Perirhinal cortex supports encoding and familiarity-based recognition of novel associations

Results from imaging and lesion studies of item recognition memory have suggested that the hippocampus supports memory for the arbitrary associations that form the basis of episodic recollection, whereas the perirhinal cortex (PRc) supports familiarity for individual items. This view has been challenged, however, by findings showing that PRc may contribute to associative recognition, a task thought to measure relational or recollective memory. Here, using functional magnetic resonance imaging, we demonstrate that PRc activity is increased when pairs of items are processed as a single configuration or unit and that this activity predicts subsequent familiarity-based associative memory. These results explain the discrepancy in the literature by showing that novel associations can be encoded in a unitized manner, thereby allowing PRc to support associative recognition based on familiarity.     

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．     

Implicit associative learning engages the hippocampus and interacts with explicit associative learning

The hippocampus is crucial for conscious, explicit memory, but whether it is also involved in nonconscious, implicit memory is uncertain. We investigated with functional magnetic resonance imaging whether implicit learning engages the hippocampus and interacts with subsequent explicit learning. The presentation of subliminal faces-written profession pairs for implicit learning was followed by the explicit learning of supraliminal pairs composed of the same faces combined with written professions semantically incongruous to those presented subliminally (experiment 1), semantically congruous professions (experiment 2), or identical professions (experiment 3). We found that implicit face-profession learning interacted with explicit face-profession learning in all experiments, impairing the explicit retrieval of the associations. Hippocampal activity increased during the subliminal presentation of face-profession pairs versus face-nonword pairs and correlated with the later impairment of explicit retrieval. These findings suggest that implicit semantic associative learning engages the hippocampus and influences explicit memory.     

Memory for semantically related and unrelated declarative information: the benefit of sleep, the cost of wake

Numerous studies have examined sleep's influence on a range of hippocampus-dependent declarative memory tasks, from text learning to spatial navigation. In this study, we examined the impact of sleep, wake, and time-of-day influences on the processing of declarative information with strong semantic links (semantically related word pairs) and information requiring the formation of novel associations (unrelated word pairs). Participants encoded a set of related or unrelated word pairs at either 9 am or 9 pm, and were then tested after an interval of 30 min, 12 hr, or 24 hr. The time of day at which subjects were trained had no effect on training performance or initial memory of either word pair type. At 12 hr retest, memory overall was superior following a night of sleep compared to a day of wakefulness. However, this performance difference was a result of a pronounced deterioration in memory for unrelated word pairs across wake; there was no sleep-wake difference for related word pairs. At 24 hr retest, with all subjects having received both a full night of sleep and a full day of wakefulness, we found that memory was superior when sleep occurred shortly after learning rather than following a full day of wakefulness. Lastly, we present evidence that the rate of deterioration across wakefulness was significantly diminished when a night of sleep preceded the wake period compared to when no sleep preceded wake, suggesting that sleep served to stabilize the memories against the deleterious effects of subsequent wakefulness. Overall, our results demonstrate that 1) the impact of 12 hr of waking interference on memory retention is strongly determined by word-pair type, 2) sleep is most beneficial to memory 24 hr later if it occurs shortly after learning, and 3) sleep does in fact stabilize declarative memories, diminishing the negative impact of subsequent wakefulness.     

Increased resting-state perfusion after repeated encoding is related to later retrieval of declarative associative memories

Electrophysiological studies in animals have shown coordinated reactivation of neuronal ensembles during a restricted time period of behavioral inactivity that immediately followed active encoding. In the present study we directly investigated off-line processing of associative memory formation in the human brain. Subjects' regional cerebral blood flow (rCBF) as a surrogate marker of neural activity during rest was measured by MR-based perfusion imaging in a sample of 14 healthy male subjects prior to (Pre2) and after (Post) extensive learning of 24 face-name associations within a selective reminding task (SR). Results demonstrated significant Post-Pre2 rCBF increases in hippocampal and temporal lobe regions, while in a control comparison of two perfusion scans with no learning task in-between (Pre2-Pre1) no differences in rCBF emerged. Post perfusion scanning was followed by a surprise cued associative recall task from which two types of correctly retrieved names were obtained: older names already correctly retrieved at least once during one of the SR blocks, and recent names acquired during the last SR block immediately prior to the Post scan. In the anterior hippocampus individual perfusion increases were correlated with both correct retrievals of older and recent names. By contrast, older but not recently learned names showed a significant correlation with perfusion increases in the left lateral temporal cortex known to be associated with long-term memory. Recent, but not older names were correlated with dopaminergic midbrain structures reported to contribute to the persistence of memory traces for novel information. Although the direct investigation of off-line memory processing did not permit concomitant experimental control, neither intentional rehearsal, nor substantial variations in subjects' states of alertness appear to contribute to present results. We suggest that the observed rCBF increases might reflect processes that possibly contribute to the long-term persistence of memory traces.     

