Neural Mechanisms of Learning and Memory in Vision

视觉学习和记忆的神经机制

基本信息

批准号：
9568238
负责人：
MORTIMER MISHKIN
金额：
$ 27.69万
依托单位：
NATIONAL INSTITUTE OF MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9568238
关键词：
Address Age Aging Alzheimer&apos s Disease Amnesia Anterior Anterior Nuclear Group Atrophic Back Behavioral Bilateral Biological Preservation Birth Body part Brain Injuries Cerebrum Characteristics Child Child health care Chronic Cognitive Collaborations Corpus striatum structure Cues Cyanosis Data Detection Development Electrophysiology (science)Environment Episodic memory Event Familiarity Functional Magnetic Resonance Imaging Goals Heart Diseases Hippocampus (Brain)Hypoxia Image Impairment Infant Injury Institutes Investigation Joystick Knowledge Lead Learning Left Lesion Life Location London Macaca mulatta Medial Medial Dorsal Nucleus Mediating Memory Memory impairment Metabolic Methods Mind Modality Monkeys Neurobiology Neurologic Operative Surgical Procedures Participant Pathology Patients Pattern Pediatric Hospitals Performance Perinatal Pharmacology Play Prefrontal Cortex Process Research Retrieval Rewards Risk Rodent Role Rural Schizophrenia Semantics Sensory Side Stimulus Stream Structure Syndrome System Techniques Testing Thalamic structure Transposition of Great Vessels Travel Universities Variant Vision Visual Visual Cortex Visual Fields Work base cohort college experience extrastriate visual cortex habit learning infancy insight memory process memory recognition middle childhood morris water maze multidisciplinary neonate neuroimaging neuromechanism nonhuman primate preference professor relating to nervous system response sound spatial memory virtual reality visual memory way finding

