| Abstract: | 探討決策認知行為的神經基礎，是最近神經科學研究的重點之一。決策選擇背後的動機因素，是多種認知行為內含的核心歷程。神經科學研究大腦內多巴胺主導行為發展與建構初等級之酬賞動機議題的工作雖然都是持續的在推展，但是對於與酬賞相關的較高等認知學習功能的議題研究則仍有許多不明之處，例如：以成本利益為分析導向的決策。雖然與這個例子有關的延宕酬賞減扣的研究已於近期開始受到注意，但對於另一類由不等機率況下獲得酬賞影響的減扣效果所致之行為反應（又稱風險選擇），則尚有更多待釐清其行為神經機制之處。已有漸增的文獻指出大腦多巴胺有參與注意力歷程，或以成本利益分析行為增強的歷程，或甚至預測失誤之心智監控反應。本研究循此進一步假設大腦多巴胺的行為功能與風險選擇是有關的，然而這項假設尚未建立嚴謹實驗控制的資料，特別是針對鼠類動物實驗探討風險選擇行為的神經機制。據此，本研究計劃將以三年的時間設定六項實驗以檢視大腦多巴胺是如何參與支配風險選擇行為。實驗一及實驗二分別操弄獲較高酬賞的風險機率、不等的期望值、及不同動機狀態，有系統的測試以建立鼠類動物在T 型迷津上的風險選擇行為。實驗三操弄神經毒素破壞八個大腦多巴胺有關的腦區部位，以測試其對風險選擇行為表現的影響效果。實驗四就其中有明顯破壞影響效果的腦區，針對在該區的多巴胺D1 及D2 亞型受器，以周邊及中樞的神經藥理的方式檢視多巴胺致效劑及拮抗劑對風險選擇行為的影響。實驗六將以上述實驗所收集的行為數據建立數學函數，模擬風險選擇行為及其內涵大腦在解剖部位及受器層面的機制。本計畫將以嚴謹的動物實驗操弄大腦多巴胺系統與風險選擇行為所得之動物實驗資料，來剖析大腦多巴胺的認知功能。
To study the neural mechanisms for cognitive behavior such as decision making is now a major mission in contemporary neuroscience. The motivation involved in decision making or choice is the core of many kinds of cognitive behavior, which could serve as the basis of economical activity in humans and/or other animal species. The progress of investigating the neural mechanisms of brain dopamine (DA) underlying the primary reward motivation to drive the organization and development of behavior has been continuing in neuroscience. However, it remains uncertain about how brain DA systems mediate the higher order cognitive function such as decision making or choice behavior. Despite the issue of delay reward discounting is getting focused in recent years, a similar but in different domain of reward discounting so-called probabilistic reward discounting remains obscure for its underlying neurobehavioral mechanisms. In real life, for all kinds of animals including human, there is no perfect certainty that will (not) lead to a certain end. This type of behavioral phenomena has been studied as the risky choice in the decision science, but not in neuroscience until recently. A growing body of evidence shows that brain DA systems are involved in attention processing, the cost/benefit analysis of behavioral reinforcement, or prediction error. Thus, it is posited that behavioral function of mesocorticolimbic DA systems could be sub-serving for risky choice. However, there is still short of well-controlled empirical data collected from the rodent animal to deal with the neural mechanisms of risky choice. Accordingly, this 3-year project proposes, with six experiments designed, to study how the brain DA systems are involved in risky choice behavior in the rat. First two experiments intend to establish an animal model of risky choice behavior in a T-maze by systemically manipulating the probabilities with different expected values and further tested in different motivational states. Following this animal model set up, Experiment 3 applying neurotoxin lesion techniques will examine whether the performance of risky choice would be affected after the damage of certain brain DA area(s). The eight brain sites to be detected are all related to the terminal areas of the mesocorticolimbic DA systems including the medial prefrontal cortex, orbital frontal cortex, anterior cingulated cortex, nucleus accumbens, dorsolateral striatum, amygdale, dorsal hippocampus and ventral hippocampus. Experiment 4 and Experiment 5 will run neuropharmacological challenges from systemic injection to local infusion of DA agonists and antagonists to verify the role of DA in modulating the performance of risky choice. Experiment 6 will take behavioral data of risky choice into axiomatic modeling, which will be further tested for the fitness or deviation by emerging with other related data of pharmacological tests. This proposed project manipulates dopamine and risky choice behavior, which data collected from these stringent animal experiments are expected to further elaborate the cognitive function of brain dopamine. |