Effect of daytime nap on consolidation of declarative memory in humans

We studied effects of a daytime nap (1 hour) with including only NREM sleep on performance of declarative memory task (60 semantically unrelated word pairs) and general functional state. During training, procedure of learning of 30 word pairs was presented once, and that of the other 30 pairs was repeated twice. Strength of the task acquisition was tested. Subjects participated in two experiments: basic and control one. After learning participants either took a nap (basic experiment) or kept awake looking movies (control experiment). In 4.5 hours after the training session all the subjects were retested. As compared to the subjects who stayed awake during the training-retesting interval, subjects who had a NREM nap demonstrated enhanced performance. Concerning the strength of task acquisition, sleep-dependent performance was observed only for the word pairs learned once. Naps did not affect the functional state assessed by the reaction time dynamics and psychological testing.     

Offline persistence of memory-related cerebral activity during active wakefulness

Much remains to be discovered about the fate of recent memories in the human brain. Several studies have reported the reactivation of learning-related cerebral activity during post-training sleep, suggesting that sleep plays a role in the offline processing and consolidation of memory. However, little is known about how new information is maintained and processed during post-training wakefulness before sleep, while the brain is actively engaged in other cognitive activities. We show, using functional magnetic resonance imaging, that brain activity elicited during a new learning episode modulates brain responses to an unrelated cognitive task, during the waking period following the end of training. This post-training activity evolves in learning-related cerebral structures, in which functional connections with other brain regions are gradually established or reinforced. It also correlates with behavioral performance. These processes follow a different time course for hippocampus-dependent and hippocampus-independent memories. Our experimental approach allowed the characterization of the offline evolution of the cerebral correlates of recent memories, without the confounding effect of concurrent practice of the learned material. Results indicate that the human brain has already extensively processed recent memories during the first hours of post-training wakefulness, even when simultaneously coping with unrelated cognitive demands.     

Social Rewards Enhance Offline Improvements in Motor Skill

Motor skill memory is first encoded online in a fragile form during practice and then converted into a stable form by offline consolidation, which is the behavioral stage critical for successful learning. Praise, a social reward, is thought to boost motor skill learning by increasing motivation, which leads to increased practice. However, the effect of praise on consolidation is unknown. Here, we tested the hypothesis that praise following motor training directly facilitates skill consolidation. Forty-eight healthy participants were trained on a sequential finger-tapping task. Immediately after training, participants were divided into three groups according to whether they received praise for their own training performance, praise for another participant''s performance, or no praise. Participants who received praise for their own performance showed a significantly higher rate of offline improvement relative to other participants when performing a surprise recall test of the learned sequence. On the other hand, the average performance of the novel sequence and randomly-ordered tapping did not differ between the three experimental groups. These results are the first to indicate that praise-related improvements in motor skill memory are not due to a feedback-incentive mechanism, but instead involve direct effects on the offline consolidation process.     

Neural representation of visual objects: encoding and top-down activation

Knowledge or experiences are voluntarily recalled from memory by reactivation of their neural representations in the association cortex. Mnemonic representations of visual objects, located in the ventral processing stream of visual perception, provide the best indication of how neuronal codes are created, organized and reactivated. Associative codes are created by neurons that have the ability to link the representations of temporally associated stimuli. Recent experiments suggest that not only bottom-up signals from the retina but also top-down signals from the prefrontal cortex can trigger the retrieval of associative codes, which may serve as a neural basis for conscious recall.     

Effects of daytime food intake on memory consolidation during sleep or sleep deprivation

Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin), the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD) could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory) and a list of semantically associated word pairs (declarative memory). After the learning period, standardized meals were administered, equaling either ～50% or ～150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG). Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep's capacity to boost the consolidation of declarative and procedural memories, nor sleep's quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also sensitive to the fluctuations in the energy state of the body.     

