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• Early life Western diet (WD) disrupts memory despite healthy diet intervention. • Early life WD yields long-lasting reductions in hippocampus cholinergic tone. • Early life WD disrupts novelty-induced hippocampal acetylcholine release. • Gut microbiome changes due to early life Western diet are reversible. • Impaired acetylcholine signaling underlies WD-induced memory deficits. Western diet (WD) consumption during early life developmental periods is associated with impaired memory function, particularly for hippocampus (HPC)-dependent processes. We developed an early life WD rodent model associated with long-lasting HPC dysfunction to investigate the neurobiological mechanisms mediating these effects. Rats received either a cafeteria-style WD (ad libitum access to various high-fat/high-sugar foods; CAF) or standard healthy chow (CTL) during the juvenile and adolescent stages (postnatal days 26–56). Behavioral and metabolic assessments were performed both before and after a healthy diet intervention period beginning at early adulthood. Results revealed HPC-dependent contextual episodic memory impairments in CAF rats that persisted despite the healthy diet intervention. Given that dysregulated HPC acetylcholine (ACh) signaling is associated with memory impairments in humans and animal models, we examined protein markers of ACh tone in the dorsal HPC (HPCd) in CAF and CTL rats. Results revealed significantly lower protein levels of vesicular ACh transporter in the HPCd of CAF vs. CTL rats, indicating chronically reduced ACh tone. Using intensity-based ACh sensing fluorescent reporter (iAChSnFr) in vivo fiber photometry targeting the HPCd, we next revealed that ACh release during object-contextual novelty recognition was highly predictive of memory performance and was disrupted in CAF vs. CTL rats. Neuropharmacological results showed that alpha 7 nicotinic ACh receptor agonist infusion in the HPCd during training rescued memory deficits in CAF rats. Overall, these findings reveal a functional connection linking early life WD intake with long-lasting dysregulation of HPC ACh signaling, thereby identifying an underlying mechanism for WD-associated memory impairments. [ABSTRACT FROM AUTHOR]

• The neural changes associated with WM training occur in the frontoparietal network and dopamine-related brain areas. • Shorter training durations predominantly impact the frontoparietal regions. • Longer durations affect subcortical areas, including the striatum and insula. • Updating tasks induce broader neural changes compared to maintenance tasks. Working memory (WM) can be improved by cognitive training. Numerous studies examined neural mechanisms underlying WM training, although with differing conclusions. Therefore, we conducted a meta-analysis to examine the neural substrates underlying WM training in healthy adults. Findings from global analyses showed substantial neural changes in the frontoparietal and subcortical regions. Results from training dosage analyses of WM training showed that shorter WM training could produce neural changes in the frontoparietal regions, whereas longer WM training could produce changes in the subcortical regions (striatum, anterior cingulate cortex, and insula). WM training-induced neural changes were also moderated by the type of training task, with updating tasks inducing neural changes in more regions than maintenance tasks. Overall, these results indicate that the neural changes associated with WM training occur in the frontoparietal network and dopamine-related brain areas, extending previous meta-analyses on WM training and advancing our understanding of the neural underpinnings of WM training effects. [ABSTRACT FROM AUTHOR]

• Working memory training in preschoolers can transfer to other cognitive domains. • However, there is no evidence for transfer to fluid intelligence. • The training enhanced the neural signals associated with ERP components in preschoolers. Working memory (WM) refers to the ability to actively maintain and process information needed to complete complex tasks such as comprehension, learning, and reasoning. Recent studies have examined the efficacy of computerized working memory training (WMT) in improving cognitive functions in general and WM in particular, with mixed results. Thus, to what extent can WMT produce near and far transfer effects to cognitive function is currently unclear. This study investigated the transfer effects of a computerized WMT for preschool children and also examined the possible neural correlates using the event-related potential (ERP) technique. A total of 50 Chinese preschoolers (64.44 ± 7.76 months old; 24 girls) received 4-week training during school hours. Compared with those in the active control group, children in the training group showed better gains in behavioral performance in the WM task and significantly more changes in ERP markers of the WM and inhibitory control tasks (near transfer effect). However, no evidence was found for transfer to fluid intelligence (far transfer effect). These findings suggest that WMT is capable of enhancing cognitive functioning in preschool children, and as such this work has important implications for educational practice and it may help to design and refine cognitive interventions for typically developing children and those with WM problems or other cognitive deficits (e.g., children with attention-deficit/hyperactivity disorder). [ABSTRACT FROM AUTHOR]

• Following an 8-week computerized working memory training, participants exhibited a notable alternation in the amplitude of low-frequency fluctuations (ALFF) in the fronto-occipital regions. • An increase in gray matter volume (GMV) was observed in the right dorsal superior frontal gyrus of the training group post-training. • Significant correlations was found between neuroimaging measures (ALFF and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA). Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl- D -aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Early life stress reduces acquisition and contextual recall of fear memories. • Early life stress alters immediate early gene expression after training and recall. • Early life stress effects on immediate early genes depend on brain region. • Colocalization of immediate early genes is altered after memory recall. • Adolescent treatment with RU486 does not mitigate effects of early life stress. The ability to learn and remember, which is fundamental for behavioral adaptation, is susceptible to stressful experiences during the early postnatal period, such as abnormal levels of maternal care. The exact mechanisms underlying these effects still remain elusive. This study examined whether early life stress (ELS) alters memory and brain activation patterns in male mice. Therefore, we examined the expression of the immediate early genes (IEGs) c-Fos and Arc in the dentate gyrus (DG) and basolateral amygdala (BLA) after training and memory retrieval in a fear conditioning task. Furthermore, we examined the potential of RU38486 (RU486), a glucocorticoid receptor antagonist, to mitigate ELS-induced memory deficits by blocking stress signalling during adolescence. Arc::dVenus reporter mice, which allow investigating experience-dependent expression of the immediate early gene Arc also at more remote time points, were exposed to ELS by housing dams and offspring with limited bedding and nesting material (LBN) between postnatal days (PND) 2–9 and trained in a fear conditioning task at adult age. We found that ELS reduced both fear acquisition and contextual memory retrieval. RU486 did not prevent these effects. ELS reduced the number of Arc::dVenus+ cells in DG and BLA after training, while the number of c-Fos+ cells were left unaffected. After memory retrieval, ELS decreased c-Fos+ cells in the ventral DG and BLA. ELS also altered the colocalization of c-Fos+ cells with Arc::dVenus+ cells in the ventral DG, possibly indicating impaired engram allocation in the ventral DG after memory retrieval. In conclusion, this study shows that ELS alters neuronal activation patterns after fear acquisition and retrieval, which may provide mechanistic insights into enduring impact of ELS on the processing of fear memories, possibly via changes in cell (co–) activation and engram cell allocation. [ABSTRACT FROM AUTHOR]

