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To efficiently process information, the brain shifts between encoding and retrieval states, prioritizing bottom-up or top-down processing accordingly. Expectation violation before or during learning has been shown to trigger an adaptive encoding mechanism, resulting in better memory for unexpected events. Using fMRI, we explored (1) whether this encoding mechanism is also triggered during retrieval, and if so, (2) what the temporal dynamics of its mnemonic consequences are. Male and female participants studied object images, then, with new objects, they learned a contingency between a cue and a semantic category. Rule-abiding (expected) and violating (unexpected) targets and similar foils were used at test. We found interactions between previous and current similar events' expectation, such that when an expected event followed a similar but unexpected event, its performance was boosted, underpinned by activation in the hippocampus, midbrain, and occipital cortex. In contrast, a sequence of two unexpected similar events also triggered occipital engagement; however, this did not enhance memory performance. Taken together, our findings suggest that when the goal is to retrieve, encountering surprising events engages an encoding mechanism, supported by bottom-up processing, that may enhance memory for future related events. SIGNIFICANCE STATEMENT Optimizing the balance between new learning and the retrieval of existing knowledge is an ongoing process, at the core of human cognition. Previous research into memory encoding suggests experiencing surprise leads to the prioritization of the learning of new memories, forming an adaptive encoding mechanism. We examined whether this mechanism is also engaged when the current goal is to retrieve information. Our results demonstrate that an expectation-driven shift toward an encoding state, supported by enhanced perceptual processing, is beneficial for the correct identification of subsequent expected similar events. These findings have important implications for our understanding of the temporal dynamics of the adaptive encoding of information into memory.

Acute physical exercise improves memory functions by increasing neural plasticity in the hippocampus. In animals, a single session of physical exercise has been shown to boost anandamide (AEA), an endocannabinoid known to promote hippocampal plasticity. Hippocampal neuronal networks encode episodic memory representations, including the temporal organization of elements, and can thus benefit motor sequence learning. While previous work established that acute physical exercise has positive effects on declarative memory linked to hippocampal plasticity mechanisms, its influence on memory for motor sequences, and especially on neural mechanisms underlying possible effects, has been less investigated.Here we studied the impact of acute physical exercise on motor sequence learning, and its underlying neurophysiological mechanisms in humans, using a cross-over randomized within-subjects design. We measured behavior, fMRI activity, and circulating AEA levels in fifteen healthy participants while they performed a serial reaction time task (SRTT) before and after a short period of exercise (moderate or high intensity) or rest.We show that exercise enhanced motor sequence memory, significantly for high intensity exercise and tending towards significance for moderate intensity exercise. This enhancement correlated with AEA increase, and dovetailed with local increases in caudate nucleus and hippocampus activity.These findings demonstrate that acute physical exercise promotes sequence learning, thus attesting the overarching benefit of exercise to hippocampus-related memory functions.

Contains fulltext : 218973.pdf (Publisher’s version ) (Open Access) Aging is associated with cognitive decline, specifically in episodic memory. However, there are large individual differences in the extent of this decline and previous research suggests that these are associated with differences in executive functioning (EF). These EF differences, and associated differences in the encoding and retrieval of episodic information, have been linked to differences in the activation of particular brain regions. The "encoding/retrieval flip" (E/R flip) framework assumes deactivation and activation of specific brain regions during successful encoding and retrieval, respectively. The present study assessed whether this framework can be used to explain EF-based individual differences in memory performance of young and older participants. Young adults (N = 19) and older adults (N = 39) performed an incidental semantic encoding and memory recognition task in an fMRI setting, focusing on brain regions that show the E/R flip. The association between an index of EF and fMRI activity in brain regions showing the E/R flip was tested in each age group. EF predicted E/R flip activity in the older, but not young adults. These findings underscore the importance of individual differences in ageing research and provide empirical evidence for the association between EF and the E/R flip. 5 p.

