Search

Dorsal striatum has been shown to contribute to spatial learning and memory, but the role of striatal subregions in this important aspect of cognitive functioning remains unclear. Moreover, the spatial-cognitive mechanisms that underlie the involvement of these regions in spatial navigation have scarcely been studied. We therefore compared spatial learning and memory performance in mice with lesions in dorsomedial (DMS) and dorsolateral striatum (DLS) using the hidden-platform version of the Morris water maze (MWM) task. Compared to sham-operated controls, animals with DMS damage were impaired during MWM acquisition training. These mice displayed delayed spatial learning, increased thigmotaxis, and increased search distance to the platform, in the absence of major motor dysfunction, working memory defects or changes in anxiety or exploration. They failed to show a preference for the target quadrant during probe trials, which further indicates that spatial reference memory was impaired in these animals. Search strategy analysis moreover demonstrated that DMS-lesioned mice were unable to deploy cognitively advanced spatial search strategies. Conversely, MWM performance was barely affected in animals with lesions in DLS. In conclusion, our results indicate that DMS and DLS display differential functional involvement in spatial learning and memory. Our results show that DMS, but not DLS, is crucial for the ability of mice to acquire spatial information and their subsequent deployment of spatial search strategies. These data clearly identify DMS as a crucial brain structure for spatial learning and memory, which could explain the occurrence of neurocognitive impairments in brain disorders that affect the dorsal striatum.

How do animals adaptively integrate innate with learned behavioral tendencies? We tackle this question using chemotaxis as a paradigm. Chemotaxis in the Drosophila larva largely results from a sequence of runs and oriented turns. Thus, the larvae minimally need to determine (i) how fast to run, (ii) when to initiate a turn, and (iii) where to direct a turn. We first report how odor-source intensities modulate these decisions to bring about higher levels of chemotactic performance for higher odor-source intensities during innate chemotaxis. We then examine whether the same modulations are responsible for alterations of chemotactic performance by learned odor "valence" (understood throughout as level of attractiveness). We find that run speed (i) is neither modulated by the innate nor by the learned valence of an odor. Turn rate (ii), however, is modulated by both: the higher the innate or learned valence of the odor, the less often larvae turn whenever heading toward the odor source, and the more often they turn when heading away. Likewise, turning direction (iii) is modulated concordantly by innate and learned valence: turning is biased more strongly toward the odor source when either innate or learned valence is high. Using numerical simulations, we show that a modulation of both turn rate and of turning direction is sufficient to account for the empirically found differences in preference scores across experimental conditions. Our results suggest that innate and learned valence organize adaptive olfactory search behavior by their summed effects on turn rate and turning direction, but not on run speed. This work should aid studies into the neural mechanisms by which memory impacts specific aspects of behavior. We received project support by the European Commission (FP7-ICT project Miniature Insect Model for Active Learning [MINIMAL]). M.L. and S.F.R. acknowledge further funding from the Spanish Ministry of Science and Innovation (MICINN, BFU2011-483 26208) and the EMBL/CRG Systems Biology Program. A.D. acknowledges support via the grants EP/F500385/1 and BB/F529254/1 for the University of Edinburgh School of Informatics Doctoral Training Centre in Neuroinformatics and Computational Neuroscience, the UK Engineering and Physical Sciences Research Council (EPSRC), UK Biotechnology and Biological Sciences Research Council (BBSRC), and the UK Medical Research Council (MRC). B.G. received additional support from the Deutsche Forschungsgemeinschaft (DFG) (SFB 779 Motivated behavior), and the Bundesministerium fu¨r Bildung und Forschung (BMBF) (Bernstein Network Insect inspired robotics).

The target of rapamycin (TOR) is a conserved Ser/Thr kinase that regulates cell growth and metabolism in response to environmental cues. Here, highlighting contributions from studies in model organisms, we review mammalian TOR complexes and the signaling branches they mediate. TOR is part of two distinct multiprotein complexes, TOR complex 1 (TORC1), which is sensitive to rapamycin, and TORC2, which is not. The physiological consequences of mammalian TORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.

GABA(B) (gamma-aminobutyric acid type B) receptors are important for keeping neuronal excitability under control. Cloned GABA(B) receptors do not show the expected pharmacological diversity of native receptors and it is unknown whether they contribute to pre- as well as postsynaptic functions. Here, we demonstrate that Balb/c mice lacking the GABA(B(1)) subunit are viable, exhibit spontaneous seizures, hyperalgesia, hyperlocomotor activity, and memory impairment. Upon GABA(B) agonist application, null mutant mice show neither the typical muscle relaxation, hypothermia, or delta EEG waves. These behavioral findings are paralleled by a loss of all biochemical and electrophysiological GABA(B) responses in null mutant mice. This demonstrates that GABA(B(1)) is an essential component of pre- and postsynaptic GABA(B) receptors and casts doubt on the existence of proposed receptor subtypes.

