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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：
10297334
负责人：
Dhakshin Ramanathan
金额：
$ 35.88万
依托单位：
VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
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：
https://reporter.nih.gov/project-details/10297334
关键词：
Affect Alcohol dependence Animals Attention deficit hyperactivity disorder Behavior Behavioral Behavioral inhibition Biological Assay Bipolar Disorder Brain Brain region Categories Citalopram Clinical Pharmacology Corpus striatum structure Cues Data Development Diagnostic Dimensions Disease Dopamine Dose Drug Addiction Drug usage Electroencephalography Electrophysiology (science)Environment Evaluation Frequencies Frontotemporal Dementia Goals Grant High Frequency Oscillation Human Impairment Impulsivity Learning Link Measurable Measures Medial Mental Depression Mental disorders Modeling Mood Disorders Motor Motor Cortex Neurotransmitters Obsessive compulsive behavior Performance Pharmaceutical Preparations Pharmacology Pharmacology Study Phase Physiologic Monitoring Physiological Physiological Processes Physiology Prefrontal Cortex Probability Process Reflex action Research Reversal Learning Rewards Ritalin Serotonin Substance abuse problem System Testing Thinking Traumatic Brain Injury Ventral Striatum Visual activity marker autism spectrum disorder base behavior change behavioral construct behavioral pharmacology cell type design discounting dopaminergic neuron dosage drug testing flexibility improved nervous system disorder neurophysiology optogenetics pre-clinical response substance use suicidal targeted agent therapeutic development tool translation 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.

项目总结