Age-Related Decline in Associative Learning in Healthy Chinese Adults

Paired associates learning (PAL) has been widely used in aging-related research, suggesting an age-related decline in associative learning. However, there are several cognitive processes (attention, spatial and recognition memory, strategy, and associative learning) involved in PAL. It is unclear which component contributes to the decline in PAL performance associated with age effects. The present study determines whether age effects on associative learning are independent of other cognitive processes involved in PAL. Using a validated computerized cognitive program (CANTAB), we examined cognitive performance of associative learning, spatial and recognition memory, attention and strategy use in 184 Singaporean Chinese adults aged from 21 to 80 years old. Linear regression revealed significant age-related decline in associative learning, spatial and recognition memory, and the level of strategy use. This age-related decline in associative learning remains even after adjusting for attention, spatial and recognition memory, and strategy use. These results show that age effects on associative learning are independent of other cognitive processes involved in PAL.     

Neural encoding in ventral striatum during olfactory discrimination learning

A growing body of evidence implicates the ventral striatum in using information acquired through associative learning. The present study examined the activity of ventral striatal neurons in awake, behaving rats during go/no-go odor discrimination learning and reversal. Many neurons fired selectively to odor cues predictive of either appetitive (sucrose) or aversive (quinine) outcomes. Few neurons were selective when first exposed to the odors, but many acquired this differential activity as rats learned the significance of the cues. A substantial proportion of these neurons encoded the cues' learned motivational significance, and these neurons tended to reverse their firing selectivity after reversal of odor-outcome contingencies. Other neurons that became selectively activated during learning did not reverse, but instead appeared to encode specific combinations of cues and associated motor responses. The results support a role for ventral striatum in using the learned significance, both appetitive and aversive, of predictive cues to guide behavior.     

Are spatial memories strengthened in the human hippocampus during slow wave sleep?

In rats, the firing sequences observed in hippocampal ensembles during spatial learning are replayed during subsequent sleep, suggesting a role for posttraining sleep periods in the offline processing of spatial memories. Here, using regional cerebral blood flow measurements, we show that, in humans, hippocampal areas that are activated during route learning in a virtual town are likewise activated during subsequent slow wave sleep. Most importantly, we found that the amount of hippocampal activity expressed during slow wave sleep positively correlates with the improvement of performance in route retrieval on the next day. These findings suggest that learning-dependent modulation in hippocampal activity during human sleep reflects the offline processing of recent episodic and spatial memory traces, which eventually leads to the plastic changes underlying the subsequent improvement in performance.     

Functional-anatomic correlates of individual differences in memory

Memory abilities differ greatly across individuals. To explore a source of these differences, we characterized the varied strategies people adopt during unconstrained encoding. Participants intentionally encoded object pairs during functional MRI. Principal components analysis applied to a strategy questionnaire revealed that participants variably used four main strategies to aid learning. Individuals' use of verbal elaboration and visual inspection strategies independently correlated with their memory performance. Verbal elaboration correlated with activity in a network of regions that included prefrontal regions associated with controlled verbal processing, while visual inspection correlated with activity in a network of regions that included an extrastriate region associated with object processing. Activity in regions associated with use of these strategies was also correlated with memory performance. This study reveals functional-anatomic correlates of verbal and perceptual strategies that are variably used by individuals during encoding. These strategies engage distinct brain regions and may separately influence memory performance.     

Sleep Promotes the Extraction of Grammatical Rules

Grammar acquisition is a high level cognitive function that requires the extraction of complex rules. While it has been proposed that offline time might benefit this type of rule extraction, this remains to be tested. Here, we addressed this question using an artificial grammar learning paradigm. During a short-term memory cover task, eighty-one human participants were exposed to letter sequences generated according to an unknown artificial grammar. Following a time delay of 15 min, 12 h (wake or sleep) or 24 h, participants classified novel test sequences as Grammatical or Non-Grammatical. Previous behavioral and functional neuroimaging work has shown that classification can be guided by two distinct underlying processes: (1) the holistic abstraction of the underlying grammar rules and (2) the detection of sequence chunks that appear at varying frequencies during exposure. Here, we show that classification performance improved after sleep. Moreover, this improvement was due to an enhancement of rule abstraction, while the effect of chunk frequency was unaltered by sleep. These findings suggest that sleep plays a critical role in extracting complex structure from separate but related items during integrative memory processing. Our findings stress the importance of alternating periods of learning with sleep in settings in which complex information must be acquired.     

Lateralization and unilateral transfer of spatial memory in marsh tits

Summary The results reported in this paper demonstrate lateralization and transfer of spatial memory processing in an adult, food-storig bird. The technique of monocular occlusion was used to investigate lateralization and memory transfer in food-storing marsh tits (Parus palustris) for two tasks, food-storing and one-trial associative learning, which rely on one-trial learning for the spatial location of hidden food items. In the food-storing task, marsh tits had to return to the sites where they had previously stored a seed; in the one-trial associative learning task, the birds had to return to sites where they had been allowed to eat some, but not all, of a piece of peanut. For both spatial memory tasks, it was demonstrated that although the visual systems fed by both eyes are involved in short-term storage, the right eye system is associated with long-term storage, and that memories are transferred from the left to the right eye system between 3 and 24 h after memory formation.     