The synaptic plasticity and memory hypothesis asserts that activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the encoding and trace storage of the type of memory mediated by the brain area in which it is observed. Criteria for establishing the necessity and sufficiency of such plasticity in mediating trace storage have been identified and are here reviewed in relation to new work using some of the diverse techniques of contemporary neuroscience. Evidence derived using optical imaging, molecular-genetic and optogenetic techniques in conjunction with appropriate behavioural analyses continues to offer support for the idea that changing the strength of connections between neurons is one of the major mechanisms by which engrams are stored in the brain.

Sleep spindles are distinctive electroencephalographic (EEG) oscillations emerging during non-rapid-eye-movement sleep (NREMS) that have been implicated in multiple brain functions, including sleep quality, sensory gating, learning, and memory. Despite considerable knowledge about the mechanisms underlying these neuronal rhythms, their function remains poorly understood and current views are largely based on correlational evidence. Here, we review recent studies in humans and rodents that have begun to broaden our understanding of the role of spindles in the normal and disordered brain. We show that newly identified molecular substrates of spindle oscillations, in combination with evolving technological progress, offer novel targets and tools to selectively manipulate spindles and dissect their role in sleep-dependent processes.

Reason and emotion have long been considered opposing forces. However, recent psychological and neuroscientific research has revealed that emotion and cognition are closely intertwined. Cognitive processing is needed to elicit emotional responses. At the same time, emotional responses modulate and guide cognition to enable adaptive responses to the environment. Emotion determines how we perceive our world, organise our memory, and make important decisions. In this review, we provide an overview of current theorising and research in the Affective Sciences. We describe how psychological theories of emotion conceptualise the interactions of cognitive and emotional processes. We then review recent research investigating how emotion impacts our perception, attention, memory, and decision-making. Drawing on studies with both healthy participants and clinical populations, we illustrate the mechanisms and neural substrates underlying the interactions of cognition and emotion.

WOS: 000321476400010, Introduction: The objective of this study is to investigate effects of testing time and emotional valence of words on implicit and explicit memory in young and elderly individuals. Materials and Method: After valence words were presented to 240 subjects composed of adolescents (11-14), early adults (25-25) and elderly people (65 and above) performance of word stem completion and free recall were tested. Results: Main effects of the age, testing time and valence of words on implicit and explicit memory were significant. While the dual effects of age and valence; testing time and valence were found significant in implicit memory, the dual effects of testing time and age; testing time and valence were also significant in explicit memory. Moreover, the triad effects of these variables on explicit memory were also found significant. Conclusion: Performance of explicit and implicit memory, in other words conscious and inconscious retrieval declines with aging. Emotional content affects explicit and implicit memory in all ages and positive stimulations are retrieved better. The increase in performance of implicit memory brought about by positive words in all groups was interpreted as inclination of the memory inconsciously towards positive words showing a "positivity effect".

Introduction: The objective of this study is to investigate effects of testing time and emotional valence of words on implicit and explicit memory in young and elderly individuals. Materials and Method: After valence words were presented to 240 subjects composed of adolescents (11-14), early adults (25-25) and elderly people (65 and above) performance of word stem completion and free recall were tested. Results: Main effects of the age, testing time and valence of words on implicit and explicit memory were significant. While the dual effects of age and valence; testing time and valence were found significant in implicit memory, the dual effects of testing time and age; testing time and valence were also significant in explicit memory. Moreover, the triad effects of these variables on explicit memory were also found significant. Conclusion: Performance of explicit and implicit memory, in other words conscious and inconscious retrieval declines with aging. Emotional content affects explicit and implicit memory in all ages and positive stimulations are retrieved better. The increase in performance of implicit memory brought about by positive words in all groups was interpreted as inclination of the memory inconsciously towards positive words showing a "positivity effect"., Sayar, F.; Cumhuriyet Üniversitesi Psikoloji, Sivas, Turkey; email: filiz1976sayar@yahoo.com

International audience; Destination memory refers to remembering the destination of information that people output. This present paper establishes a new distinction between external and internal processes within this memory system for both normal aging and Alzheimer's Disease (AD). Young adults, older adults, and mild AD patients were asked either to tell facts (i.e., external destination memory condition) or to imagine telling facts (i.e., internal destination memory condition) to pictures of famous people. The experiment established three major findings. First, the destination memory performance of the AD patients was significantly poorer than that of older adults, which in turn was poorer than that of the young adults. Furthermore, internal destination processes were more prone to being forgotten than external destination memory processes. In other words, participants had more difficulty in remembering whether they had previously imagined telling the facts to the pictures or not (i.e., imagined condition) than in remembering whether they had previously told the facts to the pictures or not (i.e., enacted condition). Second, significant correlations were detected between performances on destination memory and several executive measures such as the Stroop, the Plus-Minus and the Binding tasks. Third, among the executive measures, regression analyses showed that performance on the Stroop task was a main factor in explaining variance in destination memory performance. Our findings reflect the difficulty in remembering the destination of internally generated information. They also demonstrate the involvement of inhibitory processes in destination memory.

