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A key aspect of human cognitive flexibility concerns the ability to convert complex symbolic instructions into novel behaviors. Previous research proposes that this transformation is supported by two neurocognitive states: an initial declarative maintenance of task knowledge, and an implementation state necessary for optimal task execution. Furthermore, current models predict a crucial role of frontal and parietal brain regions in this process. However, whether declarative and procedural signals independently contribute to implementation remains unknown. We report the results of an fMRI experiment in which participants executed novel instructed stimulus-response associations. We then used a pattern-tracking procedure to quantify the contribution of format-unique signals during instruction implementation. This revealed independent procedural and declarative representations of novel S-Rs in frontoparietal areas, prior to execution. Critically, the degree of procedural activation predicted subsequent behavioral performance. Altogether, our results suggest an important contribution of frontoparietal regions to the neural architecture that regulates cognitive flexibility.

Whereas the effects of attention switches occurring within perception or memory are relatively well understood, much less is known about switches of attention between them. We discuss the methodological limitations of initial research on this topic, which was never integrated with the broader cognitive literature. On the basis of this discussion, we present here a new paradigm, in which participants performed a simple probe-to-target matching task where targets were either perceived on screen or retrieved from memory. Across successive trials, repetitions or alternations (in both directions) between these 2 conditions were created, and eventually compared with each other. In line with our prediction, derived from the assumption of a top-down control mechanism, we found a cost for switching between external and internal attention in Experiment 1. Furthermore, this switch cost was asymmetric, being substantially larger when switching from (external) perception to (internal) memory than the other way around. In Experiments 2-4, we ruled out an imbalance in practice, learning, and preparation as confounds for this asymmetry. We propose that switches of attention between internal and external information are underpinned by a supervisory attention control mechanism, and that this asymmetry can be explained in terms of priming, associative interference or memory retrieval. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Attention and memory may be impaired in individuals at-risk for Alzheimer’s disease (AD), though standard cognitive assessments typically study the two in parallel. In reality, attention and memory interact to facilitate information processing, and thus a more integrative approach is required. Here, we used a novel auditory paradigm to assess how long-term memory for auditory scenes facilitates detection of an auditory target in asymptomatic carriers of Apolipoprotein E4 (APOE4), the principle risk gene for late-onset AD. We tested 60 healthy middle-aged adults with varying doses of APOE4 - 20 APOE4 homozygotes (E4/E4), 20 heterozygotes (E3/E4) and 20 non-carriers (E3/E3) - to determine effect on memory-guided attention. While explicit memory was unaffected by genotype, APOE4 dose significantly impaired memory-guided attention. A relationship between explicit memory and memory-guided attention was observed in non-carriers, but this correlation was not significant in E3/E4 and E4/E4 carriers, suggesting that APOE4 carriers rely less on explicit memory to facilitate attention. Since memory-guided attention declined with age in APOE4 homozygotes, this impairment may reflect early disease rather than being a life-long trait. In sum, asymptomatic individuals at increased genetic risk of AD show an age-dependent decline in attention-memory interaction when memory alone is not impaired.

In natural settings, the prospect of reward often influences the focus of our attention, but how cognitive and motivational systems influence sensory cortex is not well understood. Also, challenges in training nonhuman animals on cognitive tasks complicate cross-species comparisons and interpreting results on the neurobiological bases of cognition. Incentivized attention tasks could expedite training and evaluate the impact of attention on sensory cortex. Here we develop an Incentivized Attention Paradigm (IAP) and use it to show that macaque monkeys readily learn to use auditory or visual reward cues, drastically influencing their performance within a simple auditory task. Next, this paradigm was used with functional neuroimaging to measure activation modulation in the monkey auditory cortex. The results show modulation of extensive auditory cortical regions throughout primary and non-primary regions, which although a hallmark of attentional modulation in human auditory cortex, has not been studied or observed as broadly in prior data from nonhuman animals. Psycho-physiological interactions were identified between the observed auditory cortex effects and regions including basal forebrain sites along acetylcholinergic and dopaminergic pathways. The findings reveal the impact and regional interactions in the primate brain during an incentivized attention engaging auditory task.

