scholarly journals Thalamic projections to the subthalamic nucleus contribute to movement initiation and rescue of parkinsonian symptoms

2021 ◽  
Vol 7 (6) ◽  
pp. eabe9192
Author(s):  
Glenn D. R. Watson ◽  
Ryan N. Hughes ◽  
Elijah A. Petter ◽  
Isabella P. Fallon ◽  
Namsoo Kim ◽  
...  
Keyword(s):  
Subthalamic Nucleus ◽  
Dopamine Depletion ◽  
Movement Initiation ◽  
Thalamic Projections ◽  
Subcortical Nuclei ◽  
Stn Dbs ◽  
Shed Light ◽  
Major Target ◽  
Deep Brain ◽  
Action Initiation

The parafascicular nucleus (Pf) of the thalamus provides major projections to the basal ganglia, a set of subcortical nuclei involved in action initiation. Here, we show that Pf projections to the subthalamic nucleus (STN), but not to the striatum, are responsible for movement initiation. Because the STN is a major target of deep brain stimulation treatments for Parkinson’s disease, we tested the effect of selective stimulation of Pf-STN projections in a mouse model of PD. Bilateral dopamine depletion with 6-OHDA created complete akinesia in mice, but Pf-STN stimulation immediately and markedly restored a variety of natural behaviors. Our results therefore revealed a functionally novel neural pathway for the initiation of movements that can be recruited to rescue movement deficits after dopamine depletion. They not only shed light on the clinical efficacy of conventional STN DBS but also suggest more selective and improved stimulation strategies for the treatment of parkinsonian symptoms.

Identification of Somatotopic Organization and Optimal Stimulation Site Within the Subthalamic Nucleus for Parkinson's Disease

2018 ◽  
Vol 17 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Tatsuya Sasaki ◽  
Ken Kuwahara ◽  
Ittetsu Kin ◽  
Mihoko Okazaki ◽  
Susumu Sasada ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Subthalamic Nucleus ◽  
Lower Limbs ◽  
Somatotopic Organization ◽  
First Contact ◽  
Upper Third ◽  
Stn Dbs ◽  
Passive Movements ◽  
Common Target ◽  
Deep Brain

Abstract BACKGROUND Details of the somatotopy within the subthalamic nucleus (STN) are still poorly understood; however, the STN is a common target of deep brain stimulation (DBS) for Parkinson disease. OBJECTIVE To examine somatotopic organization within the STN and identify optimal stimulation sites from 77 surgical cases with microelectrode recording. METHODS STN-DBS was performed for 77 patients with Parkinson disease between 2010 and 2014. We performed passive movements of each joint and captured single neuronal activities to identify movement-related cells (MRCs). The sites of MRCs and active contacts were determined by measuring their distances from the first contact of DBS electrode. Their positional correlations were directly and indirectly analyzed. RESULTS The number of obtained MRCs was 264, of which 151 responded to multiple joints. The average x-, y-, and z-coordinates of the cells of the upper and lower limbs from the midcommisural point were 13.1 ± 1.1 and 12.7 ± 1.2, 0.22 ± 1.3 and −0.45 ± 1.5, and −2.5 ± 1.1 and −3.0 ± 1.4 mm, respectively. Most MRCs were distributed in the upper third of the STN, in its superior, lateral, and posterior regions, along the DBS electrode routes. Active contacts were observed to lie slightly inferior, medial, and posterior to the average MRC position. CONCLUSION Somatotopic organization of the STN was easier to observe in the present study than in previous studies. Optimal stimulation sites were located inferior, medial, and posterior to the average MRC location. The sites may correspond to associative or motor parts through which fibers from the supplementary motor area pass.

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.

Comparison of Subthalamic Nucleus and Globus Pallidus Deep Brain Stimulation in Parkinson’s Disease: A Systematic Review

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Azari H ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Adverse Effects ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Stn Dbs ◽  
Deep Brain

Background: Deep Brain Stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson’s Disease (PD). The two most common sites for DBS are the Subthalamic Nucleus (STN) and Globus Pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared. Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3) at least five participants in each group; (4) conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS III scores. Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.

Stimulation-Induced Dyskinesia, Interleaving Settings, and Management of Subthalamic Nucleus Deep Brain Stimulation in DYT1 Dystonia

2020 ◽  
pp. 201-204
Author(s):  
Kyle T. Mitchell ◽  
Kristen A. Dodenhoff ◽  
Philip A. Starr ◽  
Jill L. Ostrem
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Complete Resolution ◽  
Symptomatic Improvement ◽  
Zona Incerta ◽  
Dyt1 Dystonia ◽  
Primary Dystonia ◽  
Stn Dbs ◽  
Deep Brain

DYT1 dystonia is a primary dystonia with potential for significant symptomatic improvement after bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi). GPi is the historical target of choice for this disease. This chapter presents a case of an adolescent with disabling generalized DYT1 dystonia who underwent bilateral subthalamic nucleus (STN) DBS as part of a prospective clinical trial. While limb and cervical dystonia dramatically improved with DBS, programming was limited by stimulation-induced bilateral limb dyskinesia, including in the left arm, which was previously unaffected by dystonia. After years of evolving symptoms and complex programming, bilateral interleaved settings using both a contact in motor STN and the most dorsal DBS contact in the zona incerta resulted in sustained, near-complete resolution of dystonia without side effects. This case illustrates the use of the STN as an effective DBS target for primary dystonia, although complex programming was necessary to mitigate stimulation-induced dyskinesia.