This review article summarizes evidence that multisensory experiences at one point in time have long-lasting effects on subsequent unisensory visual and auditory object recognition. The efficacy of single-trial exposure to task-irrelevant multisensory events is its ability to modulate memory performance and brain activity to unisensory components of these events presented later in time. Object recognition (either visual or auditory) is enhanced if the initial multisensory experience had been semantically congruent and can be impaired if this multisensory pairing was either semantically incongruent or entailed meaningless information in the task-irrelevant modality, when compared to objects encountered exclusively in a unisensory context. Processes active during encoding cannot straightforwardly explain these effects; performance on all initial presentations was indistinguishable despite leading to opposing effects with stimulus repetitions. Brain responses to unisensory stimulus repetitions differ during early processing stages (-100 ms post-stimulus onset) according to whether or not they had been initially paired in a multisensory context. Plus, the network exhibiting differential responses varies according to whether or not memory performance is enhanced or impaired. The collective findings we review indicate that multisensory associations formed via single-trial learning exert influences on later unisensory processing to promote distinct object representations that manifest as differentiable brain networks whose activity is correlated with memory performance. These influences occur incidentally, despite many intervening stimuli, and are distinguishable from the encoding/learning processes during the formation of the multisensory associations. The consequences of multisensory interactions that persist over time to impact memory retrieval and object discrimination.

The aim of this study was to evaluate surgical outcome of unruptured intracranial aneurysms (UIAs) in a low-volume hospital and compare the results with the recent literature.

Humans are unique in developing large lexicons as their communication tool; to achieve this, they are able to learn new words rapidly. However, neural bases of this rapid learning, which may be an expression of a more general cognitive mechanism likely rooted in plasticity at cellular and synaptic levels, are not yet understood. In this update, the author highlights a selection of recent studies that attempted to trace word learning in the human brain noninvasively. A number of brain areas, most notably in hippocampus and neocortex, appear to take part in word acquisition. Critically, the currently available data not only demonstrate the hippocampal role in rapid encoding followed by slow-rate consolidation of cortical word memory traces but also suggest immediate neocortical involvement in the word memory trace formation. Echoing early behavioral studies in ultra-rapid word learning, the reviewed neuroimaging experiments can be taken to suggest that our brain may effectively form new cortical circuits online, as it gets exposed to novel linguistic patterns in the sensory input.

Perceptual filling-in occurs when visual stimuli are recognized in impoverished viewing conditions. Whether missing information is filled-in during face perception and which stages might be involved in this process are still unresolved questions. Because an identity can be brought to mind by seeing eyes only, we hypothesized that missing information might be filled-in from a memory trace for the whole face identity. We presented participants with faces in phase 1 and later we presented eyes-only in phase 2. For some of these eyes in phase 2, the whole face had been presented in the previous phase, for others identical eyes had been presented. Event-related potentials (ERPs) revealed an N170 component that was more negative when eyes were preceded by a whole face in the previous phase compared to eyes preceded by identical eyes-only. A more positive-going late positive complex (LPC) was also found, suggesting enhanced retrieval of face memory representations when eyes were preceded by whole faces. Our results show that pre-existing representations of face identity can influence early stages of visual encoding, 170 ms after stimulus onset. These effects may reflect top–down modulation by memory on visual recognition processes by filling-in the missing facial information.

Neurofunctional patterns assessed before or after cochlear implantation (CI) are informative markers of implantation outcome. Because phonological memory reorganization in post-lingual deafness is predictive of the outcome, we investigated, using a cross-sectional approach, whether memory of non-speech sounds (NSS) produced by animals or objects (i.e. non-human sounds) is also reorganized, and how this relates to speech perception after CI. We used an fMRI auditory imagery task in which sounds were evoked by pictures of noisy items for post-lingual deaf candidates for CI and for normal-hearing subjects. When deaf subjects imagined sounds, the left inferior frontal gyrus, the right posterior temporal gyrus and the right amygdala were less activated compared to controls. Activity levels in these regions decreased with duration of auditory deprivation, indicating declining NSS representations. Whole brain correlations with duration of auditory deprivation and with speech scores after CI showed an activity decline in dorsal, fronto-parietal, cortical regions, and an activity increase in ventral cortical regions, the right anterior temporal pole and the hippocampal gyrus. Both dorsal and ventral reorganizations predicted poor speech perception outcome after CI. These results suggest that post-CI speech perception relies, at least partially, on the integrity of a neural system used for processing NSS that is based on audio-visual and articulatory mapping processes. When this neural system is reorganized, post-lingual deaf subjects resort to inefficient semantic- and memory-based strategies. These results complement those of other studies on speech processing, suggesting that both speech and NSS representations need to be maintained during deafness to ensure the success of CI.

