scholarly journals Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice

2021 ◽  
Author(s):  
Jonathan S Schor ◽  
Isabelle Gonzalez Montalvo ◽  
Perry W.E. Spratt ◽  
Rea J Brakaj ◽  
Jasmine A Stansil ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Electrophysiological Recording ◽  
Free Calcium ◽  
Motor Symptoms ◽  
Antidromic Activation ◽  
Stn Dbs ◽  
Deep Brain

Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinson Disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free calcium imaging to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of STN dynamics, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.

scholarly journals Syncope Associated with Subthalamic Nucleus Deep Brain Stimulation in a Patient with Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-2
Author(s):  
Dursun Aygun ◽  
Ersoy Kocabicak ◽  
Onur Yildiz ◽  
Musa Kazim Onar ◽  
Hatice Guz ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Early Period ◽  
Motor Symptoms ◽  
The Right ◽  
Stn Dbs ◽  
Deep Brain

In advanced Parkinson's disease (PD), deep brain stimulation (DBS) may be an alternative option for the treatment of motor symptoms. Side effects associated with subthalamic nucleus (STN) DBS in patients with PD are emerging as the most frequent sensory and motor symptoms. DBS-related syncope is reported as extremely rare. We wanted to discuss the mechanisms of syncope associated with STN DBS in a patient with Parkinson's disease.Case report.Sixty-three-year-old female patient is followed up with diagnosis of idiopathic Parkinson's disease for 6 years in our clinic. The patient has undergone STN DBS due to painful dystonia and drug resistant tremor. During the operation, when the left STN was stimulated at 5 milliampere (mAmp), the patient developed presyncopal symptoms. However, when the stimulation was stopped symptoms improved. During the early period after the operation, when the right STN was stimulated at 1.3 millivolts (mV), she developed the pre-yncopal symptoms and then syncope. Our case shows that STN DBS may lead to directly autonomic symptoms resulting in syncope during stimulation-on (stim-on).

scholarly journals Semi-automated application for estimating subthalamic nucleus boundaries and optimal target selection for deep brain stimulation implantation surgery

2019 ◽  
Vol 130 (4) ◽  
pp. 1224-1233 ◽  
Author(s):  
John A. Thompson ◽  
Salam Oukal ◽  
Hagai Bergman ◽  
Steven Ojemann ◽  
Adam O. Hebb ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Target Location ◽  
Target Selection ◽  
Brain Structures ◽  
Electrophysiological Recording ◽  
Reliable Interpretation ◽  
Stn Dbs ◽  
Deep Brain

OBJECTIVEDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has become standard care for the surgical treatment of Parkinson’s disease (PD). Reliable interpretation of microelectrode recording (MER) data, used to guide DBS implantation surgery, requires expert electrophysiological evaluation. Recent efforts have endeavored to use electrophysiological signals for automatic detection of relevant brain structures and optimal implant target location.The authors conducted an observational case-control study to evaluate a software package implemented on an electrophysiological recording system to provide online objective estimates for entry into and exit from the STN. In addition, they evaluated the accuracy of the software in selecting electrode track and depth for DBS implantation into STN, which relied on detecting changes in spectrum activity.METHODSData were retrospectively collected from 105 MER-guided STN-DBS surgeries (4 experienced neurosurgeons; 3 sites), in which estimates for entry into and exit from the STN, DBS track selection, and implant depth were compared post hoc between those determined by the software and those determined by the implanting neurosurgeon/neurophysiologist during surgery.RESULTSThis multicenter study revealed submillimetric agreement between surgeon/neurophysiologist and software for entry into and exit out of the STN as well as optimal DBS implant depth.CONCLUSIONSThe results of this study demonstrate that the software can reliably and accurately estimate entry into and exit from the STN and select the track corresponding to ultimate DBS implantation.

scholarly journals Thalamocortical Relay Fidelity Varies Across Subthalamic Nucleus Deep Brain Stimulation Protocols in a Data-Driven Computational Model

2008 ◽  
Vol 99 (3) ◽  
pp. 1477-1492 ◽  
Author(s):  
Yixin Guo ◽  
Jonathan E. Rubin ◽  
Cameron C. McIntyre ◽  
Jerrold L. Vitek ◽  
David Terman
Keyword(s):  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Computational Model ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Relay Cell ◽  
Heterogeneous Model ◽  
Normal Case ◽  
Stn Dbs ◽  
Deep Brain

