Neurohypophyseal principles and memory.

The neurohypophyseal hormones vasopressin and oxytocin modulate memory processes. Vasopressin facilitates, while oxytocin attenuates memory consolidation and retrieval. These influences are located in different regions of the molecules. Thus, the neurohypophyseal hormones act as precursor molecules for neuropeptides involved in memory processes. The covalent ring structures of both vasopressin and oxytocin mainly affect consolidation; the linear parts, retrieval processes; while nearly the whole oxytocin or vasotocin molecule is needed for attenuation of consolidation and retrieval. Regional studies, utilizing microdissection techniques in combination with a sensitive radioenzymatic catecholamine assay, revealed a distinct pattern of effects on cerebral alpha-methyl-p-tyrosine methylester-induced catecholamine disappearance following intraventricular vasopressin administration in limbic midbrain structures. In situations in which the amount of bioavailable vasopressin in the brain is absent, as is the case in the Brattleboro rat with hereditary diabetes insipidus, or neutralized in normal Wistar rats following the intraventricular administration of antivasopressin serum, regional catecholamine disappearance in most cases is altered in a direction opposite to that observed after intracerebroventricular vasopressin administration. These results indicate that vasopressin modulates memory processes by modulation of neurotransmission in distinct catecholamine systems. Recent experiments suggest that the influence of vasopressin on memory consolidation is mediated by the dorsal noradrenergic bundle via terminal regions of this bundle.     

Episodic memory: new insights from the study of semantic dementia.

The study of patients with semantic dementia, the temporal variant of frontotemporal dementia, has provided new insights into the interaction between episodic and semantic memory, and the different roles played by various structures in the temporal lobe. Recent findings indicate that the syndrome of semantic dementia can inform us about the organisation of long-term memory and the relationship between semantic memory and other cognitive systems.     

Behavioural actions of neurohypophysial peptides

The neurohypophysial hormones vasopressin and oxytocin modulate memory processes. Vasopressin facilitates while oxytocin attenuates memory consolidation and retrieval. These influences are located in different regions of the molecules. Thus, the neurohypophysial hormones act as precursor molecules for neuropeptides involved in memory processes. The covalent ring structures of both vasopressin and oxytocin mainly affect consolidation, the linear parts, retrieval processes, while nearly the whole oxytocin or vasopressin molecule is needed for attenuation of consolidation and retrieval. Regional studies by microdissection techniques in combination with a sensitive radioenzymatic catecholalmine assay, indicate that vasopressin modulates memory processes by modulation of neurotransmission in distinct catecholamine systems. Recent experiments suggest that the influence of vasopressin on memory consolidation is mediated by the dorsal noradrenergic bundle via terminal regions of this bundle. Studies on the conversion of oxytocin in synaptosomal plasma membrane preparations of rat limbic brain suggest the possible generation of fragments with specific effects on memory processes. Regional differences in enzyme activity further substantiate the implication of oxytocin as a prohormone in this respect. Clinical studies support the evidence from laboratory findings that vasopressin is also involved in memory processes in man.     

Semantic memory and the human hippocampus

It has been unclear whether the hippocampus is uniquely important for episodic memory (memory for events that are specific to time and place) or whether the hippocampus is also important for learning and remembering facts (semantic memory). In two studies, we assessed the capacity for semantic memory in patients with bilateral damage thought to be restricted primarily to the hippocampal region who developed memory impairment at a known time. Since the onset of their memory impairment, the patients have acquired less factual knowledge than controls. The patients also exhibit temporally limited retrograde amnesia for factual information from the several years preceding the onset of memory impairment. Remote memory for factual knowledge (from 11-30 years before amnesia) is intact. The results show that the hippocampal region supports semantic memory as well as episodic memory and that its role in the acquisition and storage of semantic knowledge is time limited.     

Dissociating episodic from semantic access mode by mutual information measures: evidence from aging and Alzheimer's disease.

Re-thinking the semantic vs. episodic distinction with new experimental paradigms, we have designed a simple classification task to assess episodic and semantic access modes to memory for famous faces. The task requires to post 54 cards into nine mail boxes arranged in a 3x3 (nationality by field of activity) array, allowing for a quantitative analysis of the distribution of their responses, in particular of their classification errors. By using an information theoretical approach, we have developed an index of the concentration of errors, i.e. the metric content index. High levels of metric content indicate strong dependence of the classification performance on perceived relations among the set of stimuli, and therefore a preferred semantic access mode. We have found (1) a significant effect of age on the metric content, indicative of a shift from episodic to semantic access in older subjects (Experiment 1); (2) a significant correlation between the metric content and relevant measures assessing episodic and semantic retrieval mode in the Remember (R)/Know (K) paradigm introduced by Tulving [Tulving, E. 1985. Memory and consciousness. Can. Psychol. 26, 1-12] (Experiment 2); (3) a significant increase in metric content in early Alzheimer's disease patients compared to normal controls, consistent with their specific impairment in episodic access (Experiment 3).     

