Dissociating Basal Forebrain vs. Medial Temporal Amnesia

描述（由申请人提供）：顺行性遗忘症是一种特殊的记忆障碍，可由内侧颞叶（包括海马体）损伤以及基底前脑损伤引起。在临床上，MT和基底前脑健忘症表现相似，这使得许多研究人员假设一个统一的“器质性健忘症”综合征。提出的研究将更仔细地检查这种记忆障碍的潜在大脑机制，并提供导致这两种病因分离的替代模型。基于动物研究和海马-基底前脑相互作用的计算模型的证据，我们提出区分MT和基底前脑失忆症患者之间不同的学习和记忆障碍模式。具体来说，我们开发的计算模型预测，MT损伤后，简单的联想学习通常不会受到影响，但基底前脑损伤后，联想学习的速度会减慢（尽管没有完全消除）。相反，我们的模型预测，在动物中需要海马区调解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完整。因此，该模型预测，不同形式的健忘症对特定记忆区域的影响是不同的。测试我们的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（经典延迟眨眼条件反射），以前被证明在MT健忘症患者中不受影响，在ACoA健忘症患者中被证明严重破坏。该研究旨在扩展这些发现，并通过使用一系列迭代获得的联想学习任务，将试点发现扩展到各种其他学习范式，比较MT失忆症患者、ACoA动脉瘤后基底前脑失忆症患者和匹配对照组的表现，为人类失忆症中的这种分离提供进一步的证据。如果我们提出的分离理论成立，这一发现不仅将扩大我们对海马和基底前脑相互作用的理解，而且可能为开发有用的治疗干预措施提供基础。具体地说，这两组之间记忆损伤的不同模式的识别可能会为未来优化患者康复的方法提供建议，即根据失忆症个体的特定损伤模式定制治疗。

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.