Cognitive and affective impairments are the most characterized consequences following cerebral ischemia. BAY 60-7550, a selective phosphodiesterase type 2 inhibitor (PDE2-I), presents memory-enhancing and anxiolytic-like properties. The behavioral effects of BAY 60-7550 have been associated with its ability to prevent hydrolysis of both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) thereby interfering with neuronal plasticity. Here, we hypothesize that PDE2-I treatment could promote functional recovery after brain ischemia. Mice C57Bl/6 were submitted to bilateral common carotid artery occlusion (BCCAO), an experimental model of transient brain ischemia, for 20 min. During 21 days after reperfusion, the animals were tested in a battery of behavioral tests including the elevated zero maze (EZM), object location task (OLT) and forced swim test (FST). The effects of BAY 60-7550 were evaluated on neuronal nuclei (NeuN), caspase-9, cAMP response element- binding protein (CREB), phosphorylated CREB (pCREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. BCCAO increased anxiety levels, impaired hippocampus-dependent cognitive function and induced despair-like behavior in mice. Hippocampal neurodegeneration was evidenced by a decrease in NeuN and increase incaspase-9 protein levels in BCCAO mice. Ischemic mice also showed low BDNF protein levels in the hippocampus. Repeated treatment with BAY 60-7550 attenuated the behavioral impairments induced by BCCAO in mice. Concomitantly, BAY 60-7550 enhanced expression of pCREB and BDNF protein levels in the hippocampus of ischemic mice. The present findings suggest that chronic inhibition of PDE2 provides functional recovery in BCCAO mice possibly by augmenting hippocampal neuronal plasticity.

Available online: 29 June 2016 The two-component framework of episodic memory (EM) development posits that the contributions of medial temporal lobe (MTL) and prefrontal cortex (PFC) to successful encoding differ across the lifespan. To test the framework's hypotheses, we compared subsequent memory effects (SME) of 10-12 year-old children, younger adults, and older adults using functional magnetic resonance imaging (fMRI). Memory was probed by cued recall, and SME were defined as regional activation differences during encoding between subsequently correctly recalled versus omitted items. In MTL areas, children's SME did not differ in magnitude from those of younger and older adults. In contrast, children's SME in PFC were weaker than the corresponding SME in younger and older adults, in line with the hypothesis that PFC contributes less to successful encoding in childhood. Differences in SME between younger and older adults were negligible. The present results suggest that, among individuals with high memory functioning, the neural circuitry contributing to successful episodic encoding is reorganized from middle childhood to adulthood. Successful episodic encoding in later adulthood, however, is characterized by the ability to maintain the activation patterns that emerged in young adulthood. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.

We recently provided evidence that an intrinsic reward-related signal—triggered by successful learning in absence of any external feedback—modulated the entrance of new information into long-term memory via the activation of the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop; Ripollés et al., 2016). Here, we used a double-blind, within-subject randomized pharmacological intervention to test whether this learning process is indeed dopamine-dependent. A group of healthy individuals completed three behavioral sessions of a language-learning task after the intake of different pharmacological treatments: a dopaminergic precursor, a dopamine receptor antagonist or a placebo. Results show that the pharmacological intervention modulated behavioral measures of both learning and pleasantness, inducing memory benefits after 24 hr only for those participants with a high sensitivity to reward. These results provide causal evidence for a dopamine-dependent mechanism instrumental in intrinsically regulated learning and further suggest that subject-specific reward sensitivity drastically alters learning success.

