The impact on Parkinson’s disease of electrical parameter settings in STN stimulation

Moro, Elena; Esselink, Rianne J. A.; Xie, Jing; Hommel, Marc; Benabid, Alim Louis; Pollak, Pierre

doi:10.1212/wnl.59.5.706

Cited by 463 publications

(422 citation statements)

References 36 publications

(34 reference statements)

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“…Substantial clinical effort has been invested in determining optimal stimulation parameters for STN DBS for PD (Limousin et al, 1998;Rizzone et al, 2001;Moro et al, 2002;Volkmann et al, 2006). These studies have resulted in general guidelines on the selection of stimulation parameters, as well as clinical algorithms for programming the devices.…”

Section: Discussionmentioning

confidence: 99%

Patient-specific analysis of the volume of tissue activated during deep brain stimulation

et al. 2007

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Despite the clinical success of deep brain stimulation (DBS) for the treatment of movement disorders, many questions remain about its effects on the nervous system. We have developed a methodology to predict the volume of tissue activated (VTA) by DBS on a patient-specific basis. Our goals are to identify the intersection between the VTA and surrounding anatomical structures and to compare activation of these structures with clinical outcomes. The model system consists of three fundamental components: 1) a 3D anatomical model of the subcortical nuclei and DBS electrode position in the brain, each derived from magnetic resonance imaging (MRI); 2) a finite element model of the DBS electrode and electric field transmitted to the brain, with tissue conductivity properties derived from diffusion tensor MRI; 3) VTA prediction derived from the response of myelinated axons to the applied electric field, which is a function of the stimulation parameters (contact, impedance, voltage, pulse width, frequency). We used this model system to analyze the effects of subthalamic nucleus (STN) DBS in a patient with Parkinson's disease. Quantitative measurements of bradykinesia, rigidity, and corticospinal tract (CST) motor thresholds were evaluated over a range of stimulation parameter settings. Our model predictions showed good agreement with CST thresholds. Additionally, stimulation through electrode contacts that improved bradykinesia and rigidity generated VTAs that overlapped the zona incerta / fields of Forel (ZI/H2). Application of DBS technology to various neurological disorders has preceded scientific characterization of the volume of tissue directly affected by the stimulation. Synergistic integration of clinical analysis, neuroimaging, neuroanatomy, and neurostimulation modeling provides the opportunity to address wide ranging questions on the factors linked with the therapeutic benefits and side effects of DBS.

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Section: Discussionmentioning

confidence: 99%

Patient-specific analysis of the volume of tissue activated during deep brain stimulation

et al. 2007

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“…3,12 In subjects with PD, treatment of the three cardinal motor symptoms (i.e., 1, tremor, 2, bradykinesia, and 3, rigidity) improved as the frequency of subthalamic nucleus (STN) DBS was increased and reached a plateau between 130 and 185 Hz. 13 Similarly, DBS at 130 Hz led to significant decreases in movement times (i.e., improved bradykinesia) in subjects with PD as compared with stimulation off, 14 and 130 Hz stimulation improved scores on the entire motor subset of the Unified Parkinson's Disease Rating Scale (UPDRS). 15 Conversely, DBS of the STN at 10 Hz significantly lengthened movement times (i.e., worsened bradykinesia) and significantly worsened UPDRS motor scores.…”

Section: Dependence Of Motor Symptoms On Frequency Of Stimulationmentioning

confidence: 99%

“…59 High-frequency (Ͼ70 Hz) STN DBS reduced pallidal beta oscillations (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) in PD subjects in a manner similar to the administration of dopamine precursors, whereas 25 Hz DBS increased the power of pallidal beta oscillations. 60 In addition, high-frequency STN DBS at 130 Hz or 185 Hz attenuated STN beta oscillations in subjects with PD during the period just after DBS was turned off.…”

