Neural Substrates Of Stimulus Recognition And Associatio

刺激识别和联想的神经基质

• 批准号: 7312866
• 负责人: ELISABETH A MURRAY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7312866
• 关键词: Neural; Substrates; Stimulus; Recognition; Associatio

This project made progress in several areas within the past year, including: (1) providing further evidence that a specific part of the medial temporal lobe (MTL) functions in both perception and memory, contrary to the prevailing, memory-only view; (2) establishing, also contrary to the view of many authorities, that the amygdala does not function in general stimulus-reward associations or primarily in negative emotions, but instead acts to update the current assessment of value based on drive states of both a positive and negative nature; and (3) showing that certain parts of the frontal lobe do not always need to be functioning for the inhibition of automatic behaviors to occur normally. These advances are briefly elaborated below, in turn. (1) The perirhinal cortex, a region located at the ventromedial aspect of the MTL, lies at the interface of the so-called ?MTL memory system? and the ventral visual stream. It receives inputs from both unimodal sensory areas such as area TE (which plays a key role in color and form vision) and the caudal, granular insular cortex (which plays a key role in touch), as well as from multimodal regions including the cingulate cortex and orbital frontal cortex. In studies of the perirhinal cortex, we found, contrary to the prevailing view of MTL function, that damage to each part of the MTL causes a unique set of behavioral deficits, some involving memory, others involving perception, and yet others involving response selection. The prevailing view of medial temporal lobe MTL function has two principal elements: first, that the MTL subserves memory but not perception, and second, that the many anatomically distinctive parts of the MTL function together in the service of declarative memory. Recent neuropsychological studies have, however, overturned both opinions. First, the perirhinal cortex represents information about objects for both mnemonic and perceptual purposes, including the conjunctions of features that compose individual objects, as well as the conjunctions of objects that compose visual scenes. Second, the idea that MTL components such as the hippocampus and perirhinal cortex contribute roughly equally to declarative memory has also been contradicted. The perirhinal cortex, but not the hippocampus, is essential for object recognition memory, the key test of declarative memory. By contrast, the hippocampus appears to be essential for processing information about places and paths, but it plays a small role, if any, in object recognition. These findings have been published in a follow-up of our original findings (Bussey, Saksida and Murray, 2006) and in two papers by Saksida, Bussey, Buckmaster and Murray in 2006, one in the journal Cerebral Cortex and the other in the journal Hippocampus. (2) Also in the past year, we studied the role of the amygdala and orbitofrontal cortex in affect and learning. The amygdala is widely accepted to be important for the recognition of negative emotions, such as fear, as well as for associating stimuli with aversive sensory inputs. Accordingly, research on the neuropsychology of the amygdala has focused largely on its role in learning about negative events, as assessed through fear conditioning paradigms. Its role in positive reinforcement has been relatively neglected, and sometimes denied. In contrast to the view that the amygdala functions primarily in negative reinforcement, our evidence, and those of others, shows that the amygdala also plays a central role in positive reinforcement. Accordingly, its contribution to positive emotions probably differs little, if at all, from its role in negative emotions. The amygdala endows the products of brain function with emotional valence by linking initially neutral neural representations with innate responses and performance rules. Higher brain functions so endowed include concepts and categories, learned response rules and strategies, analogies and inferences, and emotionally laden language. In addition, the amygdala functions in close relationship with the orbitofrontal cortex. The behavioral effects of amygdala lesions generally parallel those of orbitofrontal cortex lesions, and several investigators have emphasized the consistent association between the emotional changes and deficits in reversal learning and extinction that accompany either amygdala or orbitofrontal cortex damage. Dysfunctional interactions of the amygdala and orbitofrontal cortex with other regions are thought to underlie a host of psychiatric disorders, including clinical depression, bipolar disorder, obsessive-compulsive disorder, and schizophrenia. Our work has examined the specific and joint contributions of these two key components of the limbic system in order to correct misconceptions inherent in current medical thinking about their functions and to guide future research. We found that unilateral lesions of the amygdala-orbitofrontal cortex circuit disrupt affective processing, that the orbitofrontal cortex is critical for response selection based on predicted reward outcomes, regardless of whether the value of the outcome is predicted by affective signals (reinforcer devaluation) or by visual signals conveying reward contingency (object-reversal learning), that amygdala lesions facilitated the extinction of instrumental responses, and that lesions of the orbitofrontal cortex had the opposite effect (Izquierdo and Murray, 2006; Murray, Izquierdo and Malkova, 2006, chapter in preparation; Murray and Baxter, 2006). (3) In addition, we followed up an earlier study which found that subjects can master the reversed-contingency task, a task in which the smaller of two payoffs must be chosen in order to receive the larger of the two. We discovered that orbitofrontal lesions do not affect this aspect of inhibitory control (Chadusama, Kralik and Murray, 2006). In addition to these three main lines of research, we found that mental predictions, called prospective memories, are necessary in order to learn how to learn, a process called a ?learning set? (Murray and Gaffan, 2006).