OBJECTIVE: To summarise the current research on the effectiveness of the Amsterdam Memory and Attention Training for Children (Amat-c).METHODS: A literature search was conducted to find articles published about the Amat-c, using PubMed, psychINFO, and PsychBITE databases. Relevant search terms included Amat-c, attention and memory, and childhood ABI.RESULTS: Our literature search identified 7 articles that described 5 separate studies including 61 children in total (mostly TBI). Only one study had a control group. All results indicated positive effects on memory and attention, although in three of the studies, these results were not statistically tested. Positive results were generally maintained six months follow up.CONCLUSIONS: This review showed that the Amat-c is effective for treating attention and memory disturbances in children with ABI. However, evidence is limited and training material is outdated. We suggest that the Amat-c should be digitised and implemented in a school setting and further evaluated.

OBJECTIVE: To summarise the current research on the effectiveness of the Amsterdam Memory and Attention Training for Children (Amat-c). METHODS: A literature search was conducted to find articles published about the Amat-c, using PubMed, psychINFO, and PsychBITE databases. Relevant search terms included Amat-c, attention and memory, and childhood ABI. RESULTS: Our literature search identified 7 articles that described 5 separate studies including 61 children in total (mostly TBI). Only one study had a control group. All results indicated positive effects on memory and attention, although in three of the studies, these results were not statistically tested. Positive results were generally maintained six months follow up. CONCLUSIONS: This review showed that the Amat-c is effective for treating attention and memory disturbances in children with ABI. However, evidence is limited and training material is outdated. We suggest that the Amat-c should be digitised and implemented in a school setting and further evaluated.

Introduction: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.Methods: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.Results: Eight metabolites were associated with amyloid b and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.Discussion: PFAMs have been found increased and associated with amyloid b burden in CSF and clinical measures. Crown Copyright (C) 2019 Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).

It is well documented that women have an increased risk of emotional disorders, such as anxiety and depression. Such disorders are typically characterized by intrusive memories and rumination of past events, but findings are mixed as to whether women have enhanced access to memories of emotional events. Some studies have found that women, compared with men, report more frequent and more intense memories of emotionally stressful events, whereas other studies have failed to replicate this effect. These conflicting findings may reflect the use of different memory sampling techniques (e.g., retrospective vs. experimental data) and limited control for factors associated with both gender and emotional memory. The purpose of the present study was to investigate gender differences in memory for emotionally negative events, using three different sampling methods, while at the same time controlling for parameters that might co-vary with gender. Consistent with some previous studies, we found that women and men did not differ in their frequencies of emotionally negative involuntary memories. However, women rated their memories as more intense and arousing than men did, and women also reported higher increases in state anxiety after retrieval. Female gender accounted for unique variance in the emotional intensity and subjective arousal associated with negative memories, when controlling for other theoretically derived variables. The findings provide evidence that female gender is associated with a stronger emotional response to memories of negative events, but not that women remember such events more frequently than men do.

Astrocytes serve important roles that affect recruitment and function of neurons at the local and network levels. Here we review the contributions of astrocyte signaling to synaptic plasticity, neuronal network oscillations, and memory function. The roles played by astrocytes are not fully understood, but astrocytes seem to contribute to memory consolidation and seem to mediate the effects of vigilance and arousal on memory performance. Understanding the role of astrocytes in cognitive processes may also advance our understanding of how these processes go awry in pathological conditions. Indeed, abnormal astrocytic signaling can cause or contribute to synaptic and network imbalances, leading to cognitive impairment. We discuss evidence for this from animal models of Alzheimer's disease and multiple sclerosis and from animal studies of sleep deprivation and drug abuse and addiction. Understanding the emerging roles of astrocytes in cognitive function and dysfunction will open up a large array of new therapeutic opportunities.