• Sensorimotor training reduces plasmatic ccl11/eotaxin-1 in aged humans and mice. • High levels of ccl11 abolish the benefits of training on long-term memory retention. • Increasing ccl11 hinders training-induced enhancement of hippocampal neurogenesis. • High levels of ccl11 block training-induced boost of neural plasticity signaling. • Anti-ccl11 antibodies reproduce the effects of sensorimotor training on memory. A deterioration in cognitive performance accompanies brain aging, even in the absence of neurodegenerative pathologies. However, the rate of cognitive decline can be slowed down by enhanced cognitive and sensorimotor stimulation protocols, such as environmental enrichment (EE). Understanding how EE exerts its beneficial effects on the aged brain pathophysiology can help in identifying new therapeutic targets. In this regard, the inflammatory chemokine ccl11/eotaxin-1 is a marker of aging with a strong relevance for neurodegenerative processes. Here, we demonstrate that EE in both elderly humans and aged mice decreases circulating levels of ccl11. Interfering, in mice, with the ccl11 decrease induced by EE ablated the beneficial effects on long-term memory retention, hippocampal neurogenesis, activation of local microglia and of ribosomal protein S6. On the other hand, treatment of standard-reared aged mice with an anti-ccl11 antibody resulted in EE-like improvements in spatial memory, hippocampal neurogenesis, and microglial activation. Taken together, our findings point to a decrease in circulating ccl11 concentration as a key mediator of the enhanced hippocampal function resulting from exposure to EE. [ABSTRACT FROM AUTHOR]

On June 7th, 2020, the statue of Edward Colston in Bristol City Centre was pulled down by an anonymous group of Black Lives Matter protestors following a global uprising against police brutality in the wake of George Floyd's murder by Minneapolis police officer Derek Chauvin. This article combines a first-person account of the build-up to the statue falling and its aftermath with reflections on some of the broader debates, historical and current, around public monuments, state violence, and collective life. • Colston falling should be interpreted in the context of the production of Black British history. • The politics of participating in public mnemonics is a site of racialised struggle. • Reflexive state violence after Colston falling seeks to foreclose its historic intervention. [ABSTRACT FROM AUTHOR]

Letrozole, an aromatase inhibitor preventing estrogen synthesis from testosterone, is used as an adjuvant therapy in estrogen receptor-positive breast cancer patients. However, like other aromatase inhibitors, it induces many side effects, including impaired cognition. Despite its negative effect in humans, results from animal models are inconsistent and suggest that letrozole can either impair or improve cognition. Here, we studied the effects of chronic letrozole treatment on cognitive behavior of adult female BALB/c mice, a relevant animal model for breast cancer studies, to develop an appropriate animal model aimed at testing therapies to mitigate side effects of letrozole. In Morris water maze, letrozole 0.1 mg/kg impaired reference learning and memory. Interestingly, most of the letrozole 0.1 mg/kg-treated mice were able to learn the new platform position in reversal training and performed similar to control mice in a reversal probe test. Results of the reversal test suggest that letrozole did not completely disrupt spatial navigation, but rather delayed acquisition of spatial information. The delay might be related to increased anxiety as suggested by increased thigmotactic behavior during the reference memory training. The learning impairment was water maze-specific since we did not observe impairment in other spatial tasks such as in Y-maze or object location test. In contrast, the dose of 0.3 mg/kg did not have effect on water maze learning and facilitated locomotor habituation and recognition in novel object recognition test. The current study shows that letrozole dose-dependently modulates behavioral response and that its effects are task-dependent. • Letrozole induces cognitive impairment or improvement depending on the dose. • Expression of letrozole-induced cognitive impairment is task dependent. • Letrozole-induced anxiety may contribute to the observed impairment of water maze performance. [ABSTRACT FROM AUTHOR]

• Novelty preference assessed by eye tracking measured memory for images. • Controls had intact novelty preference at 2-sec to 5-min delays, but not at 30 min. • Epilepsy patients had intact novelty preference only at 2- and 30-sec delays. • Eye gaze may be more sensitive to temporal lobe memory deficits than standard tests. Epilepsy patients often report memory deficits despite normal objective testing, suggesting that available measures are insensitive or that non-mnemonic factors are involved. The Visual Paired Comparison Task (VPCT) assesses novelty preference, the tendency to fixate on novel images rather than previously viewed items, requiring recognition memory for the "old" images. As novelty preference is a sensitive measure of hippocampal-dependent memory function, we predicted impaired VPCT performance in epilepsy patients compared to healthy controls. We assessed 26 healthy adult controls and 31 epilepsy patients (16 focal-onset, 13 generalized-onset, 2 unknown-onset) with the VPCT using delays of 2 or 30 s between encoding and recognition. Fifteen healthy controls and 17 epilepsy patients (10 focal-onset, 5 generalized-onset, 2 unknown-onset) completed the task at 2-, 5-, and 30-minute delays. Subjects also performed standard memory measures, including the Medical College of Georgia (MCG) Paragraph Test, California Verbal Learning Test-Second Edition (CVLT-II), and Brief Visual Memory Test-Revised (BVMT-R). The epilepsy group was high functioning, with greater estimated IQ (p = 0.041), greater years of education (p = 0.034), and higher BVMT-R scores (p = 0.024) compared to controls. Both the control group and epilepsy cohort, as well as focal- and generalized-onset subgroups, had intact novelty preference at the 2- and 30-second delays (p-values ≤ 0.001) and declined at 30 min (p-values > 0.05). Only the epilepsy patients had early declines at 2- and 5-minute delays (controls with intact novelty preference at p = 0.003 and p ≤ 0.001, respectively; epilepsy groups' p-values > 0.05). Memory for the "old" items decayed more rapidly in overall, focal-onset, and generalized-onset epilepsy groups. The VPCT detected deficits while standard memory measures were largely intact, suggesting that the VPCT may be a more sensitive measure of temporal lobe memory function than standard neuropsychological batteries. [ABSTRACT FROM AUTHOR]

