Targeting language-specific and executive-control networks with transcranial direct current stimulation in aphasic AD
通过经颅直流电刺激治疗失语性 AD,针对语言特异性和执行控制网络
基本信息
- 批准号:10701784
- 负责人:
- 金额:$ 80.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-15 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdjuvantAffectAftercareAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAmericanAnodesAnomiaAphasiaAreaAtrophicBehavior TherapyBiological MarkersBloodBrainCOVID-19 pandemicCaregiver BurdenCessation of lifeCharacteristicsClinicalClinical ResearchCognitiveCognitive deficitsCoinCombined Modality TherapyComplementControlled Clinical TrialsCoupledDevelopmentDiffusion Magnetic Resonance ImagingDiseaseDorsalDouble-Blind MethodEtiologyFunctional Magnetic Resonance ImagingGlutathioneImpairmentIndividualInferior frontal gyrusInterventionInvestigationLanguageLanguage DisordersLanguage TherapyLeftMagnetic Resonance SpectroscopyMeasuresMembrane PotentialsMemory impairmentModelingMonitorNamesNerve DegenerationNeurodegenerative DisordersNeuronal PlasticityNeuronsNeurosciencesNeurotransmittersOralOutcomeOxidative StressPathologyPatternPerformancePerfusionPharmacological TreatmentPhenotypePhysiologicalPrefrontal CortexPrimary Progressive AphasiaProbabilityRandomized Controlled Clinical TrialsResearchRestShort-Term MemorySleepSpeechStructure of supramarginal gyrusSymptomsSynaptic TransmissionTechniquesTestingTherapeuticTimeTrainingTranslatingUpdateVariantVerbal LearningWritingbehavior predictionbiomarker identificationbrain pathwaybrain volumeclinically significantcognitive functioncognitive performancecomparative efficacycostcost effective treatmentdisabilityeffective therapyexecutive functiongamma-Aminobutyric Acidimprovedlanguage impairmentlanguage outcomeneuralneuroimagingneurological rehabilitationneuroregulationnoveloutcome predictionperfusion imagingphonologypost interventionpredict responsivenesssexspellingstroke-induced aphasiatargeted treatmenttranscranial direct current stimulationtreatment effecttreatment researchverbalwhite matter
项目摘要
This project aims in developing treatments for an atypical Alzheimer's disease (AD) variant, usually affecting
the left hemisphere and comprising the logopenic variant primary progressive aphasia (lvPPA), thus, PPA-AD.
There are no pharmacological treatments available for PPA, and the only treatment shown to alleviate language
deficits is speech-language therapy. Treatment research in AD has emphasized targeting neuronal synaptic
transmission. We were amongst the first groups in the world to show the efficacy of a neuromodulation technique
that targets synaptic transmission (transcranial direct current stimulation, tDCS) in providing significant
symptomatic relief of language impairments in PPA. In the largest-to-date, double-blind, sham-controlled clinical
trial we demonstrated the efficacy of tDCS as an adjuvant for speech-language therapy for the treatment of
naming and spelling deficits in PPA. However, the efforts to slow language degeneration are hindered by the
fact that these individuals also suffer from additional cognitive deficits. This is especially true for individuals with
AD etiology (pathology and atrophy distribution). Early in the disease, individuals with PPA-AD present with
additional cognitive deficits such as verbal short-term memory impairment, even believed to be a primary
underlying cause of language deficits. However, treatment of these deficits has not been investigated in PPA-
AD using neuromodulation approaches. To address this gap, the proposed research aims to answer the following
question: How can we implement neurostimulation-based treatments to maximally generalize their
benefits to vital language/cognitive functions? We will do that by employing: (a) a behavioral therapy that
directly targets verbal short-term and working memory (vSTM/WM) deficits and that has been shown to
effectively generalize even to untrained language functions in post-stroke aphasia, and, (b) targeted neuro-
stimulation (high-definition tDCS) based on recent network-neuroscience and neuro-rehabilitation models. In
Aim 1, we will compare the efficacy of tDCS delivered over the left supramarginal gyrus (LSMG) vs. the left
dorsolateral prefrontal cortex (LDLPFC), both coupled with vSTM/WM behavioral treatment, specifically
examining the generalization of treatment effects to untrained vital language-specific and executive cognitive
functions in PPA-AD. In Aim 2, we will implement neuroimaging techniques to understand the mechanisms of
tDCS-induced changes in terms of: (a) network functional connectivity, (b) previous and novel metabolites such
as GABA and glutathione (related to oxidative stress in neurodegeneration), and (c) blood oxygenation, using
perfusion imaging. Finally, in Aim 3, we will evaluate novel predictors of responsiveness to tDCS such as
perfusion, sex and sleep, thus complementing our previously identified clinical, neural and behavioral predictors
(variant, brain volume and initial language/cognitive performance). A better understanding, based on recent
advances in network neuroscience, of how tDCS benefits may generalize to untrained language and executive
cognitive functions has the potential to revolutionize the development of effective treatments for PPA-AD.