Whether a novel stimulus is expected or unexpected may have implications for the kind of ensuing encoding and the type of subsequent memory. Pupil response was used in the present study to explore the way expected and unexpected stimuli are encoded and whether encoding-linked pupil response is modulated by expectation. Participants first established a contingency relationship between a series of symbols and the type of stimulus (man-made or natural) that followed each one. At encoding, some of the target stimuli violated the previously established relationship (i.e., unexpected), while the majority conformed to this relationship (i.e., expected). Expectation at encoding had opposite effects on familiarity and recollection, the two types of memory that support recognition, and modulated differently the way pupil responses predicted subsequent memory. Encoding of unexpected novel stimuli was associated with increased pupil dilation as a predictor of subsequent memory type and strength. In contrast, encoding of expected novel stimuli was associated with decreased pupil response (constriction), which was predictive of subsequent memory type and strength. The findings support the close link between pupil response and memory formation, but critically indicate that this is modulated by the type of novelty as defined by expectation. These novel findings have important implications for the encoding mechanisms involved when different types of novelty are detected and is proposed to indicate the operation of different neurotransmitters in memory formation.

Summary Novelty facilitates memory formation and is detected by both the dorsal and ventral hippocampus. Although dentate granule cells (GCs) in the dorsal hippocampus are known to mediate the formation of novelty-induced contextual memories, the required pathways and mechanisms remain unclear. Here we demonstrate that a powerful excitatory pathway from mossy cells (MCs) in the ventral hippocampus to dorsal GCs is necessary and sufficient for driving dorsal GC activation in novel environment exploration. In vivo Ca2+ imaging in freely moving mice indicated that this pathway relays environmental novelty. Furthermore, manipulation of ventral MC activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MC activity gates contextual memory formation through an intra-hippocampal interaction activated by environmental novelty., Graphical Abstract, Highlights • Mossy cells in ventral hilus directly excite granule cells in dorsal hippocampus • Activity of ventral mossy cells positively correlates with environmental novelty • Inhibiting ventral mossy cells disrupts novelty-induced contextual fear memory • Exciting ventral mossy cells enhances contextual memory in a familiar environment, Novelty facilitates memory formation. Fredes et al. show that mossy cells in the ventral dentate gyrus detect environmental novelty. This information is conveyed to dorsal dentate granule cells and is necessary for novelty-induced contextual memory formation. Conversely, activating this pathway enhances contextual memory in a familiar environment.

Background: The positive relationship between cognitive and physical performance has been widely established. The influence of brain structure on both domains has been shown as well. Objective: We studied whether the relationship between brain structure and physical performance is independent of cognitive performance. Methods: This was a cross-sectional analysis of 297 middle-aged to older adults (mean age ± SD 65.4 ± 6.8 years). Memory function, executive function and physical performance measured by the Tandem Stance Test, Chair Stand Test, 4-meter walk and 25-meter walk were assessed. Magnetic resonance imaging was available in 237 participants and used to determine the (sub)cortical gray matter, white matter, hippocampal and basal ganglia volumes and the presence of cerebral small-vessel disease, i.e. white matter hyperintensities, cerebral microbleeds (CMBs) and lacunar infarcts (LIs). Regression analysis was used adjusting for age, gender, education and whole-brain volume. A Bonferroni correction was applied considering p values Results: Poor memory function was associated with a slower 4-meter walking speed (p < 0.01). No association was found between brain structure and cognitive performance. The presence of CMBs and LIs was associated with a slower 25-meter walking speed (p < 0.001). This result did not change after additional adjustment for cognitive performance. Conclusions: In middle-aged to older adults, CMBs and LIs are associated with walking speed independent of cognitive performance. This emphasizes the clinical relevance of identifying each of the possible underlying mechanisms of physical performance, which is required for the development of timely and targeted therapies.

Summary Hippocampal neurons activated during encoding drive the recall of contextual fear memory. Little is known about how such ensembles emerge during acquisition and eventually form the cellular engram. Manipulating the activity of granule cells (GCs) of the dentate gyrus (DG) we reveal a mechanism of lateral inhibition that modulates the size of the cellular engram. GCs engage somatostatin positive interneurons that inhibit the dendrites of surrounding GCs. Our findings reveal a microcircuit within the DG that controls the size of the cellular engram and the stability of contextual fear memory.