Long-term recognition memory for some pictures is consistently better than for others (Isola, Xiao, Parikh, Torralba, & Oliva, IEEE Transaction on Pattern Analysis and Machine Intelligence (PAMI), 36(7), 1469–1482, 2014). Here, we investigated whether pictures found to be memorable in a long-term memory test are also perceived more easily when presented in ultra-rapid RSVP. Participants viewed 6 pictures they had never seen before that were presented for 13 to 360 ms per picture in a rapid serial visual presentation (RSVP) sequence. In half the trials, one of the pictures was a memorable or a nonmemorable picture and perception of this picture was probed by a visual recognition test at the end of the sequence. Recognition for pictures from the memorable set was higher than for those from the nonmemorable set, and this difference increased with increasing duration. Nonmemorable picture recognition was low initially, did not increase until 120 ms, and never caught up with memorable picture recognition performance. Thus, the long-term memorability of an image is associated with initial perceptibility: A picture that is hard to grasp quickly is hard to remember later.

Animals can adjust their behaviour according to previous experience gained during foraging. In parasitoids, experience plays a key role in host location, a hierarchical process in which air-borne and substrate-borne semiochemicals are used to find hosts. In nature, chemical traces deposited by herbivore hosts when walking on the plant are adsorbed by leaf surfaces and perceived as substrate-borne semiochemicals by parasitoids. Chemical traces left on cabbage leaves by adults of the harlequin bug (Murgantia histrionica) induce an innate arrestment response in the egg parasitoid Trissolcus brochymenae characterized by an intense searching behaviour on host-contaminated areas. Here we investigated whether the T. brochymenae response to host walking traces left on leaf surfaces is affected by previous experience in the context of parasitoid foraging behaviour. We found that: 1) an unrewarded experience (successive encounters with host-contaminated areas without successful oviposition) decreased the intensity of the parasitoid response; 2) a rewarded experience (successful oviposition) acted as a reinforcing stimulus; 3) the elapsed time between two consecutive unrewarded events affected the parasitoid response in a host-gender specific manner. The ecological role of these results to the host location process of egg parasitoids is discussed.

The delay associated with cerebral processing time implies a lack of real-time representation of changes in the observed environment. To bridge this gap for motor actions in a dynamical environment, the brain uses predictions of the most plausible future reality based on previously provided information. To optimise these predictions, adjustments to actual experiences are necessary. This requires a perceptual memory buffer. In our study we gained more insight how the brain treats (real-time) information by comparing cerebral activations related to judging past-, present- and future locations of a moving ball, respectively. Eighteen healthy subjects made these estimations while fMRI data was obtained. All three conditions evoked bilateral dorsal-parietal and premotor activations, while judgment of the location of the ball at the moment of judgment showed increased bilateral posterior hippocampus activation relative to making both future and past judgments at the one-second time-sale. Since the condition of such 'real-time' judgments implied undistracted observation of the ball's actual movements, the associated hippocampal activation is consistent with the concept that the hippocampus participates in a top-down exerted sensory gating mechanism. In this way, it may play a role in novelty (saliency) detection.

D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [(11)C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions.

It is well established that the activity of chromatin-modifying enzymes is crucial for regulating gene expression associated with hippocampal-dependent memories. However, very little is known about how these epigenetic mechanisms influence the formation of cortically dependent memory, particularly when there is competition between opposing memory traces, such as that which occurs during the acquisition and extinction of conditioned fear. Here we demonstrate, in C57BL/6 mice, that the activity of p300/CBP-associated factor (PCAF) within the infralimbic prefrontal cortex is required for long-term potentiation and is necessary for the formation of memory associated with fear extinction, but not for fear acquisition. Further, systemic administration of the PCAF activator SPV106 enhances memory for fear extinction and prevents fear renewal. The selective influence of PCAF on fear extinction is mediated, in part, by a transient recruitment of the repressive transcription factor ATF4 to the promoter of the immediate early genezif268, which competitively inhibits its expression. Thus, within the context of fear extinction, PCAF functions as a transcriptional coactivator, which may facilitate the formation of memory for fear extinction by interfering with reconsolidation of the original memory trace.