The therapeutic effectiveness of deep brain stimulation (DBS) of the subthalamic nucleus (STN) may arise through its effects on inhibitory basal ganglia outputs, including those from the internal segment of the globus pallidus (GPi). Changes in GPi activity will impact its thalamic targets, representing a possible pathway for STN-DBS to modulate basal ganglia-thalamocortical processing. To study the effect of STN-DBS on thalamic activity, we examined thalamocortical (TC) relay cell responses to an excitatory input train under a variety of inhibitory signals, using a computational model. The inhibitory signals were obtained from single-unit GPi recordings from normal monkeys and from monkeys rendered parkinsonian through arterial 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. The parkinsonian GPi data were collected in the absence of STN-DBS, under sub-therapeutic STN-DBS, and under therapeutic STN-DBS. Our simulations show that inhibition from parkinsonian GPi activity recorded without DBS-compromised TC relay of excitatory inputs compared with the normal case, whereas TC relay fidelity improved significantly under inhibition from therapeutic, but not sub-therapeutic, STN-DBS GPi activity. In a heterogeneous model TC cell population, response failures to the same input occurred across multiple TC cells significantly more often without DBS than in the therapeutic DBS case and in the normal case. Inhibitory signals preceding successful TC relay were relatively constant, whereas those before failures changed more rapidly. Computationally generated inhibitory inputs yielded similar effects on TC relay. These results support the hypothesis that STN-DBS alters parkinsonian GPi activity in a way that may improve TC relay fidelity.

scholarly journals Weight Change After Subthalamic Nucleus Deep Brain Stimulation in Patients With Isolated Dystonia

2021 ◽  
Vol 12 ◽  
Author(s):  
Weibin He ◽  
Hongxia Li ◽  
Yijie Lai ◽  
Yunhao Wu ◽  
Yiwen Wu ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Rating Scale ◽  
The Body ◽  
Motor Symptoms ◽  
Motor Effects ◽  
Stn Dbs ◽  
Deep Brain

Purpose: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment method for advanced Parkinson's disease (PD) and isolated dystonia and provides marked improvement of major motor symptoms. In addition, non-motor effects have been reported including weight gain (WG) in patients with PD after STN-DBS. However, it is still unclear whether patients with isolated dystonia also experience WG.Methods: Data from 47 patients with isolated dystonia who underwent bilateral STN-DBS surgery between October 2012 and June 2019 were retrospectively collected. The severity of dystonia was assessed via the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Changes in the body mass index (BMI) and BFMDRS score were analyzed using paired Student's t-tests. Regression analysis was performed to identify factors that affected the BMI after surgery.Results: Postoperative WG was observed in 78.7% of patients. The percentage of overweight and obese patients increased from 25.5% (before STN-DBS) to 48.9% (at the last follow-up). The mean BMI and mean percentage change in BMI increased by 1.32 ± 1.83 kg/m2 (P < 0.001) and 6.28 ± 8.34%, respectively. BMI increased more in female than in male patients. At the last follow-up, BFMDRS movement and disability scores improved by 69.76 ± 33.23% and 65.66 ± 31.41%, respectively (both P < 0.001). The final regression model analysis revealed that sex and preoperative BMI alone were independently associated with BMI change (P < 0.05).Conclusions: STN-DBS is associated with postoperative WG with patients with isolated dystonia. WG is more prominent in female patients and is associated with preoperative weight but not with the efficacy of STN-DBS on motor symptoms.

scholarly journals Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation

2018 ◽  
Vol 120 (2) ◽  
pp. 662-680 ◽  
Author(s):  
Karthik Kumaravelu ◽  
Chintan S. Oza ◽  
Christina E. Behrend ◽  
Warren M. Grill
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Pyramidal Neurons ◽  
Antidromic Activation ◽  
Long Latency ◽  
Latency Response ◽  
Stn Dbs ◽  
Deep Brain

Parkinson’s disease is associated with altered neural activity in the motor cortex. Chronic high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in suppressing parkinsonian motor symptoms and modulates cortical activity. However, the anatomical pathways responsible for STN DBS-mediated cortical modulation remain unclear. Cortical evoked potentials (cEP) generated by STN DBS reflect the response of cortex to subcortical stimulation, and the goal of this study was to determine the neural origin of STN DBS-generated cEP using a two-step approach. First, we recorded cEP over ipsilateral primary motor cortex during different frequencies of STN DBS in awake healthy and unilateral 6-OHDA-lesioned parkinsonian rats. Second, we used a detailed, biophysically based model of the thalamocortical network to deconstruct the neural origin of the recorded cEP. The in vivo cEP included short (R1)-, intermediate (R2)-, and long-latency (R3) responses. Model-based cortical responses to simulated STN DBS matched remarkably well the in vivo responses. The short-latency response was generated by antidromic activation of layer 5 pyramidal neurons, whereas recurrent activation of layer 5 pyramidal neurons via excitatory axon collaterals reproduced the intermediate-latency response. The long-latency response was generated by polysynaptic activation of layer 2/3 pyramidal neurons via the cortico-thalamic-cortical pathway. Antidromic activation of the hyperdirect pathway and subsequent intracortical and cortico-thalamo-cortical synaptic interactions were sufficient to generate cortical potential evoked by STN DBS, and orthodromic activation through basal ganglia-thalamus-cortex pathways was not required. These results demonstrate the utility of cEP to determine the neural elements activated by STN DBS that might modulate cortical activity and contribute to the suppression of parkinsonian symptoms. NEW & NOTEWORTHY Subthalamic nucleus (STN) deep brain stimulation (DBS) is increasingly used to treat Parkinson’s disease (PD). Cortical potentials evoked by STN DBS in patients with PD exhibit consistent short-latency (1–3 ms), intermediate-latency (5–15 ms), and long-latency (18–25 ms) responses. The short-latency response occurs as a result of antidromic activation of the hyperdirect pathway comprising corticosubthalamic axons. However, the neural origins of intermediate- and long-latency responses remain elusive, and the dominant view is that these are produced through the orthodromic pathway (basal ganglia-thalamus-cortex). By combining in vivo electrophysiology with computational modeling, we demonstrate that antidromic activation of the cortico-thalamic-cortical pathway is sufficient to generate the intermediate- and long-latency cortical responses to STN DBS.

