Study finds role of mid-brain in integrating heart and respiratory response to exercise

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.