Identifying and Targeting Physiological Assays of Circuit Engagement to Improve Impulsivity
识别和针对回路参与的生理分析以改善冲动
基本信息
- 批准号:10615875
- 负责人:
- 金额:$ 35.88万
- 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:2021-07-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAlcohol dependenceAnimalsAttention deficit hyperactivity disorderBehaviorBehavioralBehavioral inhibitionBiological AssayBipolar DisorderBrainBrain regionCategoriesCitalopramClassificationCorpus striatum structureCuesDataDevelopmentDiagnosticDimensionsDiseaseDopamineDoseDrug AddictionDrug usageElectroencephalographyElectrophysiology (science)EnvironmentEvaluationFrequenciesFrontotemporal DementiaGoalsGrantHigh Frequency OscillationHumanImpairmentImpulsivityLearningLinkMeasurableMeasuresMedialMental DepressionMental disordersModelingMood DisordersMotorMotor CortexNeurotransmittersObsessive compulsive behaviorPerformancePharmaceutical PreparationsPharmacologyPharmacology StudyPhasePhysiologic MonitoringPhysiologicalPhysiological ProcessesPhysiologyPrefrontal CortexProbabilityProcessResearchReversal LearningRewardsRitalinSerotoninSpecific qualifier valueSubstance abuse problemSystemTestingThinkingTraumatic Brain InjuryVentral StriatumVisualactivity markerautism spectrum disorderbehavior changebehavioral constructbehavioral pharmacologybiomarker identificationcell typedesigndiscountingdopaminergic neurondosagedrug testingflexibilityimprovednervous system disorderneurophysiologyoptogeneticspharmacologicpre-clinicalresponsesubstance usesuicidal acttargeted agenttherapeutic developmenttooltranslation to humans
项目摘要
Project Summary
Behavioral inhibition includes our ability to inhibit prepotent, reflexive or perseverative behaviors in the pursuit
of longer-term goals. Impairments in behavioral inhibition are associated with greater levels of impulsivity.
Impulsivity can be classified into at three major categories. Motor impulsivity is measured using tasks focused
on waiting – impulsive subjects cannot wait as long prior to responding. Impulsivity can also be related to
choice – for example, choosing a smaller immediate reward instead of a larger delayed reward. Finally,
impulsive subjects tend to perseverate (i.e. act without thinking), and thus cannot flexibly shift behaviors as
needed when the environment changes. Impulsivity is pan-diagnostic, occurring in attention deficit hyperactivity
disorder (ADHD), drug & alcohol addiction, affective disorders and even neurologic disorders like
frontotemporal dementia.
Various behavioral tasks have been designed to measure the above features of impulsivity. Such models have
been used to test the effects of drugs on minimizing impulsivity. Drugs used in these tasks can modulate
behavior, but not always in a predictable or even replicable manner across labs, strains or species. This has
precluded simple attempts at testing how pharmacologic agents can improve impulsivity. This grant, following
RFA specifications, is focused on assessing whether electrophysiological measures of impulsivity can provide
a more stable “intermediary” measure of circuit activity relevant to impulsivity that can be used for preclinical
pharmacologic testing and development.
The goals of this grant are first to identify neurophysiological (LFP-based) markers of subdomains of
impulsivity described above, with a particular focus on identifying physiological markers that are translationally
relevant and potentially measurable non-invasively in humans. Next, we will assess whether these physiologic
measures can be used as an assay for therapeutic development by testing how the identified physiological
marker changes in response to varying dosages of drugs known to affect specific subdomains of impulsivity.
Finally, using optogenetics targeted at serotonin or dopamine, we will be able to directly test whether
modulation of these neurotransmitter systems in a temporally refined way affects physiology and behavior.
项目摘要
行为抑制包括我们在追求过程中抑制优势、反射或坚持行为的能力
长期目标。行为抑制的损害与更高水平的冲动有关。
冲动可以分为三大类。运动冲动性是用专注于
关于等待-冲动的受试者不能在反应之前等待那么长时间。冲动也可能与
选择-例如,选择较小的即时奖励而不是较大的延迟奖励。最后,
冲动的受试者倾向于固执(即不假思索地行动),因此不能灵活地改变行为,
当环境发生变化时。冲动是泛诊断,发生在注意缺陷多动
注意力缺陷多动障碍(ADHD),药物和酒精成瘾,情感障碍,甚至神经系统疾病,
额颞叶痴呆
人们设计了各种行为任务来测量冲动性的上述特征。这些模型具有
被用来测试药物对减少冲动的影响。在这些任务中使用的药物可以调节
行为,但并不总是以可预测的甚至可复制的方式跨实验室,菌株或物种。这
排除了简单地测试药物如何改善冲动的尝试。这笔赠款,继
RFA规范的重点是评估冲动的电生理测量是否可以提供
与冲动性相关的回路活动的更稳定的"中间"测量,
药理学测试和开发。
这项资助的目标是首先确定神经生理学(基于LFP)的亚结构域标记物,
以上描述的冲动,特别关注于识别生理标记,
相关的和潜在的可测量的非侵入性的人类。接下来,我们将评估这些生理
测量可以用作治疗开发的测定,
标记物的变化对不同剂量的药物的反应,这些药物已知会影响冲动的特定子域。
最后,使用针对血清素或多巴胺的光遗传学,我们将能够直接测试是否
这些神经递质系统以时间上精确的方式的调节影响生理和行为。
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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