Probabilistic sweet spots predict motor outcome for deep brain stimulation in Parkinson disease

Abstract

ObjectiveTo investigate whether functional sweet spots of deep brain stimulation (DBS) in the subthalamic nucleus (STN) can predict motor improvement in Parkinson disease (PD) patients.MethodsStimulation effects of 449 DBS settings in 21 PD patients were clinically and quantitatively assessed through standardized monopolar reviews and mapped into standard space. A sweet spot for best motor outcome was determined using voxelwise and nonparametric permutation statistics. Two independent cohorts were used to investigate whether stimulation overlap with the sweet spot could predict acute motor outcome (10 patients, 163 settings) and long‐term overall Unified Parkinson's Disease Rating Scale Part III (UPDRS‐III) improvement (63 patients).ResultsSignificant clusters for suppression of rigidity and akinesia, as well as for overall motor improvement, resided around the dorsolateral border of the STN. Overlap of the volume of tissue activated with the sweet spot for overall motor improvement explained R2 = 37% of the variance in acute motor improvement, more than triple what was explained by overlap with the STN (R2 = 9%) and its sensorimotor subpart (R2 = 10%). In the second independent cohort, sweet spot overlap explained R2 = 20% of the variance in long‐term UPDRS‐III improvement, which was equivalent to the variance explained by overlap with the STN (R2 = 21%) and sensorimotor STN (R2 = 19%).InterpretationThis study is the first to predict clinical improvement of parkinsonian motor symptoms across cohorts based on local DBS effects only. The new approach revealed a distinct sweet spot for STN DBS in PD. Stimulation overlap with the sweet spot can predict short‐ and long‐term motor outcome and may be used to guide DBS programming. ANN NEUROL 2019;86:527–538

Parcellation of the Subthalamic Nucleus in Parkinson’s Disease: A Retrospective Analysis of Atlas- and Diffusion-Based Methods

“…As the SMA cluster was located at the anterior border of the motor part of the STN, the association of LED reduction with the lead distance to this cluster corresponds to the observations from previous studies that the stimulation sweet spot for improvement of motor symptoms is located at the border between the motor and associative STN clusters [18,[27][28][29]. Most importantly, our analysis revealed that this sweet spot, described with relatively high consistency in the literature, might correspond to the SMA cluster.…”

Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson’s disease

“…Furthermore, a modulation of the medial thalamus could, e.g., improve restlessness in legs or arms [19]. Future studies are required to assess the role of directional DBS towards subregions of the STN and the adjacent target region [16,17,40]. Another possible explanation could be mediated through projections from the STN to the globus pallidus externus as electrophysiological animal studies have shown that during STN-DBS the activity in the globus pallidus externus is increased which may result in an improvement of sleep [22,24,27,34,41].…”

Directional Local Field Potentials in the Subthalamic Nucleus During Deep Brain Implantation of Parkinson’s Disease Patients

“…It can reduce undesired activation of adjacent structures such as the internal capsule, and indeed, it has demonstrated higher side effect thresholds than classical omnidirectional stimulation in implanted patients (Steigerwald et al, 2016;Dembek et al, 2017). Directional stimulation may further be leveraged to target very specific and clinically effective regions of the subthalamic nucleus, also known as "sweet spots" obtained from probabilistic mapping (Horn et al, 2017;Dembek et al, 2019;Nguyen et al, 2019b). These regions are associated with abnormal electrophysiological activity recorded through local field potentials (LFPs).…”