Although many genetic association studies have been carried out, it remains unclear which genes contribute to depression. This may be due to heterogeneity of the DSM-IV category of depression. Specific symptom-dimensions provide a more homogenous phenotype. Furthermore, as effects of individual genes are small, analysis of genetic data at the pathway-level provides more power to detect associations and yield valuable biological insight. In 1,398 individuals with a Major Depressive Disorder, the symptom dimensions of the tripartite model of anxiety and depression, General Distress, Anhedonic Depression, and Anxious Arousal, were measured with the Mood and Anxiety Symptoms Questionnaire (30-item Dutch adaptation; MASQ-D30). Association of these symptom dimensions with candidate gene sets and gene sets from two public pathway databases was tested using the Global test. One pathway was associated with General Distress, and concerned molecules expressed in the endoplasmatic reticulum lumen. Seven pathways were associated with Anhedonic Depression. Important themes were neurodevelopment, neurodegeneration, and cytoskeleton. Furthermore, three gene sets associated with Anxious Arousal regarded development, morphology, and genetic recombination. The individual pathways explained up to 1.7% of the variance. These data demonstrate mechanisms that influence the specific dimensions. Moreover, they show the value of using dimensional phenotypes on one hand and gene sets on the other hand. (C) 2012 Wiley Periodicals, Inc.

In the present study, we investigated the functional characteristics of task sets that were never applied before and were formed only on the basis of instructions. We tested if such task sets could elicit a task-rule congruency effect, which implies the automatic activation of responses in the context of another task. To this end, a novel procedure was developed that revealed instruction-based task-rule congruency effects in 2 experiments. Although the effect seems quite general (Experiment 1), it still necessitates the formation of a task set, as it cannot be induced by the mere maintenance of instructions in declarative working memory (Experiment 2). We conclude that a task set representing only key features of an upcoming task can be formed on the basis of instructions alone to such a degree that it can automatically trigger a response tendency in another task. Implications of our results for the impact of instructions on performance in general and for the occurrence of task-rule congruency effects in particular are discussed.

Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Δ9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans.

Objective: To assess consolidation in amnestic mild cognitive impairment (aMCI), controlling for differences in initial learning and using a protracted delay period for recall. Method: 15 individuals with aMCI were compared with 15 healthy older adult controls on a story learning task. Subjects were trained to criteria to equalize initial learning across subjects. Recall was tested at both the 30-min typically used delay and a 1-week delay used to target consolidation. Results: Using repeated measures ANOVAs adjusted for age, we found group × time point interactions across the entire task between the final trial and 30-min delay, and again between the 30-min and 1-week delay periods, with aMCI having greater declines in recall as compared with controls. Significant group main effects were also found, with aMCI recalling less than controls. Conclusion: Consolidation was impaired in aMCI as compared with controls. Our findings indicate that aMCI-related performance typically measured at 30 min underestimates aMCI-associated memory deficits. This is the first study to isolate consolidation by controlling for initial learning differences and using a protracted delay period to target consolidation in an aMCI sample. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

In this study, we investigated the stages of information processing in associative recognition. We recorded EEG data while participants performed an associative recognition task that involved manipulations of word length, associative fan, and probe type, which were hypothesized to affect the perceptual encoding, retrieval, and decision stages of the recognition task, respectively. Analyses of the behavioral and EEG data, supplemented with classification of the EEG data using machine-learning techniques, provided evidence that generally supported the sequence of stages assumed by a computational model developed in the Adaptive Control of Thought-Rational cognitive architecture. However, the results suggested a more complex relationship between memory retrieval and decision-making than assumed by the model. Implications of the results for modeling associative recognition are discussed. The study illustrates how a classifier approach, in combination with focused manipulations, can be used to investigate the timing of processing stages.

