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Multi-scale Orbitofrontal Networks Underlying Reward Processing

奖励处理背后的多尺度眶额网络

基本信息

批准号：
8868828
负责人：
Erin L Rich
金额：
$ 13.05万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-15 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8868828
关键词：
Abstinence Accounting Acute Affective Anterior Area Brain Brain Mapping Characteristics Choice Behavior Code Communication Cues Decision Making Dimensions Disease Drug Addiction Electrocorticogram Epilepsy Goals Human Individual Language Lead Learning Lesion Link Measures Memory Mentors Monitor Monkeys Neurons Neurosurgeon Operative Surgical Procedures Output Patients Pharmaceutical Preparations Phonetics Play Population Positioning Attribute Prefrontal Cortex Preparation Process Property Psychological reinforcement Relapse Research Research Personnel Rewards Role Sensory Sensory Process Series Signal Transduction Site Stimulus Structure Substance abuse problem Superior temporal gyrus Temporal Lobe Testing Therapeutic Time Training Work abstracting addiction awake base cognitive ability cognitive process craving drug addict drug craving experience insight neuromechanism neurophysiology neuroregulation neurotransmission nonhuman primate novel novel therapeutic intervention preference programs public health relevance relating to nervous system research study reward processing sensory cortex sensory stimulus spatiotemporal stimulus processing theories translational approach

项目摘要

DESCRIPTION (provided by applicant): In substance abuse disorders, cravings and relapses can occur even after long periods of abstinence, posing a key challenge for successful long-term treatment. These phenomena arise when brain circuits that support reward-based learning and decision-making associate arbitrary cues with behaviorally reinforcing effects of drugs. The orbitofrontal cortex is a region crucial to reward-based decision-making, and has been strongly implicated in addiction. To date, it is known that the orbitofrontal cortex encodes the subjective value of predicted rewards, but the precise mechanism by which orbitofrontal networks use value information to inform learning and choice remains unclear. One theory suggests that orbitofrontal neurons combine multiple inputs, including sensory information to compute an abstract value, so that stimulus information contributes to orbitofrontal value coding in a bottom-up fashion. Another view holds that orbitofrontal cortex makes value-related predictions that influences downstream stimulus representations in a top-down fashion. Crucially, both accounts predict that orbitofrontal neurons encode value information; the distinction lies in how that information is used at a network level. Here, we will investigate how stimulus values are processed in both local orbitofrontal networks and broader functional circuits. To assess local network properties, we will use acute neurophysiology approaches in awake, behaving monkeys as they perform a reward preference task. We will record both single neurons and local field potentials, signals believed to reflect underlying network-level function, and focus on spatiotemporal dynamics in local field potentials, and their relationship to value-encoding neurons. To assess large-scale functional networks, we will record electrocorticography (ECoG) signals from the brains of human patients undergoing intracranial monitoring in preparation for epilepsy surgery. Patients will be tested in a reinforcement-learning task, while we simultaneously record from orbitofrontal cortex and anatomically linked sensory areas that process the stimuli used in the learning task. Over the course of learning, we will determine how orbitofrontal value representations interact with sensory stimulus representations. Overall, this work will use translational approaches to determine how orbitofrontal value coding relates to network-level activity at multiple scales, which could lead to novel therapeutic approaches for conditions of aberrant reward processing, such as addiction disorders. In addition, this proposal offers outstanding training potential. I will benefit from the expertise of two established mentors Dr. Wallis who specializes in non-human primate neurophysiology, and Dr. Chang, a neurosurgeon and researcher specializing in functional brain mapping and ECoG in human patients. Their training will help me build an independent research program that combines multiple approaches to understand how reward processing impacts higher cognitive abilities such as learning, memory and decision-making.