Treu, S. | bioRxiv Science

bioRxiv2020

Deep Brain Stimulation: Imaging on a group level

Deep Brain Stimulation (DBS) is an established treatment option for movement disorders and is investigated to treat a growing number of other brain disorders. It has been shown that DBS effects are highly dependent on exact electrode placement, which is especially important when probing novel indications or stereotactic targets. Thus, considering precise electrode placement is crucial when investigating efficacy of DBS targets. To measure clinical improvement as a function of electrode placement, neuroscientific methodology and specialized software tools are needed. Such tools should have the goal to make electrode placement comparable across patients and DBS centers, and include statistical analysis options to validate and define optimal targets. Moreover, to allow for comparability across different research sites, these need to be performed within an algorithmically and anatomically standardized and openly available group space. With the publication of Lead-DBS software in 2014, an open-source tool was introduced that allowed for precise electrode reconstructions based on pre- and postoperative neuroimaging data. Here, we introduce Lead Group, implemented within the Lead-DBS environment and specifically designed to meet aforementioned demands. In the present article, we showcase the various processing streams of Lead Group in a retrospective cohort of 51 patients suffering from Parkinsons disease, who were implanted with DBS electrodes to the subthalamic nucleus (STN). Specifically, we demonstrate various ways to visualize placement of all electrodes in the group and map clinical improvement values to subcortical space. We do so by using active coordinates and volumes of tissue activated, showing converging evidence of an optimal DBS target in the dorsolateral STN. Second, we relate DBS outcome to the impact of each electrode on local structures by measuring overlap of stimulation volumes with the STN. Finally, we explore the software functions for connectomic mapping, which may be used to relate DBS outcomes to connectivity estimates with remote brain areas. We isolate a specific fiber bundle - which structurally resembles the hyperdirect pathway - that is associated with good clinical outcome in the cohort. The manuscript is accompanied by a walkthrough tutorial through which users are able to reproduce all main results presented in the present manuscript. All data and code needed to reproduce results are openly available. HighlightsO_LIWe present a novel toolbox to carry out DBS imaging analyses on a group-level C_LIO_LIGroup electrodes are visualized in 2D and 3D and related to clinical regressors C_LIO_LIA favorable target and connectivity profiles for the treatment of PD are validated C_LI

neuroscience↗

bioRxiv2019

Toward a unified connectomic target for deep brain stimulation in obsessive-compulsive disorder

Multiple surgical targets have been proposed for treating obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS). However, different targets may modulate the same neural network responsible for clinical improvement. Here we analyzed data from four cohorts of OCD patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens (NAcc) or the subthalamic nucleus (STN). Fiber tracts that were predominantly connected to electrodes in good or poor DBS responders were isolated from a normative structural connectome and assigned a predictive value. Strikingly, the same fiber bundle was related to treatment response when independently analyzing two large training cohorts that targeted either ALIC or STN. This discriminative tract is a subsection of the ALIC and connects frontal regions (such as the dorsal anterior cingulate, dACC, and ventral prefrontal, vlPFC, cortices to the STN). When informing the tract solely based on one cohort (e.g. ALIC), clinical improvements in the other (e.g. STN) could be significantly predicted, and vice versa. Finally, clinical improvements of eight patients from a third center with electrodes in the NAcc and six patients from a fourth center in which electrodes had been implanted in both STN and ALIC were significantly predicted based on this novel tract-based DBS target. Results suggest a functional role of a limbic hyperdirect pathway that projects from dACC and vlPFC to anteriomedial STN. Obsessive-compulsive symptoms seem to be tractable by modulating the specific bundle isolated here. Our results show that connectivity-derived improvement models can inform clinical improvement across DBS targets, surgeons and centers. The identified tract is now three-dimensionally defined in stereotactic standard space and will be made openly available.

neuroscience↗