该项目旨在开发一种非典型阿尔茨海默病(AD)变体的治疗方法,
左半球,包括逻辑缺失变异型原发性进行性失语症(lvPPA),因此,PPA-AD。
PPA没有可用的药物治疗,唯一的治疗显示,以减轻语言
就是语言治疗AD的治疗研究强调靶向神经元突触,
传输我们是世界上第一批展示神经调节技术有效性的团队之一
靶向突触传递(经颅直流电刺激,tDCS),
PPA语言障碍症状缓解。在迄今为止最大的,双盲,假对照临床试验中,
一项试验证明了tDCS作为辅助语言治疗的有效性,
PPA中的命名和拼写缺陷。然而,减缓语言退化的努力受到了
事实上,这些人还患有额外的认知缺陷。这对于那些
AD病因学(病理学和萎缩分布)。在疾病早期,患有PPA-AD的个体表现为
额外的认知缺陷,如语言短期记忆障碍,甚至被认为是主要的
语言缺陷的根本原因。然而,这些缺陷的治疗尚未在PPA中进行研究-
AD使用神经调节方法。为了解决这一差距,拟议的研究旨在回答以下问题
问:我们如何实施基于神经刺激的治疗,以最大限度地推广他们的
对重要的语言/认知功能有好处吗?我们将通过以下方式做到这一点:(a)行为疗法,
直接针对语言短期和工作记忆(vSTM/WM)缺陷,并已被证明
有效地推广到中风后失语症中甚至未经训练的语言功能,和,(B)靶向神经-
刺激(高清晰度tDCS)基于最近的网络神经科学和神经康复模型。在
目的1,我们将比较tDCS在左侧缘上回(LSMG)与左侧
背外侧前额叶皮层(LDLPFC),两者都与vSTM/WM行为治疗相结合,特别是
检查治疗效果对未经训练的重要语言特异性和执行认知的推广
PPA-AD中的功能。在目标2中,我们将实施神经影像学技术,以了解
tDCS诱导的变化:(a)网络功能连接,(B)先前和新的代谢产物,如
如GABA和谷胱甘肽(与神经变性中的氧化应激有关),和(c)血氧,使用
灌注成像最后,在目标3中,我们将评估对tDCS反应性的新预测因子,如
灌注,性和睡眠,从而补充了我们以前确定的临床,神经和行为预测因子
(变量,脑容量和初始语言/认知表现)。更好的理解,基于最近的
网络神经科学的进展,tDCS的好处如何推广到未经训练的语言和执行
认知功能具有革命性地开发PPA-AD的有效治疗的潜力。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Kyrana Tsapkini其他文献
Kyrana Tsapkini的其他文献
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{{ truncateString('Kyrana Tsapkini', 18)}}的其他基金
Targeting language-specific and executive-control networks with transcranial direct current stimulation in aphasic AD
通过经颅直流电刺激治疗失语性 AD,针对语言特异性和执行控制网络
- 批准号:
10522359 - 财政年份:2022
- 资助金额:
$ 80.15万 - 项目类别:
Transcranial direct current stimulation in typical and atypical Alzheimer's disease
经颅直流电刺激治疗典型和非典型阿尔茨海默病
- 批准号:
10045358 - 财政年份:2020
- 资助金额:
$ 80.15万 - 项目类别:
Transcranial direct current stimulation in typical and atypical Alzheimer's disease
经颅直流电刺激治疗典型和非典型阿尔茨海默病
- 批准号:
10631954 - 财政年份:2020
- 资助金额:
$ 80.15万 - 项目类别:
Transcranial direct current stimulation in typical and atypical Alzheimer's disease
经颅直流电刺激治疗典型和非典型阿尔茨海默病
- 批准号:
10260455 - 财政年份:2020
- 资助金额:
$ 80.15万 - 项目类别:
Transcranial direct current stimulation in typical and atypical Alzheimer's disease
经颅直流电刺激治疗典型和非典型阿尔茨海默病
- 批准号:
10447136 - 财政年份:2020
- 资助金额:
$ 80.15万 - 项目类别:
Effects of tDCS on spoken and written production in Primary Progressive Aphasia
经颅直流电刺激 (tDCS) 对原发性进行性失语症口语和书面表达的影响
- 批准号:
9245668 - 财政年份:2015
- 资助金额:
$ 80.15万 - 项目类别:
Effects of tDCS on spoken and written production in Primary Progressive Aphasia
经颅直流电刺激 (tDCS) 对原发性进行性失语症口语和书面表达的影响
- 批准号:
8861556 - 财政年份:2015
- 资助金额:
$ 80.15万 - 项目类别:
Effects of tDCS on spoken and written production in Primary Progressive Aphasia
经颅直流电刺激 (tDCS) 对原发性进行性失语症口语和书面表达的影响
- 批准号:
9044746 - 财政年份:2015
- 资助金额:
$ 80.15万 - 项目类别:
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