Neuroimaging Cholinergic Mechanisms of Fear Extinction in PTSD
PTSD 恐惧消退的神经影像学胆碱能机制
基本信息
- 批准号:10734244
- 负责人:
- 金额:$ 83.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2028-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcetylcholineAddressAmygdaloid structureAnti-Anxiety AgentsArousalBasic ScienceBehavioralBrainBrain regionChronic Post Traumatic Stress DisorderChronic stressComputer ModelsDataDevelopmentDimensionsDiseaseEvaluationExhibitsExtinctionFrightFunctional Magnetic Resonance ImagingFunctional disorderFutureGoalsHippocampusHumanImageImpairmentIndividualLearningLinkMapsMeasuresMediatingMolecular TargetNeurosciencesNicotinic ReceptorsParticipantPersonsPharmacological TreatmentPharmacotherapyPositron-Emission TomographyPost-Traumatic Stress DisordersPre-Clinical ModelPrefrontal CortexProcessPublic HealthReceptor SignalingReportingRoleSamplingSampling StudiesScanningSeveritiesSymptomsTherapeuticTranslatingacetylcholine receptor agonistalpha-bungarotoxin receptoranxiouscholinergicclinical developmentclinically relevantdiagnostic criteriahuman studyimprovedlearning extinctionmeetingsmemory processmultidisciplinarymultimodalityneuralneural circuitneuroimagingneuronal circuitryphysiologic modelpre-clinicalradioligandreceptorreceptor densityrecruitresponsesymptom clustertherapeutic developmenttrauma exposure
项目摘要
PROJECT SUMMARY
Post-traumatic stress disorder (PTSD) is a deeply debilitating disorder with severe public health burden. Yet,
current pharmacological treatments are glaringly suboptimal. The α7 nicotinic acetylcholine receptor (nAChR) is
a salient molecular target for PTSD therapeutics. Acetylcholine regulates fear learning and memory processes
that are impaired in people with PTSD, and α7 nAChR density is reduced by chronic stress in preclinical models.
Despite this compelling evidence, the role of α7 nAChRs in the pathophysiology of PTSD in humans is not fully
understood. To address this gap, this proposal will characterize α7 nAChR contributions to behavioral and neural
markers of fear learning in trauma-exposed participants representing the full spectrum of PTSD severity. Using
[18F]ASEM, a positron emission tomography (PET) radioligand specific to α7 nAChRs, we obtained exciting
preliminary data indicating lower α7 nAChR availability in people with PTSD that is associated with the severity
of PTSD symptom clusters. Further, lower α7 nAChR availability in amygdala corresponded to weakened
functional connectivity of the amygdala and ventromedial prefrontal cortex, which is a key circuit that underpins
fear learning processes. Motivated by these exciting data, the primary objective of this project is to characterize
α7 nAChR contributions to fear extinction learning and circuitry in PTSD. To achieve this goal, we will recruit 80
participants with trauma exposure sampled across the full dimensional spectrum of PTSD symptoms. All
participants will be scanned with [18F]ASEM PET and participate in an established fear reversal task with
concurrent functional magnetic resonance imaging (fMRI). The acquired data will be used to address three
Specific Aims. AIM 1 will determine if people with PTSD have lower α7 nAChR availability than trauma exposed
controls, and which PTSD symptom cluster severities correspond to lower α7 nAChR availability. AIM 2 will
determine if lower α7 nAChR availability in amygdala predicts impaired learning rates during fear extinction. AIM
3 will determine if lower α7 nAChR availability in amygdala predicts weaker vmPFC-amygdala connectivity during
fear extinction. A final analysis will determine if amygdala α7 nAChR availability mediates the relationship of
amygdala-vmPFC connectivity with fear extinction learning rates, assessing these receptors a mechanism
underlying disrupted fear extinction circuits in PTSD. The findings will determine α7 nAChR roles in the
pathophysiology of fear extinction and its brain circuits in living people, informing future therapeutic development
to address fear extinction impairments that underlie chronic PTSD symptoms.
项目摘要
创伤后应激障碍(PTSD)是一种严重的衰弱性疾病,具有严重的公共卫生负担。然而,
目前的药物治疗显然不太理想。α7烟碱乙酰胆碱受体(nAChR)是
创伤后应激障碍治疗的重要分子靶点乙酰胆碱调节恐惧学习和记忆过程
在临床前模型中,慢性应激会降低α7 nAChR密度。
尽管有这些令人信服的证据,α7 nAChRs在人类PTSD病理生理学中的作用还不完全清楚。
明白为了解决这一差距,该提案将描述α7 nAChR对行为和神经的贡献,
暴露于创伤的参与者的恐惧学习标志物代表了创伤后应激障碍严重程度的全谱。使用
[18 F]ASEM是一种特异于α7 nAChRs的正电子发射断层扫描(PET)放射性配体,我们获得了令人兴奋的结果。
初步数据表明,PTSD患者的α7 nAChR可用性较低,这与严重程度有关。
创伤后应激障碍症状群此外,杏仁核中α7 nAChR的可用性较低,
杏仁核和腹内侧前额叶皮层的功能连接,这是一个关键的电路,
害怕学习过程。受这些令人兴奋的数据的激励,本项目的主要目标是描述
α7 nAChR对PTSD中恐惧消退学习和回路的贡献为了实现这一目标,我们将招募80名
创伤暴露的参与者在创伤后应激障碍症状的全维度谱中取样。所有
参与者将接受[18F]ASEM PET扫描,并参与既定的恐惧逆转任务,
同步功能性磁共振成像(fMRI)。获取的数据将用于解决三个
具体目标。AIM 1将确定PTSD患者的α7 nAChR可用性是否低于创伤暴露者
对照组,以及PTSD症状群的严重程度对应于较低的α7 nAChR可用性。AIM 2将
确定杏仁核中较低的α7 nAChR可用性是否预示着恐惧消退期间的学习率受损。目的
3将确定杏仁核中较低的α7 nAChR可用性是否预示着在治疗期间vmPFC-杏仁核连接较弱
害怕灭绝。最后的分析将确定杏仁核α7 nAChR的可用性是否介导了
杏仁核-vmPFC连接与恐惧消退学习率,评估这些受体的机制
创伤后应激障碍中潜在的恐惧消退回路中断。这些发现将确定α7 nAChR在
恐惧消退的病理生理学及其在活人中的脑回路,为未来的治疗发展提供信息
来解决作为慢性创伤后应激障碍症状基础的恐惧消退障碍
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Ansel Hillmer其他文献
Ansel Hillmer的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Ansel Hillmer', 18)}}的其他基金
Neuroimaging Adaptive Microglia Processes During Extended Alcohol Drinking
长期饮酒期间的神经影像适应性小胶质细胞过程
- 批准号:
10511295 - 财政年份:2022
- 资助金额:
$ 83.55万 - 项目类别:
Neuroimaging Adaptive Microglia Processes During Extended Alcohol Drinking
长期饮酒期间的神经影像适应性小胶质细胞过程
- 批准号:
10704077 - 财政年份:2022
- 资助金额:
$ 83.55万 - 项目类别:
Multimodal Neuroimaging of Alcohol Withdrawal: The Role of Glutamate in Neural Reorganization
酒精戒断的多模式神经影像学:谷氨酸在神经重组中的作用
- 批准号:
10092045 - 财政年份:2017
- 资助金额:
$ 83.55万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 83.55万 - 项目类别:
Research Grant














{{item.name}}会员