Highlights • First investigation of the role of NMNAT1 in the early stage of tauopathies in mice. • htau mice display a robust deficit in food burrowing prior to onset of cognitive symptoms. • NMNAT1 overexpression rescues this behavioral abnormality., NAD metabolism and the NAD biosynthetic enzymes nicotinamide nucleotide adenylyltransferases (NMNATs) are thought to play a key neuroprotective role in tauopathies, including Alzheimer’s disease. Here, we investigated whether modulating the expression of the NMNAT nuclear isoform NMNAT1, which is important for neuronal maintenance, influences the development of behavioral and neuropathological abnormalities in htau mice, which express non-mutant human tau isoforms and represent a model of tauopathy relevant to Alzheimer’s disease. Prior to the development of cognitive symptoms, htau mice exhibit tau hyperphosphorylation associated with a selective deficit in food burrowing, a behavior reminiscent to activities of daily living which are impaired early in Alzheimer’s disease. We crossed htau mice with Nmnat1 transgenic and knockout mice and tested the resulting offspring until the age of 6 months. We show that overexpression of NMNAT1 ameliorates the early deficit in food burrowing characteristic of htau mice. At 6 months of age, htau mice did not show neurodegenerative changes in both the cortex and hippocampus, and these were not induced by downregulating NMNAT1 levels. Modulating NMNAT1 levels produced a corresponding effect on NMNAT enzymatic activity but did not alter NAD levels in htau mice. Although changes in local NAD levels and subsequent modulation of NAD-dependent enzymes cannot be ruled out, this suggests that the effects seen on behavior may be due to changes in tau phosphorylation. Our results suggest that increasing NMNAT1 levels can slow the progression of symptoms and neuropathological features of tauopathy, but the underlying mechanisms remain to be established.

ObjectiveStroke patients often suffer from delayed disturbances of mood and cognition. In rodents, the prefrontal cortex (PFC) is involved in both higher order cognition and emotion. Our objective was to determine if bilateral focal ischaemic lesions restricted to the medial prefrontal cortex (mPFC) could be used to model post-stroke anxiety and/or cognitive deficits.MethodsGroups of adult male Sprague-Dawley rats (n=9) received bilateral injections of either endothelin-1 (ET-1) (400 pmol) or vehicle (artificial cerebrospinal fluid) into the mPFC and were tested at various times using both a test of temporal order memory and in an elevated plus maze. Lesions were verified histologically.ResultsET-1 lesioned rats had reduced mobility on post-surgery day 8 that had resolved by day 29 at which time they spent significantly more time in the closed arm of the plus mazeConclusionWe conclude that ischaemic lesions localised to the mPFC can be used to model post-stroke anxiety in rats.

Cognitive deficits are clearly associated with poor everyday life functioning in persons diagnosed with schizophrenia. However, previous studies have primarily used questionnaires to assess everyday life functioning. We developed a computerized real-life activity task (shopping task), where participants are required to shop for a list of seven grocery store items. Thirty individuals diagnosed with schizophrenia and 30 healthy controls were administered an extensive battery of cognitive tests and the computerized shopping task. Performances on the computerized shopping task significantly differentiated patients and healthy controls for several variables. Moreover, performance on the shopping task was significantly correlated with verbal episodic memory, cognitive flexibility, planning, processing speed, and inhibition. Finally, performance on the computerized shopping task was significantly correlated with various clinical variables and with a global measure of social functioning. These findings suggest that the computerized task used in the present study provides an indication of the level of everyday life functioning and cognitive functioning of persons diagnosed with schizophrenia, and, therefore, may be viewed as a valuable instrument in both an evaluation and remediation context. (JINS, 2010, 16, 180–189.)

