Dissociating Basal Forebrain vs. Medial Temporal Amnesia

描述(由申请人提供)：顺行性健忘症是一种特殊的记忆障碍，可由内侧颞叶(MT)损伤--包括海马体--以及基底前脑损伤引起。临床上，MT和基底前脑遗忘症看起来很相似，这导致许多研究人员提出了一个统一的“器质性遗忘症”综合征，遵循这两种病因。这项拟议的研究将更仔细地研究这种记忆障碍的潜在大脑机制，并提供一种导致这两种病因分离的替代模型。基于来自动物研究和计算模型的海马-基底前脑相互作用的证据，我们建议区分MT患者和基底前脑健忘症患者不同的学习和记忆障碍模式。具体地说，我们开发的计算模型预测，在MT损伤后，简单的联想学习通常应该是免费的，但在基底前脑损伤后，简单联想学习应该减慢(尽管不是取消)。相反，我们的模型预测，需要动物海马区调节的更复杂形式的联想学习可能在MT健忘症中被取消，但在基底前脑健忘症中保持不变。因此，该模型预测，记忆的特定区域在不同形式的健忘症中受到不同的影响。测试我们模型的初步试点工作为这种分离提供了进一步的证据，即一种简单形式的联想记忆(经典的延迟眨眼条件作用)，以前被证明在MT健忘症患者中是不存在的，但在ACoA健忘症患者中被证明是严重中断的。这项拟议的研究试图扩展这些发现，并通过使用一组反复获得的联想学习任务将试点结果扩展到各种其他学习范式，比较MT健忘症患者、前脑动脉瘤后基底前脑健忘症患者和匹配的对照组的表现，从而为人类健忘症的这种分离提供进一步的证据。如果我们提出的分离成立，这些发现不仅将扩大我们对海马体和基底前脑相互作用的理解，还可能为开发有用的治疗干预措施提供基础。具体地说，识别这两组之间不同的记忆损害模式可能会建议未来通过根据健忘症患者的特定损害模式量身定做治疗来优化患者康复的方法。

DESCRIPTION (provided by applicant): Anterograde amnesia is a specific memory impairment that can result from damage to the medial temporal (MT) lobes -- including hippocampus -- as well as from damage to the basal forebrain. Clinically, both MT and basal forebrain amnesics appear similar, which has led many researchers to posit a unified "organic amnesia" syndrome following either etiology. The proposed study will more closely examine the underlying brain mechanisms of this memory impairment and offer an alternate model resulting in the dissociation of these two etiologies. Based on evidence from both animal studies and computational modeling of hippocampal-basal forebrain interaction, we propose to differentiate distinct patterns of learning and memory impairments between persons with MT and basal forebrain amnesia. Specifically, our developed computational model predicts that simple associative learning should generally be spared following MT damage but slowed (although not abolished) following basal forebrain damage. Conversely, our model predicts that more complex forms of associative learning, which require hippocampal-region mediation in animals, may be abolished in MT amnesia but remain intact in basal forebrain amnesia. Thus, the model predicts that specific areas of memory are differentially affected in different forms of amnesia. Initial pilot work to test our model has provided further evidence for this dissociation, whereby a simple form of associative memory (classical delay eyeblink conditioning), which has previously been shown to be spared in persons with MT amnesia, was demonstrated to be severely disrupted in persons with ACoA amnesia. The proposed study seeks to extend these findings and provide further evidence for this dissociation in human amnesia by using a battery of iteratively acquired associative learning tasks to extend the pilot findings to a variety of other learning paradigms, comparing performance among individuals with MT amnesia, individuals with basal forebrain amnesia subsequent to ACoA aneurysm, and matched controls. If our proposed dissociation holds, the findings will not only expand our understanding of hippocampus and basal forebrain interactions, but may also provide a foundation for the development of useful therapeutic interventions. Specifically, the identification of distinct patterns of memory impairments between these two groups may suggest future approaches for optimizing patient rehabilitation by tailoring therapy based on an amnesic individual's specific pattern of impairment.