Using RDoC Negative and Positive Valence Paradigms to Investigate the Mechanisms of Neuropsychiatric Symptoms (NPS) in Alzheimer's Disease and Related Dementias
使用 RDoC 负价和正价范式研究阿尔茨海默病和相关痴呆症中神经精神症状 (NPS) 的机制
基本信息
- 批准号:10824824
- 负责人:
- 金额:$ 43.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:Adverse effectsAlzheimer&aposs DiseaseAlzheimer&aposs disease patientAlzheimer&aposs disease related dementiaAnatomyAnimal ExperimentationAnimalsAnteriorAnxietyBehaviorBehavioralBehavioral ParadigmBrainCaringCessation of lifeClinicalClinical TrialsCorpus striatum structureDNADSM-VDataDeep Brain StimulationDevelopmentDiagnosisDiagnosticDiseaseDorsalElementsEmotionalFeedbackFrightFunctional Magnetic Resonance ImagingGoalsHabitsHumanHuntington DiseaseImpairmentInterviewInvestigationKnowledgeLaboratoriesLearningLinkLiteratureMagnetic Resonance ImagingMeasuresMental DepressionModalityNegative ValenceNerve DegenerationNeuroanatomyNeurobiologyNeurodegenerative DisordersPainParticipantPatientsPersonsPharmaceutical PreparationsPharmacological TreatmentPlayPositive ValencePrefrontal CortexPreparationPrimary Progressive AphasiaProcessPublic HealthPunishmentResearchResearch Domain CriteriaResourcesRestRewardsRoleSamplingSemanticsSignal TransductionStructureSymptomsSystemTemporal LobeTestingThinkingTimeTranscranial magnetic stimulationUnited States National Institutes of HealthVariantbasebehavioral variant frontotemporal dementiaclinical investigationclinically relevantcommon symptomcostdiagnostic strategyhabit learningimprovedmortalityneuropsychiatric symptomnovelpsychiatric symptomrepetitive behaviorresponsetherapy developmenttranscranial direct current stimulation
项目摘要
The goal of this study is to determine the effects of degeneration of RDoC Negative and Positive Valence
Circuit Elements, and how these effects are associated with specific Neuropsychiatric Symptoms (NPS), in
persons with Alzheimer’s disease and related dementias (ADRD). Current pharmacological treatments for
NPS in ADRD were developed 50 years ago, are often inefficacious, and can have serious adverse effects
including increased mortality. Neuroanatomically-based treatments such as TMS, DBS, and tDCS for NPS are
promising, but their development has been hampered by our lack of knowledge about the mechanistic and
neuroanatomical bases of NPS in ADRD. The proposed project will leverage NIH-supported resources,
including the RDoC Project and a project in our laboratory (R01AG062268) to determine the factor structure of
NPS in ADRD, to better understand the connections between changes in the Negative (for example fear, pain,
and anxiety) and Positive (for example rewarding behaviors) Valence Systems and specific NPS across
different neurodegenerative disorders. The same NPS (e.g., apathy) occur across many ADRD diagnoses,
necessitating a trans-diagnostic approach to identify common neurobiologically-informed mechanisms of NPS
across diagnoses. We will study 40 participants with Alzheimer’s disease (AD), 20 with behavioral-variant
Frontotemporal dementia (bvFTD), 20 with Huntington’s disease (HD), and 20 with semantic-variant Primary
Progressive Aphasia (svPPA). We have chosen these disorders as they target specific RDoC Negative and
Positive Valence Circuit Elements including the prefrontal cortex (PFC), dorsal striatum, and anterior temporal
lobes. The first hypothesis is that the ventromedial (vm)PFC plays a central role in Negative Valence and
degeneration of the vmPFC will be associated with low Negative Valence on RDoC Paradigms, low
Internalizing psychiatric symptoms (including anxiety and depression), and the NPS of apathy. We also
hypothesize that degeneration of Negative Valence Circuit Elements that modulate the vmPFC, including the
dorsal PFC, dorsal striatum, and anterior temporal lobes, will be associated with high Negative Valence and
Internalizing psychiatric NPS. The ventral PFC and dorsal striatum are involved in goal-directed learning and
transferring learning from goal-directed to habit systems. We hypothesize that degeneration of the ventral PFC
will be associated with deficits in learning from feedback on RDoC Positive Valence Paradigms and with the
NPS of repetitive behaviors, and degeneration of the dorsal striatum with deficits in learning from punishment
vs. reward and habit learning and the NPS of repetitive thoughts. These investigations could, for the first time,
utilize RDoC Paradigms to better understand the development of NPS in humans from neurodegenerative
processes, to specific deficits in RDoC Valence Paradigms, to neuroanatomical findings, to NPS. These
investigations are clinically relevant as they will improve our knowledge of the mechanistic and neuroana-
tomical bases of NPS for use in clinical trials of novel neuroanatomically-based treatments for NPS in ADRD.
