Targeting of the Subthalamic Nucleus for Deep Brain Stimulation: A Survey Among Parkinson Disease Specialists

Hamel, Wolfgang; Köppen, Johannes; Alesch, François; Antonini, Angelo; Barcia, Juan A.; Bergman, Hagai; Chabardès, Stéphan; Contarino, Maria Fiorella; Cornu, Philippe; Demmel, Walter; Deuschl, Günther; Fasano, Alfonso; Kühn, Andrea A.; Limousin, Patricia; McIntyre, Cameron C.; Mehdorn, H. Maximilian; Pilleri, Manuela; Pollak, Pierre; Rodríguez‐Oroz, María C.; Rumià, Jordi; Samuel, Michael; Timmermann, Lars; Valldeoriola, Francesc; Vesper, Jan; Visser‐Vandewalle, Veerle; Volkmann, Jens; Lozano, Andrés M.

doi:10.1016/j.wneu.2016.11.012

Cited by 48 publications

(43 citation statements)

References 46 publications

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“…Thus, STN border-based programming and the therapeutic VTAs used for reference exhibit the same systematic error, artifactually inflating the measured specificity. When interpreted together with the anatomical diversity of therapeutic activation regions observed across subjects, as reported by earlier studies [24,56], these findings support opportunities for Although this study treats therapeutic tissue activation as a binary variable, presentations of Parkinson disease and its response to STN DBS are known to be multidimensional and varied across patients. A robust body of work suggests that different symptoms may be optimally treated by activation of different subthalamic regions and neural pathways with unique electrophysiological markers [20,26,57,58].…”

Section: Discussionsupporting

confidence: 81%

High density microelectrode recording predicts span of therapeutic tissue activation volumes in subthalamic deep brain stimulation for Parkinson disease

Malaga

Chou

et al. 2020

Brain Stimulation

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Background: Subthalamic deep brain stimulation alleviates motor symptoms of Parkinson disease by activating precise volumes of neural tissue. While electrophysiological and anatomical correlates of clinically effective electrode sites have been described, therapeutic stimulation likely acts through multiple distinct neural populations, necessitating characterization of the full span of tissue activation. Microelectrode recordings have yet to be mapped to therapeutic tissue activation volumes and surveyed for predictive markers. Objective: Combine high-density, broadband microelectrode recordings with detailed computational models of tissue activation to describe and to predict regions of therapeutic tissue activation. Methods: Electrophysiological features were extracted from microelectrode recordings along 23 subthalamic deep brain stimulation implants in 16 Parkinson disease patients. These features were mapped in space against tissue activation volumes of therapeutic stimulation, modeled using clinicallydetermined stimulation programming parameters and fully individualized, atlas-independent anisotropic tissue properties derived from 3T diffusion tensor magnetic resonance images. Logistic LASSO was applied to a training set of 17 implants out of the 23 implants to identify predictors of therapeutic stimulation sites in the microelectrode recording. A support vector machine using these predictors was used to predict therapeutic activation. Performance was validated with a test set of six implants. Results: Analysis revealed wide variations in the distribution of therapeutic tissue activation across the microelectrode recording-defined subthalamic nucleus. Logistic LASSO applied to the training set identified six oscillatory predictors of therapeutic tissue activation: theta, alpha, beta, high gamma, high frequency oscillations (HFO, 200e400 Hz), and high frequency band (HFB, 500e2000 Hz), in addition to interaction terms: theta x HFB, alpha x beta, beta x HFB, and high gamma x HFO. A support vector classifier using these features predicted therapeutic sites of activation with 64% sensitivity and 82% specificity in the test set, outperforming a beta-only classifier. A probabilistic predictor achieved 0.87 area under the receiver-operator curve with test data. Conclusions: Together, these results demonstrate the importance of personalized targeting and validate a set of microelectrode recording signatures to predict therapeutic activation volumes. These features may be used to improve the efficiency of deep brain stimulation programming and highlight specific neural oscillations of physiological importance.

