Identifying cardiorespiratory neurocircuitry involved in central command during exercise in humans

For almost one hundred years, the exact role of human brain structures controlling the cardiorespiratory response to exercise (‘central command’) has been sought. Animal experiments and functional imaging studies have provided clues, but the underlying electrophysiological activity of proposed relevant neural sites in humans has never been measured. In this study, local field potentials were directly recorded in a number of ‘deep’ brain nuclei during an exercise task designed to dissociate the exercise from peripheral feedback mechanisms. Several patient groups had electrodes implanted sterotaxically for the treatment of movement disorder or chronic pain. Fast Fourier transform analysis was applied to the neurograms to identify the power of fundamental spectral frequencies. Anticipation of exercise resulted in increases in heart rate, blood pressure and ventilation. The greatest neural changes were found in the periaqueductal grey area (PAG) where anticipation of exercise was accompanied by an increase of 43% in the power of the 12–25 Hz frequency band (P = 0.007). Exercise increased the activity by 87% compared to rest (P = 0.006). Changes were also seen in the 60–90 Hz band when anticipation or exercise increased power by 32% (P = 0.006) and 109% (P < 0.001), respectively. In the subthalamic nucleus there was a reduction in the power of the beta frequency during both anticipation (7.6 ± 0.68% P = 0.001) and exercise (17.3 ± 0.96% P < 0.001), whereas an increase was seen with exercise only at higher frequencies (93 ± 1.8% P = 0.007). No significant changes were seen in the globus pallidus during anticipation of exercise. We provide direct electrophysiological evidence highlighting the PAG as an important subcortical area in the neural circuitry of the cardiorespiratory response to exercise, since stimulation of this structure is known to alter blood pressure in awake humans

Striatal origin of the pathologic beta oscillations in Parkinson's disease

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. 1073/pnas.1107748108/-/DCSupplemental.Enhanced oscillations at beta frequencies (8–30 Hz) are a signature neural dynamic pathology in the basal ganglia and cortex of Parkinson's disease patients. The mechanisms underlying these pathological beta oscillations remain elusive. Here, using mathematical models, we find that robust beta oscillations can emerge from inhibitory interactions between striatal medium spiny neurons. The interaction of the synaptic GABAa currents and the intrinsic membrane M-current promotes population oscillations in the beta frequency range. Increased levels of cholinergic drive, a condition relevant to the parkinsonian striatum, lead to enhanced beta oscillations in the striatal model. We show experimentally that direct infusion of the cholinergic agonist carbachol into the striatum, but not into the neighboring cortex, of the awake, normal rodent induces prominent beta frequency oscillations in the local field potential. These results provide evidence for amplification of normal striatal network dynamics as a mechanism responsible for the enhanced beta frequency oscillations in Parkinson's disease.National Science Foundation (U.S.). (Grant DMS-0717670)National Science Foundation (U.S.). (Director’s New Innovator Award DP2 OD002002-01)Helen Hay Whitney Foundation FellowshipUnited States. National Institutes of Health (Grant K99MH085944)National Institute of Neurological Disorders and Stroke (U.S.) (Grant 1 R01 NS062955-01