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Isolating causal roles of norepinephrine neuromodulation in mediating distinct components of attention control

分离去甲肾上腺素神经调节在介导注意力控制的不同组成部分中的因果作用

基本信息

批准号：
10667842
负责人：
Supriya Ghosh
金额：
$ 24.6万
依托单位：
UNIVERSITY OF CHICAGO
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：
2023-04-03 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10667842
关键词：
Adaptive Behaviors Animals Anterior Area Arousal Attention Attention deficit hyperactivity disorder Behavior Behavior Control Behavioral Brain Brain Stem Cerebral cortex Classification Clinical Cognitive Conflict (Psychology)Contralateral Data Diagnosis Disease Dissociation Elements Feedback Functional disorder Goals Human Individual Intervention Link Measures Mediating Methods Monitor Monkeys Motor Nervous System Neurobiology Neurons Noise Norepinephrine Pattern Performance Phase Play Prefrontal Cortex Process Psychology Regulation Research Resources Response to stimulus physiology Role Sensory Stimulus Structure System Testing Therapeutic Intervention Training Uncertainty Wakefulness Work attentional control cingulate cortex cognitive control environmental change executive function flexibility improved insight locus ceruleus structure neurobiological mechanism neurophysiology neuroregulation optogenetics response selective attention sensory input sensory stimulus success therapeutic target visual stimulus

项目摘要

PROJECT SUMMARY/ABSTRACT When faced with environmental uncertainty, optimum top-down control facilitates attention shifts and improves performance. Several functionally distinct stages of attention are well stablished in psychology. Recent studies have associated some of these cognitive constructs with specific brain structures. However, less is known about the neurobiological mechanisms that transform contextual information into distinct components of attention control such as selection of relevant sensory inputs, perceptual decision and motor action responsible for adaptive behaviors in humans. Lack of appropriate attention control leads to various attention disorders such as attention-deficit/hyperactivity disorder (ADHD). Our long-term goal is to dissociate distinct neuronal processes underlying adaptive behavior, particularly neuromodulatory contributions to cognitive control within interacting brain structures. Neuronal activity in the anterior cingulate cortex (ACC) and dorso-lateral prefrontal cortex (dLPFC), two crucial brain areas involved in cognitive control are strongly regulated by norepinephrine (NE) neuromodulation from the locus coeruleus (LC) in the brainstem. The LC-NE neuromodulatory system projects throughout the cerebral cortex, and has been linked to sensory processing regulation, arousal and attention. Our preliminary data in monkeys show that spatially selective attention strongly modulates spiking dynamics of NE neurons in the LC including an increased spiking to attended visual stimuli. Moreover, optogenetic activation of these LC-NE neurons enhanced attentional performance. Our central hypothesis is that: 1) the LC receives contextual information about behavioral performance from the ACC, and is activated with increased performance errors; 2) LC-NE neuromodulation differentially regulates neuronal activity in the ACC and dLPFC respectively to mediate motor selection, and sensory and perceptual decision selections of attention control. To test these hypotheses, we will isolate neurophysiological correlates of performance errors, and attentional shifts in sensory relevance, perceptual decision criterion and motor criterion within the LC, ACC and dLPFC in monkeys. We will optogenetically activate LC-NE neurons while simultaneously record from the ACC and dLPFC to test which aspects of LC-NE activity dynamics (tonic and stimulus-locked phasic burst spiking) causally regulate ACC and dLPFC to mediate distinct components of attention control. The results from this proposed study will provide a direct, detailed neurobiological understanding of specialized neuromodulatory contributions that transform contextual information into different stages of attention control in improving adaptive behavioral performance in humans. This will further expedite progress in better classification and identifying potential therapeutic targets for various attention disorders associated with functionally specific deficits.

项目总结/文摘