scholarly journals Purkinje cell misfiring generates high-amplitude action tremors that are corrected by cerebellar deep brain stimulation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Amanda M Brown ◽  
Joshua J White ◽  
Meike E van der Heijden ◽  
Joy Zhou ◽  
Tao Lin ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Purkinje Cell ◽  
Brain Stimulation ◽  
Cell Activity ◽  
High Amplitude ◽  
Cerebellar Nuclei ◽  
Brain Regions ◽  
Body Parts ◽  
Neural Signals ◽  
Deep Brain

Tremor is currently ranked as the most common movement disorder. The brain regions and neural signals that initiate the debilitating shakiness of different body parts remain unclear. Here, we found that genetically silencing cerebellar Purkinje cell output blocked tremor in mice that were given the tremorgenic drug harmaline. We show in awake behaving mice that the onset of tremor is coincident with rhythmic Purkinje cell firing, which alters the activity of their target cerebellar nuclei cells. We mimic the tremorgenic action of the drug with optogenetics and present evidence that highly patterned Purkinje cell activity drives a powerful tremor in otherwise normal mice. Modulating the altered activity with deep brain stimulation directed to the Purkinje cell output in the cerebellar nuclei reduced tremor in freely moving mice. Together, the data implicate Purkinje cell connectivity as a neural substrate for tremor and a gateway for signals that mediate the disease.

scholarly journals Cerebellar Purkinje cell microcircuits are essential for tremor

2019 ◽  
Author(s):  
Amanda M Brown ◽  
Joshua J White ◽  
Meike E van der Heijden ◽  
Tao Lin ◽  
Roy V Sillitoe
Keyword(s):  
Purkinje Cell ◽  
Cell Activity ◽  
Cerebellar Nuclei ◽  
Brain Regions ◽  
Cerebellar Purkinje Cell ◽  
Body Parts ◽  
Neural Signals ◽  
Neural Substrate ◽  
Cell Firing ◽  
The Brain

AbstractTremor is currently ranked as the most common movement disorder. The brain regions and neural signals that initiate the debilitating shakiness of different body parts remain unclear. Here, we found that genetically silencing cerebellar Purkinje cell activity blocked tremor in mice that were given the tremorgenic drug harmaline. We show in awake behaving mice that the onset of tremor is coincident with rhythmic Purkinje cell firing, which alters the output of their target cerebellar nuclei cells. We mimic the tremorgenic action of the drug with optogenetics and present evidence that highly patterned Purkinje cell activity drives a powerful tremor in otherwise normal mice. Modulating the altered activity with deep brain stimulation directed to the Purkinje cell output in the cerebellar nuclei reduced tremor in freely moving mice. Together, the data implicate Purkinje cell connectivity as a neural substrate for tremor and a gateway for signals that mediate the disease.

scholarly journals Speech Function Following Deep Brain Stimulation of the Caudal Zona Incerta: Effects of Habitual and High-Amplitude Stimulation

2021 ◽  
pp. 1-13
Author(s):  
Linda Sandström ◽  
Ellika Schalling ◽  
Fredrik Karlsson ◽  
Patric Blomstedt ◽  
Lena Hartelius
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Amplitude ◽  
Nonparametric Tests ◽  
Zona Incerta ◽  
Maximal Amplitude ◽  
Significant Group ◽  
Preliminary Study ◽  
Deep Brain ◽  
Stimulation Of

Purpose Deep brain stimulation (DBS) is often successful in alleviating motor symptoms of essential tremor (ET); however, DBS may also induce adverse speech effects. The caudal zona incerta (cZi) is a promising DBS target for tremor, but less is known about the consequences of cZi DBS for speech. This preliminary study examined how habitual cZi DBS and cZi stimulation at high amplitudes may affect speech function in persons with ET. Method Fourteen participants with ET were evaluated: off stimulation, on habitual cZi DBS, and with unilateral cZi stimulation at increasing stimulation amplitudes. At each stimulation condition, the participants read three 16-word sentences. Two speech-language pathologists made audio-perceptual consensus ratings of overall speech function, articulation, and voice using a visual sort and rate method. Rated functions when off stimulation, on habitual cZi DBS, and at maximal-amplitude stimulation were compared using Friedman nonparametric tests. For participants with bilateral habitual DBS ( n = 5), the effects of bilateral and unilateral stimulation were described in qualitative terms. Results Habitual cZi DBS had no significant group-level effect on any of the investigated speech parameters. Maximal-amplitude stimulation had a small but significant negative effect on articulation. Participants with reduced articulatory precision ( n = 9) had more medially placed electrodes than the nonaffected group ( n = 5). Bilateral and unilateral left stimulation had comparable effects on speech. Conclusions Findings from this preliminary study of cZi DBS indicate that speech is generally not affected by stimulation at habitual levels. High-amplitude cZi stimulation may, however, induce adverse effects, particularly on articulation. Instances of decreased articulatory function were associated with stimulation of more medial electrode contacts, which could suggest cerebello-rubrospinal involvement.

