Semantic memory disorders

Semantic memory encompasses knowledge of objects, facts and words. A number of brain regions are probably involved, but the left infero-lateral temporal lobe appears to play a key role. The separability of semantic memory from episodic (or autobiographical) memory is a focus of current debate. Impaired semantic memory is a common feature of Alzheimer's disease but is invariably overshadowed by a profound deficit in episodic memory. In semantic dementia, a rarer disorder associated with focal temporal-lobe atrophy, there is selective loss of semantic memory, characterized by preservation of superordinate knowledge of words, and objects, but loss of finer-grained information. This pattern can be interpreted as a degradation of features from a distributed network of semantic representations. Following Herpes simplex encephalitis, patients sometimes show disproportionate loss of knowledge for natural kinds (e.g. animals) with relative preservation of knowledge about artefacts, this may reflect differential damage to neural systems critical for perceptual as opposed to functional features, perceptual properties being more salient in knowledge about natural kinds.     

Neural correlates of autobiographical memory retrieval in children and adults

Autobiographical memory (AM) is a critically important form of memory for life events that undergoes substantial developmental changes from childhood to adulthood. Relatively little is known regarding the functional neural correlates of AM retrieval in children as assessed with fMRI, and how they may differ from adults. We investigated this question with 14 children ages 8–11 years and 14 adults ages 19–30 years, contrasting AM retrieval with semantic memory (SM) retrieval. During scanning, participants were cued by verbal prompts to retrieve previously selected recent AMs or to verify semantic properties of words. As predicted, both groups showed AM retrieval-related increased activation in regions implicated in prior studies, including bilateral hippocampus, and prefrontal, posterior cingulate, and parietal cortices. Adults showed greater activation in the hippocampal/parahippocampal region as well as prefrontal and parietal cortex, relative to children; age-related differences were most prominent in the first 8?sec versus the second 8?sec of AM retrieval and when AM retrieval was contrasted with semantic retrieval. This study is the first to characterise similarities and differences during AM retrieval in children and adults using fMRI.     

The neural correlates of everyday recognition memory

We used a novel automatic camera, SenseCam, to create a recognition memory test for real-life events. Adapting a 'Remember/Know' paradigm, we asked healthy undergraduates, who wore SenseCam for 2 days, in their everyday environments, to classify images as strongly or weakly remembered, strongly or weakly familiar or novel, while brain activation was recorded with functional MRI. Overlapping, widely distributed sets of brain regions were activated by recollected and familiar stimuli. Within the medial temporal lobes, 'Remember' responses specifically elicited greater activity in the right anterior and posterior parahippocampal gyrus than 'Know' responses. 'New' responses activated anterior parahippocampal regions. A parametric analysis, across correctly recognised items, revealed increasing activation in the right hippocampus and posterior parahippocampal gyrus (pPHG). This may reflect modulation of these regions by the degree of recollection or, alternatively, by increasing memory strength. Strong recollection elicited greater activity in the left posterior hippocampus/pPHG than weak recollection indicating that this region is specifically modulated by the degree of recollection.     

FUNCTIONAL MAGNETIC RESONANCE IMAGING OF SEMANTIC MEMORY PROCESSES IN THE FRONTAL LOBES

Abstract— Frontal-lobe activation during semantic memory performance was examined using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing neural activity associated with cognitive function. Left inferior prefrontal cortex was more activated for semantic than for perceptual encoding of words, and for initial than for repeated semantic encoding of words. Decreased activation for semantic encoding of repeated words reflects repetition priming, that is, implicit retrieval of memory gained in the initial semantic encoding of a word. The left inferior prefrontal region may sub-serve semantic working memory processes that participate in semantic encoding and that have decreased demands when such encoding can be facilitated by recent semantic experience. These results demonstrate that fMRI can visualize changes in an individual's brain function associated with the encoding and retrieval of new memories.     

情景记忆成功年老化的神经机制

随着年龄的增长, 大部分老年人的情景记忆会出现衰退, 但也会有一部分老年人的情景记忆表现出成功的年老化, 即记忆成绩较好或随增龄的衰退程度较小。脑保持理论、神经去分化理论、认知储备理论以及神经补偿理论分别从不同角度解释了情景记忆成功年老化的神经机制。基于选择性优化与补偿模型对现有理论进行整合, 发现情景记忆成功年老化可能与个体的认知储备水平直接相关：高认知储备的老年人能够对情景记忆相关的脑区和脑网络进行优化且具备更强的神经补偿能力, 因而其脑功能(比如, 神经表征和神经加工通路的特异性)可能会保持地更好。未来研究需要更多地采用纵向设计来考察各理论之间的关系及其影响因素, 从而更好地解释记忆成功年老化的神经机制并为提升老年人的脑与认知健康提供支持。     