• We tested individual and additive benefits of numerical knowledge and WM training. • Kindergarten children played tablet-based training games for 10 sessions. • WM training led to improvements in math knowledge. • Combined WM and numerical training led to sustained improvements in math knowledge. • Results provide evidence for reciprocal relation between numerical knowledge and WM. The acquisition of domain-specific number knowledge and domain-general cognitive processes, including working memory, have shown to contribute to math learning and achievement. Correlational work has emphasized a reciprocal relationship between these processes; however, little is known about their relative and causal contributions to math learning. Here, we test the individual and additive benefits of playing tablet-based games targeting domain-specific and domain-general skills to improve mathematical knowledge and working memory in a diverse population of kindergarten children (N = 235, 50 % female, 45 % Hispanic/Latino, 35 % African American/Black, 21 % White, 6 % biracial/mixed race, 51 % annual household income less than $30,000). Our results provide causal evidence for the reciprocal relations between numerical knowledge and working memory. Specifically, we found that playing a working memory game led to improvements in mathematical knowledge as compared to an active control and after taking into account baseline performance. Importantly, we also found that children who played both a working memory game and a numerical knowledge game showed the most pronounced and sustained benefits in mathematical knowledge, with benefits remaining present several weeks after intervention completion. Our findings illustrate the importance of targeting both domain-general and domain-specific skills in order to maximize the benefits of interventions to improve mathematical knowledge. Yet, given the inconsistent results across various studies, we argue that it is critical to further investigate underlying mechanisms and training features, as even subtle variations seem to dramatically affect training outcomes. [ABSTRACT FROM AUTHOR]

Spatial navigation critically underlies hippocampal-entorhinal circuit function that is early affected in Alzheimer's disease (AD). There is growing evidence that AD pathophysiology dynamically interacts with the sleep/wake cycle impairing hippocampal memory. To elucidate sleep-dependent consolidation in a cohort of symptomatic AD patients (n = 12, 71.25 ± 2.16 years), we tested hippocampal place learning by means of a virtual reality task and verbal memory by a word-pair association task before and after a night of sleep. Our results show an impaired overnight memory retention in AD compared with controls in the verbal task, together with a significant reduction of sleep spindle activity (i.e., lower amplitude of fast sleep spindles, p = 0.016) and increased duration of the slow oscillation (SO; p = 0.019). Higher spindle density, faster down-to-upstate transitions within SOs, and the time delay between SOs and nested spindles predicted better memory performance in healthy controls but not in AD patients. Our results show that mnemonic processing and memory consolidation in AD is slightly impaired as reflected by dysfunctional oscillatory dynamics and spindle-SO coupling during NonREM sleep. In this translational study based on experimental paradigms in animals and extending previous work in healthy aging and preclinical disease stages, our results in symptomatic AD further deepen the understanding of the memory decline within a bidirectional relationship of sleep and AD pathology. • Sleep-dependent consolidation of verbal memory is impaired in Alzheimer's disease. • AD patients show a significant reduction in spindle activity and duration of SOs. • SO-spindle coupling predicted better memory performance in controls but not in AD. [ABSTRACT FROM AUTHOR]

Congenitally blind individuals have been shown to activate the visual cortex during non-visual tasks. The neuronal mechanisms of such cross-modal activation are not fully understood. Here, we used an auditory working memory training paradigm in congenitally blind and in sighted adults. We hypothesized that the visual cortex gets integrated into auditory working memory networks, after these networks have been challenged by training. The spectral profile of functional networks was investigated which mediate cross-modal reorganization following visual deprivation. A training induced integration of visual cortex into task-related networks in congenitally blind individuals was expected to result in changes in long-range functional connectivity in the theta-, beta- and gamma band (imaginary coherency) between visual cortex and working memory networks. Magnetoencephalographic data were recorded in congenitally blind and sighted individuals during resting state as well as during a voice-based working memory task; the task was performed before and after working memory training with either auditory or tactile stimuli, or a control condition. Auditory working memory training strengthened theta-band (2.5–5 Hz) connectivity in the sighted and beta-band (17.5–22.5 Hz) connectivity in the blind. In sighted participants, theta-band connectivity increased between brain areas typically involved in auditory working memory (inferior frontal, superior temporal, insular cortex). In blind participants, beta-band networks largely emerged during the training, and connectivity increased between brain areas involved in auditory working memory and as predicted, the visual cortex. Our findings highlight long-range connectivity as a key mechanism of functional reorganization following congenital blindness, and provide new insights into the spectral characteristics of functional network connectivity. • Auditory working memory training resulted in indistinguishable improvements in blind and sighted adults. • Training was mediated by an increase in theta band connectivity in sighted adults. • Training resulted in an increased beta connectivity in congenitally blind adults. • Beta band connectivity increases included visual cortex and the auditory WM network. [ABSTRACT FROM AUTHOR]

• Prelimbic muscarinic signaling is required for trace and contextual fear memories. • The estrous cycle gates the fear memory-impairing effects of scopolamine in females. • A higher dose of scopolamine is required to impair fear memory in females than males. • Scopolamine suppresses subsequent drug-free acquisition to the originally trained cue. The association of a sensory cue and an aversive footshock that are separated in time, as in trace fear conditioning, requires persistent activity in prelimbic cortex during the cue-shock interval. The activation of muscarinic acetylcholine receptors has been shown to facilitate persistent firing of cortical cells in response to brief stimulation, and muscarinic antagonists in the prefrontal cortex impair working memory. It is unknown, however, if the acquisition of associative trace fear conditioning is dependent on muscarinic signaling in the prefrontal cortex. Here, we delivered the muscarinic receptor antagonist scopolamine to the prelimbic cortex of rats prior to trace fear conditioning and tested their memories of the cue and training context the following day. The effect of scopolamine on working memory performance was also tested using a spatial delayed non-match to sample task. Male and female subjects were included to examine potential sex differences in the modulation of memory formation, as we have previously observed for pituitary adenylate cyclase-activating polypeptide signaling in the prefrontal cortex (Kirry et al., 2018). We found that pre-training administration of intra-prelimbic scopolamine impaired the formation of cued and contextual fear memories in males, but not females at a dose that impairs spatial working memory in both sexes. Fear memory formation in females was impaired by a higher dose of scopolamine and this impairment was gated by estrous cycle stage: scopolamine failed to impair memory in rats in the diestrus or proestrus stages of the estrous cycle. These findings add to the growing body of evidence that the prefrontal cortex is sexually dimorphic in learning and memory and additionally suggest that males and females differentially engage prefrontal neuromodulatory systems in support of learning. [ABSTRACT FROM AUTHOR]

