Deep brain stimulation induced normalization of the human functional connectome in Parkinson’s disease

Horn, Andreas; Wenzel, Gregor; Irmen, Friederike; Huebl, Julius; Li, Ningfei; Neumann, Wolf‐Julian; Krause, Patricia; Böhner, Georg; Scheel, Michael; Kühn, Andrea A.

doi:10.1093/brain/awz239

Cited by 115 publications

(145 citation statements)

References 89 publications

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…Binary VTAs are based on specific thresholds that assume a certain type of axon diameter and orientation and do not grasp the anatomic complexity of the subcortex . To account for this general limitation of the VTA concept, we repeated all analyses using the unthresholded E‐field magnitude instead of the VTAs …”

Section: Methodsmentioning

confidence: 99%

Left Prefrontal Connectivity Links Subthalamic Stimulation with Depressive Symptoms

Irmen

Horn

Mosley

et al. 2020

Annals of Neurology

Self Cite

View full text Add to dashboard Cite

Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well-characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS, which have been reported to improve, worsen, or remain unchanged. Methods: Depressive symptoms before and after STN-DBS surgery were documented in 116 patients with PD from 3 DBS centers (Berlin, Queensland, and Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTAs) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as the test-set for which depressive symptom change was predicted. Results: Structural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity. Interpretation: Fibers connecting the electrode with left prefrontal areas were associated with worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms.

show abstract

Section: Methodsmentioning

confidence: 99%

Left Prefrontal Connectivity Links Subthalamic Stimulation with Depressive Symptoms

Irmen

Horn

Mosley

et al. 2020

Annals of Neurology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Within Lead-DBS, four structural group connectomes are currently available and can be chosen depending on the cohort of study. For the present work, a PD-specific connectome was used, which was obtained from 85 patients included in the Parkinson's Progression Markers Initiative connectome has been used in prior studies (Ewert et al, 2018a;Horn et al, 2019aHorn et al, , 2019bHorn et al, , 2017aHorn et al, , 2017cIrmen et al, 2019b) and processing details are reported elsewhere (Ewert et al, 2018a).…”

Section: Connectomic Analysesmentioning

confidence: 99%

“…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%

“…A different study applied Lead group to investigate a novel parietal surgical approach for ANT-DBS in epilepsy . In another recent study, resting-state functional MRI was acquired in PD patients while DBS was simultaneously switched on and off (Horn et al, 2019c). Here, DBS was able to shift functional connectivity profiles towards the ones observed in healthy controls.…”

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

confidence: 99%

See 1 more Smart Citation

Deep Brain Stimulation: Imaging on a group level

Treu

Strange

Oxenford

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Whole-brain structural connectivity profiles seeding from bilateral VTAs or E-Fields were estimated using a PD group connectome that is based on publicly available data (Parkinson's patients (n=90; age 61.38±10.42, 28 female) was priorly computed 24 and has been used in context of DBS multiple times before 2,26,27 . For each patient, fibers passing through the VTA or a non-zero voxel of the E-Field were selected from this normative connectome and projected onto a voxelized volume in standard space (1mm isotropic resolution) while keeping count of the fibers traversing each voxel.…”

Section: Volume Of Tissue Activated and Connectivity Estimationmentioning

confidence: 99%

Left prefrontal impact links subthalamic stimulation with depressive symptoms

Irmen

Horn

Mosley

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

AbstractObjectiveSubthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s Disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS which have been reported to improve, worsen or remain unchanged.MethodsDepressive symptoms before and after STN-DBS surgery were documented in 116 PD patients from three DBS centers (Berlin, Queensland, Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTA) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as test-set for which depressive symptom change was predicted.ResultsStructural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity.InterpretationFibers linking the STN electrode with left prefrontal areas predicted worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms.

show abstract

Deep brain stimulation induced normalization of the human functional connectome in Parkinson’s disease

Cited by 115 publications

References 89 publications

Left Prefrontal Connectivity Links Subthalamic Stimulation with Depressive Symptoms

Left Prefrontal Connectivity Links Subthalamic Stimulation with Depressive Symptoms

Deep Brain Stimulation: Imaging on a group level

Left prefrontal impact links subthalamic stimulation with depressive symptoms

Contact Info

Product

Resources

About