Learning of novel semantic relationships via sudden comprehension is associated with a hippocampus-independent network

Sudden comprehension—or insight—during problem-solving can enhance learning, but the underlying neural processes are largely unknown. We investigated neural correlates of learning from sudden comprehension using functional magnetic resonance imaging and a verbal problem-solving task. Solutions and “solutions” to solvable and unsolvable verbal problems, respectively, were presented to induce sudden comprehension or continued incomprehension. We found activations of the hippocampus, medial prefrontal cortex (mPFC), amygdala, and striatum during sudden comprehension. Notably, however, mPFC and temporo-parietal neocortical structures rather than the hippocampus were associated with later learning of suddenly comprehended solutions. Moreover, difficult compared to easy sudden comprehension elicited midbrain activations and was associated with successful learning, pointing to learning via intrinsic reward. Sudden comprehension of novel semantic associations may constitute a special case of long-term memory formation primarily mediated by the mPFC, expanding our knowledge of its role in prior-knowledge-dependent memory.     

Working memory maintenance contributes to long-term memory formation: Evidence from slow event-related brain potentials

Behavioral research has led to conflicting views regarding the relationship between working memory (WM) maintenance and long-term memory (LTM) formation. We used slow event-related brain potentials to investigate the degree to which neural activity during WM maintenance is associated with successful LTM formation. Participants performed a WM task with objects and letter strings, followed by a surprise LTM test. Slow potentials were found to be more negative over the parietal and occipital cortex for objects and over the left frontal cortex for letter strings during WM maintenance. Within each category, they were enhanced for items that were subsequently successfully remembered. These effects were topographically distinct, with maximum effects at those electrodes that showed the maximum negativity during WM maintenance in general. Together, these results are strongly consistent with the ideas that WM maintenance contributes to LTM formation and that this may occur through strengthening of stimulus-specific cortical memory traces.     

Components of Short-Term Memory and Their Relation to Language Processing

Abstract— Verbal working memory consists of separable capacities for the retention of phonological and semantic information. Within the phonological domain, there are independent capacities for retaining input-phonological codes and output-phonological codes. The input-phonological capacity does not appear to be critical for language comprehension but is involved in verbatim repetition and long-term learning of new words. The semantic capacity is critical for both comprehension and production and for the learning of new semantic information. Different neural structures appear to underlie these capacities, with a left-parietal region involved in input-phonological retention and a left-frontal region involved in semantic retention.     

Gamma- and theta-band synchronization during semantic priming reflect local and long-range lexical–semantic networks

Anterior and posterior brain areas are involved in the storage and retrieval of semantic representations, but it is not known how these areas dynamically interact during semantic processing. We hypothesized that long-range theta-band coherence would reflect coupling of these areas and examined the oscillatory dynamics of lexical–semantic processing using a semantic priming paradigm with a delayed letter-search task while recording subjects’ EEG. Time–frequency analysis revealed facilitation of semantic processing for Related compared to Unrelated conditions, which resulted in a reduced N400 and reduced gamma power from 150 to 450 ms. Moreover, we observed greater anterior–posterior theta coherence for Unrelated compared to Related conditions over the time windows 150–425 ms and 600–900 ms. We suggest that while gamma power reflects activation of local functional networks supporting semantic representations, theta coherence indicates dynamic coupling of anterior and posterior areas for retrieval and post-retrieval processing and possibly an interaction between semantic relatedness and working memory.     

Bi-hemispheric engagement in the retrieval of autobiographical episodes

Functional magnetic resonance imaging (fMRI) was used to study the neural correlates of neutral, stressful, negative and positive autobiographical memories. The brain activity produced by these different kinds of episodic memory did not differ significantly, but a common pattern of activation for different kinds of autobiographical memory was revealed that included (1) largely bilateral portions of the medial and superior temporal lobes, hippocampus and parahippocampus, (2) portions of the ventral, medial, superior and dorsolateral prefrontal cortex, (3) the anterior and posterior cingulate, including the retrosplenial, cortex, (4) the parietal cortex, and (5) portions of the cerebellum. The brain regions that were mainly activated constituted an interactive network of temporal and prefrontal areas associated with structures of the extended limbic system. The main bilateral activations with left-sided preponderance probably reflected reactivation of complex semantic and episodic self-related information representations that included previously experienced contexts. In conclusion, the earlier view of a strict left versus right prefrontal laterality in the retrieval of semantic as opposed to episodic autobiographical memory, may have to be modified by considering contextual variables such as task demands and subject variables. Consequently, autobiographical memory integration should be viewed as based on distributed bi-hemispheric neural networks supporting multi-modal, emotionally coloured components of personal episodes.     