Abstract The precise roles of the hippocampus (HPC) and medial prefrontal cortex (mPFC) in initially constructing imagined events remains unclear. HPC activity during imagination may be modulated by mnemonic load, given its role in working memory for complex materials, and/or by the semantic relatedness (i.e. congruency) between items and their context. MPFC activation may track with congruency or mnemonic load, given the role of ventral mPFC in schema processing and the dorsal mPFC in working memory for social information. Sixteen healthy adults (M age = 22.3) underwent an event construction task, wherein participants were provided with a context and item words and imagined an event, forming as many inter-item associations as possible among the items. The stimuli varied by set size and by normatively-defined congruence (normative congruency) to explore their effects on HPC and mPFC activity and functional connectivity. We observed HPC connectivity during event construction in general, whereas dorsal mPFC connectivity occurred during imagining only at higher set sizes. Moreover, anterior hippocampal activity correlated positively with increasing coherence between items during imagining, suggesting that the anterior HPC is sensitive to the relational demands of constructing a novel event. Parahippocampal, hippocampal, temporal pole, and mPFC activity tracked only with individual differences in subjective ratings of congruency of imagined events, which may contribute to construction by retrieving existing schema-related information. Collectively, these findings provide new insights into the factors that modulate HPC and mPFC activity when constructing mental simulations. [ABSTRACT FROM AUTHOR]

Highlights • Glucocorticoid response to SECPT peaked during initial motor sequence learning. • Stress exposure did not influence learning or ensuing consolidation on average. • Stress-induced cortisol levels were negatively related to overnight performance gains. Abstract Hippocampal activity during early motor sequence learning is critical to trigger subsequent sleep-related consolidation processes. Based on previous evidence that stress-induced cortisol release modulates hippocampal activity, the current study investigates whether exposure to stress prior to motor sequence learning influences the ensuing learning and overnight consolidation process. Seventy-four healthy young adults were exposed to a stressor (i.e., the socially evaluated cold pressor test, SECPT) or a control procedure before initial training on a bimanual motor sequence learning task. Participants were retested on the motor task 24 h (including a night of sleep) after training to assess memory consolidation. Our results indicate that the SECPT, as compared to the control condition, induced significant physiological stress responses as evidenced by increased heart rate and blood pressure as well as elevated salivary cortisol concentrations. Cortisol concentration in the stress group reached peak levels immediately before and stayed significantly elevated for the full duration of initial motor learning before returning to baseline during the consolidation period. Stress induction prior to learning did not, on average, influence initial performance nor subsequent motor memory consolidation as indicated by similar overnight gains in performance in both groups. However, higher levels of stress-induced cortisol prior to training were correlated to smaller overnight gains in performance speed. These results indicate that the glucocorticoid response to a stressful encounter experienced prior to hippocampal-mediated motor learning is negatively related to subsequent memory consolidation processes. [ABSTRACT FROM AUTHOR]

We present a scalable strategy for development of mesh-free hybrid neuro-symbolic partial differential equation solvers based on existing mesh-based numerical discretization methods. Particularly, this strategy can be used to efficiently train neural network surrogate models of partial differential equations by (i) leveraging the accuracy and convergence properties of advanced numerical methods, solvers, and preconditioners, as well as (ii) better scalability to higher order PDEs by strictly limiting optimization to first order automatic differentiation. The presented neural bootstrapping method (hereby dubbed NBM) is based on evaluation of the finite discretization residuals of the PDE system obtained on implicit Cartesian cells centered on a set of random collocation points with respect to trainable parameters of the neural network. Importantly, the conservation laws and symmetries present in the bootstrapped finite discretization equations inform the neural network about solution regularities within local neighborhoods of training points. We apply NBM to the important class of elliptic problems with jump conditions across irregular interfaces in three spatial dimensions. We show the method is convergent such that model accuracy improves by increasing number of collocation points in the domain and preconditioning the residuals. We show NBM is competitive in terms of memory and training speed with other PINN-type frameworks. The algorithms presented here are implemented using JAX in a software package named JAX-DIPS (https://github.com/JAX-DIPS/JAX-DIPS), standing for differentiable interfacial PDE solver. We open sourced JAX-DIPS to facilitate research into use of differentiable algorithms for developing hybrid PDE solvers. • Scalable training of compact neural networks with mixed differentiation. • Finite discretization for PDE gradients and automatic differentiation for training. • Method is applied to elliptic PDEs with jump conditions over irregular geometries. • An end-to-end differentiable 3D PDE solver library is open sourced. • JAX-DIPS is a multi-GPU/TPU and differentiable solver for 3D interfacial PDEs. [ABSTRACT FROM AUTHOR]

Neurofeedback (NF) is a promising method to self-regulate human brain activity for cognition enhancement. Due to the unclear results of alpha NF training on working memory updating as well as the impact of feedback modality on NF learning, this study aimed to understand further the underlying neural mechanism of alpha NF training effects on working memory updating, where the NF learning was also compared between visual and auditory feedback modalities. A total of 30 participants were assigned to Visual NF, Auditory NF, and Control groups. Working memory updating was evaluated by n-back (n = 2 , 3) tasks before and after five alpha upregulation NF sessions. The result showed no significant difference in NF learning performance between the Visual and Auditory groups, indicating that the difference in feedback modality did not affect NF learning. In addition, compared to the control group, the participants who achieved successful NF learning showed a significant increase in n-back behavioral performance and P3a amplitude in 2-back and a significant decrease in P3a latency in 3-back. Our results in n-back further suggested that successful alpha NF training might improve updating performance in terms of the behavioral and related event-related potential (ERP) measures. These findings contribute to the understanding of the effect of alpha training on memory updating and the design of NF experimental protocol in terms of feedback modality selection. [ABSTRACT FROM AUTHOR]