该项目在过去一年中在多个领域取得了进展，包括：（1）提供了进一步的证据，证明内侧颞叶（MTL）的特定部分在感知和记忆方面都有功能，这与普遍的仅记忆观点相反； （2）与许多权威人士的观点相反，确定杏仁核不在一般刺激-奖励关联或主要在消极情绪中发挥作用，而是根据积极情绪和积极情绪的驱动状态来更新当前的价值评估。和消极的性质； （3）表明额叶的某些部分并不总是需要发挥作用才能抑制自动行为的正常发生。下面依次简要阐述这些进展。 (1) 鼻周皮层是位于 MTL 腹内侧的区域，位于所谓的“MTL 记忆系统”的接口处。和腹侧视觉流。它接收来自单模态感觉区域的输入，例如 TE 区域（在颜色和形状视觉中发挥关键作用）和尾部颗粒岛叶皮层（在触觉中发挥关键作用），以及来自包括扣带回在内的多模态区域的输入皮质和眶额皮质。在对鼻周皮层的研究中，我们发现，与 MTL 功能的普遍观点相反，MTL 各部分的损伤会导致一系列独特的行为缺陷，一些涉及记忆，另一些涉及感知，还有一些涉及反应选择。内侧颞叶 MTL 功能的流行观点有两个主要要素：首先，MTL 促进记忆，但不促进感知；其次，MTL 的许多解剖学上独特的部分共同发挥作用，为陈述性记忆服务。然而，最近的神经心理学研究推翻了这两种观点。首先，鼻周皮层代表用于记忆和感知目的的物体信息，包括构成单个物体的特征的连接，以及构成视觉场景的物体的连接。其次，海马体和嗅周皮层等 MTL 成分对陈述性记忆的贡献大致相同的观点也受到了矛盾。鼻周皮层（而非海马体）对于物体识别记忆至关重要，而物体识别记忆是陈述性记忆的关键测试。相比之下，海马体似乎对于处理有关地点和路径的信息至关重要，但它在物体识别中发挥的作用很小（如果有的话）。这些发现已发表在我们最初发现的后续文章中（Bussey、Saksida 和 Murray，2006 年）以及 Saksida、Bussey、Buckmaster 和 Murray 在 2006 年发表的两篇论文中，一篇发表在《大脑皮层》杂志上，另一篇发表在《大脑皮层》杂志上海马体。 (2) 同样在过去的一年里，我们研究了杏仁核和眶额皮质在情感和学习中的作用。杏仁核被广泛认为对于识别负面情绪（例如恐惧）以及将刺激与厌恶的感官输入联系起来很重要。因此，对杏仁核神经心理学的研究主要集中在其在学习负面事件中的作用，通过恐惧调节范式进行评估。它的积极强化作用相对被忽视，有时甚至被否认。与杏仁核主要在负强化中发挥作用的观点相反，我们和其他人的证据表明，杏仁核在正强化中也发挥着核心作用。因此，它对积极情绪的贡献可能与其在消极情绪中的作用几乎没有差别（如果有的话）。杏仁核通过将最初的中性神经表征与先天反应和表现规则联系起来，赋予大脑功能的产物以情感效价。如此赋予的高级大脑功能包括概念和类别、习得的反应规则和策略、类比和推理以及充满情感的语言。此外，杏仁核的功能与眶额皮质密切相关。杏仁核损伤的行为影响通常与眶额皮层损伤的行为影响相似，一些研究人员强调了伴随杏仁核或眶额皮层损伤的情绪变化与逆转学习和消退缺陷之间的一致关联。杏仁核和眶额皮质与其他区域功能失调的相互作用被认为是许多精神疾病的基础，包括临床抑郁症、双相情感障碍、强迫症和精神分裂症。我们的工作研究了边缘系统这两个关键组成部分的具体和共同贡献，以纠正当前医学思维中对其功能固有的误解并指导未来的研究。我们发现，杏仁核-眶额皮层回路的单侧损伤会破坏情感处理，并且眶额皮层对于基于预测奖励结果的反应选择至关重要，无论结果的价值是通过情感信号（强化物贬值）还是通过情感信号（强化物贬值）来预测。传达奖励偶然性的视觉信号（对象反转学习），杏仁核损伤促进了工具反应的消失，以及眶额皮质的损伤产生了相反的效果（Izquierdo 和 Murray，2006 年；Murray、Izquierdo 和 Malkova，2006 年，准备章节；Murray 和 Baxter，2006 年）。 （3）此外，我们跟进了一项早期研究，发现受试者可以掌握反向偶然任务，在该任务中，必须选择两个收益中较小的一个，才能获得两个收益中较大的一个。我们发现眶额损伤不会影响抑制控制的这方面（Chadusama、Kralik 和 Murray，2006）。除了这三个主要研究方向之外，我们发现，为了学习如何学习，称为“学习集”的过程，心理预测（称为前瞻性记忆）是必要的。 （默里和加凡，2006）。