IntroductionIn phenylketonuria (PKU), a gene mutation in the phenylalanine metabolic pathway causes accumulation of phenylalanine (Phe) in blood and brain. Although early introduction of a Phe-restricted diet can prevent severe symptoms from developing, patients who are diagnosed and treated early still experience deficits in cognitive functioning indicating shortcomings of current treatment. In the search for new and/or additional treatment strategies, a specific nutrient combination (SNC) was postulated to improve brain function in PKU. In this study, a long-term dietary intervention with a low-Phe diet, a specific combination of nutrients designed to improve brain function, or both concepts together was investigated in male and female BTBR PKU and WT mice.Material & methods48 homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice received dietary interventions from postnatal day 31 till 10 months of age and were distributed in the following six groups: high Phe diet (WT C-HP, PKU C-HP), high Phe plus specific nutrient combination (WT SNC-HP, PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC- LP). Memory and motor function were tested at time points 3, 6, and 9 months after treatment initiation in the open field (OF), novel object recognition test (NOR), spatial object recognition test (SOR), and the balance beam (BB). At the end of the experiments, brain neurotransmitter concentrations were determined.ResultsIn the NOR, we found that PKU mice, despite being subjected to high Phe conditions, could master the task on all three time points when supplemented with SNC. Under low Phe conditions, PKU mice on control diet could master the NOR at all three time points, while PKU mice on the SNC supplemented diet could master the task at time points 6 and 9 months. SNC supplementation did not consistently influence the performance in the OF, SOR or BB in PKU mice. The low Phe diet was able to normalize concentrations of norepinephrine and serotonin; however, these neurotransmitters were not influenced by SNC supplementation.ConclusionThis study demonstrates that both a long-lasting low Phe diet, the diet enriched with SNC, as well as the combined diet was able to ameliorate some, but not all of these PKU-induced abnormalities. Specifically, this study is the first long-term intervention study in BTBR PKU mice that shows that SNC supplementation can specifically improve novel object recognition.

Disorientation is frequent after brain damage. It is a constituent component of post traumatic amnesia and was part of the original definition of the Korsakoff syndrome together with amnesia and confabulations. Orbitofrontal reality filtering is a pre conscious memory control process that has been held accountable for disorientation and a specific type of spontaneous confabulation that patients act upon. A recent study questioned the specificity of this process and suggested that confabulating patients who failed in orbitofrontal reality filtering similarly failed to monitor the precise content of memories a critical step within the strategic retrieval account which describes a series of processes leading up to the recollection of memories. In the present study we combined the proposed experimental requirements of both processes in a single continuous recognition task and tested a group of 21 patients with a matched deficit of delayed free recall. We found that only deficient reality filtering but not content monitoring significantly correlated with disorientation and distinguished between confabulators and non confabulators. Thus reality confusion as evident in disorientation and behaviourally spontaneous confabulation primarily reflects an inability to monitor memories' relation with ongoing reality rather than to monitor their precise content.

A 57-year-old man suffered severe amnesia and disorientation, accompanied by content-specific confabulation, due to an alcoholic Wernicke-Korsakoff syndrome. For months, he was deeply concerned about a single obligation that he thought he had to respond to, but which he had already assumed 20 years previously. This monothematic, prospective confabulation was associated with failures of reality filtering as previously documented in behaviorally spontaneous confabulation and disorientation: the patient failed to suppress the interference of currently irrelevant memories and to abandon anticipations that were no longer valid (impaired extinction capacity). Magnetic resonance imaging showed damage to the mamillary bodies and the dorsomedial thalamic nucleus. Positron emission tomography (FDG-PET) showed extended orbitofrontal hypometabolism. We suggest that isolated prospective confabulation shares the core feature (acts and thoughts based on currently irrelevant memory), mechanism (failure of reality filtering), and anatomical basis (orbitofrontal dysfunction) with behaviorally spontaneous confabulations.