• tDCS-enhanced cognitive training tended to boost acquisition and retention. • tDCS-enhanced motor training did not help learning. • The studies included were overall homogeneous but showed high risk of bias. • The current results do not support clinical implementation of tDCS during training. Older adults with and without Parkinson's disease show impaired retention after training of motor or cognitive skills. This systematic review with meta-analysis aims to investigate whether adding transcranial direct current stimulation (tDCS) to motor or cognitive training versus placebo boosts motor sequence and working memory training. The effects of interest were estimated between three time points, i.e. pre-training, post-training and follow-up. This review was conducted according to the PRISMA guidelines (PROSPERO: CRD42022348885). Electronic databases were searched from conception to March 2023. Following initial screening, 24 studies were eligible for inclusion in the qualitative synthesis and 20 could be included in the meta-analysis, of which 5 studies concerned motor sequence learning (total n = 186) and 15 working memory training (total n = 650). Results were pooled using an inverse variance random effects meta-analysis. The findings showed no statistically significant additional effects of tDCS over placebo on motor sequence learning outcomes. However, there was a strong trend showing that tDCS boosted working memory training, although methodological limitations and some heterogeneity were also apparent. In conclusion, the present findings do not support wide implementation of tDCS as an add-on to motor sequence training at the moment, but the promising results on cognitive training warrant further investigations. [ABSTRACT FROM AUTHOR]

• Maintaining a conservative vs. liberal criterion drastically affects target > nontarget response contrasts during recognition memory and visual detection tests. • Changes in discriminability show virtually no differences in activity in target > nontarget response or item contrasts when controlling for the decision criterion. • A similar frontoparietal network associated with the decision criterion is observed across recognition memory and visual detection tasks (though the magnitude and spatial extent is more robust during recognition memory tests). Widespread frontoparietal activity is consistently observed in recognition memory tests that compare studied ("target") versus unstudied ("nontarget") responses. However, there are conflicting accounts that ascribe various aspects of frontoparietal activity to mnemonic evidence versus decisional processes. According to Signal Detection Theory, recognition judgments require individuals to decide whether the memory strength of an item exceeds an evidence threshold—the decision criterion—for reporting previously studied items. Yet, most fMRI studies fail to manipulate both memory strength and decision criteria, making it difficult to appropriately identify frontoparietal activity associated with each process. In the current experiment, we manipulated both discriminability and decision criteria across recognition memory and visual detection tests during fMRI scanning to assess how frontoparietal activity is affected by each manipulation. Our findings revealed that maintaining a conservative versus liberal decision criterion drastically affects frontoparietal activity in target versus nontarget response contrasts for both recognition memory and visual detection tests. However, manipulations of discriminability showed virtually no differences in frontoparietal activity in target versus nontarget response or item contrasts. Comparing across task domains, we observed similar modulations of frontoparietal activity across criterion conditions, though the recognition memory task revealed larger activations in both magnitude and spatial extent in these contrasts. Nonetheless, there appears to be some domain specificity in frontoparietal activity associated with the maintenance of a conservative versus liberal criterion. We propose that widespread frontoparietal activity observed in target versus nontarget contrasts is largely attributable to response bias where increased activity may reflect inhibition of a prepotent response, which differs depending on whether a person maintains a conservative versus liberal decision criterion. [ABSTRACT FROM AUTHOR]

Abstract Memory functioning undergoes dynamic changes between childhood and adulthood. Spontaneous use of elaborative strategies, which can enhance the recall of information, expands with age and contributes to age-associated improvement in memory functioning. Findings from lesion and neuroimaging studies suggest that the ability to use elaborative strategies is dependent upon intact functioning of the prefrontal cortex (PFC), particularly the dorsolateral PFC region. Because the PFC undergoes protracted maturation, we examined whether age difference in the structure of the PFC is correlated with age-associated increase in strategy use. Here, we investigated the relationship between PFC volume and spontaneous strategy use in a sample of 120 participants aged 5–25 years. We assessed semantic clustering during recall with a standardized word-list recall task (California Verbal Learning Task children's version, CVLT-C) and computed PFC regional volumes from participants' structural brain images. We observed an age-associated increase in the use of semantic clustering and an age-associated decrease in volumes of the PFC. Further, we found that smaller PFC volume was linked to increased use of semantic clustering. Importantly, the volume of the right dorsolateral PFC partially explained the relation between age and the use of semantic clustering. These findings suggest that PFC maturation supports the development of strategy use and lends further support for the notion that brain-behavior relations change across development. Highlights • We assessed age difference in spontaneous mnemonic strategy use in word list recall. • Age difference in spontaneous semantic strategy use between age 5–25-years. • Age difference in PFC volume partially mediated age increase in semantic strategy use. • Age difference in number of words recalled was not mediated by PFC volume. [ABSTRACT FROM AUTHOR]

• Instructional load induces a shift in functional integration of lateral PFC regions. • Coupling to 'task-positive' areas was stronger after low-load instructions. • Default mode network was increasingly connected after high-load instructions. • Coupling profile implies difference in task automaticity and memory system access. • Ventrolateral PFC couplings are associated with distinct instructional features. Learning new rules rapidly and effectively via instructions is ubiquitous in our daily lives, yet the underlying cognitive and neural mechanisms are complex. Using functional magnetic resonance imaging we examined the effects of different instructional load conditions (4 vs. 10 stimulus-response rules) on functional couplings during rule implementation (always 4 rules). Focusing on connections of lateral prefrontal cortex (LPFC) regions, the results emphasized an opposing trend of load-related changes in LPFC-seeded couplings. On the one hand, during the low-load condition LPFC regions were more strongly coupled with cortical areas mostly assigned to networks such as the fronto-parietal network and the dorsal attention network. On the other hand, during the high-load condition, the same LPFC areas were more strongly coupled with default mode network areas. These results suggest differences in automated processing evoked by features of the instruction and an enduring response conflict mediated by lingering episodic long-term memory traces when instructional load exceeds working memory capacity limits. The ventrolateral prefrontal cortex (VLPFC) exhibited hemispherical differences regarding whole-brain coupling and practice-related dynamics. Left VLPFC connections showed a persistent load-related effect independent of practice and were associated with 'objective' learning success in overt behavioral performance, consistent with a role in mediating the enduring influence of the initially instructed task rules. Right VLPFC's connections, in turn, were more susceptible to practice-related effects, suggesting a more flexible role possibly related to ongoing rule updating processes throughout rule implementation. [ABSTRACT FROM AUTHOR]

