Item and associative memory in amnestic mild cognitive impairment: performance on standardized memory tests

The earliest neuroanatomical changes in amnestic mild cognitive impairment (aMCI) involve the hippocampus and entorhinal cortex, structures implicated in the integration and learning of associative information. The authors hypothesized that individuals with aMCI would have impairments in associative memory above and beyond the known impairments in item memory. A group of 29 individuals with aMCI and 30 matched control participants were administered standardized tests of object-location recall and symbol-symbol recall, from which both item and associative recall scores were derived. As expected, item recall was impaired in the aMCI group relative to controls. Associative recall in the aMCI group was even more impaired than was item recall. The best group discriminators were measures of associative recall, with which the sensitivity and specificity for detecting aMCI were 76% and 90% for symbol-symbol recall and were 86% and 97% for object-location recall. Associative recall may be particularly sensitive to early cognitive change in aMCI, because this ability relies heavily on the medial temporal lobe structures that are affected earliest in aMCI. Incorporating measures of associative recall into clinical evaluations of individuals with memory change may be useful for detecting aMCI.     

Brain activation during encoding and recognition of verbal and figural information in older adults

Positron emission tomography (PET) patterns of cerebral blood flow associated with verbal and figural memory are described in relation to their value as functional probes for studying longitudinal changes that occur in the aging brain. Relative to a matching control task, verbal and figural encoding increase blood flow in prefrontal cortex (PFC), anterior cingulate, insular, lateral and medial temporal, occipital cortex and the cerebellum. Additionally, medial temporal regions exhibited greater activity during figural encoding relative to verbal encoding. During recognition, blood flow increases in prefrontal, cingulate, insular, and lateral temporal and Broca's areas. Analysis of hemispheric asymmetry reveals that the prefrontal cortex exhibits regionally dependent results. Prefrontal region BA 10 demonstrates more bilateral activation during encoding and retrieval, whereas BA 46 shows right greater than left activation during both encoding and retrieval. Overall, the two tasks activate diverse regions within the frontal, temporal and occipital lobes of the brain, including areas that show age-related structural changes, proving their usefulness in the longitudinal assessment of brain function in the elderly.     

Distinct cortical anatomy linked to subregions of the medial temporal lobe revealed by intrinsic functional connectivity

The hippocampus and adjacent cortical structures in the medial temporal lobe (MTL) contribute to memory through interactions with distributed brain areas. Studies of monkey and rodent anatomy suggest that parallel pathways converge on distinct subregions of the MTL. To explore the cortical areas linked to subregions of the MTL in humans, we examined cortico-cortical and hippocampal-cortical correlations using high-resolution, functional connectivity analysis in 100 individuals. MTL seed regions extended along the anterior to posterior axis and included hippocampus and adjacent structures. Results revealed two separate brain pathways that correlated with distinct subregions within the MTL. The body of the hippocampus and posterior parahippocampal cortex correlated with lateral parietal cortex, regions along the posterior midline including posterior cingulate and retrosplenial cortex, and ventral medial prefrontal cortex. By contrast, anterior hippocampus and the perirhinal/entorhinal cortices correlated with distinct regions in the lateral temporal cortex extending into the temporal pole. The present results are largely consistent with known connectivity in the monkey and provide a novel task-independent dissociation of the parallel pathways supporting the MTL memory system in humans. The cortical pathways include regions that have undergone considerable areal expansion in humans, providing insight into how the MTL memory system has evolved to support a diverse array of cognitive domains.     

Relationship Between Brain and Cognitive Processes in Down Syndrome

We investigated regional grey matter (GM) density in adolescents with Down syndrome (DS) compared to age-matched controls and correlated MRI data with neuropsychological measures in the DS group. Inter-group comparisons documented several GM concentration abnormalities in the participants with DS compared to controls. In the adolescents with DS, intra-group results also showed associations between regional GM density and the neuropsychological measures considered. In particular, GM density of the cerebellum and middle and inferior temporal gyrus was associated with linguistic measures. Short-term memory performances were correlated with the inferior parietal lobule, insula, superior temporal gyrus, medial occipital lobe, and cerebellum. Long-term memory abilities were correlated with GM density in the orbitofrontal cortex, lateral and medial temporal lobe regions, and anterior cingulum and visuo-perceptual abilities with GM density the left middle frontal gyrus. Results of this preliminary study are consistent with a not always efficient brain organization in DS.     