Patients with peripheral dysgraphia due to impairment at the allographic level produce writing errors that affect the letter-form and are characterized by case confusions or the failure to write in a specific case or style (e.g., cursive). We studied the writing errors of a patient with pure peripheral dysgraphia who had entirely intact oral spelling, but produced many well-formed letter errors in written spelling. The comparison of uppercase print and lowercase cursive spelling revealed an uncommon pattern: while most uppercase errors were case substitutions (e.g., A - a), almost all lowercase errors were letter substitutions (e.g., n - r). Analyses of the relationship between target letters and substitution errors showed that errors were neither influenced by consonant-vowel status nor by letter frequency, though word length affected error frequency in lowercase writing. Moreover, while graphomotor similarity did not predict either the occurrence of uppercase or lowercase errors, visuospatial similarity was a significant predictor of lowercase errors. These results suggest that lowercase representations of cursive letter-forms are based on a description of entire letters (visuospatial features) and are not - as previously found for uppercase letters - specified in terms of strokes (graphomotor features).

Memory traces for words are frequently conceptualized neurobiologically as networks of neurons interconnected via reciprocal links developed through associative learning in the process of language acquisition. Neurophysiological reflection of activation of such memory traces has been reported using the mismatch negativity brain potential (MMN), which demonstrates an enhanced response to meaningful words over meaningless items. This enhancement is believed to be generated by the activation of strongly intraconnected long-term memory circuits for words that can be automatically triggered by spoken linguistic input and that are absent for unfamiliar phonological stimuli. This conceptual framework critically predicts different amounts of activation depending on the strength of the word's lexical representation in the brain. The frequent use of words should lead to more strongly connected representations, whereas less frequent items would be associated with more weakly linked circuits. A word with higher frequency of occurrence in the subject's language should therefore lead to a more pronounced lexical MMN response than its low-frequency counterpart. We tested this prediction by comparing the event-related potentials elicited by low- and high-frequency words in a passive oddball paradigm; physical stimulus contrasts were kept identical. We found that, consistent with our prediction, presenting the high-frequency stimulus led to a significantly more pronounced MMN response relative to the low-frequency one, a finding that is highly similar to previously reported MMN enhancement to words over meaningless pseudowords. Furthermore, activation elicited by the higher-frequency word peaked earlier relative to low-frequency one, suggesting more rapid access to frequently used lexical entries. These results lend further support to the above view on word memory traces as strongly connected assemblies of neurons. The speed and magnitude of their activation appears to be linked to the strength of internal connections in a memory circuit, which is in turn determined by the everyday use of language elements.

Patients with Alzheimer's disease (AD) and schizophrenia display cognitive, behavioural disturbances and morphological abnormalities. Although these latter reflect progressive neurodegeneration in AD, their significance in schizophrenia is still unclear. We explored the patterns of hippocampal and amygdalar atrophy in those patients and their associations with clinical parameters. Structural magnetic resonance imaging was performed in 20 elderly schizophrenia patients, 20 AD and 19 healthy older controls. Hippocampal and amygdalar volumes were obtained by manual segmentation with a standardized protocol and compared among groups. In both schizophrenia and AD patients, left hippocampal and amygdalar volumes were significantly smaller. The hippocampus/amygdala ratio was significantly lower in schizophrenia compared to both AD cases [2.4 bilaterally, 95% C.I. 2.2 to 2.7] and healthy controls bilaterally [2.5, 95% C.I. 2.3 to 2.9 in left and 2.7, 95% C.I. 2.4 to 3.1 in right hemisphere]. In schizophrenia patients, a significant positive correlation was found between age at disease onset and the right hippocampus/amygdala volume ratio (Spearman rho=0.56). Negative symptoms correlated with higher right/left amygdala volume ratio (Spearman's rho=0.43). Our data show that unlike AD, the hippocampus/amygdala ratio is abnormally low and correlates with the age at onset in schizophrenia, being a neurodevelopmental signature of the disease.

The objective of this study was to evaluate the efficiency and the effects of changes in parameters of chronic amygdala–hippocampal deep brain stimulation (AH-DBS) in mesial temporal lobe epilepsy (TLE).Eight pharmacoresistant patients, not candidates for ablative surgery, received chronic AH-DBS (130Hz, follow-up 12–24 months): two patients with hippocampal sclerosis (HS) and six patients with non-lesional mesial TLE (NLES). The effects of stepwise increases in intensity (0-Off to 2V) and stimulation configuration (quadripolar and bipolar), on seizure frequency and neuropsychological performance were studied.The two HS patients obtained a significant decrease (65–75%) in seizure frequency with high voltage bipolar DBS (≥1V) or with quadripolar stimulation. Two out of six NLES patients became seizure-free, one of them without stimulation, suggesting a microlesional effect. Two NLES patients experienced reductions of seizure frequency (65–70%), whereas the remaining two showed no significant seizure reduction. Neuropsychological evaluations showed reversible memory impairments in two patients under strong stimulation only.AH-DBS showed long-term efficiency in most of the TLE patients. It is a valuable treatment option for patients who suffer from drug resistant epilepsy and who are not candidates for resective surgery. The effects of changes in the stimulation parameters suggest that a large zone of stimulation would be required in HS patients, while a limited zone of stimulation or even a microlesional effect could be sufficient in NLES patients, for whom the importance of the proximity of the electrode to the epileptogenic zone remains to be studied. Further studies are required to ascertain these latter observations.

