Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor

Al‐Fatly, Bassam; Ewert, Siobhan; Kübler, Dorothee; Horn, Andreas; Horn, Andreas; Kühn, Andrea A.

doi:10.1093/brain/awz236

Cited by 134 publications

(136 citation statements)

References 93 publications

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“…Similarly, connectivity from electrodes to M1 was associated with tremor improvement in Essential Tremor 68 .…”

Section: Toward Symptom-specific Circuitopathiesmentioning

confidence: 89%

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

Baldermann

Kibleur

et al. 2019

Preprint

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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. Obsessivecompulsive 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 threedimensionally defined in stereotactic standard space and will be made openly available.

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“…Similarly, connectivity from electrodes to M1 was associated with tremor improvement in Essential Tremor 68 .…”

Section: Toward Symptom-specific Circuitopathiesmentioning

confidence: 89%

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

Baldermann

Kibleur

et al. 2019

Preprint

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“…A possible (but unknown) explanation for the variability in outcome would be that responders had optimal lead placement while non-responders did not. By investigating their differential electrode placements, one could possibly find relationships between clinical outcome and modulated anatomical space and brain connectivity measures, as was shown for other diseases (Al-Fatly et al, 2019;Baldermann et al, 2019;Dembek et al, 2019a;Horn, 2019;Reich et al, 2019).…”

Section: Introductionmentioning

confidence: 90%

“…Examples that utilized group statistics span across different diseases like PD (Bouthour et al, 2019;Horn et al, 2019c), essential tremor (Al-Fatly et al, 2019;Kroneberg et al, 2019), Dystonia (Neumann et al, 2017), Meige syndrome (Yao et al, 2019), OCD Huys et al, 2019), epilepsy (Middlebrooks et al, 2018;Wang et al, 2019), Tourette's Syndrome (W. J. or refractory thalamic pain syndrome (Levi et al, 2019). Using Lead-DBS, a sweet spot for STN-DBS in PD was defined and used to predict improvement of motor symptoms in out-of-sample data (Dembek et al, 2019a).…”

Section: A Tool To Shift Dbs Imaging Research To a Group Levelmentioning

confidence: 99%

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Deep Brain Stimulation: Imaging on a group level

Treu

Strange

Oxenford

et al. 2020

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Highlights We present a novel toolbox to carry out DBS imaging analyses on a grouplevel  Group electrodes are visualized in 2D and 3D and related to clinical regressors  A favorable target and connectivity profiles for the treatment of PD are validated Abstract 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 Parkinson's 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 bundlewhich structurally resembles the hyperdirect pathwaythat 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.

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“…(Fiechter et al, 338 2017;Herrington et al, 2016). This suggests that direct targeting of the white matter, in other words 339 connection-based targeting, may be central to efficacy, which has increasingly been acknowledged for 340 essential tremor(Akram et al, 2018;Al-Fatly et al, 2019) and other disorders(Horn et al, 2017). Our 341 approach using T1 mapping for visualizing local WM tracts might be considered divergent from recent 342 approaches using diffusion-based imaging.…”

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confidence: 99%

Direct visualization and characterization of the human zona incerta and surrounding structures

Lau

Xiao

Haast

et al. 2020

Preprint

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The zona incerta (ZI) is a small deep brain region first identified in the 19th century, yet direct in 18 vivo visualization and characterization has remained elusive. Noninvasive detection is critical to further our 19 understanding of this widely connected but poorly understood region and could contribute to the 20 development and optimization of neuromodulatory therapies. We demonstrate that high resolution 21 longitudinal (T1) relaxometry measurements at high magnetic field strength can be used to delineate the ZI 22 from surrounding white matter structures (fasciculus cerebellothalamicus, fields of Forel, and medial 23 lemniscus). We derived estimates of the morphology, location, and tissue characteristics of the ZI region, 24 confirming observations only previously possible through histological evaluation, that this region is not just 25 a space between structures but contains distinct entities that should be considered separately. Our findings 26 pave the way for increasingly detailed in vivo study and provide a structural foundation for precise functional 27 investigation. 28 Nieuwenhuys et al., 2007). The rostral ZI (rZI) is continuous with the reticular nucleus of the thalamus 46 laterally and with the lateral hypothalamus anteromedially. The caudal ZI (cZI) is laterally bounded by the 47

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Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor

Cited by 134 publications

References 93 publications

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

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

Deep Brain Stimulation: Imaging on a group level

Direct visualization and characterization of the human zona incerta and surrounding structures

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