Evaluating and Optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in Deep Brain Stimulation for Essential Tremor

2021 ◽  
Author(s):  
Maarten Bot ◽  
Anne-Fleur van Rootselaari ◽  
Vincent Odekerken ◽  
Joke Dijk ◽  
Rob M A de Bie ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Red Nucleus ◽  
Brain Regions ◽  
Superior Cerebellar Peduncle ◽  
Beneficial Effects ◽  
Ventral Intermediate Nucleus ◽  
Cerebellar Peduncle ◽  
Deep Brain

Abstract BACKGROUND Dentato-rubro-thalamic tract (DRT) deep brain stimulation (DBS) suppresses tremor in essential tremor (ET) patients. However, DRT depiction through tractography can vary depending on the included brain regions. Moreover, it is unclear which section of the DRT is optimal for DBS. OBJECTIVE To evaluate deterministic DRT tractography and tremor control in DBS for ET. METHODS After DBS surgery, DRT tractography was conducted in 37 trajectories (20 ET patients). Per trajectory, 5 different DRT depictions with various regions of interest (ROI) were constructed. Comparison resulted in a DRT depiction with highest correspondence to intraoperative tremor control. This DRT depiction was subsequently used for evaluation of short-term postoperative adverse and beneficial effects. RESULTS Postoperative optimized DRT tractography employing the ROI motor cortex, posterior subthalamic area (PSA), and ipsilateral superior cerebellar peduncle and dentate nucleus best corresponded with intraoperative trajectories (92%) and active DBS contacts (93%) showing optimal tremor control. DRT tractography employing a red nucleus or ventral intermediate nucleus of the thalamus (VIM) ROI often resulted in a more medial course. Optimal stimulation was located in the section between VIM and PSA. CONCLUSION This optimized deterministic DRT tractography strongly correlates with optimal tremor control. This technique is readily implementable for prospective evaluation in DBS target planning for ET.

Dystonia

2017 ◽  
Author(s):  
Jeri Yvonne Williams ◽  
David G Standaert
Keyword(s):  
Clinical Practice ◽  
Deep Brain Stimulation ◽  
Movement Disorder ◽  
Brain Stimulation ◽  
Age Of Onset ◽  
Anticholinergic Drugs ◽  
Body Parts ◽  
Botulinum Toxins ◽  
Deep Brain

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions. Classification of dystonia is based on age of onset, distribution of body parts affected, and underlying etiology. A large number of different genetic forms of dystonia have been discovered in recent years. Although these syndromes are important to recognize, the majority of dystonias encountered in clinical practice are of unknown cause. Therapy of dystonia includes medications, particularly anticholinergic drugs, use of botulinum toxins, and deep brain stimulation.

scholarly journals Stimulation related artifacts and a multipurpose template-based offline removal solution for a novel sensing-enabled deep brain stimulation device

2021 ◽  
Author(s):  
Lauren H Hammer ◽  
Ryan B Kochanski ◽  
Philip A Starr ◽  
Simon Little
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Field Potential ◽  
Low Frequency ◽  
Clinical Settings ◽  
Multiple Sources ◽  
Beta Band ◽  
Neural Signals ◽  
Value Decomposition ◽  
Deep Brain

AbstractBackgroundThe Medtronic “Percept” is the first FDA approved deep brain stimulation (DBS) device with sensing capabilities during active stimulation. Its real-world signal recording properties have yet to be fully described.ObjectiveThis study details sources of artifact (and potential mitigations) in local field potential (LFP) signals collected by the Percept, and assesses the potential impact of artifact on the future development of adaptive DBS (aDBS) using this device.MethodsLFP signals were collected from seven subjects in both experimental and clinical settings. The presence of artifacts and their effect on the spectral content of neural signals were evaluated in both the stimulation ON and OFF states using three distinct offline artifact removal techniques.ResultsTemplate subtraction successfully removed multiple sources of artifact, including 1) electrocardiogram (ECG), 2) non-physiologic polyphasic artifacts, and 3) ramping related artifacts seen when changing stimulation amplitudes. ECG removal from stimulation ON (at 0 mA) signals recovered the spectral shape seen when OFF stimulation (averaged difference in normalized power in theta, alpha, and beta bands ≤ 3.5%). ECG removal using singular value decomposition was similarly successful, though required subjective researcher input. QRS interpolation produced similar recovery of beta-band signal, but resulted in residual low-frequency artifact.ConclusionsArtifacts present when stimulation is enabled notably affected the spectral properties of sensed signals using the Percept. Multiple discrete artifacts could be successfully removed offline using an automated template subtraction method. The presence of unrejected artifact likely influences online power estimates, with the potential to affect aDBS algorithm performance.

scholarly journals Practical Closed-Loop Strategies for Deep Brain Stimulation: Lessons From Chronic Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Jordan Prosky ◽  
Jackson Cagle ◽  
Kristin K. Sellers ◽  
Ro’ee Gilron ◽  
Cora de Hemptinne ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Closed Loop ◽  
Open Loop ◽  
Neural Signals ◽  
Variable Success ◽  
Control Stimulation ◽  
Tonic Stimulation ◽  
Deep Brain

Deep brain stimulation (DBS) is a plausible therapy for various neuropsychiatric disorders, though continuous tonic stimulation without regard to underlying physiology (open-loop) has had variable success. Recently available DBS devices can sense neural signals which, in turn, can be used to control stimulation in a closed-loop mode. Closed-loop DBS strategies may mitigate many drawbacks of open-loop stimulation and provide more personalized therapy. These devices contain many adjustable parameters that control how the closed-loop system operates, which need to be optimized using a combination of empirically and clinically informed decision making. We offer a practical guide for the implementation of a closed-loop DBS system, using examples from patients with chronic pain. Focusing on two research devices from Medtronic, the Activa PC+S and Summit RC+S, we provide pragmatic details on implementing closed- loop programming from a clinician’s perspective. Specifically, by combining our understanding of chronic pain with data-driven heuristics, we describe how to tune key parameters to handle feature selection, state thresholding, and stimulation artifacts. Finally, we discuss logistical and practical considerations that clinicians must be aware of when programming closed-loop devices.

Correction of medial prefrontal cortex and adrenal gland left/right imbalance by deep brain stimulation for depression in rats

2020 ◽  
Author(s):  
Yukitoshi Sakaguchi
Keyword(s):  
Deep Brain Stimulation ◽  
Chronic Stress ◽  
Brain Stimulation ◽  
Brain Activity ◽  
Brain Regions ◽  
Depression Symptoms ◽  
Original Weight ◽  
Depression Disorders ◽  
Left And Right ◽  
Deep Brain

Hemispheric brain asymmetries are related to stress coping in both humans and rodents, and imbalanced neural activity between the left and right medial prefrontal cortexes (mPFCs) is observed in depression disorders. Brain stimulation of the PFC is effective to cure depression symptoms. We therefore hypothesized that the imbalanced activity of the mPFCs as well as depression-like behaviors can be induced by chronic stress in rats, and that deep brain stimulation (DBS) can treat such behavior by correcting the asymmetrical activity of the brain regions. Our results indeed show that chronic stress exposure by social isolation (SI) causes depression-like behavior and left/right mPFC activity changes. SI suppressed the activity of both the prelimbic and the infralimbic cortex; however, the extent of the suppression in these regions was oppositely asymmetric. Two weeks of DBS recovered the depression-like behavior and corrected the imbalanced brain activity. In addition, original weight differences between the left and right adrenal glands (AGs) were decreased by SI and recovered by DBS. The integrated index obtained from the mPFCs and AGs asymmetry scores could be useful for estimating the degree of depression. In conclusion, DBS can recover depression-like behavior accompanied by correcting imbalances in both the mPFCs and the AGs.

scholarly journals Parkinson patients have a presynaptic serotonergic deficit: A dynamic deep brain stimulation PET study

2021 ◽  
pp. 0271678X2098238
Author(s):  
Louise M Jørgensen ◽  
Tove Henriksen ◽  
Skirmante Mardosiene ◽  
Sune H Keller ◽  
Dea S Stenbæk ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Brain Regions ◽  
Significant Loss ◽  
Serotonergic System ◽  
Motor Symptom ◽  
Motor Symptoms ◽  
Serotonin System ◽  
Non Motor Symptoms ◽  
Deep Brain

Patients with Parkinson’s disease (PD) often suffer from non-motor symptoms, which may be caused by serotonergic dysfunction. Apart from alleviating the motor symptoms, Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) may also influence non-motor symptoms. The aim of this study is to investigate how turning DBS off affects the serotonergic system. We here exploit a novel functional PET neuroimaging methodology to evaluate the preservation of serotonergic neurons and capacity to release serotonin. We measured cerebral 5-HT1BR binding in 13 DBS-STN treated PD patients, at baseline and after turning DBS off. Ten age-matched volunteers served as controls. Clinical measures of motor symptoms were assessed under the two conditions and correlated to the PET measures of the static and dynamic integrity of the serotonergic system. PD patients exhibited a significant loss of frontal and parietal 5-HT1BR, and the loss was significantly correlated to motor symptom severity. We saw a corresponding release of serotonin, but only in brain regions with preserved 5-HT1BR, suggesting the presence of a presynaptic serotonergic deficit. Our study demonstrates that DBS-STN dynamically regulates the serotonin system in PD, and that preservation of serotonergic functions may be predictive of DBS-STN effects.

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