Background Reality monitoring processes serve the critical function of discriminating between externally derived information and self-generated information. Several reality monitoring studies with healthy adult participants have identified the anterior prefrontal cortex (PFC) as consistently engaged during the recollection of self-generated contextual cues. Furthermore, reduced activity of medial PFC has been linked with schizotypal trait expression of delusion and hallucination-like symptoms in healthy adults undergoing fMRI reality-monitoring tasks. The present study seeks to examine the cerebral underpinnings of reality monitoring during adolescence, a developmental stage where the expression of schizotypal traits may increase risk for psychosis. Method A group of 33 adolescents, assessed using the Schizotypal Personality Scale (SPQ), underwent fMRI while performing a reality monitoring task. After an encoding session where the subject or the experimenter read out a series of complete or incomplete word pairs, subjects were presented with the first word of studied word pairs and asked whether the corresponding word had been: (1) perceived or produced (context monitoring), or (2) read by the subject or by the experimenter (origin monitoring). Results Analyses revealed a common set of activated brain areas during both context and origin monitoring conditions. When compared to context monitoring, origin monitoring was associated with greater activation in anterior PFC within Brodmann area 10 (BA 10). Correlation analyses revealed that reduced signal change in BA 10 during origin monitoring was associated with greater schizotypal trait expression. Conclusion Much like adults performing a similar reality monitoring task, adolescents exhibit a common pattern of brain activity during origin and context monitoring, with functional specialization within the prefrontal cortex involving preferential activation of BA 10 during origin monitoring. Greater schizotypal trait expression appears to be significantly associated to reduced BA 10 activity during origin monitoring trials. Results are discussed in relation to cortical specialization within the PFC and trait expression during adolescence.

Strong evidence suggests that memory for emotional information is much better than for neutral one. Thus, one may expect that forgetting of emotional information is difficult and requires considerable effort. The aim of this item-method directed forgetting functional magnetic resonance imaging study was to investigate this hypothesis both at behavioral and neural levels. Directed forgetting effects were observed for both neutral and emotionally negative International Affective Picture System images. Moreover, recognition rate of negative to-be-forgotten images was higher than in case of neutral ones. In the study phase, intention to forget and successful forgetting of emotionally negative images were associated with widespread activations extending from the anterior to posterior regions mainly in the right hemisphere, whereas in the case of neutral images, they were associated with just one cluster of activation in the right lingual gyrus. Therefore, forgetting of emotional information seems to be a demanding process that strongly activates a distributed neural network in the right hemisphere. In the test phase, in turn, successfully forgotten images--either neutral or emotionally negative--were associated with virtually no activation, even at the lowered P value threshold. These results suggest that intentional inhibition during encoding may be an efficient strategy to cope with emotionally negative memories.

Insomniacs often complain of memory deficits, yet objective measures have not consistently corroborated their subjective impressions. A possible explanation for the partial gap between self-report and behavioral measures of memory impairment is that insomniacs recruit extra effort to compensate for the consequences of poor sleep. The present study investigated whether subjective insomnia severity would predict objective effort mobilization, as indexed by cardiovascular measures, in an easy memory task. Seventy-seven university students, mostly women, with a mean age of 22 years were asked to memorize four strings of four random letters in 5 min while cardiovascular measures were obtained. After taking an immediate recall test, participants completed the Insomnia Severity Index, the Multidimensional Fatigue Inventory, and a questionnaire on last night's sleep and today's fatigue. Finally, they were given a surprise delayed recall test. Analyses indicated that self-reported insomnia severity was associated with an increase in systolic blood pressure during the learning phase. Regarding memory performance, insomnia severity was unrelated to immediate recall but related to a decrement in delayed recall. These findings reveal for the first time that subjective insomnia severity predicts objective effort mobilization in an easy memory task, suggesting that young poor sleepers recruit extra resources to cope with everyday cognitive challenges.

Previous studies have shown that patients with schizophrenia are impaired in recalling specific events from their personal past. However, the relationship between autobiographical memory impairments and disturbance of the sense of identity in schizophrenia has not been investigated in detail. In this study the authors investigated schizophrenic patients' ability to recall self-defining memories; that is, memories that play an important role in building and maintaining the self-concept. Results showed that patients recalled as many specific self-defining memories as healthy participants. However, patients with schizophrenia exhibited an abnormal reminiscence bump and reported different types of thematic content (i.e., they recalled less memories about past achievements and more memories regarding hospitalisation and stigmatisation of illness). Furthermore, the findings suggest that impairments in extracting meaning from personal memories could represent a core disturbance of autobiographical memory in patients with schizophrenia.

The mammalian brain oscillates through three distinct global activity states: wakefulness, non-rapid eye movement (NREM) sleep and REM sleep. The regulation and function of these 'vigilance' or 'behavioural' states can be investigated over a broad range of temporal and spatial scales and at different levels of functional organization, i.e. from gene expression to memory, in single neurons, cortical columns or the whole brain and organism. We summarize some basic questions that have arisen from recent approaches in the quest for the functions of sleep. Whereas traditionally sleep was viewed to be regulated through top-down control mechanisms, recent approaches have emphasized that sleep is emerging locally and regulated in a use-dependent (homeostatic) manner. Traditional markers of sleep homeostasis, such as the electroencephalogram slow-wave activity, have been linked to changes in connectivity and plasticity in local neuronal networks. Thus waking experience-induced local network changes may be sensed by the sleep homeostatic process and used to mediate sleep-dependent events, benefiting network stabilization and memory consolidation. Although many questions remain unanswered, the available data suggest that sleep function will best be understood by an analysis which integrates sleep's many functional levels with its local homeostatic regulation.