Differential involvement of the human temporal lobe structures in short- and long-term memory processes assessed by intracranial ERPs

Intracranial event-related potentials (ERPs) elicited during a recognition memory task were recorded in 25 epileptic patients by using depth electrodes sampling four different regions within the temporal lobe (amygdala, hippocampus, anterior and posterior temporal cortices). The task was a continuous recognition memory task in which repeated items were presented after 6 or 19 intervening items following their first presentation. This study was performed to investigate the respective role of the different temporal lobe structures in short-term memory (STM) and long-term memory (LTM) processing. Subregions of the temporal lobe were differently involved in these two memory systems. The posterior temporal cortex is specifically involved in STM processing, whereas the amygdala, hippocampus, and anterior temporal cortex contribute to both STM and LTM. Moreover, it appeared that the latter structures play their own role in LTM. The anterior temporal cortex and amygdala may contribute to recency discrimination, and the hippocampus seems rather to be involved in maintaining memory traces. These findings suggest that the temporal lobe structures may function in a complementary way by subserving different aspects of information processing.     

Development of the declarative memory system in the human brain

Brain regions that are involved in memory formation, particularly medial temporal lobe (MTL) structures and lateral prefrontal cortex (PFC), have been identified in adults, but not in children. We investigated the development of brain regions involved in memory formation in 49 children and adults (ages 8-24), who studied scenes during functional magnetic resonance imaging. Recognition memory for vividly recollected scenes improved with age. There was greater activation for subsequently remembered scenes than there was for forgotten scenes in MTL and PFC regions. These activations increased with age in specific PFC, but not in MTL, regions. PFC, but not MTL, activations correlated with developmental gains in memory for details of experiences. Voxel-based morphometry indicated that gray matter volume in PFC, but not in MTL, regions reduced with age. These results suggest that PFC regions that are important for the formation of detailed memories for experiences have a prolonged maturational trajectory.     

Exercise moderates age-related atrophy of the medial temporal lobe

Regional deterioration of brain structure is a typical feature of aging, but emerging evidence suggests that exercise may mitigate the decline. The purpose of the present investigation was to examine the moderating influence of exercise engagement on cross-sectional estimates of age-related brain atrophy at both global and regional levels. Estimates of exercise engagement over the past 10 years and MRI-based measures of global (gray and white) and regional volumes were obtained in a sample of 52 healthy older adults aged 55-79. Volume estimates were obtained in prefrontal, parietal, temporal, occipital, neostriatal, and medial temporal regions. Higher levels of exercise engagement were related to larger superior frontal volumes. Most critically, exercise engagement selectively moderated age-related medial temporal lobe atrophy. Specifically, significant age-related atrophy was observed for older adults who engaged in low levels of exercise, but not for those who engaged in high levels of exercise. This novel finding extends support for the efficacy of exercise to the potential maintenance of medial temporal lobe integrity in older adults.     

Neural activation and memory for natural scenes: Explicit and spontaneous retrieval

Stimulus repetition elicits either enhancement or suppression in neural activity, and a recent fMRI meta‐analysis of repetition effects for visual stimuli (Kim, 2017) reported cross‐stimulus repetition enhancement in medial and lateral parietal cortex, as well as regions of prefrontal, temporal, and posterior cingulate cortex. Repetition enhancement was assessed here for repeated and novel scenes presented in the context of either an explicit episodic recognition task or an implicit judgment task, in order to study the role of spontaneous retrieval of episodic memories. Regardless of whether episodic memory was explicitly probed or not, repetition enhancement was found in medial posterior parietal (precuneus/cuneus), lateral parietal cortex (angular gyrus), as well as in medial prefrontal cortex (frontopolar), which did not differ by task. Enhancement effects in the posterior cingulate cortex were significantly larger during explicit compared to implicit task, primarily due to a lack of functional activity for new scenes. Taken together, the data are consistent with an interpretation that medial and (ventral) lateral parietal cortex are associated with spontaneous episodic retrieval, whereas posterior cingulate cortical regions may reflect task or decision processes.     