Activation of right parietal cortex during memory retrieval of nonlinguistic auditory stimuli

In neuroimaging studies, the left ventral posterior parietal cortex (PPC) is particularly active during memory retrieval. However, most studies have used verbal or verbalizable stimuli. We investigated neural activations associated with the retrieval of short, agrammatical music stimuli (Blackwood, 2004), which have been largely associated with right hemisphere processing. At study, participants listened to music stimuli and rated them on pleasantness. At test, participants made old/new recognition judgments with high/low confidence ratings. Right, but not left, ventral PPC activity was observed during the retrieval of these music stimuli. Thus, rather than indicating a special status of left PPC in retrieval, both right and left ventral PPC participate in memory retrieval, depending on the type of information that is to be remembered.     

Adult age differences in visual word identification: functional neuroanatomy by positron emission tomography

Adult age differences in the neural systems mediating semantic (context-independent) memory were investigated using positron emission tomography (PET). Younger (20-29 years) and older (62-70 years) participants performed lexical decision (word/nonword discrimination) and nonsemantic (simple visual search) baseline tasks during PET scanning. Within the lexical decision task, display duration and presentation rate were varied across scans. The behavioral data suggested that although an age-related slowing was evident in visual feature and response processing, the retrieval of semantic/lexical information was similar for younger and older adults. For both age groups, lexical-related activation occurred in inferior prefrontal and occipitotemporal regions of the left hemisphere. Differential activation, as a function of age group, was observed in the left occipitotemporal pathway as a result of older adults' maintaining higher levels of neural activity in striate cortex (during visual search) and in inferior temporal cortex (during lexical decision). The prefrontal activation was similar for the two age groups. Thus, although this form of semantic memory retrieval does not undergo significant age-related decline, an age-related change in the associated pattern of neural activation is evident. These findings differ from previous neuroimaging studies of episodic (context-dependent) memory retrieval, which have suggested that age-related compensatory mechanisms are expressed primarily by greater activation of prefrontal regions for older adults than for younger adults.     

Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions

A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system coactivates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to assess how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study–test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants’ selectivity index, which measures how close participants were to their optimal point total, given the number of items recalled. Greater selectivity scores were associated with greater differences in the activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during the encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items.     

Short theta burst stimulation to left frontal cortex prior to encoding enhances subsequent recognition memory

Deep semantic encoding of verbal stimuli can aid in later successful retrieval of those stimuli from long-term episodic memory. Evidence from numerous neuropsychological and neuroimaging experiments demonstrate regions in left prefrontal cortex, including left dorsolateral prefrontal cortex (DLPFC), are important for processes related to encoding. Here, we investigated the relationship between left DLPFC activity during encoding and successful subsequent memory with transcranial magnetic stimulation (TMS). In a pair of experiments using a 2-session within-subjects design, we stimulated either left DLPFC or a control region (Vertex) with a single 2-s train of short theta burst stimulation (sTBS) during a semantic encoding task and then gave participants a recognition memory test. We found that subsequent memory was enhanced on the day left DLPFC was stimulated, relative to the day Vertex was stimulated, and that DLPFC stimulation also increased participants’ confidence in their decisions during the recognition task. We also explored the time course of how long the effects of sTBS persisted. Our data suggest 2 s of sTBS to left DLPFC is capable of enhancing subsequent memory for items encoded up to 15 s following stimulation. Collectively, these data demonstrate sTBS is capable of enhancing long-term memory and provide evidence that TBS protocols are a potentially powerful tool for modulating cognitive function.     

Neuroimaging evidence for agenda-dependent monitoring of different features during short-term source memory tests

A short-term source monitoring procedure with functional magnetic resonance imaging assessed neural activity when participants made judgments about the format of 1 of 4 studied items (picture, word), the encoding task performed (cost, place), or whether an item was old or new. The results support findings from long-term memory studies showing that left anterior ventrolateral prefrontal cortex (PFC) is engaged when people make source attributions about reflectively generated information (cognitive operations, conceptual features). The findings also point to a role for right lateral PFC in attention to perceptual features and/or familiarity in making source decisions. Activity in posterior regions also differed depending on what was evaluated. These results provide neuroimaging evidence for theoretical approaches emphasizing that agendas influence which features are monitored during remembering (e.g., M. K. Johnson, S. Hashtroudi, & D. S. Lindsay, 1993). They also support the hypothesis that some of the activity in left lateral PFC and posterior regions associated with remembering specific information is not unique to long-term memory but rather is associated with agenda-driven source monitoring processes common to working memory and long-term memory.     

