Medial temporal lobe contributions to short-term memory in amnesia

描述（申请人提供）：大量证据表明，内侧颞叶（MTL）在长期记忆（LTM）中起关键作用，但在短期记忆（STM）中作用很小或没有作用。然而，最近的数据对MTL功能的标准观点提出了挑战，证明了(1)当信息在短时间延迟的记忆中保存时，MTL的活动，以及(2)MTL损伤的失忆症患者的STM损伤。LTM中MTL的一个关键功能是将不同的经验元素绑定到一个统一的记忆中，这样项目就可以在以后与它们的上下文关联（情景记忆）一起被记住。一种可能性是MTL的关系绑定功能扩展到LTM域之外，也支持STM。本应用中的实验采用神经影像学和神经心理学相结合的方法，在一组MTL损伤的失忆症患者和一组神经功能完整的对照组中检验这一假设。神经心理学实验研究了(1)MTL损伤是否在多个表征层面选择性地干扰关系STM； (2) MTL损伤是否损害了STM中跨事件整合的能力，以支持泛化。如果健忘症患者在相关STM和泛化方面表现出障碍，这将反驳STM和LTM之间传统的神经解剖学区别，并将为MTL在记忆中的作用提供重要的新见解。为了补充这种神经心理学方法，神经成像程序提供了对健忘症神经病理学的全面评估，超出了标准的病变体积分析。将收集白质结构完整性（弥散张量成像）和神经元功能（功能性磁共振成像）的测量，以更好地表征可能伴随失忆症MTL损伤的局部和网络中断。通过联合解决健忘症中认知和神经中断的问题，本应用程序中的实验将为这两个领域之间的关系提供更深入的见解。将神经病理学的具体测量与行为联系起来，将澄清MTL对STM的贡献，并推进MTL功能的机制解释以及STM的理论解释。由于记忆障碍在神经系统紊乱和疾病患者中很常见，因此对这些障碍的本质及其神经基质的更深入了解将为减轻此类疾病的负担提供新的策略。

DESCRIPTION (provided by applicant): A large body of evidence suggests that the medial temporal lobes (MTL) play a critical role in long-term memory (LTM) but little or no role in short-term memory (STM). However, recent data have challenged this standard view of MTL function by demonstrating (1) activity in the MTL when information is held in memory over short delays and (2) STM impairments in amnesic patients with MTL damage. A key function of the MTL in LTM is to bind distinct elements of experience into a unified memory so that items can later be remembered with their contextual associations (episodic memory). One possibility is that the relational binding function of the MTL extends beyond the LTM domain to support STM as well. The experiments in this application use a combined neuroimaging and neuropsychological approach to test this hypothesis in a group of amnesic patients with MTL damage and a comparison group of neurologically intact controls. The neuropsychological experiments investigate (1) whether MTL damage selectively interferes with relational STM at multiple levels of representation and (2) whether MTL damage impairs the ability to integrate across events in STM to support generalization. If amnesic patients demonstrate impairments in relational STM and generalization, this would argue against traditional neuroanatomical distinctions between STM and LTM and would provide important new insight into the role of the MTL in memory. [To compliment this neuropsychological approach, the neuroimaging procedures provide a comprehensive assessment of the neuropathology in amnesia that goes beyond standard lesion volumetric analyses. Measures of both white matter structural integrity (diffusion tensor imaging) and neuronal function (functional magnetic resonance imaging) will be collected to better characterize the local and network disruptions that may accompany damage to the MTL in amnesia. By jointly addressing questions of both cognitive and neural disruptions in amnesia, the experiments in this application will provide greater insights into the relationship between these two domains.] Linking specific measures of neuropathology to behavior will clarify the contributions of the MTL to STM and advance both mechanistic accounts of MTL function as well as theoretical accounts of STM. Because memory impairments are common in patients with neurological disorders and disease, a greater understanding of the nature of these impairments and their neural substrates will inform new strategies for reducing the burden of such illnesses.