespiratory response to exercise in humans.
Twelve patients (10 male, 2 female, mean age 47.5 years) undergoing deep brain stimulation (DBS) were selected for the study. Five patients underwent stimulation of the subthalamic nucleus (STN) for Parkinson's disease; four had globus pallidus interna (GPi) stimulation for generalized dystonia (a neurological disorder characterized by involuntary muscle contractions resulting in twisted movements and abnormal postures); and three had periaqueductal grey (PAG) stimulation for the treatment of chronic neuropathic pain. Patients were excluded if they were considered unable to exercise for any prolonged length or time, or took medication likely to affect heart rate. Fully informed consent was obtained and the study conformed with the Declaration of Helsinki.
Experiments took place at least two hours after any meal. Exercise took place in the semi recumbent position on a custom made examination couch, with a pedal ergometer attached to one end. The load was fixed at 15 watts. After resting for approximately four minutes, subjects were alerted orally to an exercise cue. The patients were then given a signal to start exercising. Patients performed light exercise for at least 30 seconds at which time another oral cue and countdown signaled them to rest. This was repeated five times with approximately one minute of rest in between each exercise session.
The results revealed that anticipation of exercise, with associated increases in cardiorespiratory variables, is associated with an increase in periaqueductal grey (PAG) activity. This suggests that this portion of the brain is directly involved in the neurocircuitry of central command before the actual onset of movement, whereas subthalamic nucleus (STN) activity decreased.
During exercise itself, PAG activity further increases alongside increases in STN activity. When combined with animal data, the findings offer direct neurophysiological evidence in the human that these structures are involved in an aspect of the central command response to anticipation of exercise, and actual exercise.
The researchers demonstrated marked increases in neural activity in the PAG region of awake humans during anticipation of exercise and with exercise. This pattern offers evidence that the midbrain PAG is an important neural structure for autonomic regulation and modulation of the cardiovascular changes that are associated with integrated behavioral 'defense' responses. But while the PAG is an important site, it is unclear whether it is a “central command” area of the brain. The 100-year search for answers appears to continue.
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