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

描述(申请人提供)：在过去五年中，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。支持这种联系的大部分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。这些发现启发了对情节记忆功能的新思考方式，重新塑造了它的目的，即促进未来替代情景的产生或模拟，为计划和决策服务。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的大脑区域的必要性；这些信息必须来自对有病变的患者对候选大脑区域的研究。因此，关于记忆和未来思维之间功能联系的一个重要证据来源来自健忘症患者，他们的内侧颞叶结构受损，继而出现情景记忆障碍。到目前为止，这类研究仅限于少数几项研究，主要是对个别病例的审查。这项研究采用了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：阐明健忘症未来思维障碍的性质和程度；测试关于海马体对未来思维贡献的认知机制的替代理论；以及探索改善健忘症未来思维障碍的方法。该提案的第二部分代表了对默认网络的首次健忘症检查，默认网络是一个大脑区域星座，与正常认知中的未来思维有关。这些神经成像研究将使我们能够检查健忘症患者未来思维的障碍是否与默认网络区域的连接和/或激活减少有关，而这些区域之前与未来思维有关。此外，这些研究将阐明缺省网络一部分(内侧颞叶)的局灶性病变对缺省网络中其他结构之间的相关活动的影响。组成这一建议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，并形成对涉及未来思维的各种临床障碍的干预方法。 与公共健康相关：最近的研究揭示了记忆过去的能力和展望未来的能力之间的联系。在这项研究中，我们将调查健忘症患者的记忆与未来思维之间的关系，他们在记忆过去方面存在明显缺陷。我们的发现可能会形成对各种临床障碍的干预方法，这些障碍可能与记忆和未来思维有关。

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.