项目摘要

The essential circuit for both item and associative stimulus recognition in any given sensory modality consists of the relevant cortical sensory processing stream(s), the medial temporal rhinal cortex, the ventromedial prefrontal cortex, and the medial dorsal nucleus of the thalamus. Context-free recall, familiarity based recognition, or fact memory, seems to depend primarily on the above basic memory circuit. Associative recall, recollection-based recognition, or event memory, seems to depend in addition on a higher-order circuit superimposed on the basic one and consisting of the hippocampus, mammillary body, and anterior thalamic nuclei. Several years ago we discovered that hypoxic/ischemic events sustained within the first year of life may result in a form of amnesia. This 'developmental amnesia' (DA) is characterized by markedly impaired episodic (or event) memory combined with relative preservation of both semantic (or fact) memory and familiarity-based recognition memory, and is associated with medial temporal pathology restricted to the hippocampus. Transposition of the great arteries (TGA) is the second most common chronic heart disease in early infancy. As a result, infants often suffer significant cyanosis at birth and are at risk of HI damage prior to and during corrective surgery. The hippocampus is particularly sensitive to HI insults during development, therefore we studied the effects of early HI on hippocampal structure and function in infants with TGA. We examined neonates who had surgery for TGA shortly after birth and a group of normally developing controls. Age corrected mean hippocampal volumes were shown to be significantly smaller in the TGA group compared to normal controls. Controls demonstrated a significant novelty preference in contrast to infants with TGA who did not. Larger mean hippocampal volumes were associated with stronger novelty preference across all subjects, albeit, this association was particularly strong in the TGA cohort. This study provides important new information giving us insight into the cascade of events that lead to a profile of compromised hippocampal volumes and memory impairments in middle childhood in patients with TGA. In addition, it provides support to the idea that the hippocampus contributes to the detection of novelty from an early age. In DA subjects despite the systemic impact of HI, the resulting brain damage is largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hippocampal-diencephalic network and are therefore also at risk of injury following HI events. We therefore conducted a neuroimaging investigation of diencephalic damage in a group of 18 patients with DA (age range 11-35 years), and an equal number of controls. Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in two thirds of our patients. In addition, as a group, patients had mildly reduced thalamic volumes. The size of the anterior-mid thalamic segment was correlated with patients' visual memory performance. Thus, in addition to the hippocampus, diencephalic structures also appear to play a role in the patients' memory deficit. Recollection involves bringing back to mind a prior event, including the sights and sounds associated with that experience. Patients with DA show a deficit in recollection such that they are not able to recall unique experiences, yet are able to generalise across multiple similar events. It is possible that some contextual information is retrieved in DA at a level which is insufficient to support recall, but sufficient for a decontextualized representation of the event. To test this hypothesis, we investigated context reinstatement in patients with DA. On each encoding trial, a word was overlaid on an image and presented on the left, center, or right side of the visual field. The background images were rural, urban and scrambled scenes. Two memory tasks were conducted during fMRI. In the Background task, participants were instructed to remember the image that accompanied each word, whereas in the Location task, they had to remember the location in which each word was presented. Behaviorally, all controls performed above chance, whereas patients performed at chance levels. fMRI data in the controls showed the typical pattern of scene reinstatement, such that words that were previously paired with scenes were associated with greater activity in the parahippocampal and retrosplenial cortices than words paired with scrambled scenes. Interestingly, patients also showed scene reinstatement effects, but these were localized in the visual cortex, and not the regions that are typically associated with scene memory. For both groups, scene reinstatement effects were present in the Background Task, but not in the Location Task, suggesting that reinstatement is dependent on the retrieval goal. A functional localizer indicated that scene processing engaged the same regions in both groups. These data indicate that DA patients are able to reinstate aspects of their prior experience (i.e. visual context) in a strategically-directed way, but that this reinstatement is qualitatively different from that of controls and is insufficient to support context-dependent memory responses. We conclude that limited sub-threshold context memory processes occur in DA, despite the profound impairment in recollection. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic or recollection memory but to allocentric spatial memory. We investigated the effect of hippocampal lesions on allocentric spatial navigational memory in monkeys using a virtual environment. The task, a variant of the Morris Water Maze, which has been used extensively to test navigational spatial memory in rodents, required monkeys to use a joystick to navigate to a rewarded location within a circular arena. This circular arena resided in a larger hexagonal room, with six unique images at the walls of the room providing cues for orientation. The orientation cues, as well as the rewarded location within the arena, were different on each testing day, thus providing a different allocentric spatial memory problem in each session. In each trial, monkeys started navigating from a random location within the circular arena. Performance was assessed as the ratio between the distance traveled and the optimal distance, given each trial's starting location. To our surprise, neither learning rate nor ceiling performance was significantly reduced after bilateral lesions of the hippocampus. The results thus suggest that the integrity of the hippocampus in rhesus monkeys may not be critical for memory-based allocentric spatial navigation in this virtual reality environment.