The aim of this study was to compare the performance of elderly and young participants on a series of memory tasks involving either intentional or unintentional inhibitory control of memory content. Intentional inhibition processes in working and episodic memory were explored with directed forgetting tasks and in semantic memory with the Hayling task. Unintentional inhibitory processes in working memory, long-term memory, and semantic memory were explored with an interference resolution task, the retrieval practice paradigm, and the flanker task, respectively. The results indicate that elderly participants' performance on the two directed forgetting tasks and the Hayling task is lower than that of young ones, and that this impairment is not related to their initial memory capacity. This suggests that there is a specific dysfunction affecting intentional inhibitory control of memory contents in normal ageing.

It is known that sleep reshapes the neural representations that subtend the memories acquired while navigating in a virtual environment. However, navigation is not process-pure, as manifold learning components contribute to performance, notably the spatial and contextual memory constituents. In this context, it remains unclear whether post-training sleep globally promotes consolidation of all of the memory components embedded in virtual navigation, or rather favors the development of specific representations. Here, we investigated the effect of post-training sleep on the neural substrates of the consolidation of spatial and contextual memories acquired while navigating in a complex 3D, naturalistic virtual town. Using fMRI, we mapped regional cerebral activity during various tasks designed to tap either the spatial or the contextual memory component, or both, 72 h after encoding with or without sleep deprivation during the first post-training night. Behavioral performance was not dependent upon post-training sleep deprivation, neither in a natural setting that engages both spatial and contextual memory processes nor when looking more specifically at each of these memory representations. At the neuronal level however, analyses that focused on contextual memory revealed distinct correlations between performance and neuronal activity in frontal areas associated with recollection processes after post-training sleep, and in the parahippocampal gyrus associated with familiarity processes in sleep-deprived participants. Likewise, efficient spatial memory was associated with posterior cortical activity after sleep whereas it correlated with parahippocampal/medial temporal activity after sleep deprivation. Finally, variations in place-finding efficiency in a natural setting encompassing spatial and contextual elements were associated with caudate activity after post-training sleep, suggesting the automation of navigation. These data indicate that post-training sleep modulates the neural substrates of the consolidation of both the spatial and contextual memories acquired during virtual navigation., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

The medial temporal lobe participates not only in episodic memory, but also in visual object processing. Here we asked whether these processes are linked within the human hippocampus. To this end, we recorded field potentials directly from the hippocampus proper during a visual object decision task in temporal lobe epilepsy patients with either normal or below normal visual memory performance. Only in patients with normal visual memory, did the hippocampus proper differentiate reliably between real and nonsense objects, whereas neural responses to both kinds of objects were virtually the same in patients whose visual memory performance was reduced. These findings suggest that neural responses to visual objects within the hippocampus proper are directly linked to visual memory performance.

While changes in the efficacy of synaptic transmission are believed to represent the physiological bases of learning mechanisms, other recent studies have started to highlight the possibility that a structural reorganization of synaptic networks could also be involved. Morphological changes of the shape or size of dendritic spines or of the organization of postsynaptic densities have been described in several studies, as well as the growth and formation following stimulation of new protrusions. Confocal in vivo imaging experiments have further revealed that dendritic spines undergo a continuous turnover and replacement process that may vary as a function of development, but can be markedly enhanced by sensory activation or following brain damage. The implications of these new aspects of plasticity for learning and memory mechanisms are discussed.

Velo-cardio-facial syndrome (VCFS) is a neurogenetic disorder associated with very high risk for developing schizophrenia. More than half of affected individuals experience transient psychotic symptoms during childhood and a third may develop schizophrenia. Memory regulation deficits disturbing both the encoding and retrieval stages of memory represent core deficits in the cognitive profile associated with schizophrenia. In this study, the authors investigate memory regulation processes in 33 individuals with VCFS along with 33 age- and sex-matched control participants. By using a directed forgetting paradigm and a continuous recognition paradigm, the authors examined selective encoding and suppression of irrelevant contents during retrieval in VCFS. Group comparison analyses revealed comparable performances on selective encoding and recognition accuracy between the VCFS group and control group. However, individuals with VCFS were more likely to make false recognitions and showed deficits in the suppression of irrelevant contents. Results suggest that trait-like deficits of memory regulation in VCFS can be observed during the retrieval stage, while selective encoding remains efficient. Memory regulation processes during retrieval may constitute a trait deficit in the memory profile of individuals with VCFS and may contribute to the cognitive deficits underlying an increased risk for developing schizophrenia in this population.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

