High frequency deep brain stimulation: what are the therapeutic mechanisms?

High frequency deep brain stimulation (HFS) used to treat the symptoms of Parkinson's disease (PD) was first assumed to act by reducing an excessive tonic GABAergic inhibitory output from the internal globus pallidus (GPi). Stimulation in GPi might produce this directly by mechanisms such as depolarization block or activation of presynaptic inhibitory fibers, and the same mechanisms evoked by HFS in the subthalamic nucleus (STN) could reduce the excitatory action of STN on GPi neurons. Although somatic recordings from neurons near the stimulation site may appear to support this potential mechanism, the action downstream from the site of stimulation often is not consistent with this interpretation. A more parsimonious explanation for the similar effects of HFS in STN or GPi and a lesion of either of these structures is that both HFS and pallidotomy interrupt an abnormal pattern of firing in cortico-basal ganglia-thalamocortical loops that is responsible for the symptoms of PD.

Automatic microelectrode recording analysis and visualization of the globus pallidus interna and stereotactic trajectory.

Locating deep brain neuronal structures is required to accurately place deep brain stimulation (DBS) electrodes during stereotactic surgery in patients with Parkinson's disease and other movement disorders. This study investigates the efficacy of automatic microelectrode visualization and analysis methods to help neurosurgeons locate target structures more objectively, consistently, and easily during surgery. Ten patients (4 males and 6 females) who underwent bilateral implantation of DBS electrodes in the globus pallidus interna (Gpi), from 2001 to 2003, at the Oregon Health and Science University and the Portland Veterans Administration Medical Center were included. We compared the efficacy of the microelectrode recording signal energy, power spectral density (PSD), marginal probability density (mPDF), autocorrelation function (ACF), and partial ACF. mPDF and PSD estimates most accurately indicated the borders of the GPi target structure.

Automatic analysis and visualization of microelectrode recording trajectories to the subthalamic nucleus: preliminary results.

Although microelectrode recordings (MER) are commonly used to confirm stereotactic targets during surgery for movement disorders, there is no consensus on whether the additional risks and cost of MER are worth the benefits. This may be due, in part, to the inconsistency and inefficiency of subjective interpretation of MER data that is currently used in practice. We describe several fully automatic visualization methods for MER that efficiently and clearly indicate segments of the microelectrode trajectories with homogeneous neural activity that correspond to expected deep brain nuclei. Specifically we demonstrate that these visualization methods can help identify the subthalamic nucleus in Parkinson's disease patients. These methods have the potential to significantly improve patient outcome by helping neurosurgeons objectively identify target structures more quickly and accurately.

Muscle strength following direct injection of doxorubicin into rabbit sternocleidomastoid muscle in situ.

Direct intramuscular injection of doxorubicin results in permanent myofiber loss. A previous phase I trial demonstrated that such injections could successfully treat blepharospasm and hemifacial spasm. Our previous in vitro study demonstrated that doxorubicin resulted in a dose-dependent reduction in isometric force generation in sternocleidomastoid muscle in rabbits. This present study examined alterations in force generation in these treated muscles in situ, i.e., with the blood and nerve supply intact. Two months after a single doxorubicin injection, functional changes in peak twitch, tetanic force generation, and fatigue rate were assessed in control and doxorubicin-treated sternocleidomastoid muscles in rabbits. Peak force measurements were reduced in the treated muscles. These reductions in muscle strength were significantly greater at tetanic peak amplitudes. Fatigue rate was not altered by doxorubicin treatment of the sternocleidomastoid muscles. These findings support the potential clinical use of doxorubicin chemomyectomy for the treatment of patients with cervical dystonia.