Background : Working Memory Capacity (WMC) is thought to be related to executive control and focused memory search abilities. These two hypotheses make contrasting predictions regarding the effects of retrieval on forgetting. Executive control during memory retrieval is believed to lead to retrieval induced forgetting (RIFO) because inhibition of competing memory traces during retrieval renders them temporarily less accessible. According to this suggestion, superior executive control should increase RIFO. Alternatively, superior focused search abilities could diminish RIFO, because delimiting the search set reduces the amount of competition between traces and thus the need for inhibition. Some evidence suggests that high WMC is related to more RIFO, which is inconsistent with the focused search hypothesis.Methodology/Principal Findings: Using the RIFO paradigm, we created distinct and overlapping categories to manipulate the amount of competition between them. This overlap increased competition between some categories while exclusive use of weak exemplars ensured negligible effects of output interference and integration. Low WMC individuals exhibited RIFO within and between overlapping categories, indicating the effect of resolving competition during retrieval. High WMC individuals only exhibited between-category RIFO, suggesting they experienced reduced competition resolution demands. Low WMC Individuals exhibited the strongest RIFO and no retrieval benefits when interference resolution demands were high.Conclusions/Significance: Our findings qualify the inhibitory explanation for RIFO by incorporating the focused search hypothesis for materials that are likely to pose extraordinary challenges at retrieval. The results highlight the importance of considering individual differences in retrieval-induced effects and qualify existing models of these effects.

OBJECTIVES: The context of memory experiences is referred to as source memory and can be distinguished from the content of episodic item memory. Source memory represents a crucial part of biographic events and elaborate memory experiences. Whereas individuals with attention deficit hyperactivity disorder (ADHD) were shown to have inefficient item memory, little is known about the context of memory experiences. METHODS: The present study compared 37 adult patients with a diagnosed ADHD with 40 matched healthy participants on a word list paradigm. Memory functions of encoding, retention and source discrimination were assessed. Furthermore, standardized measures of memory and executive control were applied in order to explore a qualitative differentiation of memory components. RESULTS: Adult patients with ADHD showed impaired performance in encoding of new information whereas the retention of encoded items was found to be preserved. The most pronounced impairment of patients with ADHD was observed in source discrimination. Regression models of cognitive functions on memory components supported some qualitative differentiation. CONCLUSIONS: Data analysis suggests a differential pattern of memory impairment in adults suffering from ADHD with a particular deficit in source discrimination. Inefficient source discrimination in adults with ADHD can affect daily functioning by limiting biographic awareness and disturbing general cognitive processes.

It is well established that glucocorticoid hormones strengthen the consolidation of long-term memory of emotionally arousing experiences but have little effect on memory of low-arousing experiences. Although both positive and negative emotionally arousing events tend to be well remembered, studies investigating the neural mechanism underlying glucocorticoid-induced memory enhancement focused primarily on negatively motivated training experiences. In the present study we show an involvement of glucocorticoids within the nucleus accumbens (NAc) in enhancing memory consolidation of both an appetitive and aversive form of taste learning. The specific glucocorticoid receptor (GR) agonist RU 28362 (1 or 3 ng) administered bilaterally into the NAc shell, but not core, of male Sprague-Dawley rats immediately after an appetitive saccharin drinking experience dose-dependently enhanced 24-h retention of the safe taste, resulting in a facilitated attenuation of neophobia. Similarly, GR agonist infusions given into the NAc shell immediately after pairing of the saccharin taste with a malaise-inducing agent enhanced memory of this negative experience, resulting in an intensified conditioned aversion. Importantly, a suppression of noradrenergic activity within the NAc shell with the beta-adrenoceptor antagonist propranolol blocked the facilitating effect of a concurrently administered GR agonist on memory consolidation in both the appetitive and aversive learning task. Thus, these findings indicate that GR activation interacts with the noradrenergic arousal system within the NAc to enhance memory consolidation of emotionally arousing training experiences regardless of valence. (C) 2012 Elsevier Inc. All rights reserved.