任何给定的感觉方式中项目和联想刺激识别的基本电路包括相关的皮质感觉加工流（S），内侧颞鼻皮层，腹前额叶皮层和丘脑的内侧背核。无上下文召回，基于熟悉的识别或事实记忆似乎主要取决于上述基本内存电路。联想召回，基于回忆的识别或事件记忆似乎还取决于叠加在基本层面的高阶电路，并由海马，乳房乳腺和前丘脑核组成。几年前，我们发现在生命的第一年内进行的低氧/缺血事件可能导致失忆症。这种“发育性健忘症”（DA）的特征在于显着受损的情节性（或事件）记忆，以及对语义（或事实）记忆和基于熟悉度的识别记忆的相对保留，并且与限于海马的内侧时间病理相关。大动脉（TGA）的转位是婴儿早期第二常见的慢性心脏病。结果，婴儿在出生时经常遭受明显的紫cy症，并且在矫正手术前和矫正手术期间都有HI损害的风险。海马在发育过程中对HI侮辱特别敏感，因此我们研究了早期HI对TGA婴儿海马结构和功能的影响。我们检查了出生后不久接受过TGA手术的新生儿，并进行了一组正常的控制控制。与正常对照相比，TGA组的年龄校正平均海马体积在TGA组中明显小得多。与没有TGA的婴儿相比，对照表现出很大的新颖性偏好。较大的平均海马体积与所有受试者的新颖性偏好相关，尽管这种关联在TGA队列中尤为强。这项研究提供了重要的新信息，使我们深入了解了一系列事件，这些事件导致TGA患者中童年中期童年时期的海马体积和记忆障碍。此外，它为海马有贡献从小发现新颖性的想法提供了支持。在DA受试者中，尽管有HI的全身影响，但最大程度的脑损伤在很大程度上仅限于海马。但是，丘脑和乳房机构是海马 - 缺乏脑网络的一部分，因此在HI事件后也有受伤的风险。因此，我们对18例DA患者（年龄范围11-35岁）和相等数量的对照组进行了神经成像研究。重要的是，我们在三分之二的患者中发现了乳腺体体的显着萎缩程度。另外，作为一个小组，患者的丘脑体积略有减少。前中丘脑段的大小与患者的视觉记忆表现相关。因此，除了海马外，双脑结构似乎在患者的记忆不足中也起作用。回忆涉及将事先事件带回来，包括相关的景点和声音有了这种经验。 DA患者在回忆方面表现出不足，因此他们无法回忆起独特的经历，但能够在多个类似事件中概括。在DA中，某些上下文信息可能以不足以支持召回的级别检索，但足以对事件的脱皮表表示。为了检验这一假设，我们研究了DA患者的恢复环境。在每个编码试验中，一个单词被覆盖在图像上，并在视野的左，中心或右侧呈现。背景图像是乡村城市和争夺场景。在fMRI期间进行了两项记忆任务。在背景中任务，指示参与者记住每个单词随附的图像，而在他们必须记住每个单词的位置。在行为上，所有控件均在上述机会上进行，而患者则以偶然的水平进行。控件中的fMRI数据显示了场景恢复的典型模式，因此，与现场相比，以前与场景配对的单词与与拼命的场景配对的单词相关。有趣的是，患者还表现出场景恢复效果，但这些效果位于视觉皮层中，而不是通常与场景记忆相关的区域。对于这两个组，背景任务中都存在场景恢复效果，但在位置任务中不存在，这表明恢复原状取决于检索目标。功能定位器表明，场景处理在两组中都参与了相同的区域。这些数据表明，DA患者能够以战略性指导的方式恢复其先前经验（即视觉上下文）的各个方面，但是这种恢复与控制的质量不同，并且不足以支持上下文依赖上下文的内存响应。我们得出的结论是，尽管回忆严重损害，但在DA中发生了有限的子阈值上下文记忆过程。在整个物种中，海马对记忆的最公认的贡献可能不是对情节性或回忆记忆，而是对同源的空间记忆。我们使用虚拟环境研究了海马病变对猴子中同类空间导航记忆的影响。这项任务是莫里斯水迷宫的一种变体，已广泛用于测试啮齿动物中的导航空间内存，要求猴子使用操纵杆来导航到圆形竞技场内的奖励位置。这个圆形的竞技场位于更大的六角室，房间的墙壁上有六个独特的图像，提供了方向提示。在每个测试日，方向提示以及竞技场内的奖励位置都是不同的，因此在每个会话中都提供了不同的以中为中心的空间记忆问题。在每个试验中，猴子开始从圆形竞技场内的一个随机位置导航。鉴于每个试验的起始位置，绩效被评估为行进距离与最佳距离之间的比率。令我们惊讶的是，在海马双侧病变后，学习率和天花板性能都没有大大降低。因此，结果表明，在这个虚拟现实环境中，恒河猴中海马的完整性对于基于内存的中心空间导航可能并不重要。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.

DOI：
10.1093/cercor/bht332
发表时间：
2015-06
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
0
作者：
Cooper JM;Gadian DG;Jentschke S;Goldman A;Munoz M;Pitts G;Banks T;Chong WK;Hoskote A;Deanfield J;Baldeweg T;de Haan M;Mishkin M;Vargha-Khadem F
通讯作者：
Vargha-Khadem F

Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy.

早期获得性海马萎缩患者的自序工作记忆任务受损。

DOI：
10.1016/j.dcn.2016.06.001
发表时间：
2016
期刊：
Developmental cognitive neuroscience
影响因子：
4.7
作者：
Geva,Sharon;Cooper,JanineM;Gadian,DavidG;Mishkin,Mortimer;Vargha-Khadem,Faraneh
通讯作者：
Vargha-Khadem,Faraneh

Complementary Patterns of Direct Amygdala and Hippocampal Projections to the Macaque Prefrontal Cortex.