Sensorimotor subthalamic stimulation restores risk‐reward trade‐off in Parkinson's disease

Irmen, Friederike; Horn, Andreas; Meder, D.; Neumann, Wolf‐Julian; Plettig, Philip; Schneider, Gerd‐Helge; Siebner, Hartwig R.; Kühn, Andrea A.

doi:10.1002/mds.27576

Cited by 32 publications

(33 citation statements)

References 82 publications

(133 reference statements)

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“…Impulsivity scores on the Barratt Impulsiveness Scale (BIS-11, Patton and Stanford, 1995) were measured in six studies (total of 165 patients) comparing scores either between DBS On and Off conditions (Torta et al, 2012;Seinstra et al, 2016), or between DBS On and PD-patients On medication or healthy controls (Hälbig et al, 2009;Evens et al, 2015;Hagelweide et al, 2018;Irmen et al, 2019). One study reported significantly worse impulsivity scores in a DBS-group compared to healthy controls (Hälbig et al, 2009).…”

Section: Clinical Scalesmentioning

confidence: 99%

Impulsivity and Compulsivity After Subthalamic Deep Brain Stimulation for Parkinson’s Disease

Scherrer

Smith

Gowatsky

et al. 2020

Front. Behav. Neurosci.

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Impulsivity and compulsivity are prominent non-motor problems in Parkinson's disease (PD). Despite 20 years of research, there is still an ongoing debate as to whether subthalamic deep brain stimulation (STN DBS) for PD exacerbates or improves these symptoms. Here, we review how STN DBS affects clinical symptoms and neurocognitive aspects of impulsivity and compulsivity. When comparing patients post-to pre-surgery, in the majority of studies STN DBS for PD is associated with a decrease in clinically diagnosed impulse-control disorders and disorders of compulsivity. To avoid confounds, such as post-surgical decreases in dopaminergic medication doses, comparisons can also be made between DBS "On" versus "Off" conditions. These experimentally assayed effects of STN DBS with respect to neurocognitive aspects of impulsivity and compulsivity are more mixed. STN DBS improves behavioral flexibility without impairing negative feedback learning, delay discounting, or inhibitory control, as long as stimulation is restricted to the dorsal STN. However, STN DBS may drive impulsive actions when a subject is faced with competing choices. We discuss how motivated responses may be either enhanced or impaired by STN DBS depending on engagement of dorsal or ventral STN-mediated circuits. Future studies should combine structural and functional circuit measures with behavioral testing in PD patients on and off medication and stimulation. A more sophisticated understanding of how to modulate corticostriatal-thalamo-cortical loops will increase the likelihood that these circuit manipulation techniques can successfully be applied to a wider range of neuropsychiatric disorders.

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Section: Clinical Scalesmentioning

confidence: 99%

Impulsivity and Compulsivity After Subthalamic Deep Brain Stimulation for Parkinson’s Disease

Scherrer

Smith

Gowatsky

et al. 2020

Front. Behav. Neurosci.

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“…Although STN-sensorimotor-cortex connectivity has primarily been associated with improvements in motor performances a recent study showed mood improvement actually relies on DBS of the motor STN 47 . Similarly, motor STN stimulation can normalize cognitive performance 48 . This implicates the overlapping presence of affective/associative and motor processing neurons in the STN motor segment 4 and suggests that retuning the motor loop may improve non-motor features as well.…”

Section: Discussionmentioning

confidence: 99%

“…Two studies have validated the pipeline using electrophysiological recordings 52,53 and others have demonstrated that results are capable of explaining clinical improvements across patients, DBS centers and cohorts 2,3,48,54,55 . Still, residual errors of electrode reconstructions cannot be excluded.…”

Section: Stn-dbsmentioning

confidence: 99%

Left prefrontal impact links subthalamic stimulation with depressive symptoms

Irmen

Horn

Mosley

et al. 2019

Preprint

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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.

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“…De Almeida showed that functional connectivity between STN-DBS electrodes and a specific site in the ipsilateral cerebellum was associated with partly restoring motor learning in PD patients (de Almeida Marcelino et al, 2019). Finally, focusing on localized instead of connectivity-mediated effects, Irmen et al showed that modulating specific subregions of the STN could restore risk-taking behavior to a level observed in healthy controls (Irmen et al, 2019a).…”

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

confidence: 99%

“…The application is continuously extended to other indications and targets (for a review see Lozano and Lipsman, 2013). Aside from its clinical value, DBS opens an invaluable window to the human brain and it is increasingly adopted to probe causal relationships between stimulated targets and certain behavioral effects, such as risk control (Irmen et al, 2019a;Nachev et al, 2015), movement speed (W.-J. , memory learning (de Almeida Marcelino et al, 2019) or verbal fluency (Ehlen et al, 2017;Mikos et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Deep Brain Stimulation: Imaging on a group level

Treu

Strange

Oxenford

et al. 2020

Preprint

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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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Sensorimotor subthalamic stimulation restores risk‐reward trade‐off in Parkinson's disease

Cited by 32 publications

References 82 publications

Impulsivity and Compulsivity After Subthalamic Deep Brain Stimulation for Parkinson’s Disease

Impulsivity and Compulsivity After Subthalamic Deep Brain Stimulation for Parkinson’s Disease

Left prefrontal impact links subthalamic stimulation with depressive symptoms

Deep Brain Stimulation: Imaging on a group level

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