Cocaine exposure triggers molecular events that lead to long-lasting changes in brain structure and function. These changes can lead to the development of persistent and robust behavioral adaptations that characterize addiction. Recent evidence suggests the regulation of transcription via chromatin modification, such as histone acetylation, has an important role in the development of addictive behavior. Histone acetylation is regulated by histone acetyltransferases (HATs), which acetylate histones and promote transcription, and histone deacetylases (HDACs), which remove acetyl groups and silence transcription. Studies have demonstrated that HDACs may negatively regulate cocaine-induced behaviors, but very little is known about the role of specific HATs in long-lasting drug-induced plasticity. The histone acetyltransferase CREB-binding protein (CBP) mediates transcriptional activation by recruiting basal transcription machinery and acetylating histones. CBP is a critically important chromatin-modifying enzyme involved in regulating gene expression required for long-term plasticity and memory. However, the role of CBP in cocaine-induced behaviors remains largely unknown. We examined the role of CBP in drug-induced plasticity using CBP-FLOX genetically modified mice in combination with adeno-associated virus expressing Cre-recombinase to generate focal homozygous deletions ofCbpin the nucleus accumbens (NAc). A complete loss of CBP in NAc neurons results in decreased histone acetylation and significantly altered c-fosexpression in response to cocaine. Furthermore, the deletion of CBP in the NAc correlates with significant impairments in cocaine sensitivity and context–cocaine associated memory. This is the first study to demonstrate a definitive role for CBP in modulating gene expression that may subserve drug-seeking behaviors.

Many insects possess a sexual communication system that is vulnerable to chemical espionage by parasitic wasps. We recently discovered that a hitch-hiking (H) egg parasitoid exploits the antiaphrodisiac pheromone benzyl cyanide (BC) of the Large Cabbage White butterfly Pieris brassicae . This pheromone is passed from male butterflies to females during mating to render them less attractive to conspecific males. When the tiny parasitic wasp Trichogramma brassicae detects the antiaphrodisiac, it rides on a mated female butterfly to a host plant and then parasitizes her freshly laid eggs. The present study demonstrates that a closely related generalist wasp, Trichogramma evanescens , exploits BC in a similar way, but only after learning. Interestingly, the wasp learns to associate an H response to the odors of a mated female P. brassicae butterfly with reinforcement by parasitizing freshly laid butterfly eggs. Behavioral assays, before which we specifically inhibited long-term memory (LTM) formation with a translation inhibitor, reveal that the wasp has formed protein synthesis-dependent LTM at 24 h after learning. To our knowledge, the combination of associatively learning to exploit the sexual communication system of a host and the formation of protein synthesis-dependent LTM after a single learning event has not been documented before. We expect it to be widespread in nature, because it is highly adaptive in many species of egg parasitoids. Our finding of the exploitation of an antiaphrodisiac by multiple species of parasitic wasps suggests its use by Pieris butterflies to be under strong selective pressure.

The effect of different formats on the accuracy of dating news and the distribution of personal events was examined in four conditions. In the first, participants had to date events in the absolute time format (e.g., "July 2004"), and in the second, they had to date events in the relative time format (e.g., "3 weeks ago). In the other conditions, they were asked to choose between the two formats. We found a small backward telescoping effect for recent news events and a large forward telescoping effect for remote events. Events dated in the absolute time format were more accurate than those dated in the relative time format. Furthermore, participants preferred to date news events with the relative time format and personal events with the absolute time format, as well as preferring to date remote events in the relative time format and recent events in the absolute time format.

Twenty-four young and 24 middle-aged academics carried out a language recognition task in which sentences were presented that made either a high or a low demand on working memory (WM). The sentences ended either normally (i.e., congruent) or with an incongruous word. Middle-aged subjects had smaller WM scores, a marginally slowed down recognition performance, and a smaller and delayed N400 component. The event-related potential (ERP) difference between congruent and incongruent endings was smaller in the high-load condition for younger subjects and totally disappeared for the middle-aged subjects. ERPs for all subjects showed a WM-related positivity in the middle of the sentence and a WM-related negativity at the sentence ending. These shifts could be associated with either storage and retrieval processes or with clause wrap-up processes. Most ERP-effects were dependent on WM capacity. Age differences in sentence processing are not simply explained by age itself but depend to a large extent on individual memory capacity.