The Morris water maze (MWM) spatial learning task has been demonstrated to involve a cognitive switch of action control to serve the transition from an early towards a late learning phase. However, the molecular mechanisms governing this switch are largely unknown. We employed MALDI MS imaging (MSI) to screen for changes in expression of small proteins in brain structures implicated in the different learning phases. We compared mice trained for 3days and 30days in the MWM, reflecting an early and a late learning phase in relation to the acquisition of a spatial learning task. An ion with m/z of 6724, identified as PEP-19/pcp4 by top-down tandem MS, was detected at higher intensity in the dorsal striatum of the late learning phase group compared with the early learning phase group. In addition, mass spectrometric analysis of synaptosomes confirmed the presence of PEP-19/pcp4 at the synapse. PEP-19/pcp4 has previously been identified as a critical determinant of synaptic plasticity in locomotor learning. Our findings extend PEP-19/pcp4 function to spatial learning in the forebrain and put MSI forward as a valid and unbiased research strategy for the discovery and identification of the molecular machinery involved in learning, memory and synaptic plasticity. publisher: Elsevier articletitle: MS imaging and mass spectrometric synaptosome profiling identify PEP-19/pcp4 as a synaptic molecule involved in spatial learning in mice journaltitle: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics articlelink: http://dx.doi.org/10.1016/j.bbapap.2016.10.007 content_type: article copyright: © 2016 Elsevier B.V. All rights reserved. ispartof: Biochimica et Biophysica Acta vol:1865 issue:7 pages:936-945 ispartof: location:Netherlands status: published

Complex social behaviors lie at the heart of many of the challenges facing evolutionary biology, sociology, economics, and beyond. For evolutionary biologists the question is often how group behaviors such as collective action, or decision making that accounts for memories of past experience, can emerge and persist in an evolving system. Evolutionary game theory provides a framework for formalizing these questions and admitting them to rigorous study. Here we develop such a framework to study the evolution of sustained collective action in multi-player public-goods games, in which players have arbitrarily long memories of prior rounds of play and can react to their experience in an arbitrary way. We construct a coordinate system for memory-m strategies in iterated n-player games that permits us to characterize all cooperative strategies that resist invasion by any mutant strategy, and stabilize cooperative behavior. We show that, especially when groups are small, longer-memory strategies make cooperation easier to evolve, by increasing the number of ways to stabilize cooperation. We also explore the co-evolution of behavior and memory. We find that even when memory has a cost, longer-memory strategies often evolve, which in turn drives the evolution of cooperation, even when the benefits for cooperation are low.

In this issue of Neuron, Oettl et al. (2016) show how oxytocin can boost processing of olfactory information in female rats by a top-downregulation from the anterior olfactory nucleus onto the main olfactory bulb. As a result, interactions with juvenile conspecifics receive more attention and are longer memorized.

Introduction: Lumbar puncture (LP) is increasingly performed in memory clinics. We investigated patient-acceptance of LP, incidence of and risk factors for post-LP complications in memory clinic populations. Methods: We prospectively enrolled 3868 patients (50% women, age 66 +/- 11 years, mini mental state examination 25 +/- 5) at 23 memory clinics. We used logistic regression analysis using generalized estimated equations to investigate risk factors for post-LP complications, such as typical postlumbar puncture headache (PLPH) and back pain. Results: A total of 1065 patients (31%) reported post-LP complaints; 589 patients (17%) reported back pain, 649 (19%) headache, of which 296 (9%) reported typical PLPH. Only few patients needed medical intervention: 11 (0.3%) received a blood patch, 23 (0.7%) were hospitalized. The most important risk factor for PLPH was medical history of headache. An atraumatic needle and age >65 years were preventive. Gender, rest after LP, or volume of cerebrospinal fluid had no effect. Discussions: The overall risk of complications is relatively low. If risk factors shown in this study are taken into account, LPs can be safely performed in memory clinics. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Recent studies indicated that the human medial temporal lobe (MTL) may not only be important for long-term memory consolidation but also for certain forms of short-term memory. In this study, we explored the interplay between short- and long-term memory using high-density event-related potentials. We found that pictures immediately repeated after an unfilled interval were better recognized than pictures repeated after intervening items. After 30 min, however, the immediately repeated pictures were significantly less well recognized than pictures repeated after intervening items. This processing advantage at immediate repetition but disadvantage for long-term storage had an electrophysiological correlate: spatiotemporal analysis showed that immediate repetition induced a strikingly different electrocortical response after 200-300 ms, with inversed polarity, than new stimuli and delayed repetitions. Inverse solutions indicated that this difference reflected transient activity in the MTL. The findings demonstrate behavioral and electrophysiological dissociation between recognition during active maintenance and recognition after intervening items. Processing of novel information seems to immediately initiate a consolidation process, which remains vulnerable during active maintenance and increases its effectiveness during off-line processing.