Working memory retention systems: a state of activated long-term memory

High temporal resolution event-related brain potential and electroencephalographic coherence studies of the neural substrate of short-term storage in working memory indicate that the sustained coactivation of both prefrontal cortex and the posterior cortical systems that participate in the initial perception and comprehension of the retained information are involved in its storage. These studies further show that short-term storage mechanisms involve an increase in neural synchrony between prefrontal cortex and posterior cortex and the enhanced activation of long-term memory representations of material held in short-term memory. This activation begins during the encoding/comprehension phase and evidently is prolonged into the retention phase by attentional drive from prefrontal cortex control systems. A parsimonious interpretation of these findings is that the long-term memory systems associated with the posterior cortical processors provide the necessary representational basis for working memory, with the property of short-term memory decay being primarily due to the posterior system. In this view, there is no reason to posit specialized neural systems whose functions are limited to those of short-term storage buffers. Prefrontal cortex provides the attentional pointer system for maintaining activation in the appropriate posterior processing systems. Short-term memory capacity and phenomena such as displacement of information in short-term memory are determined by limitations on the number of pointers that can be sustained by the prefrontal control systems.     

Behavioral and neural correlates of memory selection and interference resolution during a digit working memory task

Neuroimaging studies have shown the involvement of prefrontal and posterior parietal cortexes in regulating information processing. We conducted behavioral and fMRI experiments to investigate the relationship between memory selection and proactive interference (PI), using a delayed recognition task with a selection cue presented during the delay indicating which two of the four studied digits were relevant to the present test. PI was indexed by the response time differences between rejecting probes matching and not matching the no longer relevant digits. By varying the delay intervals, we found that the effect of PI did not diminish, even for cases in which the postcue interval was extended to 9 sec, but was stronger when the precue interval was lengthened to 5 sec. By examining the correlation between PI index and neural correlates of memory selection, we found that stronger PI is predicted by lower selection-related activity in the left inferior parietal lobe, the precuneus, and the dorsal middle frontal gyrus. Our results suggest that activity in the prefrontal-parietal network may contribute to one’s ability to focus on the task-relevant information and may proactively reduce PI in working memory.     

Object-location memory: A lesion-behavior mapping study in stroke patients

Object-location memory is an important form of spatial memory, comprising different subcomponents that each process specific types of information within memory, i.e. remembering objects, remembering positions and binding these features in memory. In the current study we investigated the neural correlates of binding categorical (relative) or coordinate (exact) position information with objects in memory. Therefore, an object-location memory battery was used, including different task conditions assessing object-location memory, i.e. memory for position information per se, and binding object information with coordinate and categorical position information. Sixty-one stroke patients with focal brain lesions were examined and compared with 77 healthy matched controls. The lesion subtraction method was used to define the area of overlap. Results indicate an important role of the left posterior parietal cortex in the binding of both categorical and coordinate positions with object information. Additionally, the hippocampus seems important for categorical object-location memory. This suggests that categorical and coordinate object-location memory depend on similar cognitive and neural systems.     

Episodic encoding and recognition of pictures and words: role of the human medial temporal lobes

In the present PET study, we examined brain activity related to processing of pictures and printed words in episodic memory. Our goal was to determine how the perceptual format of objects (verbal versus pictorial) is reflected in the neural organization of episodic memory for common objects. We investigated this issue in relation to encoding and recognition with a particular focus on medial temporal-lobe (MTL) structures. At encoding, participants saw pictures of objects or their written names and were asked to make semantic judgments. At recognition, participants made yes-no recognition judgments in four different conditions. In two conditions, target items were pictures of objects; these objects had originally been encoded either in picture or in word format. In two other conditions, target items were words; they also denoted objects originally encoded either as pictures or as words. Our data show that right MTL structures are differentially involved in picture processing during encoding and recognition. A posterior MTL region showed higher activation in response to the presentation of pictures than of words across all conditions. During encoding, this region may be involved in setting up a representation of the perceptual information that comprises the picture. At recognition, it may play a role in guiding retrieval processes based on the perceptual input, i.e. the retrieval cue. Another more anterior right MTL region was found to be differentially involved in recognition of objects that had been encoded as pictures, irrespective of whether the retrieval cue provided was pictorial or verbal in nature; this region may be involved in accessing stored pictorial representations. Our results suggest that left MTL structures contribute to picture processing only during encoding. Some regions in the left MTL showed an involvement in semantic encoding that was picture specific; others showed a task-specific involvement across pictures and words. Together, our results provide evidence that the involvement of some but not all MTL regions in episodic encoding and recognition is format specific.