The stress response facilitates survival through adaptation and is intimately related to cognitive processes. The Morris water maze task probes spatial learning and memory in rodents and glucocorticoids (i.e. corticosterone (CORT) in rats) have been suggested to elicit a facilitating action on memory formation. Moreover, the early aging period (around 16-18 months of age) is susceptible to stress- and glucocorticoid-mediated acceleration of cognitive decline. In this study, we tested three lines of rats selectively bred according to their individual differences in CORT responsiveness to repeated stress exposure during juvenility. We investigated whether endogenous differences in glucocorticoid responses influenced spatial learning, long-term memory, and reversal learning abilities in a Morris water maze task at early aging. Additionally, we assessed the quality of the different swimming strategies of the rats. Our results indicate that rats with differential CORT responsiveness exhibit similar spatial learning abilities but different long-term memory retention and reversal learning. Specifically, the high CORT responding line had a better long-term spatial memory, while the low CORT responding line was impaired for both long-term retention and reversal learning. Our modeling analysis of performance strategies revealed further important line-related differences. Therefore, our findings support the view that individuals with high CORT responsiveness would form stronger long-term memories to navigate in stressful environments. Conversely, individuals with low CORT responsiveness would be impaired at different phases of spatial learning and memory. LAY SUMMARY Rats selected for different glucocorticoid responses to stress show differences in spatial learning and cognition. While the high responding animals have a better long-term spatial memory retention, the low responding rats have an inferior spatial memory and impaired reversal learning abilities.

Down syndrome (DS) patients exhibit abnormalities of hippocampal-dependent explicit memory, a feature that is replicated in relevant mouse models of the disease. Adult hippocampal neurogenesis, which is impaired in DS and other neuropsychiatric diseases, plays a key role in hippocampal circuit plasticity and has been implicated in learning and memory. However, it remains unknown whether increasing adult neurogenesis improves hippocampal plasticity and behavioral performance in the multifactorial context of DS. We report that, in the Ts65Dn mouse model of DS, chronic administration of lithium, a clinically used mood stabilizer, promoted the proliferation of neuronal precursor cells through the pharmacological activation of the Wnt/β-catenin pathway and restored adult neurogenesis in the hippocampal dentate gyrus (DG) to physiological levels. The restoration of adult neurogenesis completely rescued the synaptic plasticity of newborn neurons in the DG and led to the full recovery of behavioral performance in fear conditioning, object location, and novel object recognition tests. These findings indicate that reestablishing a functional population of hippocampal newborn neurons in adult DS mice rescues hippocampal plasticity and memory and implicate adult neurogenesis as a promising therapeutic target to alleviate cognitive deficits in DS patients.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by language and communication impairments, social impairments, and repetitive behaviors or restricted interests. Previous studies of semantic functions have found differences in semantic processing and differences in the activation of the language network in adults with ASD compared to controls. The goal of this study is to examine semantic functions in adolescents with ASD compared to typically developing adolescents. We utilized fMRI with a reading version of a response-naming task to investigate activation in 12 right-handed adolescent boys with ASD and 12 typically developing boys. Both groups performed the task at ceiling levels. Boys with ASD had significantly stronger activation than controls in Broca's area, which was less left lateralized in ASD individuals. Controls had a significant correlation between frontal and temporal language area activation in the left hemisphere, whereas ASD adolescents did not. Direct group comparisons revealed additional regions activated in the ASD group relative to the control group. These results suggest differences in semantic organization, approaches to the semantic task, or efficiency in semantic processing in ASD adolescents relative to typically developing adolescents. (JINS, 2008,14, 967–979.)