Neural Substrates Of Stimulus Recognition And Association Memory

刺激识别和关联记忆的神经基质

基本信息

项目摘要

As a first step toward the current goals and objectives of this project, we have begun to study hippocampal-prefrontal interaction with diffusion tensor imaging (DTI), a method that can reveal connections between brain regions, as well as alterations in connections that occur with normal development and following brain damage. We have proposed that prefrontal areas create the kind of cross-domain, analogical, and metaphorical knowledge that is thought to underlie advanced cognition. When that knowledge interacts with the hippocampal complex, what emerges is the human ability to encode and recollect knowledge consciously and to embed ourselves in these facts and events, both real and imagined, in both space and time, thereby creating a coherent, conscious life experience. We know that the prefrontal cortex and hippocampus interact via both direct and indirect connections. The indirect connection involves entorhinal cortex. The prevailing model of object memory emphasizes the role of the entorhinal cortex as a sensory gateway through which the neocortex sends information to the medial temporal lobe. But it is well known that the connections between these brain structures run both ways. As we focus more on the role of the hippocampal complex in object memory, the entorhinal cortex takes on increased importance as an indirect route connecting the hippocampus to the prefrontal cortex. This idea finds support in recent findings from another laboratory that damage to either direct hippocampal outputs or indirect outputs (entorhinal cortex) causes a large deficit on an object-in-scene memory task. It is in this context that we have begun collaborative work using DTI. DTI provides a valuable tool for assessing presumptive white matter alterations in human disease and in animal models. Although the brain substrates for object memory are frequently studied with lesion techniques, the distal effects of such lesions on other memory-related brain regions remains unknown. In the current project, we used DTI to examine the effects of selective neurotoxic lesions of the hippocampus on major white matter tracts and the brain regions receiving inputs from those tracts. First, we evaluated the extent of damage to the hippocampal complex, defined as the dentate gyrus, CA1-3 fields, presubiculum, subiculum, and parasubiculum. Next, DTI analysis was conducted on the corpus callosum, fornix, the white matter of the temporal stem, the cingulum bundle, the subcortical white matter of the ventromedial prefrontal cortex, and the optic radiations. The lesions caused a 72% decrease of hippocampal volume in the lesion group compared to the controls, without any apparent inadvertent damage in adjacent regions. DTI analysis showed that, of the fiber tracts examined, only the fornix and ventromedial prefrontal white matter were affected by the lesion. The findings show that hippocampal damage leads to alterations in other brain regions involved in object memory, including portions of the prefrontal cortex. This part of the project provides a new tool for examining hippocampal-complex function and hippocampal-prefrontal interactions in both clinical settings and in animal models. A second part of this project examines the possibility of studying the role of the hippocampal complex and hippocampal-prefrontal interactions in second-order assessments of object memory. Memory awareness, also called metamemory, can be assessed by measuring how often subjects collect information. When they lack any memory of an object, subjects will seek out information, but when they have a clear memory, they will not. In our study (Basile et al., 2009), subjects searched for an object after either watching the experimenter put it into of four opaque tubes or when they had not been allowed to watch the object being put into the tube. In this circumstance, the behavior of subjects can reveal what they know about the contents of their own object memories. This second part of the project should provide a new method for examining memory awareness in animal models. A third part of this project involves an exploration of the role of the hippocampal complex in the memory for object-object associations and object-response associations. We have previously shown that the hippocampal complex is necessary for rapid learning of object-response associations. However, we have also obtained some evidence that the hippocampal complex is not necessary for learning object-object associations, also known as paired-associate learning. Our work on object-response associations notwithstanding, the results from object-object learning could mean that the hippocampal system is uninvolved in associative learning when neither component of the association is spatial in nature. Later work on this project, however, showed that lesions of the hippocampal complex cause a deficit in learning object-response associations when neither the object nor the response is spatial in nature. The deficits seen in that experiment were virtually identical to those observed when the response was spatial. This finding has led us to reexamine the role of the hippocampal complex in the memory for object-object associations. In our previous study of object-object associations, subjects learned the associations slowly, so it remains an open question whether hippocampal-complex damage would cause deficits on rapid learning of this type. In the past year, we have trained subjects to learn both object-object and object-response associations rapidly. In the next year, we will examine the effects of reversible inactivations of the two main parts of the hippocampal complex, the hippocampus proper and the subiculum, separately and in combination with inactivation of the entorhinal cortex. We predict that a dramatic deficit will occur only when both the direct and indirect outputs of hippocampus to the prefrontal cortex are blocked. This means that large deficits should occur only when both subiculum and entorhinal cortex are inactivated, disrupting the direct and indirect pathways, respectively. We predict that this inactivation will show that the hippocampal complex is necessary for the rapid learning of new object-object associations, but not for the recollection of previously learned object-object associations.
作为实现本项目当前目标的第一步,我们已经开始用弥散张量成像(DTI)研究海马-前额叶相互作用,这种方法可以揭示大脑区域之间的联系,以及正常发育和脑损伤后发生的连接变化。我们已经提出,前额叶区域创造了一种跨领域、类比和隐喻的知识,被认为是高级认知的基础。当这些知识与海马体复合体相互作用时,出现的是人类有意识地编码和回忆知识的能力,并将自己嵌入这些事实和事件中,无论是真实的还是想象的,无论是空间还是时间,从而创造出连贯的、有意识的生活体验。我们知道前额皮质和海马体通过直接和间接的联系相互作用。这种间接联系涉及到内嗅皮层。客体记忆的主流模型强调内嗅皮层作为感觉通道的作用,新皮层通过它向内侧颞叶发送信息。但众所周知,这些大脑结构之间的联系是双向的。当我们更多地关注海马体复合体在物体记忆中的作用时,内嗅皮层作为连接海马体和前额叶皮层的间接途径变得越来越重要。这一观点得到了另一个实验室最近的研究结果的支持,即海马直接输出或间接输出(内嗅皮层)的损伤会导致场景中物体记忆任务的严重缺陷。正是在这种背景下,我们开始使用DTI进行协作工作。DTI为评估人类疾病和动物模型中假定的白质改变提供了有价值的工具。虽然客体记忆的脑基质经常被用损伤技术研究,但这种损伤对其他记忆相关脑区域的远端影响仍然未知。在当前的项目中,我们使用DTI来检查海马选择性神经毒性病变对主要白质束和从这些白质束接收输入的大脑区域的影响。首先,我们评估了海马复合体的损伤程度,定义为齿状回、CA1-3野、下背、下背和副耻骨。接下来,对胼胝体、穹窿、颞干白质、扣带束、腹内侧前额叶皮层皮层下白质、视神经辐射进行DTI分析。与对照组相比,病变组的海马体积减少了72%,邻近区域没有任何明显的无意损伤。DTI分析显示,在检查的纤维束中,只有穹窿和腹内侧前额叶白质受到病变的影响。研究结果表明,海马体损伤会导致与物体记忆有关的其他大脑区域发生改变,包括部分前额皮质。该项目的这一部分为在临床环境和动物模型中检查海马体复合体功能和海马体-前额叶相互作用提供了一个新的工具。