Section: Changes In Neuronal Firing During Dbsmentioning

confidence: 99%

Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus Frequency

2008

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Summary: Deep brain stimulation (DBS) is an established treatment for symptoms in movement disorders and is under investigation for symptom management in persons with psychiatric disorders and epilepsy. Nevertheless, there remains disagreement regarding the physiological mechanisms responsible for the actions of DBS, and this lack of understanding impedes both the design of DBS systems for treating novel diseases and the effective tuning of current DBS systems. Currently available data indicate that effective DBS overrides pathological bursts, low frequency oscillations, synchronization, and disrupted firing patterns present in movement disorders, and replaces them with more regularized firing. Although it is likely that the specific mechanism(s) by which DBS exerts its effects varies between diseases and target nuclei, the overriding of pathological activity appears to be ubiquitous. This review provides an overview of changes in motor symptoms with changes in DBS frequency and highlights parallels between the changes in motor symptoms and the changes in cellular activity that appear to underlie the motor symptoms.

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“…Previous studies have examined the clinical outcomes of DBS as a function of the charge or energy injected into the brain (Moro et al, 2002;Koss et al, 2005), and charge is known to be a co-factor in stimulation induced tissue damage (McCreery et al, 1990). In turn, we calculated the cathodic charge per phase for each waveform examined (Figure 2).…”

Section: Methodsmentioning

confidence: 99%

“…However, the details of the stimulation waveform become important when defining correlations between DBS parameter settings, clinical outcomes, and/or experimental threshold measurements. Several clinical studies have been conducted to determine the differential effects of various stimulation protocols on DBS outcome measures (Benabid et al, 1991;Holsheimer et al, 2000;Rizzone et al, 2001;Moro et al, 2002;O'Suilleabhain et al, 2003;Kuncel et al, 2006). And, multiple theoretical studies have calculated the voltage field generated by DBS (McIntyre and Thakor, 2002;Kuncel and Grill, 2004;McIntyre et al, 2004a;McIntyre et al, 2004b;Hemm et al, 2005;Wei and Grill, 2005;Astrom et al, 2006;Sotiropoulos and Steinmetz, 2007).…”

Section: Introductionmentioning

confidence: 99%

Differences among implanted pulse generator waveforms cause variations in the neural response to deep brain stimulation

Butson

McIntyre

2007

Clinical Neurophysiology

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Objective-Two different Medtronic implantable pulse generator (IPG) models are currently used in clinical applications of deep brain stimulation (DBS): Soletra and Kinetra. The goal of this study was to evaluate and compare the stimulation waveforms produced by each IPG model. Methods-We recorded waveforms from a broad range of stimulation parameter settings in each IPG model, and compared them to idealized waveforms that adhered to the parameters specified in the programming device. We then used a previously published computational model to predict the neural response to the various stimulation waveforms.Results-The stimulation waveforms produced by the IPGs differed from the idealized waveforms assumed in previous theoretical and clinical studies, and the waveforms differed among the IPG models. These differences were greater at higher frequencies and longer pulse widths, and caused variations of up to 0.4 V in activation thresholds for model axons located 3 mm from the DBS electrode contact.Conclusions-The specific details of the stimulation waveform directly affect the neural response to DBS and should be accounted for in theoretical and experimental studies of DBS.Significance-While the clinical selection of DBS parameters is individualized to each patient based on behavioral outcomes, scientific analysis of stimulation parameter settings and clinical threshold measurements are subject to a previously unrecognized source of error unless the actual waveforms produced by the IPG are accounted for.

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The impact on Parkinson’s disease of electrical parameter settings in STN stimulation

Abstract: This study confirms that the most beneficial effects induced by STN stimulation are obtained at high frequencies and that voltage is the most critical factor to obtain adequate alteration in STN activity. The mechanisms by which STN DBS improves parkinsonism remain speculative.

Cited by 463 publications

References 36 publications

Patient-specific analysis of the volume of tissue activated during deep brain stimulation

Patient-specific analysis of the volume of tissue activated during deep brain stimulation

Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus Frequency

Differences among implanted pulse generator waveforms cause variations in the neural response to deep brain stimulation

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