scholarly journals Bilateral Subthalamic Nucleus Deep Brain Stimulation in Elderly Patients With Parkinson Disease: A Case-Control Study

2020 ◽  
Vol 19 (3) ◽  
pp. 234-240
Author(s):  
Kyle T Mitchell ◽  
John R Younce ◽  
Scott A Norris ◽  
Samer D Tabbal ◽  
Joshua L Dowling ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Intracerebral Hemorrhages ◽  
Disease Rating ◽  
Equivalent Reduction ◽  
Stn Dbs ◽  
Deep Brain

Abstract BACKGROUND Subthalamic nucleus deep brain stimulation (STN DBS) is an effective adjunctive therapy for Parkinson disease. Studies have shown improvement of motor function but often exclude patients older than 75 yr. OBJECTIVE To determine the safety and effectiveness of STN DBS in patients 75 yr and older. METHODS A total of 104 patients (52 patients >75 yr old, 52 patients <75 yr old) with STN DBS were paired and retrospectively analyzed. The primary outcome was change in Unified Parkinson Disease Rating Scale (UPDRS) subscale III at 1 yr postoperatively, OFF medication. Secondary outcomes were changes in UPDRS I, II, and IV subscales and levodopa equivalents. Complications and all-cause mortality were assessed at 30 d and 1 yr. RESULTS Both cohorts had significant improvements in UPDRS III at 6 mo and 1 yr with no difference between cohorts. Change in UPDRS III was noninferior to the younger cohort. The cohorts had similar worsening in UPDRS I at 1 yr, no change in UPDRS II, similar improvement in UPDRS IV, and similar levodopa equivalent reduction. There were similar numbers of postoperative intracerebral hemorrhages (2/52 in each cohort, more severe in the older cohort) and surgical complications (4/52 in each cohort), and mortality in the older cohort was similar to an additional matched cohort not receiving DBS. CONCLUSION STN DBS provides substantial motor benefit and reduction in levodopa equivalents with a low rate of complications in older patients, which is also noninferior to the benefit in younger patients. STN DBS remains an effective therapy for those over 75 yr.

scholarly journals Effects of Deep Brain Stimulation of the Subthalamic Nucleus Settings on Voice Quality, Intensity, and Prosody in Parkinson’s Disease: Preliminary Evidence for Speech Optimization

2019 ◽  
Vol 46 (3) ◽  
pp. 287-294 ◽  
Author(s):  
Anita Abeyesekera ◽  
Scott Adams ◽  
Cynthia Mancinelli ◽  
Thea Knowles ◽  
Greydon Gilmore ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Pulse Width ◽  
Voice Quality ◽  
Preliminary Evidence ◽  
Clinical Settings ◽  
Stn Dbs ◽  
Deep Brain ◽  
Stimulation Of

ABSTRACT:Objective: To systematically evaluate how different deep brain stimulation of the subthalamic nucleus (STN-DBS) amplitude, frequency, and pulse-width electrical parameter settings impact speech intensity, voice quality, and prosody of speech in Parkinson’s disease (PD). Methods: Ten individuals with PD receiving bilateral STN-DBS treatments were seen for three baseline and five treatment visits. The five treatment visits involved an examination of the standard clinical settings as well as manipulation of different combinations of frequency (low, mid, and high), pulse width (low, mid, and high), and voltage (low, mid, and high) of stimulation. Measures of speech intensity, jitter, shimmer, harmonics–noise ratio, semitone standard deviation, and listener ratings of voice quality and prosody were obtained for each STN-DBS manipulation. Results: The combinations of lower frequency, lower pulse width, and higher voltage settings were associated with improved speech outcomes compared to the current standard clinical settings. In addition, decreased total electrical energy delivered to the STN appears to be associated with speech improvements. Conclusions: This study provides preliminary evidence that STN-DBS may be optimized for Parkinson-related problems with voice quality, speech intensity, and prosody of speech.

scholarly journals Systematic review of neuropsychological instruments used in subthalamic nucleus deep brain stimulation in Parkinson´s disease patients

2019 ◽  
Vol 13 (2) ◽  
pp. 162-171 ◽  
Author(s):  
Eduarda Naidel Barboza e Barbosa ◽  
Helenice Charchat-Fichman
Keyword(s):  
Systematic Review ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Motor Deficits ◽  
Evaluation Protocol ◽  
Neuropsychological Assessments ◽  
Stn Dbs ◽  
Deep Brain

ABSTRACT. In addition to drug treatment, surgical intervention represents an alternative to PD patients with motor deficits. The most common intervention is subthalamic nucleus deep brain stimulation (STN-DBS). It is extremely important to perform a neuropsychological assessment in patients with STN-DBS, not only to identify losses related to the disease, but also to compare influence on cognition both pre and postoperatively. Objective: the objective of this systematic review was to investigate the instruments frequently used in studies related to STN-DBS in PD patients. Methods: articles were retrieved from Medline/Pubmed databases published in the 2007-2017 period using PRISMA criteria. Results: after analyzing 27 articles, the absence of a specific evaluation protocol for PD with STN-DBS was evident. Conclusion: non-motor symptoms are not given due importance in neuropsychological assessments. It is crucial to acknowledge that these symptoms have a major impact on the quality of life of patients. Greater engagement in assessing these aspects is required, in order to bridge the gaps in research.

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