本研究的目的是确定RDoC正负价变性的影响
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Subjective Cognitive Decline Is More Accurate When Metamemory Is Better.
- DOI:10.3389/fnagi.2022.787552
- 发表时间:2022
- 期刊:
- 影响因子:4.8
- 作者:Chapman S;Joyce JL;Barker MS;Sunderaraman P;Rizer S;Huey ED;Dworkin J;Gu Y;Cosentino S
- 通讯作者:Cosentino S
Multimodal nonlinear correlates of behavioural symptoms in frontotemporal dementia.
额颞叶痴呆行为症状的多模态非线性相关性。
- DOI:10.21203/rs.3.rs-3271530/v1
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Zamboni,Giovanna;Mattioli,Irene;Arya,Zobair;Tondelli,Manuela;Vinceti,Giulia;Chiari,Annalisa;Jenkinson,Mark;Huey,EdwardD;Grafman,Jordan
- 通讯作者:Grafman,Jordan
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Edward D Huey其他文献
Edward D Huey的其他文献
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{{ truncateString('Edward D Huey', 18)}}的其他基金
Using RDoC Negative and Positive Valence Paradigms to Investigate the Mechanisms of Neuropsychiatric Symptoms (NPS) in Alzheimer's Disease and Related Dementias
使用 RDoC 负价和正价范式研究阿尔茨海默病和相关痴呆症中神经精神症状 (NPS) 的机制
- 批准号:
10417053 - 财政年份:2019
- 资助金额:
$ 43.9万 - 项目类别:
Using RDoC Negative and Positive Valence Paradigms to Investigate the Mechanisms of Neuropsychiatric Symptoms (NPS) in Alzheimer's Disease and Related Dementias
使用 RDoC 负价和正价范式研究阿尔茨海默病和相关痴呆症中神经精神症状 (NPS) 的机制
- 批准号:
10166948 - 财政年份:2019
- 资助金额:
$ 43.9万 - 项目类别:
Neuroanatomical associations with the factor structure underlying neuropsychiatric symptoms in Alzheimer's disease
神经解剖学与阿尔茨海默病神经精神症状因素结构的关联
- 批准号:
10804919 - 财政年份:2018
- 资助金额:
$ 43.9万 - 项目类别:
Neuroanatomical associations with the factor structure underlying neuropsychiatric symptoms in Alzheimer's disease
神经解剖学与阿尔茨海默病神经精神症状因素结构的关联
- 批准号:
10172821 - 财政年份:2018
- 资助金额:
$ 43.9万 - 项目类别:
Neuroanatomical associations with the factor structure underlying neuropsychiatric symptoms in Alzheimer's disease
神经解剖学与阿尔茨海默病神经精神症状因素结构的关联
- 批准号:
10450779 - 财政年份:2018
- 资助金额:
$ 43.9万 - 项目类别:
Neuroanatomical associations with the factor structure underlying neuropsychiatric symptoms in Alzheimer's disease
神经解剖学与阿尔茨海默病神经精神症状因素结构的关联
- 批准号:
9973180 - 财政年份:2018
- 资助金额:
$ 43.9万 - 项目类别:
Investigation of the dopamine system in frontotemporal dementia
额颞叶痴呆中多巴胺系统的研究
- 批准号:
8181355 - 财政年份:2009
- 资助金额:
$ 43.9万 - 项目类别:
Investigation of the dopamine system in frontotemporal dementia
额颞叶痴呆中多巴胺系统的研究
- 批准号:
8197820 - 财政年份:2009
- 资助金额:
$ 43.9万 - 项目类别:














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