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: 10824824
• 负责人: Edward D Huey
• 金额: $ 43.9万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10824824
• 关键词: Adverse effects; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Anatomy; Animal Experimentation; Animals; Anterior; Anxiety; Behavior; Behavioral; Behavioral Paradigm; Brain; Caring; Cessation of life; Clinical; Clinical Trials; Corpus striatum structure; DNA; DSM-V; Data; Deep Brain Stimulation; Development; Diagnosis; Diagnostic; Disease; Dorsal; Elements; Emotional; Feedback; Fright; Functional Magnetic Resonance Imaging; Goals; Habits; Human; Huntington Disease; Impairment; Interview; Investigation; Knowledge; Laboratories; Learning; Link; Literature; Magnetic Resonance Imaging; Measures; Mental Depression; Modality; Negative Valence; Nerve Degeneration; Neuroanatomy; Neurobiology; Neurodegenerative Disorders; Pain; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Play; Positive Valence; Prefrontal Cortex; Preparation; Primary Progressive Aphasia; Process; Public Health; Punishment; Research; Research Domain Criteria; Resources; Rest; Rewards; Role; Sampling; Semantics; Signal Transduction; Structure; Symptoms; System; Temporal Lobe; Testing; Thinking; Time; Transcranial magnetic stimulation; United States National Institutes of Health; Variant; base; behavioral variant frontotemporal dementia; clinical investigation; clinically relevant; common symptom; cost; diagnostic strategy; habit learning; improved; mortality; neuropsychiatric symptom; novel; psychiatric symptom; repetitive behavior; response; therapy development; transcranial direct current stimulation

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

Subjective Cognitive Decline Is More Accurate When Metamemory Is Better.

• DOI: 10.3389/fnagi.2022.787552
• 发表时间: 2022
• 期刊: Frontiers in aging neuroscience
• 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: Research square
• 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