Looking Ahead in Amnesia: Cognitive and Neural Mechanisms of Future Thinking

描述（由申请人提供）：在过去的五年中，记忆研究中最令人兴奋的发展之一是发现了记忆过去的能力和展望未来的能力之间的联系。这种联系的大部分支持证据来自正常认知的神经成像研究，这些研究表明，对未来的思考涉及到一组核心的大脑结构，这些结构传统上与情景记忆有关。这些发现启发了思考情景记忆功能的新方法，将其目的重新定位为促进未来情景的生成或模拟，以服务于规划和决策。然而，神经成像研究的一个局限性是，它们不能解决任务执行中激活大脑区域的必要性；这些信息必须来自于对候选脑区病变患者的研究。因此，关于记忆和未来思维之间的功能联系的一个重要证据来源来自于健忘症患者，他们的内侧颞叶结构受损，情节记忆受损。迄今为止，这类研究仅限于少数几个以个案检查为主的研究。本研究采用行为和神经成像技术，对健忘症患者的记忆和未来思维之间的关系进行了系统的研究。该提案的第一部分包括一系列行为实验，旨在阐明健忘症中未来思维障碍的性质和程度；测试海马体对未来思维的认知机制的替代理论；探索改善未来失忆症中思维障碍的方法。该提议的第二部分是对失忆症中默认网络的首次研究，默认网络是一组大脑区域，与正常认知中的未来思考有关。这些神经成像研究将使我们能够检查失忆症中未来思维的损伤是否与先前与未来思维相关的默认网络区域的连接减少和/或激活有关。此外，这些研究将阐明默认网络的一部分（内侧颞叶）的局灶性病变对默认网络内其他结构之间相关活动的影响。包含本提案的研究有可能加深我们对未来思维的认知和神经基础的理解，为未来思维及其与情景记忆的关系的理论提供重要的约束，并形成涉及未来思维的各种临床疾病的干预方法。

DESCRIPTION (provided by applicant): One of the most exciting developments in memory research over the past five years is the discovery of a link between the ability to remember the past and the ability to envision the future. The bulk of the supporting evidence for this link comes from neuroimaging studies in normal cognition, which demonstrate that thinking about the future engages a core set of brain structures that have traditionally been associated with episodic remembering. These findings have inspired new ways of thinking about the function of episodic memory, re- casting its purpose as one of facilitating the generation or simulation of alternative future scenarios in the service of planning and decision-making. A limitation of neuroimaging studies, however, is that they cannot address the necessity of activated brain areas for task performance; such information must come from studies of patients with lesions to candidate brain areas. Thus, an important source of evidence about the functional link between memory and future thinking comes from amnesic individuals, who have lesions to medial- temporal lobe structures and consequent impairments in episodic memory. To date, such research has been limited to a handful of studies predominated by examination of individual cases. The present proposal represents a systematic investigation of the relationship between memory and future thinking in amnesia, using both behavioral and neuroimaging techniques. The first part of the proposal comprises a series of behavioral experiments aimed at: elucidating the nature and extent of the future thinking impairment in amnesia; testing alternative theories about the cognitive mechanisms that characterize hippocampal contributions to future thinking; and exploring ways to ameliorate the future thinking impairment in amnesia. The second part of the proposal represents the first examination in amnesia of the default network, a constellation of brain areas that have been implicated in future thinking in normal cognition. These neuroimaging studies will allow us to examine whether impairments in future thinking in amnesia are associated with reduced connectivity and/or activation in regions of the default network that have previously been linked to future thinking. Further, these studies will elucidate the effect of a focal lesion in one part of the default network (the medial temporal lobe) on the correlated activity among other structures within the default network. The studies comprising this proposal have the potential to deepen our understanding of the cognitive and neural underpinnings of future thought, to provide important constraints on theories of future thinking and its relation to episodic memory, and to shape interventional approaches to a variety of clinical disorders in which future thinking is implicated. PUBLIC HEALTH RELEVANCE: Recent research has revealed a link between the ability to remember the past and the ability to envision the future. In this study, we will investigate the relationship between memory and future thinking in amnesic individuals, who have marked deficits in remembering the past. Our findings may shape interventional approaches to a variety of clinical disorders in which memory and future thinking may be implicated.