项目成果

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ELISABETH A MURRAY其他文献

ELISABETH A MURRAY的其他文献

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{{ truncateString('ELISABETH A MURRAY', 18)}}的其他基金

Neural Substrates Of Stimulus Recognition And Associatio
刺激识别和联想的神经基质
  • 批准号:
    6541858
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural Substrates Of Stimulus Recognition And Association Memory
刺激识别和关联记忆的神经基质
  • 批准号:
    8745696
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural mechanisms of reward processing and emotion
奖励处理和情绪的神经机制
  • 批准号:
    9357294
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural Substrates of Stimulus Recognition and Association Memory
刺激识别和联想记忆的神经基质
  • 批准号:
    10703908
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural Substrates Of Stimulus Recognition And Association Memory
刺激识别和关联记忆的神经基质
  • 批准号:
    8556923
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural substrates of reward processing and emotion
奖励处理和情绪的神经基质
  • 批准号:
    8158140
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural Substrates Of Stimulus Recognition And Associatio
刺激识别和联想的神经基质
  • 批准号:
    6823947
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural Substrates of Reward Processing and Emotion
奖励处理和情绪的神经基础
  • 批准号:
    10703932
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural substrates of reward processing and emotion
奖励处理和情绪的神经基质
  • 批准号:
    8939993
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
Neural mechanisms of reward processing and emotion
奖励处理和情绪的神经机制
  • 批准号:
    7969447
  • 财政年份:
  • 资助金额:
    $ 73.18万
  • 项目类别:
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