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Deep brain stimulation of the globus pallidus internus in the parkinsonian primate: local entrainment and suppression of low-frequency oscillations.

ABSTRACT: Competing theories seek to account for the therapeutic effects of high-frequency deep brain stimulation (DBS) of the internal globus pallidus (GPi) for medically intractable Parkinson's disease. To investigate this question, we studied the spontaneous activity of 102 pallidal neurons during GPiDBS in two macaques rendered parkinsonian by administration of MPTP. Stimulation through macroelectrodes in the GPi (> or =200 microA at 150 Hz for 30 s) reduced rigidity in one animal and increased spontaneous movement in both. Novel artifact subtraction methods allowed uninterrupted single-unit recording during stimulation. GPiDBS induced phasic (78% of cells) or sustained (22%) peristimulus changes in firing in both pallidal segments. A subset of cells responded at short latency (<2 ms) in a manner consistent with antidromic driving. Later phasic increases clustered at 3- to 5-ms latency. Stimulation-induced decreases were either phasic, clustered at 1-3 ms, or sustained, showing no peristimulus modulation. Response latency and magnitude often evolved over 30 s of stimulation, but responses were relatively stable by the end of that time. GPiDBS reduced mean firing rates modestly and only in GPi (-6.9 spikes/s). Surprisingly, GPiDBS had no net effect on the prevalence or structure of burst firing. GPiDBS did reduce the prevalence of synchronized low-frequency oscillations. Some cell pairs became synchronized instead at the frequency of stimulation. Suppression of low-frequency oscillations did not require high-frequency synchronization, however, or even the presence of a significant peristimulus response. In summary, the therapeutic effects of GPiDBS may be mediated by an abolition of low-frequency synchronized oscillations as a result of phasic driving.

SUBMITTER: McCairn KW

PROVIDER: S-EPMC3350155 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Deep brain stimulation of the globus pallidus internus in the parkinsonian primate: local entrainment and suppression of low-frequency oscillations.

McCairn Kevin W KW Turner Robert S RS

Journal of neurophysiology 20090121 4

Competing theories seek to account for the therapeutic effects of high-frequency deep brain stimulation (DBS) of the internal globus pallidus (GPi) for medically intractable Parkinson's disease. To investigate this question, we studied the spontaneous activity of 102 pallidal neurons during GPiDBS in two macaques rendered parkinsonian by administration of MPTP. Stimulation through macroelectrodes in the GPi (> or =200 microA at 150 Hz for 30 s) reduced rigidity in one animal and increased sponta ...[more]

PMID: 19164104

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Project description:Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson's disease. Clinical outcomes are highly dependent on applying stimulation to precise locations in the brain. However, robust neurophysiological markers are needed to determine the optimal electrode location and to guide postoperative stimulation parameter selection. In this study, we evaluated evoked resonant neural activity in the pallidum as a potential intraoperative marker to optimize targeting and stimulation parameter selection to improve outcomes of deep brain stimulation for Parkinson's disease. Intraoperative local field potential recordings were acquired in 22 patients with Parkinson's disease undergoing globus pallidus internus deep brain stimulation implantation (N = 27 hemispheres). A control group of patients undergoing implantation in the subthalamic nucleus (N = 4 hemispheres) for Parkinson's disease or the thalamus for essential tremor (N = 9 patients) were included for comparison. High-frequency (135 Hz) stimulation was delivered from each electrode contact sequentially while recording the evoked response from the other contacts. Low-frequency stimulation (10 Hz) was also applied as a comparison. Evoked resonant neural activity features, including amplitude, frequency and localization were measured and analysed for correlation with empirically derived postoperative therapeutic stimulation parameters. Pallidal evoked resonant neural activity elicited by stimulation in the globus pallidus internus or externus was detected in 26 of 27 hemispheres and varied across hemispheres and across stimulating contacts within individual hemispheres. Bursts of high-frequency stimulation elicited evoked resonant neural activity with similar amplitudes (P = 0.9) but a higher frequency (P = 0.009) and a higher number of peaks (P = 0.004) than low-frequency stimulation. We identified a 'hotspot' in the postero-dorsal pallidum where stimulation elicited higher evoked resonant neural activity amplitudes (P < 0.001). In 69.6% of hemispheres, the contact that elicited the maximum amplitude intraoperatively matched the contact empirically selected for chronic therapeutic stimulation by an expert clinician after 4 months of programming sessions. Pallidal and subthalamic nucleus evoked resonant neural activity were similar except for lower pallidal amplitudes. No evoked resonant neural activity was detected in the essential tremor control group. Given its spatial topography and correlation with postoperative stimulation parameters empirically selected by expert clinicians, pallidal evoked resonant neural activity shows promise as a potential marker to guide intraoperative targeting and to assist the clinician with postoperative stimulation programming. Importantly, evoked resonant neural activity may also have the potential to guide directional and closed-loop deep brain stimulation programming for Parkinson's disease.