Frontal lobe and cognitive development

In phylogeny as in ontogeny, the association cortex of the frontal lobe, also known as the prefrontal cortex, is a late-developing region of the neocortex. It is also one of the cortical regions to undergo the greatest expansion in the course of both evolution and individual maturation. In the human adult, the prefrontal cortex constitutes as much as nearly one-third of the totality of the neocortex. The protracted, relatively large, development of the prefrontal cortex is manifest in gross morphology as well as fine structure. In the developing individual, its late maturation is made most apparent by the late myelination of its axonal connections. This and other indices of morphological development of the prefrontal cortex correlate with the development of cognitive functions that neuropsychological studies in animals and humans have ascribed to this cortex. In broad outline, the ventromedial areas of the prefrontal cortex, which with respect to otherprefrontal areas develop relatively early, are involved in the expression and control of emotional and instinctual behaviors. On the other hand, the late maturing areas of the lateral prefrontal convexity are principally involved in higher executive functions. The most general executive function of the lateral prefrontal cortex is the temporal organization of goal-directed actions in the domains of behavior, cognition, and language. In all three domains, that global function is supported by a fundamental role of the lateral prefrontal cortex in temporal integration, that is, the integration of temporally discontinuous percepts and neural inputs into coherent structures of action. Temporal integration is in turn served by at least three cognitive functions of somewhat different prefrontal topography: working memory, preparatory set, and inhibitory control. These functions engage the prefrontal cortex in interactive cooperation with other neocortical regions. The development of language epitomizes the development of temporal integrative cognitive functions and their underlying neural substrate, notably the lateral prefrontal cortex and other late-developing cortical regions.     

Cortical network dynamics during verbal working memory function.

This study is an exploratory investigation of the regional timing of cortical activity associated with verbal working memory function. ERP activity was obtained from a single subject using a 124-channel sensor array during a task requiring the monitoring of imageable words for occasional targets. Distributed cortical activity was estimated every 2.5 ms with high spatial resolution using real head, boundary element modelling of non-target activity. High-resolution structural MRI was used for segmentation of tissue boundaries and co-registration to the scalp electrode array. The inverse solution was constrained to the cortical surface. Cortical activity was observed in regions commonly associated with verbal working memory function. This included: the occipital pole (early visual processing); the superior temporal and inferior parietal gyrus bilaterally and the left angular gyrus (visual and phonological word processing); the dorsal lateral occipital gyrus (spatial processing); and aspects of the bilateral superior parietal lobe (imagery and episodic verbal memory). Activity was also observed in lateral and superior prefrontal regions associated with working memory control of sensorimotor processes. The pattern of cortical activity was relatively stable over time, with variations in the extent and amplitude of contributing local source activations. By contrast, the pattern of concomitant scalp topography varied considerably over time, reflecting the linear summation effects of volume conduction that often confound dipolar source modelling.     

The functional neuroanatomy of working memory: contributions of human brain lesion studies

Studies of patients with focal brain lesions remain critical components of research programs attempting to understand human brain function. Whereas functional imaging typically reveals activity in distributed brain regions that are involved in a task, lesion studies can define which of these brain regions are necessary for a cognitive process. Further, lesion studies are less critical regarding the selection of baseline conditions needed in functional brain imaging research. Lesion studies suggest a functional subdivision of the visuospatial sketchpad of working memory with a ventral stream reaching from occipital to temporal cortex supporting object recognition and a dorsal stream connecting the occipital with parietal cortex enabling spatial operations. The phonological loop can be divided into a phonological short-term store in inferior parietal cortex and an articulatory subvocal rehearsal process relying on brain areas necessary for speech production, i.e. Broca's area, the supplementary motor association area and possibly the cerebellum. More uncertainty exists regarding the role of the prefrontal cortex in working memory. Whereas single cell studies in non-human primates and functional imaging studies in humans have suggested an extension of the ventral and dorsal path into different subregions of the prefrontal cortex, lesion studies together with recent single-cell and imaging studies point to a non-mnemonic role of the prefrontal cortex, including attentional control of sensory processing, integration of information from different domains, stimulus selection and monitoring of information held in memory. Our own data argue against a modulatory view of the prefrontal cortex and suggest that processes supporting working memory are distributed along ventral and dorsal lateral prefrontal cortex.     