scholarly journals A Meta-Analysis of the Effect of Subthalamic Nucleus-Deep Brain Stimulation in Parkinson's Disease-Related Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Yu Diao ◽  
Yutong Bai ◽  
Tianqi Hu ◽  
Zixiao Yin ◽  
Huangguang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Meta Analysis ◽  
Motor Symptom ◽  
Stn Dbs ◽  
Deep Brain

Pain from Parkinson's disease (PD) is a non-motor symptom affecting the quality of life and has prevalence of 20–80%. However, it is unclear whether subthalamic nucleus deep brain stimulation (STN–DBS), a well-established treatment for PD, is effective forPD-related pain. Thus, the objective of this meta-analysis was to investigate the efficacy of STN-DBS on PD-related pain and explore how its duration affects the efficacy of STN-DBS. A systematic search was performed using PubMed, Embase, and the Cochrane Library. Nine studies included numerical rating scale (NRS), visual analog scale (VAS), or non-motor symptom scale (NMSS) scores at baseline and at the last follow-up visit and therefore met the inclusion criteria of the authors. These studies exhibited moderate- to high-quality evidence. Two reviewers conducted assessments for study eligibility, risk of bias, data extraction, and quality of evidence rating. Random effect meta-analysis revealed a significant change in PD-related pain as assessed by NMSS, NRS, and VAS (P <0.01). Analysis of the short and long follow-up subgroups indicated delayed improvement in PD-related pain. These findings (a) show the efficacy of STN-DBS on PD-related pain and provide higher-level evidence, and (b) implicate delayed improvement in PD-related pain, which may help programming doctors with supplement selecting target and programming.Systematic Review Registration: This study is registered in Open Science Framework (DOI: 10.17605/OSF.IO/DNM6K).

scholarly journals Resolution of tardive tremor after bilateral subthalamic nucleus deep brain stimulation placement

2020 ◽  
Vol 11 ◽  
pp. 444
Author(s):  
Samir Kashyap ◽  
Rita Ceponiene ◽  
Paras Savla ◽  
Jacob Bernstein ◽  
Hammad Ghanchi ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Orofacial Dyskinesia ◽  
Major Depressive ◽  
History Of ◽  
Stn Dbs ◽  
Common Manifestation ◽  
Tardive Syndrome ◽  
Deep Brain

Background: Tardive tremor (TT) is an underrecognized manifestation of tardive syndrome (TS). In our experience, TT is a rather common manifestation of TS, especially in a setting of treatment with aripiprazole, and is a frequent cause of referrals for the evaluation of idiopathic Parkinson disease. There are reports of successful treatment of tardive orofacial dyskinesia and dystonia with deep brain stimulation (DBS) using globus pallidus interna (GPi) as the primary target, but the literature on subthalamic nucleus (STN) DBS for tardive dyskinesia (TD) is lacking. To the best of our knowledge, there are no reports on DBS treatment of TT. Case Description: A 75-year-old right-handed female with the medical history of generalized anxiety disorder and major depressive disorder had been treated with thioridazine and citalopram from 1980 till 2010. Around 2008, she developed orolingual dyskinesia. She was started on tetrabenazine in June 2011. She continued to have tremors and developed Parkinsonian gait, both of which worsened overtime. She underwent DBS placement in the left STN in January 2017 with near-complete resolution of her tremors. She underwent right STN implantation in September 2017 with similar improvement in symptoms. Conclusion: While DBS-GPi is the preferred treatment in treating oral TD and dystonia, DBS-STN could be considered a safe and effective target in patients with predominating TT and/or tardive Parkinsonism. This patient saw a marked improvement in her symptoms after implantation of DBS electrodes, without significant relapse or recurrence in the years following implantation.

scholarly journals Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson’s Disease Deep Brain Stimulation

2021 ◽  
Vol 15 ◽  
Author(s):  
Lila H. Levinson ◽  
David J. Caldwell ◽  
Jeneva A. Cronin ◽  
Brady Houston ◽  
Steve I. Perlmutter ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Evoked Potentials ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Therapeutic Effects ◽  
Stn Dbs ◽  
Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson’s disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p < 0.05) and latency (p < 0.001), and the end, but not the start, EP magnitude has a significant relationship (p < 0.001, adjusted for random effects of subject) to ongoing high gamma (80–150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.

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