• Similar fMRI occipitotemporal representation of 1st and 2nd items at encoding. • Advantaged representation of 1st vs. 2nd items in the post-encoding period. • The neural advantage of 1st items predicted the behavioral primacy effect in memory. Visual areas activated during perception can retain specific information held in memory without the presence of physical stimuli via distributed activity patterns. Neuroimaging studies have shown that the delay-period representation of information in visual areas is modulated by factors such as memory load and task demands, raising the possibility of serial position as another potential modulator. Specifically, enhanced representation of first items during the post-encoding delay period may serve as a mechanism underlying the well-established but not well-understood primacy effect – the mnemonic advantage of first items. To test this hypothesis, 13 males and 16 females performed a human fMRI task, wherein each trial consisted of the sequential encoding of two stimuli (a famous face and landscape, order counterbalanced), followed by a distracting task, a delay period, and then a cued recall of one of the items. Participants exhibited the expected behavioral primacy effect, manifested as faster recall of the first items. In order to elucidate the still debated neural underpinnings of this effect, using multivariate decoding, a classifier was trained on data collected during encoding to differentiate stimulus categories (i.e., faces vs. landscapes) and tested on data collected during the post-encoding period. Greater reactivation of first versus second items was observed in the ventral occipito-temporal cortex during the entire post-encoding period but not during encoding. Moreover, trial-level analyses revealed that the degree of first-item neural advantage during the post-encoding delay predicted the behavioral primacy effect. These findings highlight the role of item reinstatement in ventral occipito-temporal cortex in the primacy effect and are discussed in the context of the uniqueness of the very first item and event boundaries, illuminating putative neural mechanisms underlying the effect. [ABSTRACT FROM AUTHOR]

• Trial level gamma activity was present in discrete events during working memory. • Trial level gamma activity decreases with development during working memory. • Decrease in gamma events specific to the working memory maintenance in adulthood. • Trial level event power partially mediates the age-related changes in total power. • Trial event number partially mediates the age-related changes in total power. Adolescence is a stage of development characterized by neurodevelopmental specialization of cognitive processes. In particular, working memory continues to improve through adolescence, with increases in response accuracy and decreases in response latency continuing well into the twenties. Human electroencephalogram (EEG) studies indicate that gamma oscillations (35–65 Hz) during the working memory delay period support the maintenance of mnemonic information guiding subsequent goal-driven behavior, which decrease in power with development. Importantly, recent electrophysiological studies have shown that gamma events, more so than sustained activity, may underlie working memory maintenance during the delay period. However, developmental differences in gamma events during working memory have not been studied. Here, we used EEG in conjunction with a novel spectral event processing approach to investigate age-related differences in transient gamma band activity during a memory guided saccade (MGS) task in 164 10- to 30-year-olds. Total gamma power was found to significantly decrease through adolescence, replicating prior findings. Results from the spectral event pipeline showed age-related decreases in the mean power of gamma events and trial-by-trial power variability across both the delay period and fixation epochs of the MGS task. In addition, we found that while event number decreased with age during the fixation period, the developmental decrease during the delay period was more dramatic, resulting in an increase in event spiking from fixation to delay in adolescence but not adulthood. While average power of the transient gamma events was found to mediate age-related differences in total gamma power in the fixation and delay periods, the number of gamma events was related to total power in only the delay period, suggesting that the power of gamma events may underlie the sustained gamma activity seen in EEG literature while the number of events may directly support age-related improvements in working memory maintenance. Our findings provide compelling new evidence for mechanistic changes in neural processing characterized by refinements in neural function as behavior becomes optimized in adulthood. [ABSTRACT FROM AUTHOR]

• One key aspect of working memory development is increased mnemonic precision. • Pupillometry can index attentional allocation throughout a working memory trial. • Across trials, higher precision was linked to lower pupil dilation. • This intraindividual pupil-behavior relation was stronger for adults than children. • Improved precision in adulthood may reflect more efficient attentional allocation. Working memory (WM) precision, or the fidelity with which items can be remembered, is an important aspect of WM capacity that increases over childhood. Why individuals are more or less precise from moment to moment and why WM becomes more stable with age are not yet fully understood. Here, we examined the role of attentional allocation in visual WM precision in children aged 8 to 13 years and young adults aged 18 to 27 years, as measured by fluctuations in pupil dilation during stimulus encoding and maintenance. Using mixed models, we examined intraindividual links between change in pupil diameter and WM precision across trials and the role of developmental differences in these associations. Through probabilistic modeling of error distributions and the inclusion of a visuomotor control task, we isolated mnemonic precision from other cognitive processes. We found an age-related increase in mnemonic precision that was independent of guessing behavior, serial position effects, fatigue or loss of motivation across the experiment, and visuomotor processes. Trial-by-trial analyses showed that trials with smaller changes in pupil diameter during encoding and maintenance predicted more precise responses than trials with larger changes in pupil diameter within individuals. At encoding, this relationship was stronger for older participants. Furthermore, the pupil–performance coupling grew across the delay period—particularly or exclusively for adults. These results suggest a functional link between pupil fluctuations and WM precision that grows over development; visual details may be stored more faithfully when attention is allocated efficiently to a sequence of objects at encoding and throughout a delay period. [ABSTRACT FROM AUTHOR]

