Submyelin potassium accumulation may functionally block subsets of local axons during deep brain stimulation: a modeling study.

Deep brain stimulation has been used for over a decade to relieve the symptoms of Parkinson's disease, although its mechanism of action remains poorly understood. To better understand the direct effects of DBS on central neurons, a computational model of a myelinated axon has been constructed which includes the effects of K(+) accumulation within the peri-axonal space. Using best estimates of anatomic and electrogenic model parameters for in vivo STN axons, the model predicts a functional block along the axon due to K(+) accumulation in the submyelin space. The functional block occurs for a range of model parameters: high stimulation frequencies (>130 Hz); high extracellular K(+) concentrations (>3 x 10(-3) M); low maximum Na(+)/K(+) ATPase current densities (<0.026 A m(-2)); low diffusion coefficients for K(+) diffusion out of the submyelin space (<2.4 x 10(-9) m(2) s(-1)); small periaxonal space widths of the myelin attachment sections (<2.7 x 10(-9) m) and perinodal/internodal sections (<8.4 x 10(-9) m). These results suggest that therapeutic DBS of the STN likely results in a functional block for many STN axons, although a subset of STN axons may also be activated at the stimulating frequency.

Postnatal development of circadian rhythm in serum cortisol levels in children.

High-pressure liquid chromatography was used to study the development of blood adrenocortical circadian rhythm in a total of 64 children, ranging in age from 1 month to 15 years. Patients with endocrine diseases, congenital anomalies, and diseases of the central nervous system were excluded from this study. Determination of corticosteroid concentration was possible with 20 to 100 microL of serum. Twenty-four hour patterns were determined at six-hour intervals. A distinct circadian rhythm with an amplitude comparable to that of an adult emerged at approximately 6 months of age.