缺锌对大鼠学习记忆功能及其脑区生长抑素和加压素含量的影响

目的和方法：本实验用避暗法检测缺锌对大鼠学习记忆的影响,并用放免法测定不同脑区生长抑素和加压素含量的变化。结果：缺锌使大鼠学习记忆功能明显降低,同时下丘脑、海马和皮层等脑组织生长抑素和加压素含量明显降低。缺锌后补锌可使大鼠学习记忆功能及其海马中生长抑素和加压素含量恢复到正常状况。结论：缺锌降低大鼠学习记忆功能与锌对脑组织尤其是海马内源性生长抑素和加压素代谢的调节有关。     

衰老性记忆障碍与脑突触体内游离[Ca^2＋]i的相关性

采用行为观察和生化检测相结合的方法,在过去工作的基础上,研究了１２月龄和１８月龄小鼠学习记忆能力的变化和１８月龄小鼠四个脑区（海马、大脑皮层、四叠体和小脑）交触体内「Ｃａ＾２＋」ｉ的水平,同时还比较了老年记忆保持良好组与记忆障碍组小鼠的脑钙水平。结果表明,随着年龄的增长,小鼠的学习记忆能力显著下降,上述脑区（除大脑皮层外）突触内「Ｃａ＾２＋」ｉ均明显升高,其中老年记忆障碍小鼠脑钙水平升高最为显著。     

Functional magnetic resonance imaging of semantic memory as a presymptomatic biomarker of Alzheimer's disease risk

Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer's disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Progressive loss of semantic memory in a case of Alzheimer's disease.

The breakdown of semantic memory in a patient with Alzheimer's disease was monitored by using a word-picture matching task. Performance deteriorated from a time when target pictures were selected virtually without error to a time when targets and semantically related distractor pictures were selected equally often. From this point, selection deteriorated rapidly to random. Knowledge of category membership and semantic features declined together over the same period. No consistency in item selection could be discerned, and successful selection in early tests was not influenced by either the name frequency or the familiarity of the target. The findings are argued to support a theory of access to semantic memory which is non-hierarchical.     

Functional magnetic resonance imaging of semantic memory as a presymptomatic biomarker of Alzheimer's disease risk

Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer's disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Grey and White Matter Correlates of Recent and Remote Autobiographical Memory Retrieval – Insights from the Dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer''s disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer''s disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events.     

A neural network model of semantic memory linking feature-based object representation and words

Recent theories in cognitive neuroscience suggest that semantic memory is a distributed process, which involves many cortical areas and is based on a multimodal representation of objects. The aim of this work is to extend a previous model of object representation to realize a semantic memory, in which sensory-motor representations of objects are linked with words. The model assumes that each object is described as a collection of features, coded in different cortical areas via a topological organization. Features in different objects are segmented via γ-band synchronization of neural oscillators. The feature areas are further connected with a lexical area, devoted to the representation of words. Synapses among the feature areas, and among the lexical area and the feature areas are trained via a time-dependent Hebbian rule, during a period in which individual objects are presented together with the corresponding words. Simulation results demonstrate that, during the retrieval phase, the network can deal with the simultaneous presence of objects (from sensory-motor inputs) and words (from acoustic inputs), can correctly associate objects with words and segment objects even in the presence of incomplete information. Moreover, the network can realize some semantic links among words representing objects with shared features. These results support the idea that semantic memory can be described as an integrated process, whose content is retrieved by the co-activation of different multimodal regions. In perspective, extended versions of this model may be used to test conceptual theories, and to provide a quantitative assessment of existing data (for instance concerning patients with neural deficits).     

Peculiarities of Neurohormonal Modulation of Memory and Learning Processes in Young and Old Monkeys <Emphasis Type="Italic">Macaca mulatta</Emphasis>

Comparative data are presented about peculiarities of neurohormonal regulation of the memory and learning processes in young and old monkeys Macaca mulatta. It is shown that the hypothalamic neurohormones, vasopressin and thyroliberine, produce on the whole a unidirectional facilitating effect on the inherited and simple forms of the nervous activity in young and old animals. It is established that vasopressin, thyroliberine, and ACTH_4–10 participate differently in regulation and compensation of disturbed higher nervous functions in old monkeys. The compensatory effects of vasopressin are more pronounced at intranasal administration of its ultrasmall (0.01 jg/kg) doses. The thyroliberine administration had the longer and more expressed disinhibition effect on the conditional reflex memory in old monkeys, as compared with young ones. The question is discussed about different effects of vasopressin and thyroliberine on the higher nervous functions in young and old monkeys from the point of view of cytoarchitectonic changes in the neocortex and of immunohistochemical changes in the hypothalamus nuclear structures.     

