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

Abstract

Background: Deep brain stimulation (DBS) is an established method of treatment for Parkinson's disease (PD). A stimulation sweet spot at the interface between the motor and associative clusters of the subthalamic nucleus (STN) has recently been postulated. The aim of this study was to analyze the available clustering methods for the STN and their correlation to outcome. Methods: This is a retrospective analysis of a group of 20 patients implanted with a DBS device for PD. Atlas-based and diffusion tractography-based parcellation of the STN was performed. The distances of the electrode to the obtained clusters were compared to each other and to outcome parameters, which included levodopa equivalent dose (LED) reduction, Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, and reduction in scores for items 32 and 36 of the UPDRS-IV. Results: The implanted electrodes were located nearest to the motor clusters of the STN. The following significant associations with postoperative LED reduction were found: (1) distance of the electrode to the motor cluster in the Accolla and DISTAL atlases (p < 0.01) and (2) distance of the electrode to the supplementary motor area cluster (p = 0.02). There was no association with either the UPDRS-III or the UPDRS-IV score. Conclusions: The results of this study suggest the possibility that atlas-based clustering, as well as diffusion tractography-based parcellation, can be useful in estimating the stimulation target ("sweet spot") for STN-DBS in PD patients. Atlas-based as well as diffusion-based clustering might become a useful tool in DBS trajectory planning.

Past, Present, and Future of Deep Brain Stimulation: Hardware, Software, Imaging, Physiology and Novel Approaches

“…Another recent study has demonstrated benefits using connectomics to prospectively determine patient-specific striatal DBS targets for obsessive-compulsive disorder based on fMRI with a symptom provocation task (93). Furthermore, for DBS in movement disorders, several prospective targeting methods involving DTIbased connectivity measures have been proposed to refine patient-specific targets (Figure 3) (94)(95)(96). Since anatomical targeting can be challenging due to poor landmarks on imaging or unreliable microelectrode recordings, this connectomic approach may offer an alternative or supplemental method of targeting.…”

Functional Topography of the Human Subthalamic Nucleus: Relevance for Subthalamotomy in Parkinson's Disease

“…31,56 Previous studies using fluorodeoxyglucose-positron emission tomography suggested that long-range modulation of SMA metabolism underlies improvement of the motor score by both STN-DBS 57 and tcMRgFUS subthalamotomy, 58 and some evidence points to the border between the motor and associative clusters as the most effective target. 31,56,59 In this context, our more detailed segmentation could be helpful to define the best individualized target according to predominant motor features.…”

“…To date, few imaging-based STN atlases have explicitly parcellated the SMA-connected region, even though this cortico-STN projection is considered to play an important role in normal motor and behavioral control and in the pathophysiology of PD. 31,56 Previous studies using fluorodeoxyglucose-positron emission tomography suggested that long-range modulation of SMA metabolism underlies improvement of the motor score by both STN-DBS 57 and tcMRgFUS subthalamotomy, 58 and some evidence points to the border between the motor and associative clusters as the most effective target. 31,56,59 In this context, our more detailed segmentation could be helpful to define the best individualized target according to predominant motor features.…”

“…Various fiber‐tracking algorithms are available, including deterministic diffusion tensor imaging, 24 probabilistic tractography, 25 and analytic approaches based on generalized q‐sampling imaging (GQI) 26 and q‐space diffeomorphic reconstruction (QSDR) 27 . Connectivity‐based clustering was previously used to reveal the intrinsic structure of the STN 28‐31 . Conversely, functional magnetic resonance imaging (fMRI) provides information concerning the localization of cortical and subcortical activations.…”

“…27 Connectivitybased clustering was previously used to reveal the intrinsic structure of the STN. [28][29][30][31] Conversely, functional magnetic resonance imaging (fMRI) provides information concerning the localization of cortical and subcortical activations. Based on the intrinsic complementary information embedded in tractography and fMRI techniques, some studies have proposed integration of both methods, focusing on the set of fibers encompassed in the fMRI-activated areas recruited during motor tasks.…”