EMBARGOED FOR RELEASE UNTIL
APRIL 29, 2007
APS Contact
Donna Krupa
Office: (301) 634-7209
Cell: (703) 967-2751
dkrupa@the-aps.org
Newsroom Opens at 12:00 p.m.
Saturday April 28
APS Newsroom
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Washington Convention Center
APS Press Room: (202) 249-4174
Study Finds Role Of
Mid-Brain In Integrating Heart & Respiratory Response To Exercise
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.
Results
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.
Conclusions
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.
***
The
American Physiological Society (APS) has been an integral part of the
scientific discovery process since it was established in 1887. Physiology
is the study of how molecules, cells, tissues and organs function to create
health or disease.
# # #
NOTE TO EDITORS: The APS annual meeting is part
of the Experimental Biology 2007 (EB ’07) gathering and will be held April
28-May 2, 2007 at the Washington, DC Convention Center. To schedule an
interview with Dr. Paterson, please contact Donna Krupa in the
newsroom at 202.249.4174, 301.634.7209 (direct dial), 703.967.2751 (cell)
or
DKrupa@the-APS.org.
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