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Section: Discussionsupporting

confidence: 81%

High density microelectrode recording predicts span of therapeutic tissue activation volumes in subthalamic deep brain stimulation for Parkinson disease

Malaga

Chou

et al. 2020

Brain Stimulation

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“…However, these techniques also have limitations and their efficacy still depends on correct localization of the target. Neuroimaging techniques are advancing, but it is not certain that this will lead to more uniform targeting as experts may define the optimal STN target differently . One study showed that the final stimulation site, based on MER and intraoperative stimulation, was located more lateral and superior than both atlas and MRI based targets .…”

Section: Discussionmentioning

confidence: 99%

Multiple Microelectrode Recordings in STN‐DBS Surgery for Parkinson's Disease: A Randomized Study

Bjerknes

Toft

Konglund

et al. 2018

Movement Disord Clin Pract

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BackgroundSubthalamic nucleus deep brain stimulation improves motor symptoms and fluctuations in advanced Parkinson's disease, but the degree of clinical improvement depends on accurate anatomical electrode placement. Methods used to localize the sensory‐motor part of the nucleus vary substantially. Using microelectrode recordings, at least three inserted microelectrodes are needed to obtain a three‐dimensional map. Therefore, multiple simultaneously inserted microelectrodes should provide better guidance than single sequential microelectrodes. We aimed to compare the use of multiple simultaneous versus single sequential microelectrode recordings on efficacy and safety of subthalamic nucleus stimulation.MethodsSixty patients were included in this double‐blind, randomized study, 30 in each group. Primary outcome measures were the difference from baseline to 12 months in the MDS‐UPDRS motor score (part III) in the off‐medication state and quality of life using the Parkinson's Disease Questionnaire‐39 (PDQ‐39) scores.ResultsThe mean reduction of the MDS‐UPDRS III off score was 35 (SD 12) in the group investigated with multiple simultaneous microelectrodes compared to 26 (SD 10) in the single sequential microelectrode group (p = 0.004). The PDQ‐39 Summary Index did not differ between the groups, but the domain scores activities of daily living and bodily discomfort improved significantly more in the multiple microelectrodes group. The frequency of serious adverse events did not differ significantly.ConclusionsAfter 12 months of subthalamic nucleus stimulation, the multiple microelectrodes group had a significantly greater improvement both in MDS‐UPDRS III off score and in two PDQ‐39 domains. Our results may support the use of multiple simultaneous microelectrode recordings.Trial registration http://ClinicalTrials.gov Identifier: NCT00855621 (first received March 3, 2009).

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“…Saint-Cyr et al, 2002; Herzog et al, 2004; Nowinski et al, 2005; Butson et al, 2011; Welter et al, 2014; Eisenstein et al, 2014]. However, there is still little to no clinical consensus on the specific neural elements (and/or axonal pathways) that are necessary and sufficient for evoking therapeutic effects when stimulated [Hamel et al, 2017]. …”

Section: Introductionmentioning

confidence: 99%

Quantifying axonal responses in patient-specific models of subthalamic deep brain stimulation

2018

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Medical imaging has played a major role in defining the general anatomical targets for deep brain stimulation (DBS) therapies. However, specifics on the underlying brain circuitry that is directly modulated by DBS electric fields remain relatively undefined. Detailed biophysical modeling of DBS provides an approach to quantify the theoretical responses to stimulation at the cellular level, and has established a key role for axonal activation in the therapeutic mechanisms of DBS. Estimates of DBS-induced axonal activation can then be coupled with advances in defining the structural connectome of the human brain to provide insight into the modulated brain circuitry and possible correlations with clinical outcomes. These pathway-activation models (PAMs) represent powerful tools for DBS research, but the theoretical predictions are highly dependent upon the underlying assumptions of the particular modeling strategy used to create the PAM. In general, three types of PAMs are used to estimate activation: 1) field-cable (FC) models, 2) driving force (DF) models, and 3) volume of tissue activated (VTA) models. FC models represent the “gold standard” for analysis but at the cost of extreme technical demands and computational resources. Consequently, DF and VTA PAMs, derived from simplified FC models, are typically used in clinical research studies, but the relative accuracy of these implementations is unknown. Therefore, we performed a head-to-head comparison of the different PAMs, specifically evaluating DBS of three different axonal pathways in the subthalamic region. The DF PAM was markedly more accurate than the VTA PAMs, but none of these simplified models were able to match the results of the patient-specific FC PAM across all pathways and combinations of stimulus parameters. These results highlight the limitations of using simplified predictors to estimate axonal stimulation and emphasize the need for novel algorithms that are both biophysically realistic and computationally simple.

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Targeting of the Subthalamic Nucleus for Deep Brain Stimulation: A Survey Among Parkinson Disease Specialists

Cited by 48 publications

References 46 publications

High density microelectrode recording predicts span of therapeutic tissue activation volumes in subthalamic deep brain stimulation for Parkinson disease

High density microelectrode recording predicts span of therapeutic tissue activation volumes in subthalamic deep brain stimulation for Parkinson disease

Multiple Microelectrode Recordings in STN‐DBS Surgery for Parkinson's Disease: A Randomized Study

Quantifying axonal responses in patient-specific models of subthalamic deep brain stimulation

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