Momentary fluctuations of baseline activity have been shown to influence responses to sensory stimulation both behaviorally and neurophysiologically. This suggests that perceptual awareness does not solely arise from physical stimulus properties. Here we studied whether the momentary state of the brain immediately before stimulus presentation indicates how a physically unique but perceptually ambiguous stimulus will be perceived. A complex Necker cube was intermittently presented and subjects indicated whether their perception changed with respect to the preceding presentation. EEG was recorded from 256 channels. The prestimulus brain-state was defined as the spatial configuration of the scalp potential map within the 50 ms before stimulus arrival, representing the sum of all momentary ongoing brain processes. Two maps were found that doubly dissociated perceptual reversals from perceptual stability. For EEG sweeps classified as either map, distributed inverse solutions were computed and statistically compared. This yielded activity confined to a region in right inferior parietal cortex that was significantly more active before a perceptual reversal. In contrast, no significant topographic differences of the evoked potentials elicited by stable vs. reversed Necker cubes were found. This indicates that prestimulus activity in right inferior parietal cortex is associated with the perceptual change.

This preliminary study integrated previous findings of the distribution of autobiographical memories in the later age according to their age of occurrence, with the overgeneral memory bias predictive of depression. Twenty-five non-demented, Israeli participants between 65–89 years of age provided autobiographical memories to 4 groups of word cues reflecting events from childhood, adolescence, adulthood and late age. Their autobiographical responses were coded for degree of specificity of mentioning people, place and time. They additionally completed the Geriatric Depression Scale (Sheikh & Yesavage, 1986). We found that specificity of memories for adolescence cue-words (“the reminiscence bump”) was significantly and inversely correlated with depression ( r = −0.61), and this remained significant after controlling for gender and education. The study's limitations and the possibility that puberty hormones may be involved in memory and later age depression are discussed.

Background: Group III metabotropic glutamate receptors (mGlu4, mGlu7, mGlu8) display differential brain distribution, which suggests different behavioral functions. However, comparison across the available animal studies remains methodologically hazardous and controversial. The present report directly compares knockouts for each group III receptor subtype using a single behavioral test battery and multivariate analysis. Methods: The behavioral phenotypes of C57BL/6J mice lacking mGlu4, mGlu7, or mGlu8 and their respective littermates were examined using a multimetric test battery, which included elements of neuromotor performance, exploratory behavior, and learning and memory. Multivariate statistical methods were used to identify subtype-specific behavioral profiles and variables that distinguished between these mouse lines. Results: It generally appears that mGlu7 plays a significant role in hippocampus-dependent spatial learning and in some fear-related behaviors, whereas mGlu4 is most clearly involved in startle and motivational processes. Excepting its influence on body weight, the effect of mGlu8 deletion on behavior appears more subtle than that of the other group III receptors. These receptors have been proposed as potential drug targets for a variety of psychopathological conditions. Conclusion: On the basis of these controlled comparisons, we presently conclude that the different group III receptors indeed have quite distinct behavioral functions.

BACKGROUND: There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. OBJECTIVE: The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. METHODS: 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. RESULTS: The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. CONCLUSIONS: The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.

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.

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

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.

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).

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.