原发性失眠患者大脑背外侧前额叶的异常静息态功能连接

目的:利用功能连接方法观察原发性失眠患者静息态下的背外侧前额叶的异常功能连接。方法:采集33 例原 发性失眠患者以及33 例年龄、性别和受教育程度相匹配的健康对照的功能磁共振图像,以背外侧前额叶为感兴趣区 域,与全脑其他体素进行功能连接分析,得到两组之间功能连接的差异脑区,再对异常功能连接脑区与临床的量表分 数做相关分析。结果:与对照组相比,发现失眠患者左侧背外侧前额叶与左侧枕下回、右侧枕下回、右侧枕中回、右侧 颞叶、左侧额中回,左侧额下回以及右侧梭状回之间的功能连接增强（P<0.05,体素簇个数≥100,FDR校正）,与左侧前 扣带皮层、右侧海马旁回、右侧脑岛、右侧背外侧额上回、右侧顶上回、右侧中央后回以及右侧中央前回之间的功能连 接减弱（P<0.05,体素簇个数≥100,FDR校正）。并且左侧背外侧前额叶与左侧枕叶下回的功能连接值与睡眠状况自评 量表分数成正相关（P=0.035）。结论:原发性失眠患者背外侧前额叶与大脑多个脑区出现异常的功能连接,可能为理 解原发性失眠患者的神经机制提供一些新的影像学依据。     

Effects of aging on neural connectivity underlying selective memory for emotional scenes

Older adults show age-related reductions in memory for neutral items within complex visual scenes, but just like young adults, older adults exhibit a memory advantage for emotional items within scenes compared with the background scene information. The present study examined young and older adults' encoding-stage effective connectivity for selective memory of emotional items versus memory for both the emotional item and its background. In a functional magnetic resonance imaging (fMRI) study, participants viewed scenes containing either positive or negative items within neutral backgrounds. Outside the scanner, participants completed a memory test for items and backgrounds. Irrespective of scene content being emotionally positive or negative, older adults had stronger positive connections among frontal regions and from frontal regions to medial temporal lobe structures than did young adults, especially when items and backgrounds were subsequently remembered. These results suggest there are differences between young and older adults' connectivity accompanying the encoding of emotional scenes. Older adults may require more frontal connectivity to encode all elements of a scene rather than just encoding the emotional item.     

Differential contribution of left and right prefrontal cortex to associative cued-recall memory: a parametric PET study

Several brain imaging studies have implicated prefrontal regions bilaterally during cued-recall memory tasks and yet the functional significance of these regions remains poorly understood. Using PET, we examined the neural activity in prefrontal regions of 15 subjects while they performed three cued-recall tasks differing in pre-experimental semantic associations between cues and targets. This manipulation produced varying levels of retrieval performance when one member (a semantic category name) of the triad was used as a cue for the retrieval of the other two members. The percentage of items correctly recalled was 10, 46, and 70 in the low, medium, and high cued-recall conditions, respectively. Linear contrast analyses of the PET data identified brain regions where neural activity varied with the number of items retrieved from memory. A left lateral prefrontal region showed maximal activity during the high cued-recall condition, which likely reflects processes involved in retrieval success and possibly in the generation of memory responses. Three right prefrontal regions (anterior and dorsolateral) showed maximal activity during the low cued-recall condition, which likely reflects processes involved in memory search/monitoring. These findings add further support for a bilateral prefrontal contribution to memory cued-recall tasks and point to differential roles of the two hemispheres.     

Episodic memory meets working memory in the frontal lobe: functional neuroimaging studies of encoding and retrieval

Recent functional-neuroimaging studies have provided a wealth of new information suggesting that regions of the prefrontal cortex play a role in episodic memory encoding and retrieval. This review seeks to evaluate the results of these studies in the context of one general model that has proposed that the left prefrontal cortex is preferentially involved in episodic memory encoding, whereas the right prefrontal cortex is preferentially involved in episodic memory retrieval, irrespective of the type (e.g., modality) of information being remembered. The origins of this framework are considered in some detail and then all relevant functional-neuroimaging studies are critically reviewed. The results of this review fail to provide support for the functional-asymmetry model, suggesting instead that episodic memory encoding and retrieval may actually involve similar regions of the lateral prefrontal cortex when all factors relating to the type of stimulus material (i.e., modality), are appropriately controlled.     