How long does it take the human mind to grasp the idea when hearing or reading a sentence? Neurophysiological methods looking directly at the time course of brain activity indexes of comprehension are critical for finding the answer to this question. As the dominant cognitive approaches, models of serial/cascaded and parallel processing, make conflicting predictions on the time course of psycholinguistic information access, they can be tested using neurophysiological brain activation recorded in MEG and EEG experiments. Seriality and cascading of lexical, semantic and syntactic processes receives support from late (latency approximately 1/2s) sequential neurophysiological responses, especially N400 and P600. However, parallelism is substantiated by early near-simultaneous brain indexes of a range of psycholinguistic processes, up to the level of semantic access and context integration, emerging already 100-250ms after critical stimulus information is present. Crucially, however, there are reliable latency differences of 20-50ms between early cortical area activations reflecting lexical, semantic and syntactic processes, which are left unexplained by current serial and parallel brain models of language. We here offer a mechanistic model grounded in cortical nerve cell circuits that builds upon neuroanatomical and neurophysiological knowledge and explains both near-simultaneous activations and fine-grained delays. A key concept is that of discrete distributed cortical circuits with specific inter-area topographies. The full activation, or ignition, of specifically distributed binding circuits explains the near-simultaneity of early neurophysiological indexes of lexical, syntactic and semantic processing. Activity spreading within circuits determined by between-area conduction delays accounts for comprehension-related regional activation differences in the millisecond range.

Experimental animals can be differentiated on the basis of their horizontal or vertical activity to high responders (HR) and low responders (LR) upon exposure to a novel environment. These individual differences have been associated with behavioral and neurobiological differences in a number of experimental procedures used for studying sensitivity to psychostimulants, anxiety, depression, and cognitive function. In the present study, we differentiated the rats to HR and LR based on their vertical activity upon exposure to a novel environment. Additionally, we ascertained whether HR and LR rats differ in a battery of tests such as passive avoidance (PA), object recognition (OR), and the water-maze (WM) that provide indices for cognitive function and the forced swim test (FST), an animal model of affective responsivity and antidepressant-like activity. Potential differences in neurochemical indices between the two phenotypes were also examined. HR rats displayed impaired non-spatial object recognition memory, but enhanced spatial performance, as compared to LR rats. FST induced "depressive-like" symptoms in both phenotypes that were differently manifested in HR versus LR rats. Neurochemical findings revealed distinct differences in serotonergic and dopaminergic activity in the striatum and the prefrontal cortex of HR as compared to LR rats. The above results show that HR and LR rats exhibit important differences in a battery of tests related to cognitive performance or affective responsivity, which may be associated with differences in certain neurobiological parameters. Behav Brain Res

Preference for previously seen, unfamiliar objects reflects a memory bias on affective judgment, known as the "mere exposure effect" (MEE). Here, we investigated the effect of time, post-exposure sleep, and the brain hemisphere solicited on preference generalization toward objects viewed in different perspectives. When presented in the right visual field (RVF), which promotes preferential processing in the left hemisphere, same and mirrored exemplars were preferred immediately after exposure. MEE generalized to much dissimilar views after three nights of sleep. Conversely, object presentation in the left visual field (LVF), promoting right hemisphere processing, elicited a MEE for same views immediately after exposure, then for mirror views after sleep. Most importantly, sleep deprivation during the first post-exposure night, although followed by two recovery nights, extinguished MEE for all views in the LVF but not in the RVF. Besides demonstrating that post-exposure time and sleep facilitate the generalization process by which we integrate various representations of an object, our results suggest that mostly in the right hemisphere, sleep may be mandatory to consolidate the memory bias underlying affective preference. These interhemispheric differences tentatively call for a reappraisal of the role of cerebral asymmetries in wake- and sleep-dependent processes of memory consolidation., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Emotionally arousing events are recalled better than neutral events. This phenomenon, which helps us to remember important and potentially vital information, depends on the activation of noradrenergic transmission in the brain. Here we show that a deletion variant of ADRA2B, the gene encoding the alpha2b-adrenergic receptor, is related to enhanced emotional memory in healthy Swiss subjects and in survivors of the Rwandan civil war who experienced highly aversive emotional situations.

Stress is a potent modulator of learning and memory processes. Although there have been a few attempts in the literature to explain the diversity of effects (including facilitating, impairing, and lack of effects) described for the impact of stress on memory function according to single classification criterion, they have proved insufficient to explain the whole complexity of effects. Here, we review the literature in the field of stress and memory interactions according to five selected classifying factors (source of stress, stressor duration, stressor intensity, stressor timing with regard to memory phase, and learning type) in an attempt to develop an integrative model to understand how stress affects memory function. Summarizing on those conditions in which there was enough information, we conclude that high stress levels, whether intrinsic (triggered by the cognitive challenge) or extrinsic (induced by conditions completely unrelated to the cognitive task), tend to facilitate Pavlovian conditioning (in a linear-asymptotic manner), while being deleterious for spatial/explicit information processing (which with regard to intrinsic stress levels follows an inverted U-shape effect). Moreover, after reviewing the literature, we conclude that all selected factors are essential to develop an integrative model that defines the outcome of stress effects in memory processes. In parallel, we provide a brief review of the main neurobiological mechanisms proposed to account for the different effects of stress in memory function. Glucocorticoids were found as a common mediating mechanism for both the facilitating and impairing actions of stress in different memory processes and phases. Among the brain regions implicated, the hippocampus, amygdala, and prefrontal cortex were highlighted as critical for the mediation of stress effects.