Brain imaging and memory systems in humans: the contribution of PET methods

The development of neuroimaging methods such as PET, has provided a new impulse to the study of the neural basis of cognitive functions, and has extended the field of inquiry from the analysis of the consequences of brain lesions to the functional investigations of brain activity, either in patients with selective neuropsychological deficits or in normal subjects engaged in cognitive tasks. Specific patterns of hypometabolism in neurological patients are associated with different profiles of memory deficits. [¹⁸F]FDG PET studies have confirmed the association of episodic memory with the structures of Papez's circuit and have shown correlations between short-term and semantic memory and the language areas. The identification of anatomo-functional networks involved in specific components of memory function in normal subjects is the aim of several PET activation studies. The results are in agreement with ‘neural network’ models of the neural basis of memory, as complex functions subserved by multiple interconnected cortical and subcortical structures.     

轻度认知损伤患者的联系记忆损伤特征

遗忘型轻度认知损伤患者(aMCI)在项目记忆和联系记忆上都有损伤．本文通过临床记忆量表中的项目记忆和联系记忆测验,研究aMCI的联系记忆是否比项目记忆有更显著的损伤．另外,通过分析配对联想学习测验,进一步研究aMCI联系记忆损伤的特点．25名aMCI和28名健康老人参与了两个联系记忆测验(配对联想学习测验和联想回忆测验)和两个项目记忆测验(图像自由回忆和无意义图形再认),aMCI患者在联系记忆测验上表现出了更显著的损伤,即使控制了项目记忆的损伤,aMCI的联系记忆仍然比健康老人显著降低．另外,ROC分析表明联系记忆测验比项目记忆测验对aMCI病人有更高的区分度．对配对联想学习测验的分析表明,相对于健康老人,aMCI患者在记忆有语言联系的词对要比记忆无语义联系的词对更为困难．本研究进一步表明aMCI患者的联系记忆比项目记忆有更大的损伤．相对于健康老人,aMCI患者不仅难以在两个无关项目间创建记忆连接,而且在有效利用项目间本身的语义联系方面存在更大的损伤．联系记忆测验比项目记忆测验对aMCI患者有更高的区分度．在神经心理评估中增加联系记忆测验,能更加有效地识别aMCI患者．     

Right Inferior Frontal Gyrus Activation Is Associated with Memory Improvement in Patients with Left Frontal Low-Grade Glioma Resection

Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.     

Episodic memory: insights from semantic dementia

Semantic dementia, also known as the temporal lobe variant of fronto-temporal dementia, results in a progressive yet relatively pure loss of semantic knowledge about words, objects and people, and is associated with asymmetric, focal atrophy of the antero-lateral temporal lobes. Semantic dementia provides a unique opportunity to study the organization of long-term memory particularly since initial observations suggested sparing of episodic memory. Recent studies reveal, however, a more complex but theoretically revealing pattern. On tests of autobiographical memory, patients with semantic dementia show a 'reverse step function' with sparing of recall of events from the most recent 2 to 5 years but impairment on more distant life periods. Anterograde recognition memory for visual materials is extremely well preserved, except in the most deteriorated cases, although performance is heavily reliant upon perceptual information about the studied stimuli, particularly for items that are no longer known by the subjects. On tests of verbal anterograde memory such as word learning, performance is typically poor even for words which are 'known' to the patients. A source discrimination experiment, designed to evaluate familiarity and recollection-based anterograde memory processes, found that patients with semantic dementia showed good item detection, although recollection of source was sometimes impaired. Semantic knowledge about studied items and measures of item detection and source discrimination were largely independent. The implications of these findings for models of long-term memory are discussed. The results support the concept that episodic memory, or at least the recall of temporally specific autobiographical experiences, draws upon a number of separable memory processes, some of which can function independently of semantic knowledge.     

Spatiotemporal dynamics of modality-specific and supramodal word processing

The ability of written and spoken words to access the same semantic meaning provides a test case for the multimodal convergence of information from sensory to associative areas. Using anatomically constrained magnetoencephalography (aMEG), the present study investigated the stages of word comprehension in real time in the auditory and visual modalities, as subjects participated in a semantic judgment task. Activity spread from the primary sensory areas along the respective ventral processing streams and converged in anterior temporal and inferior prefrontal regions, primarily on the left at around 400 ms. Comparison of response patterns during repetition priming between the two modalities suggest that they are initiated by modality-specific memory systems, but that they are eventually elaborated mainly in supramodal areas.     

Hemispheric dissociation in access to the human semantic system

Patient studies suggest that speech and environmental sounds are differentially processed by the left and right hemispheres. Here, using functional imaging in normal subjects, we compared semantic processing of spoken words to equivalent processing of environmental sounds, after controlling for low-level perceptual differences. Words enhanced activation in left anterior and posterior superior temporal regions, while environmental sounds enhanced activation in a right posterior superior temporal region. This left/right dissociation was unchanged by different attentional/working memory contexts, but it was specific to tasks requiring semantic analysis. While semantic processing involves widely distributed networks in both hemispheres, our results support the hypothesis of a dual access route specific for verbal and nonverbal material, respectively.