Enhanced memory performance on an internal-internal source monitoring test following acute psychosocial stress

Research on the effect of acute stress and high levels of glucocorticoids on memory has largely focused on memory tasks involving the medial temporal lobe (e.g., declarative memory). Less is known, however, about the effects of stress and glucocorticoids on more strategic memory processes regulated by the prefrontal cortex (e.g., source monitoring). In the current study, the authors investigated whether exposure to acute psychosocial stress would result in altered source monitoring performance relative to the performance of a nonstressed control group. To this end, the authors assigned nonsmoking, healthy, young men to either a stress (n = 22) or a control (n = 18) condition, after which the men were given an internal source monitoring test. Results show that relative to control participants, stressed participants made fewer source monitoring errors. This study suggests that stress may have differential effects on memory, depending on whether the memory test is regulated by the prefrontal cortex or the medial temporal lobe.     

Neural correlates of actual and predicted memory formation

We aimed to discover the neural correlates of subjective judgments of learning-whereby participants judge whether current experiences will be subsequently remembered or forgotten-and to compare these correlates to the neural correlates of actual memory formation. During event-related functional magnetic resonance imaging, participants viewed 350 scenes and predicted whether they would remember each scene in a later recognition-memory test. Activations in the medial temporal lobe were associated with actual encoding success (greater activation for objectively remembered than forgotten scenes), but not with predicted encoding success (activations did not differ for scenes predicted to be remembered versus forgotten). Conversely, activations in the ventromedial prefrontal cortex were associated with predicted but not actual encoding success, and correlated with individual differences in the accuracy of judgments of learning. Activations in the lateral and dorsomedial prefrontal cortex were associated with both actual and predicted encoding success. These findings indicate specific dissociations and associations between the neural systems that mediate actual and predicted memory formation.     

Memory for drawings in locations: spatial source memory and event-related potentials

Event-related potentials (ERPs) were recorded during recognition tasks for line drawings (items) or for both drawings and their spatial locations (sources). Recognized drawings elicited more positive ERPs than new drawings. Independent of accuracy in the spatial judgment, the old/new effect in the source recognition task was larger over the prefrontal scalp, and of longer temporal duration than in the item recognition task, suggesting that the source memory task engaged a qualitatively distinct memory process. More posterior scalp sites were sensitive to the accuracy of the source judgment, but this effect was delayed relative to the difference between studied and unstudied drawings, suggesting that source memory processes are completed after item recognition. Similarities and differences between spatial source memory and memory for conjunctions of other stimulus attributes are discussed, together with the role of prefrontal cortex in memory.     

Deep processing activates the medial temporal lobe in young but not in old adults

Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that elderly adults are not able to perform certain cognitive operations under deep processing conditions. We further hypothesised that this inability does not involve regions commonly associated with lexical/semantic retrieval processes, but rather involves a dysfunction of the medial temporal lobe (MTL) memory system. To this end, we used functional MRI on rather extensive groups of young and elderly adults to compare brain activity patterns obtained during a deep (living/nonliving) and a shallow (uppercase/lowercase) classification task. Common activity in relation to semantic classification was observed in regions that have been previously related to semantic retrieval, including mainly left-lateralised activity in the inferior prefrontal, middle temporal, and middle frontal/anterior cingulate gyrus. Although the young adults showed more activity in some of these areas, the finding of mainly overlapping activation patterns during semantic classification supports the idea that lexical/semantic retrieval processes are still intact in elderly adults. This received further support by the finding that both groups showed similar behavioural performances as well on the deep and shallow classification tasks. Importantly, though, the young revealed significantly more activity than the elderly adults in the left anterior hippocampus during deep relative to shallow classification. This finding is in line with the idea that age-related impairments in episodic encoding are, at least partly, due to an under-recruitment of the medial temporal lobe memory system.     

Episodic temporal structure modulates associative recognition processes: An MEG study

The formation of mnemonic associations can occur between items processed in temporal proximity. It has been proposed that such intertemporal associations are not unitizable, and may therefore be retrieved only via recollective processes. To examine this claim, we conducted a magnetoencephalograph study of recognition memory for items encoded and retrieved sequentially. Participants studied successively presented pairs of object pictures, and subsequently made old‐new item judgments under several retrieval conditions, differing in degree of reinstatement of associative information. Correct recognition was accompanied by an early event‐related field (ERF) component, seemingly corresponding to the FN400 event‐related potential component asserted to reflect familiarity; this retrieval success effect was not modulated by degree of associative binding. A later ERF component, corresponding to the late positive component asserted to reflect recollection, was modulated by degree of associative reinstatement. These results suggest that memory of intertemporal associations, which are not amenable to unitization, is accessed via recollection.