The role of the hippocampus in pavlovian fear conditioning is controversial. Although lesion and pharmacological inactivation studies have suggested a key role for the dorsal hippocampus in contextual fear conditioning, the involvement of the ventral part is still uncertain. Likewise, the debate is open with regard to the putative implication of each hippocampal subdivision in fear conditioning to a discrete conditioned stimulus. We explored the potential existence of dissociations occurring in the dorsal versus ventral hippocampus at the cellular level while dealing with either contextual or cued fear conditioning and focused in a molecular “signature” linked to structural plasticity, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). We found an upregulation of PSA-NCAM expression in the dorsal (but not ventral) dentate gyrus at 24 h after contextual (but not tone) fear conditioning. Specific removal of PSA through microinfusion of the enzyme endoneuraminidase-N in the dorsal (but not ventral) hippocampus reduced freezing responses to the conditioned context. Therefore, we present evidence for a specific role of PSA-NCAM in the dorsal hippocampus in the plasticity processes occurring during consolidation of the context representation after “standard” contextual fear conditioning. Interestingly, we also found that exposing animals just to the context induced an activation of PSA-NCAM in both dorsal and ventral dentate gyrus. Altogether, these findings highlighting the distinctive occurrence of these neuroplastic processes in the dorsal hippocampus during the standard contextual fear-conditioning task enlighten the ongoing debate about the involvement of these hippocampal subdivisions in pavlovian fear conditioning.

Neurophysiological studies of sleep have increasingly focused on underlying dynamic processes. This would appear particularly relevant to the developmental aspects of sleep. Involvement of sleep-dependent mechanisms in emotional processing, as well as perceptual-sensory, perceptual-motor, and cognitive learning, mostly studied in adults, may play major roles in development. Rapid eye movement (REM) sleep, which is generated by complex neuronal interactions within the pontine reticular formation, and non-REM sleep, which arises from activities in the thalamocortical network, are specifically implicated in different aspects of long-term memory systems. They evolve from previous physiological and behavioural states which can be traced back to the fetal period. Further studies are needed to clearly identify functions reflected by hallmarks of sleep stages, such as spindles and K complexes. A better understanding of the maturational aspects of sleep should provide important insights into physiological development. Assessment approaches taking dynamic characteristics of sleep into account may contribute to the design of better targeted management of sleep-related problems in neurodevelopmental conditions., Journal Article, Review, FLWIN, info:eu-repo/semantics/published

Serotonin (5-HT) receptors 2A are expressed in brain regions involved in memory and learning processes. Recently, a functional single nucleotide polymorphism in the 5-HT2A receptor gene leading to an amino-acid substitution at residue 452 (His452Tyr) has been involved in memory performance, persons with the rare 452Tyr allele showing poorer memory performance compared to His452His subjects. To investigate a putative structural effect of this polymorphism on temporal areas typically involved in memory processes, we performed voxel-based morphometry (VBM) and region-of-interest (ROI) volumetric analysis on high-resolution magnetic resonance images in 15 carriers and 61 noncarriers of the 452Tyr allele. ROI volumetric analysis showed a significant reduction of the fractional volume of the temporal white matter in 452Tyr carriers (0.67+/-0.07 vs 0.73+/-0.08; P=0.007). VBM confirmed this finding and in addition showed reduced grey matter in the left hippocampus, left inferior temporal gyrus, and bilaterally in the middle and superior temporal gyrus. A possible effect on synaptic plasticity or neurodevelopment might explain the influence of the His452Tyr polymorphism on temporal brain structures, and this might be the basis for poorer memory performance in 452Tyr carriers. These findings should be considered preliminary and future replication is needed.

The cognitive processes supporting spatial navigation are considered in the context of a patient (CF) with possible very early Alzheimer's disease who presents with topographical disorientation. Her verbal memory and her recognition memory for unknown buildings, landmarks and outdoor scenes was intact, although she showed an impairment in face processing. By contrast, her navigational ability, quantitatively assessed within a small virtual reality (VR) town, was significantly impaired. Interestingly, she showed a selective impairment in a VR object-location memory test whenever her viewpoint was shifted between presentation and test, but not when tested from the same viewpoint. We suggest that a specific impairment in locating objects relative to the environment rather than relative to the perceived viewpoint (i.e. allocentric rather than egocentric spatial memory) underlies her topographical disorientation. We discuss the likely neural bases of this deficit in the light of related studies in humans and animals, focusing on the hippocampus and related areas. The specificity of our test indicates a new way of assessing topographical disorientation, with possible application to the assessment of progressive dementias such as Alzheimer's disease.