Dataset Information

Subthalamic Deep Brain Stimulation Lead Asymmetry Impacts the Parkinsonian Gait Disorder.

ABSTRACT:

Background

The preferable position of Deep Brain Stimulation (DBS) electrodes is proposed to be located in the dorsolateral subthalamic nucleus (STN) to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown.

Methods

In this single-center, retrospective analyses, 66 Parkinson's disease (PD) patients (24 female, age 63 ± 7 years) were assessed pre- and post-operatively (8.45 ± 4.2 months after surgery) by using MDS-UPDRS, freezing of gait (FoG) score, Giladi's gait and falls questionnaire and Berg balance scale. The clinical outcome was related to the DBS electrode coordinates in x, y, z plane as revealed by image-based reconstruction (SureTune™). Binomial generalized linear mixed models with fixed-effect variables electrode asymmetry, parkinsonian subtype, medication, age class and clinical DBS induced changes were analyzed.

Results

Subthalamic nucleus-deep brain stimulation improved all motor, balance and FoG scores in MED OFF condition, however there were heterogeneous results in MED ON condition. DBS electrode reconstructed coordinates impacted the responsiveness of axial symptoms. FoG and balance responders showed slightly more medially located STN electrode coordinates and less medio-lateral asymmetry of the electrode reconstructed coordinates across hemispheres compared to non-responders.

Conclusion

Deep brain stimulation electrode reconstructed coordinates, particularly electrode asymmetry on the medio-lateral axis affected the post-operative responsiveness of balance and FoG symptoms in PD patients.

SUBMITTER: Schott FP

PROVIDER: S-EPMC8995434 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Subthalamic Deep Brain Stimulation Lead Asymmetry Impacts the Parkinsonian Gait Disorder.

Schott Frederik P FP Gulberti Alessandro A Pinnschmidt Hans O HO Gerloff Christian C Moll Christian K E CKE Schaper Miriam M Koeppen Johannes A JA Hamel Wolfgang W Pötter-Nerger Monika M

Frontiers in human neuroscience 20220328

<h4>Background</h4>The preferable position of Deep Brain Stimulation (DBS) electrodes is proposed to be located in the dorsolateral subthalamic nucleus (STN) to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown.<h4>Methods</h4>In this single-center, retrospective analyses, 66 Parkinson's disease (PD) patients (24 female, age 63 ± 7 years) were assessed pre- and post-operatively (8.45 ± 4.2 months after surg ...[more]

PMID: 35418844

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Project description:Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process.

Project description:The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task. Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson's disease (disease duration 10 ± 3 years, Hoehn and Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated in the study. After 10 s resting, stepping at self-paced speed for 35 s was followed by short intervals of stepping in response to random 'start' and 'stop' cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional 'start' and 'stop' cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern and oscillatory activity. Subthalamic nucleus and substantia nigra neurons responded to different aspects of the stepping task. Of the subthalamic nucleus neurons, 24% exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regularization and a drop of beta oscillations during the stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity. This study shows for the first time specific, task-related subthalamic nucleus and substantia nigra single-unit activity changes during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disrupted information transfer within the gait network, resulting in freezing of gait.

Project description:ObjectiveCurrent understanding of the neuromodulatory effects of deep brain stimulation (DBS) on large-scale brain networks remains elusive, largely due to the lack of techniques that can reveal DBS-induced activity at the whole-brain level. Using a novel 3T magnetic resonance imaging (MRI)-compatible stimulator, we investigated whole-brain effects of subthalamic nucleus (STN) stimulation in patients with Parkinson disease.MethodsFourteen patients received STN-DBS treatment and participated in a block-design functional MRI (fMRI) experiment, wherein stimulations were delivered during "ON" blocks interleaved with "OFF" blocks. fMRI responses to low-frequency (60Hz) and high-frequency(130Hz) STN-DBS were measured 1, 3, 6, and 12 months postsurgery. To ensure reliability, multiple runs (48 minutes) of fMRI data were acquired at each postsurgical visit. Presurgical resting-state fMRI (30 minutes) data were also acquired.ResultsTwo neurocircuits showed highly replicable, but distinct responses to STN-DBS. A circuit involving the globus pallidus internus (GPi), thalamus, and deep cerebellar nuclei was significantly activated, whereas another circuit involving the primary motor cortex (M1), putamen, and cerebellum showed DBS-induced deactivation. These 2 circuits were dissociable in terms of their DBS-induced responses and resting-state functional connectivity. The GPi circuit was frequency-dependent, selectively responding to high-frequency stimulation, whereas the M1 circuit was responsive in a time-dependent manner, showing enhanced deactivation over time. Finally, activation of the GPi circuit was associated with overall motor improvement, whereas M1 circuit deactivation was related to reduced bradykinesia.InterpretationConcurrent DBS-fMRI using 3T revealed 2 distinct circuits that responded differentially to STN-DBS and were related to divergent symptoms, a finding that may provide novel insights into the neural mechanisms underlying DBS. ANN NEUROL 2020;88:1178-1193.

Dataset Information

Subthalamic Deep Brain Stimulation Lead Asymmetry Impacts the Parkinsonian Gait Disorder.

Background

Methods

Results

Conclusion

Publications

Subthalamic Deep Brain Stimulation Lead Asymmetry Impacts the Parkinsonian Gait Disorder.

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