Structural connectivity of subthalamic nucleus stimulation for improving freezing of gait

Strelow, Joshua N.; Baldermann, Carlos; Dembek, Till A.; Jergas, Hannah; Petry‐Schmelzer, Jan Niklas; Schott, Frederik; Dafsari, Haidar S.; Moll, Christian K.E.; Hamel, Wolfgang; Gulberti, Alessandro; Visser-Vandewalle, V.; Fink, Gereon R.; Poetter‐Nerger, Monika; Barbe, Michael T.

doi:10.1101/2021.07.01.21259612

Cited by 5 publications

(4 citation statements)

References 60 publications

(5 reference statements)

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“…There are different hypotheses on STN DBS-induced gait impairment. A recent study using normative connectomes based on MR images of PD patients after DBS implantation revealed deterioration of FoG postoperatively if the ansa lenticularis of capsula interna fibers were unintentionally stimulated by DBS (Strelow et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Combined Subthalamic and Nigral Stimulation Modulates Temporal Gait Coordination and Cortical Gait-Network Activity in Parkinson’s Disease

Wagner

Schaper

Hamel

et al. 2022

Front. Hum. Neurosci.

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BackgroundFreezing of gait (FoG) is a disabling burden for Parkinson’s disease (PD) patients with poor response to conventional therapies. Combined deep brain stimulation of the subthalamic nucleus and substantia nigra (STN+SN DBS) moved into focus as a potential therapeutic option to treat the parkinsonian gait disorder and refractory FoG. The mechanisms of action of DBS within the cortical-subcortical-basal ganglia network on gait, particularly at the cortical level, remain unclear.MethodsTwelve patients with idiopathic PD and chronically-implanted DBS electrodes were assessed on their regular dopaminergic medication in a standardized stepping in place paradigm. Patients executed the task with DBS switched off (STIM OFF), conventional STN DBS and combined STN+SN DBS and were compared to healthy matched controls. Simultaneous high-density EEG and kinematic measurements were recorded during resting-state, effective stepping, and freezing episodes.ResultsClinically, STN+SN DBS was superior to conventional STN DBS in improving temporal stepping variability of the more affected leg. During resting-state and effective stepping, the cortical activity of PD patients in STIM OFF was characterized by excessive over-synchronization in the theta (4–8 Hz), alpha (9–13 Hz), and high-beta (21–30 Hz) band compared to healthy controls. Both active DBS settings similarly decreased resting-state alpha power and reduced pathologically enhanced high-beta activity during resting-state and effective stepping compared to STIM OFF. Freezing episodes during STN DBS and STN+SN DBS showed spectrally and spatially distinct cortical activity patterns when compared to effective stepping. During STN DBS, FoG was associated with an increase in cortical alpha and low-beta activity over central cortical areas, while with STN+SN DBS, an increase in high-beta was prominent over more frontal areas.ConclusionsSTN+SN DBS improved temporal aspects of parkinsonian gait impairment compared to conventional STN DBS and differentially affected cortical oscillatory patterns during regular locomotion and freezing suggesting a potential modulatory effect on dysfunctional cortical-subcortical communication in PD.

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Section: Discussionmentioning

confidence: 99%

Combined Subthalamic and Nigral Stimulation Modulates Temporal Gait Coordination and Cortical Gait-Network Activity in Parkinson’s Disease

Wagner

Schaper

Hamel

et al. 2022

Front. Hum. Neurosci.

Self Cite

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“…For example, the dorsal region above STN can be beneficial for the cardinal motor signs of PD including rigidity and bradykinesia 27 , but also helpful for suppressing stimulation-induced dyskinesias 19 . At the same time, stimulation of the lenticular fasciculus has been associated with worsening of gait parameters 28 and worsening of freezing of gait 29 .…”

Section: Discussionmentioning

confidence: 99%

Classification of electrically-evoked potentials in the parkinsonian subthalamic nucleus region

Rosing

Doyle

Brinda

et al. 2023

Sci Rep

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Electrically evoked compound action potentials (ECAPs) generated in the subthalamic nucleus (STN) contain features that may be useful for titrating deep brain stimulation (DBS) therapy for Parkinson’s disease. Delivering a strong therapeutic effect with DBS therapies, however, relies on selectively targeting neural pathways to avoid inducing side effects. In this study, we investigated the spatiotemporal features of ECAPs in and around the STN across parameter sweeps of stimulation current amplitude, pulse width, and electrode configuration, and used a linear classifier of ECAP responses to predict electrode location. Four non-human primates were implanted unilaterally with either a directional (n = 3) or non-directional (n = 1) DBS lead targeting the sensorimotor STN. ECAP responses were characterized by primary features (within 1.6 ms after a stimulus pulse) and secondary features (between 1.6 and 7.4 ms after a stimulus pulse). Using these features, a linear classifier was able to accurately differentiate electrodes within the STN versus dorsal to the STN in all four subjects. ECAP responses varied systematically with recording and stimulating electrode locations, which provides a subject-specific neuroanatomical basis for selecting electrode configurations in the treatment of Parkinson’s disease with DBS therapy.

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“…For example, the dorsal region above STN can be beneficial for the cardinal motor signs of PD including rigidity and bradykinesia [27], but also helpful for suppressing stimulation-induced dyskinesias [19]. At the same time, stimulation of the lenticular fasciculus has been associated with worsening of gait parameters [28] and worsening of freezing of gait [29]. This approach complements other techniques for identifying DBS lead position and offers some strong advantages.…”

Section: Discussionmentioning

confidence: 99%

Classification of electrically-evoked compound action potentials in the parkinsonian subthalamic nucleus region

Rosing

Doyle

Brinda

et al. 2022

Preprint

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BackgroundElectrically evoked compound action potentials (ECAPs) generated in the subthalamic nucleus (STN) contain features that may be useful for titrating deep brain stimulation (DBS) therapy for Parkinson’s disease. While previous studies have leveraged macroscale DBS electrodes, directional DBS leads with split-band contacts are thought to enable sampling ECAPs at a higher spatial resolution both within and adjacent to the STN.ObjectiveIn this study, we investigated the spatiotemporal features of ECAPs in and around the STN across parameter sweeps of stimulation current amplitude, pulse width, and electrode configuration.MethodsFour non-human primates were implanted unilaterally with either a directional (n=3) or non-directional (n=1) DBS lead targeting the sensorimotor STN. Resting-state ECAPs were recorded before and after rendering the subjects parkinsonian with MPTP treatments.ResultsECAP responses were characterized by primary features (within 1.6ms after a stimulus pulse) and secondary features (between 1.6-7.4ms after a stimulus pulse). Using these ECAP features, a linear classifier was able to differentiate electrodes within and dorsal to the STN in all four subjects.ConclusionECAP responses varied systematically with recording and stimulating electrode location, which may provide utility in efficiently defining DBS electrode configurations to target pathways in and around the STN for treating symptoms of Parkinson’s disease.

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Structural connectivity of subthalamic nucleus stimulation for improving freezing of gait

Cited by 5 publications

References 60 publications

Combined Subthalamic and Nigral Stimulation Modulates Temporal Gait Coordination and Cortical Gait-Network Activity in Parkinson’s Disease

Combined Subthalamic and Nigral Stimulation Modulates Temporal Gait Coordination and Cortical Gait-Network Activity in Parkinson’s Disease

Classification of electrically-evoked potentials in the parkinsonian subthalamic nucleus region

Classification of electrically-evoked compound action potentials in the parkinsonian subthalamic nucleus region

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