Project description:IntroductionThe globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients.MethodsThe literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping.ResultsThere are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD.ConclusionGPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages.

Project description:IntroductionGlobus pallidus internus (GPi) deep brain stimulation (DBS) is widely used in patients with dystonia. However, 10-20% of patients receive insufficient benefits. The objectives of this study are to evaluate the effectiveness of bilateral subthalamic nucleus (STN) DBS along with unilateral posteroventral pallidotomy (PVP) in patients with dystonia who experienced unsatisfactory GPi-DBS and to address the reported rescue procedures after suboptimal DBS or lesion surgery in dystonia patients.MethodsSix patients with isolated dystonia who had previously undergone bilateral GPi-DBS with suboptimal improvement were included. Standardized assessments of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and quality of life using SF-36 were evaluated before surgery and 1, 6 months, and last follow-up (LFU) after surgery. STN bilateral OFF (bi-OFF), unilateral ON (uni-ON), and bilateral ON (bi-ON) states were recorded at LFU. Specific items were used to find publications published before 10 April 2022 regarding rescue procedures after suboptimal DBS or lesion surgery in patients with dystonia for reference. Eleven original studies including case reports/series were identified for discussion.ResultsSubstantial clinical benefits were achieved in all six patients. Significant amelioration was achieved during the 1-month (6.5 ± 7.45; p = 0.0049), 6-month (5.67 ± 6.3; p = 0.0056) follow-ups, and at LFU (4.67 ± 4.72; p = 0.0094) when compared with the baseline (LFU of GPi DBS with on status) (17.33 ± 11.79) assessed by BFMDRS. The percentage of improvement reached 70.6, 74.67, and 77.05%, respectively. At LFU, significant differences were found between the stimulation bi-OFF and uni-ON (11.08 ± 8.38 vs. 9 ± 8.52, p = 0.0191), and between the stimulation bi-OFF and bi-ON (11.08 ± 8.38 vs. 4.67 ± 4.72, p = 0.0164). Trends depicting a better improvement in stimulation bi-ON compared with uni-ON (4.67 ± 4.72 vs. 9 ± 8.52, p = 0.0538) were observed.ConclusionOur results suggest that bilateral STN-DBS plus unilateral PVP may be an effective rescue procedure for patients with isolated dystonia who experienced suboptimal movement improvement following GPi-DBS. However, given the heterogeneity of patients and the small sample size, these findings should be interpreted with caution.

Project description:IntroductionDystonic opisthotonus is defined as a backward arching of the neck and trunk, which ranges in severity from mild backward jerks to life-threatening prolonged severe muscular spasms. It can be associated with generalized dystonic syndromes or, rarely, present as a form of axial truncal dystonia. The etiologies vary from idiopathic, genetic, tardive, hereditary-degenerative, or associated with parkinsonism. We report clinical cases of dystonic opisthotonus associated with adult-onset dystonic syndromes, that benefitted from globus pallidus internus (GPi) deep brain stimulation (DBS).MethodsClinical data from patients with dystonic syndromes who underwent comprehensive medical review, multidisciplinary assessment, and tailored medical and neurosurgical managements were prospectively analyzed. Quantification of dystonia severity pre- and postoperatively was performed using the Burke-Fahn-Marsden Dystonia Rating Scale and quantification of overall pain severity was performed using the Visual Analog Scale.ResultsThree male patients, with age of onset of the dystonic symptoms ranging from 32 to 51 years old, were included. Tardive dystonia, adult-onset dystonia-parkinsonism and adult-onset idiopathic axial dystonia were the etiologies identified. Clinical investigation and management were tailored according to the complexity of the individual presentations. Although they shared common clinical features of adult-onset dystonia, disabling dystonic opisthotonus, refractory to medical management, was the main indication for GPi-DBS in all patients presented. The severity of axial dystonia ranged from disturbance of daily function to life-threatening truncal distortion. All three patients underwent bilateral GPi DBS at a mean age of 52 years (range 48-55 years), after mean duration of symptoms prior to DBS of 10.7 years (range 4-16 years). All patients showed a rapid and sustained clinical improvement of their symptoms, notably of the dystonic opisthotonos, at postoperative follow-up ranging from 20 to 175 months. In some, the ability to resume activities of daily living and reintegration into the society was remarkable.ConclusionAdult-onset dystonic syndromes predominantly presenting with dystonic opisthotonus are relatively rare. The specific nature of dystonic opisthotonus remains a treatment challenge, and thorough investigation of this highly disabling condition with varying etiologies is often necessary. Although patients may be refractory to medical management and botulinum toxin injection, Globus pallidus stimulation timed and tailored provided symptomatic control in this cohort and may be considered in other carefully selected cases.

Dataset Information

Deep brain stimulation of the globus pallidus internus in the parkinsonian primate: local entrainment and suppression of low-frequency oscillations.

Publications

Deep brain stimulation of the globus pallidus internus in the parkinsonian primate: local entrainment and suppression of low-frequency oscillations.

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