Previous studies have consistently demonstrated that superior mnemonists (SMs) outperform normal individuals in domain-specific memory tasks. However, the neural correlates of memory-related processes remain unclear. In the current EEG study, SMs and control participants performed a digit memory task during which their brain activity was recorded. Chinese SMs used a digit-image mnemonic for encoding digits, in which they associated 2-digit groups with images immediately after the presentation of each even-position digit in sequences. Behaviorally, SMs' memory of digit sequences was better than the controls'. During encoding in the study phase, SMs showed an increased right central P2 (150-250ms post onset) and a larger right posterior high-alpha (10-14Hz, 500-1720ms) oscillation on digits at even-positions compared with digits at odd-positions. Both P2 and high-alpha oscillations in the study phase co-varied with performance in the recall phase, but only in SMs, indicating that neural dynamics during encoding could predict successful retrieval of digit memory in SMs. Our findings suggest that representation of a digit sequence in SMs using mnemonics may recruit both the early-stage attention allocation process and the sustained information preservation process. This study provides evidence for the role of dynamic and efficient neural encoding processes in mnemonists. [ABSTRACT FROM AUTHOR]

It is well known that stress can affect mnemonic processes. In particular, stress before contextual fear conditioning induces a memory which exhibits resistance to being interfered with by Midazolam (MDZ) when applied after memory retrieval. Moreover, stress exposure strongly affects GABAergic transmission within the Basolateral Amygdala Complex (BLA), a brain structure critically involved in fear memory processing. The present study evaluated the involvement of GABAergic signaling within the BLA on the induction of resistance to memory reconsolidation interference. Results showed that MDZ administered intra-BLA before stress prevented the induction of resistance to the interfering effect of systemic administration of both MDZ and Propranolol on fear memory reconsolidation, when both applied after memory retrieval. The blockade of amygdala GABA-A receptors by the antagonist Bicuculline (BIC) before memory encoding induced resistance to interference by post-recall MDZ administration, similarly to that observed with stress exposure. Additionally, the systemic administration of d -cycloserine, a positive allosteric modulator of NMDA receptor, reverted the BIC-induced resistance to the MDZ interfering effect, in the same manner as that reported with stress-induced resistance. In summary, these results suggest that the GABAergic signaling in the BLA at the moment of memory encoding is determinant for the induction of fear memory resistance to the onset of the labilization/reconsolidation process. [ABSTRACT FROM AUTHOR]

Working memory (WM), the ability to hold information on-line to guide planned behavior, improves through adolescence in parallel with continued maturation of critical brain systems supporting cognitive control. Initial developmental neuroimaging studies with one or two timepoints have provided important though varied results limiting our understanding of which and how neural systems change during this transition into mature WM. In this study, we leverage functional magnetic resonance imaging (fMRI) longitudinal data spanning up to 9 years in 129 normally developing individuals to identify which systems demonstrate growth changes that accompany improvements in WM performance. We used a memory guided saccade task that allowed us to probe encoding, pure maintenance, and retrieval neural processes of WM. Consistent with prior research, we found that WM performance continued to improve into the early 20's. fMRI region of interest (ROI) analyses revealed developmental (1) increases in sensorimotor-related (encoding/retrieval) activity in visual cortex from childhood through early adulthood that were associated with WM accuracy and (2) decreases in sustained (maintenance) activity in executive regions from childhood through mid-adolescence that were associated with response latency in childhood and early adolescence. Together these results provide compelling evidence that underlying the maturation of WM is a transition from reliance on executive systems to specialized regions related to the domain of mnemonic requirements of the task leading to optimal performance. [ABSTRACT FROM AUTHOR]

Previous studies have shown that information held in visual working memory is represented in the occipital, parietal, and frontal cortices. However, less is known about whether the mnemonic information of multi-feature objects is modulated by task demand in the parietal and frontal regions. To address this question, we asked participants to remember either color or orientation of one of the two colored gratings for a delay. Using fMRI and an inverted encoding model, we reconstructed population-level, feature-selective responses in the occipital, parietal and frontal cortices during memory maintenance. We found that not only orientation but also color information can be maintained in higher-order parietal and frontal cortices as well as the early visual cortex when it was cued to be remembered. Conversely, neither the task-irrelevant feature of the cued object, nor any feature of the uncued object was maintained in the occipital, parietal, or frontal cortices. These results suggest a highly selective mechanism of visual working memory that maintains task-relevant features only. [ABSTRACT FROM AUTHOR]

Since the earliest attempts to characterize the “receptive fields” of neurons, a central aim of many neuroscience experiments is to elucidate the information that is represented in various regions of the brain. Recent studies suggest that, in the service of memory, information is represented in the medial temporal lobe in a conjunctive or associative form with the contextual aspects of the experience being the primary factor or highest level of the conjunctive hierarchy. A critical question is whether the information that has been observed in these studies reflects notions such as a cognitive representation of context or whether the information reflects the low-level sensory differences between stimuli. We performed two functional magnetic resonance imaging experiments to address this question and we found that associative representations observed between context and item (and order) in the human brain can be highly influenced by low-level sensory differences between stimuli. Our results place clear constraints on the experimental design of studies that aim to investigate the representation of contexts and items during performance of associative memory tasks. Moreover, our results raise interesting theoretical questions regarding the disambiguation of memory-related representations from processing-related representations. [ABSTRACT FROM AUTHOR]

We propose – and experimentally test – a mnemonic variant of password security that uses game positions as passwords. In Experiment 1, we report accuracy and reaction time data when high school student, younger adult, and older adult participants remembered and entered one game-based password, using chess or Monopoly. In Experiment 2, we report accuracy and reaction time data from participants' use of five game-based passwords across 24 sessions over 10 weeks. All five passwords were stored in chess or Monopoly for the initial 20 sessions, and changed (from chess to Monopoly or vice versa) for the remaining sessions. This new approach to password security is both mathematically robust and user-friendly. [ABSTRACT FROM AUTHOR]