Comparing the Effects of Nocturnal Sleep and Daytime Napping on Declarative Memory Consolidation

Nocturnal sleep and daytime napping facilitate memory consolidation for semantically related and unrelated word pairs. We contrasted forgetting of both kinds of materials across a 12-hour interval involving either nocturnal sleep or daytime wakefulness (experiment 1) and a 2-hour interval involving either daytime napping or wakefulness (experiment 2). Beneficial effects of post-learning nocturnal sleep and daytime napping were greater for unrelated word pairs (Cohen’s d = 0.71 and 0.68) than for related ones (Cohen’s d = 0.58 and 0.15). While the size of nocturnal sleep and daytime napping effects was similar for unrelated word pairs, for related pairs, the effect of nocturnal sleep was more prominent. Together, these findings suggest that sleep preferentially facilitates offline memory processing of materials that are more susceptible to forgetting.     

The effect of negative and positive emotionality on associative memory: an FMRI study

In general, emotion is known to enhance memory processes. However, the effect of emotion on associative memory and the underling neural mechanisms remains largely unexplored. In this study, we explored brain activation during an associative memory task that involved the encoding and retrieval of word and face pairs. The word and face pairs consisted of either negative or positive words with neutral faces. Significant hippocampal activation was observed during both encoding and retrieval, regardless of whether the word was negative or positive. Negative and positive emotionality differentially affected the hemodynamic responses to encoding and retrieval in the amygdala, with increased responses during encoding negative word and face pairs. Furthermore, activation of the amygdala during encoding of negative word and neutral face pairs was inversely correlated with subsequent memory retrieval. These findings suggest that activation of the amygdala induced by negative emotion during encoding may disrupt associative memory performance.     

Bryostatin enhancement of memory in Hermissenda

Bryostatin, a potent agonist of protein kinase C (PKC), when administered to Hermissenda was found to affect acquisition of an associative learning paradigm. Low bryostatin concentrations (0.1 to 0.5 ng/ml) enhanced memory acquisition, while concentrations higher than 1.0 ng/ml down-regulated the pathway and no recall of the associative training was exhibited. The extent of enhancement depended upon the conditioning regime used and the memory stage normally fostered by that regime. The effects of two training events (TEs) with paired conditioned and unconditioned stimuli, which standardly evoked only short-term memory (STM) lasting 7 min, were--when bryostatin was added concurrently--enhanced to a long-term memory (LTM) that lasted about 20 h. The effects of both 4- and 6-paired TEs (which by themselves did not generate LTM), were also enhanced by bryostatin to induce a consolidated memory (CM) that lasted at least 5 days. The standard positive 9-TE regime typically produced a CM lasting at least 6 days. Low concentrations of bryostatin (<0.5 ng/ml) elicited no demonstrable enhancement of CM from 9-TEs. However, animals exposed to bryostatin concentrations higher than 1.0 ng/ml exhibited no behavioral learning. Sharp-electrode intracellular recordings of type-B photoreceptors in the eyes from animals conditioned in vivo with bryostatin revealed changes in input resistance and an enhanced long-lasting depolarization (LLD) in response to light. Likewise, quantitative immunocytochemical measurements using an antibody specific for the PKC-activated Ca2+/GTP-binding protein calexcitin showed enhanced antibody labeling with bryostatin. Animals exposed to the PKC inhibitor bisindolylmaleimide-XI (Ro-32-0432) administered by immersion prior to 9-TE conditioning showed no training-induced changes with or without bryostatin exposure. However, if animals received bryostatin before Ro-32, the enhanced acquisition and demonstrated recall still occurred. Therefore, pathways responsible for the enhancement effects induced by bryostatin were putatively mediated by PKC. Overall, the data indicated that PKC activation occurred and calexcitin levels were raised during the acquisition phases of associative conditioning and memory initiation, and subsequently returned to baseline levels within 24 and 48 h, respectively. Therefore, the protracted recall measured by the testing regime used was probably due to bryostatin-induced changes during the acquisition and facilitated storage of memory, and not necessarily to enhanced recall of the stored memory when tested many days after training.     

Sleep loss produces false memories

People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a) as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b) as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM) false memory paradigm, subjects learned lists of semantically associated words (e.g., "night", "dark", "coal",...), lacking the strongest common associate or theme word (here: "black"). Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss.