Mechanisms and effects of pallidal deep brain stimulation on levodopa resistant motor signs in Parkinson's disease
苍白球深部脑刺激对帕金森病左旋多巴抵抗运动体征的机制和影响
基本信息
- 批准号:10282963
- 负责人:
- 金额:$ 26.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-17 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:Activities of Daily LivingAdverse effectsAfferent PathwaysAnodesAxonBasal GangliaBorder CrossingsBradykinesiaCathodesChronicClinicalCognitiveCognitive deficitsComputer ModelsCorpus striatum structureDeep Brain StimulationDiseaseDisease ProgressionDorsalElectrical Stimulation of the BrainFreezingFunctional Magnetic Resonance ImagingGaitGait abnormalityGlobus PallidusGoalsHome environmentImpaired cognitionImpairmentImplantIndividualInterventionLeadLegLevodopaLocationLower ExtremityMagnetic Resonance ImagingMeasuresMedialMediatingMonitorMorbidity - disease rateMotorMovementMusculoskeletal EquilibriumParkinson DiseasePathway interactionsPatientsPostureQuality of lifeResearchResistanceRestSTN stimulationSeveritiesSignal TransductionSiteSpeechSpeech IntelligibilityStreamStructure of subthalamic nucleusSystemUpper ExtremityWireless Technologybaseblood oxygen level dependentcatalystcognitive loaddesigndopamine replacement therapyeffective therapyelectric fieldexperimental studyfall riskfallsimprovedinsightmotor controlmotor symptomneuroimagingneurophysiologynonhuman primatenovelnovel strategiesposture instabilitywearable device
项目摘要
Project Summary/Abstract
A large percentage of people with Parkinson’s disease (PD) will develop debilitating levodopa-resistant
impairment in postural stability and gait disturbances, including freezing of gait, over the course of disease. Many
of these individuals will be become candidates for treatment with deep brain stimulation (DBS) due to disease
progression and adverse effects associated with prolonged use of dopamine replacement therapy. While
subthalamic nucleus (STN) and globus pallidus (GP) DBS using standard clinical targets and stimulation
parameters can be highly effective for the treatment of the cardinal motor symptoms of PD, both treatments often
fail to control levodopa-resistant motor features of PD. Previous studies, and our ongoing research, have
provided evidence that the most effective site for alleviating akinesia and bradykinesia was the
posterolaterodorsal region of the GPi, near the border between the internal and external (GPe) segments, dorsal
to the region typically targeted for GPi DBS. Moreover, DBS in this region can be effective for levodopa-resistant
motor signs. Currently, the mechanisms mediating the prokinetic effects of stimulation near the GPi-GPe border
(GPi/e-DBS) are poorly understood. The primary goal of this project is to gain a better understanding of the
pathways mediating the benefits of GPi/e-DBS on levodopa-resistant motor signs. The project will leverage
technical advances in DBS lead design that allow current steering and adjustment of electric field orientation, in
conjunction with patient-specific computational models, to tune stimulation to preferentially activate prokinetic
axonal pathways (Aims 1 and 3). In addition, we will wirelessly record local field potentials from leads chronically
implanted in people with GP DBS (Aim 2), and use wearable technology to monitor gait and mobility during
chronic stimulation in the home environment (Aim 2). Aim 1 will examine the effects of altering the orientation of
the electric field induced by GPi/e-DBS to be either parallel or orthogonal (lowest or highest net axonal activation
thresholds, repectively) to putative striato-GPi and GPe to GPi afferent pathways (prokinetic connections of the
basal ganglia). Aim 2 will use the Medtronic Percept™ PC DBS system with active sensing to study: (i) pallidal
oscillations associated with the re-emergence (wash-out) and suppression (wash-in) of gait impairment with
GPi/e-DBS, (2) the up- and down-stream effects of GP DBS on motor network activity using 3T fMRI, and (iii)
the relationship between fluctuations in gait and GP LFPs during activities of daily living (recorded over 4 weeks).
Aim 3 will examine the effects of stimulation in the associative/limbic region of the GPe on gait and postural
control with and without an increased cognitive load (dual-task). Together, these experiments will provide critical
insight into the mechanisms and effects of GPi/e-DBS on basal ganglia and cortical-subcortical circuitry and
measures of gait and postural control. This could lead to a new approach to using GP DBS to treat levodopa-
resistant motor signs of PD.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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COLUM D MACKINNON其他文献
COLUM D MACKINNON的其他文献
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{{ truncateString('COLUM D MACKINNON', 18)}}的其他基金
Neuroplasticity and the emergence of motor and cognitive deficits in prodromal synucleinopathy
前驱期突触核蛋白病的神经可塑性以及运动和认知缺陷的出现
- 批准号:
10419719 - 财政年份:2022
- 资助金额:
$ 26.87万 - 项目类别:
Mechanisms and effects of pallidal deep brain stimulation on levodopa resistant motor signs in Parkinson's disease
苍白球深部脑刺激对帕金森病左旋多巴抵抗运动体征的机制和影响
- 批准号:
10703246 - 财政年份:2021
- 资助金额:
$ 26.87万 - 项目类别:
Mechanisms and effects of pallidal deep brain stimulation on levodopa resistant motor signs in Parkinson's disease
苍白球深部脑刺激对帕金森病左旋多巴抵抗运动体征的机制和影响
- 批准号:
10489834 - 财政年份:2021
- 资助金额:
$ 26.87万 - 项目类别:
Predictors of progression to freezing of gait in Parkinson's disease
帕金森病进展为冻结步态的预测因子
- 批准号:
9132362 - 财政年份:2015
- 资助金额:
$ 26.87万 - 项目类别:
Mechanisms of Movement Facilitation and Release by Cueing in Parkinson's disease
帕金森病中提示的运动促进和释放机制
- 批准号:
8542905 - 财政年份:2011
- 资助金额:
$ 26.87万 - 项目类别:
Mechanisms of Movement Facilitation and Release by Cueing in Parkinson's disease
帕金森病中提示的运动促进和释放机制
- 批准号:
8188218 - 财政年份:2011
- 资助金额:
$ 26.87万 - 项目类别:
Mechanisms of Movement Facilitation and Release by Cueing in Parkinson's disease
帕金森病中提示的运动促进和释放机制
- 批准号:
8325009 - 财政年份:2011
- 资助金额:
$ 26.87万 - 项目类别:
Control of Repetitive Movement in Parkinson's Disease
控制帕金森病的重复运动
- 批准号:
7413271 - 财政年份:2006
- 资助金额:
$ 26.87万 - 项目类别:
Control of Repetitive Movement in Parkinson's Disease
控制帕金森病的重复运动
- 批准号:
7591603 - 财政年份:2006
- 资助金额:
$ 26.87万 - 项目类别:
Control of Repetitive Movement in Parkinson's Disease
控制帕金森病的重复运动
- 批准号:
7236186 - 财政年份:2006
- 资助金额:
$ 26.87万 - 项目类别:
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