The FM/AM world is shaping the future of deep brain stimulation

In this issue of Movement Disorders two studies examined the impact of low (<100 Hz) frequencies of deep brain stimulation (DBS) on the motor performance of patients with Parkinson’s disease (PD) who underwent subthalamic (STN) implants. Huang et al randomized 6 patients in the OFF medication condition to several DBS frequencies and found that many low frequencies produced a substantial improvement of finger bradykinesia, which was often equal to or greater than with high-stimulation frequencies. Well-defined peaks in response distribution were linked to the frequencies suggesting a complex and specific interaction between repetitive DBS pulses and neural oscillators, a theory recently proposed for tremor control in thalamic stimulation as well. In the second paper, Khoo et al compared the immediate efficacy of 60 Hz and 130 Hz stimulation in 14 patients in the on medication condition in a randomized, double-blind, crossover protocol. They found that 60 Hz was superior to 130 Hz in improving the overall motor function and axial motor signs (particularly gait). Further, the most effective sites for low frequency stimulation were different than those which gave optimal benefits at high frequency. The optimal low frequency stimulation sites were said to lie more ventral in the STN. There were no differences between high and low frequency stimulation on segmental symptoms, such as tremor or rigidity, although a slight tremor was observed during the low-frequency stimulation, in keeping with early notions. These two papers represent the latest contribution to the growing literature addressing the effects of frequency modulation in DBS, a concept initially developed for chorea or dystonia patients. In programming DBS devices a number of parameters can be altered including stimulation amplitude, pulse width, frequency and importantly as implanted electrodes typically have 4 separate contacts, stimulation site. The amplitude of stimulation has been classically considered the most flexible and useful parameter for the fine tuning of DBS. In contrast, changes of the pulse width are less likely to be adopted, as 60 lsec is typically used in most of DBS patients; given the chronaxic properties of the different neuronal elements, higher PWs (typically used large nuclei like thalamus or globus pallidus) are more likely to induce stimulation-induced side effects, the reason why current research is exploring values lower than the classic 60 lsec. The change in clinical responses as a function of stimulation frequency is a complex topic. Frequencies higher than 100H Hz (130 Hz in most cases) have been traditionally used since the early DBS era. However, recent studies have suggested that STN stimulation at relatively low frequency (60-80 Hz) may be beneficial in controlling a number of symptoms and particularly axial symptoms that continue to deteriorate under high-frequency stimulation. The table summarizes the current knowledge on the impact of DBS frequency on the different symptoms accompanying PD. The studies by Huang et al and Khoo et al represent a step forward in understanding the mechanisms of DBS, however they share a number of important limitations. The most important is the short evaluation period, as clinical experience clearly shows that the benefit provided by low-frequency stimulation might not be sustained. In addition, Huang et al. did not keep the total electrical energy delivered (TEED) constant across the several conditions explored. On the other hand, although Khoo et al. kept the TEED constant, the evaluation period was shorter than the 3 hours necessary to see an effect on axial signs. It is currently unknown if the decay of benefit provided by low frequency is caused by an inconstant TEED, a concept only rarely taken into account although it is conceivable that a reduction of frequency should be paralleled by an increase of voltage. The definition of TEED itself is still debated and at least two formulas has been proposed. Nevertheless, keeping the TEED constant would probably clarify whether the improvement observed under low frequency is caused by the lessening of the negative -----------------------------------------------------------*Corresponding author: Andres Lozano, Professsor and Chairman of Neurosurgery, University of Toronto. Toronto Western Hospital, 399 Bathurst St, 4-431 W, Toronto, ON Canada M5T 2S8. E-mail: lozano@uhnresearch.ca