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This Article Full Text Full Text (PDF) All Versions of this Article: 94/6/3662    most recent 00496.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Garcia, L. Articles by Hammond, C. Search for Related Content PubMed PubMed Citation Articles by Garcia, L. Articles by Hammond, C.

TRANSLATIONAL PHYSIOLOGY

Impact of High-Frequency Stimulation Parameters on the Pattern of Discharge of Subthalamic Neurons

¹Laboratoire de Neurophysiologie, Centre National de la Recherche Scientifique Unté Mixte de Recherche 5543, Université de Bordeaux 2, Bordeaux Cedex; and ²Institut de Neurobiologie de la Méditerranée, Institut National de la Recherche Médicale U 29, Marseille Cedex 9, France; and ³School of Mathematics, University of Southampton, Southampton, United Kingdom

Submitted 12 May 2005; accepted in final form 6 August 2005

In clinical conditions, high-frequency stimulation (HFS) of subthalamic (STN) neurons in Parkinson's disease is empirically applied at 100 Hz (130–185 Hz), with pulses of short duration (60–100 µs) and 1- to 3-mA amplitude. Other parameter values produce no effect or aggravate the symptoms. To gain a better understanding of the mechanisms that underlie the therapeutic action of HFS, we have compared the effects of different combinations of parameter values delivered by clinical stimulators on the activity of STN neurons recorded in whole cell patch-clamp configuration in slices. We showed that none of tested combinations of parameters silenced the neurons. Non-therapeutic combinations i.e., low-frequency pulses (10–50 Hz), even at large amplitude or width, further excited the STN neurons with respect to their spontaneous activity. In contrast, combinations in the therapeutic range (80–185 Hz, 90–200 µs, 500–800 µA) replaced the preexisting activity by spikes, time-locked to the stimuli and thus presenting a striking regularity. When increasing pulse width or amplitude in this high-frequency range, the dual effect was still present but the activity generated became more irregular. We propose that during HFS at clinically relevant parameters, STN neurons behave as stable oscillators entirely driven by the stimulation, giving an average stable STN output that overrides spontaneous activity and introduces high-frequency regular spiking in the basal ganglia network.