Intense training refers to training mediated by emotionally arousing experiences, such as aversive conditioning motivated by relatively high intensities of foot-shock, which produces a strong memory that is highly resistant to extinction. Intense training protects memory consolidation against the amnestic effects of a wide variety of treatments, administered systemically or directly into brain structures. The mechanisms of this protective effect are unknown. To determine a potential neurobiological correlate of the protective effect of intense training, rats were trained in a one-trial step-through inhibitory avoidance task using different intensities of foot-shock (0.0, 0.5, 1.0, and 2.0 mA). Some rats from each group were sacrificed 45 min after training for immunohistochemical Arc protein detection in dorsal and ventral striatum; other rats were tested for extinction during six consecutive days, starting 48 h after training. The results showed that training with 1.0 and 2.0 mA produced optimal retention scores, which were significantly higher than those of the 0.5 and 0.0 mA groups. Also, a higher resistance to extinction was obtained with 2.0 mA than with the other intensities. A high number of neurons expressed Arc in ventral, but not in dorsal striatum in both the 1.0 and 2.0 mA groups, with a larger area of Arc signal in the latter group. We conclude that an increased Arc expression may be related to enhanced synaptic plasticity in the ventral striatum, suggesting that it may be one of the physiological substrates of enhanced learning. [ABSTRACT FROM AUTHOR]

Hunger is an everyday motivational state, which biases cognition to detect food. Although evidence exists on how hunger affects basic attentional and mnemonic processes, less is known about how motivational drive for food modulates higher cognition. We aimed to investigate the effects of food deprivation on proactive interference resolution, in the presence and absence of food. Normal-weight participants performed a recency probes paradigm providing an experimental block with food and object stimuli as well as a control block with object stimuli only, in a fasted and a sated state. Results showed that the interaction of shifts in nutritional state with the perception of food cues evoked an altered resolution of proactive interference. Satiety led to impaired performance, whereas a hungry state resulted in strengthened resistance to proactive interference and lying in between, the control block presenting neutral objects remained unaffected by nutritional state manipulation. Additionally, a further increase in proactive interference resolution occurred when the conflicting probe depicted food compared to non-food objects. We conclude that when exposed to food, hunger initiates biased competition of active memory representations in favor of prioritized source information at cost of familiar, but irrelevant information. The implications of these findings are discussed in terms of an arousal-biased competition in working memory. [ABSTRACT FROM AUTHOR]

• Fixations at encoding coincided with subsequent forced-choice recognition. • More fixations to target associated with accurate recognition when guesses removed. • More fixations to original version of lure associated with recognition error. • Fixations at encoding not related to mnemonic process used to guide recognition. The primary goal of the current study was to assess whether different retrieval processes moderated the effect of encoding variability on accurate performance on the A-B' test format of the forced-choice Mnemonic Similarity Task (MST). Young adults completed the A-B' test format of the forced-choice MST and determined whether their recognition memory judgment was based on recall-to-reject processing, recall-to-accept processing, familiarity, or guessing. When guesses were excluded from correct trials, fixation counts were higher to the A stimulus than the B stimulus at encoding. Contrary to our expectation that greater fixations to the A versus B stimulus at encoding would be associated with reliance on familiarity or recall-to-accept processing and greater fixations to the B versus A stimulus would be associated with recall-to-reject processing, no interaction between the stimulus and the subsequently reported memory process was observed. [ABSTRACT FROM AUTHOR]

• Cognitive skill learning (CSL) is improving cognitive efficiency through practice. • We hypothesize that high CSL aptitude predicts resiliency to cognitive decline. • Better CSL aptitude predicted better neuropsychological performance in MS. • Low CSL aptitude also significantly predicted cognitive impairment in MS. • CSL aptitude may also contribute to accumulation of cognitive reserve in MS. Cognitive skill learning (CSL) refers to the capacity to improve performance on specific cognitive operations through repeated practice. We hypothesized that high CSL aptitude may promote accumulation of cognitive reserve, and resiliency to cognitive decline, in people with Multiple Sclerosis (MS). Using an adaptive working memory training paradigm, we obtained CSL aptitude indices (amount of improvement on the training task over time) in MS patients for a single session of practice (25–30 min), and longer-term practice (twenty sessions). Neuropsychological performance was assessed with the Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and the Raven's Advanced Progressive Matrices (RAPM). CSL aptitude measures were positively correlated with neuropsychological performance, and had high diagnostic accuracy for classifying cognitive impairment in MS, defined as 1.5 SD below the demographics-corrected normative mean of the SDMT. Positive relationships between CSL aptitude measures and neuropsychological performance tended to be more pronounced for individuals with high estimated cognitive reserve, suggesting that high CSL aptitude is a a factor that promotes the protective effects of cognitive reserve. Furthermore, regression analyses indicated that CSL aptitude is separable from baseline cognitive capacity. The findings suggest that CSL aptitude impacts the neuropsychological profile in MS, and may be a factor underlying variance in cognitive resiliency. [ABSTRACT FROM AUTHOR]

• A Randomised Control Trial with 104 children found the first cognitive transfer effects from working memory to syntax but not vice versa. • In the case of children's first language, working memory training was as effective as language training in boosting syntactic performance. • It is proposed that transfer is mediated by cognitive mechanisms common to both working memory and syntax. • These data represent some of the strongest evidence to date that domain-general cognition is deeply integrated into developmental language processes. We tested several hypotheses about the relation between syntax and working memory (WM). In a pretest/posttest randomized control trial, 104 native Cuban Spanish-speaking children (M age = 7 years 2 months; 54 girls) took part in syntax training in their first language, syntax training in their second language, WM training, or no training (control). Compared with the control, children in the training conditions showed cognitive transfer from WM to syntax but not from syntax to WM. The result was most striking in the case of their first language, where WM training was as effective as language training in boosting syntactic performance. As well as establishing cognitive transfer at the group level, we also found that individual differences in WM performance, both at baseline and in training, predicted the extent to which children's syntax improved. The directionality of transfer, the group-level and individual-level results, established in the context of a randomized control design, all point to a strong causal role for domain-general cognition in the processes of language acquisition. [ABSTRACT FROM AUTHOR]

• Episodic memory integration is often impaired in stress-related mental disorders. • Stress reduced medial temporal activity related to insight into linked events. • Stress abolished insight-driven increase in hippocampal pattern dissimilarity. • Stress-related neural changes were linked to subsequent memory. Memories are not stored in isolation. Insight into the relationship of initially unrelated events may trigger a flexible reconfiguration of the mnemonic representation of these events. Such representational changes allow the integration of events into coherent episodes and help to build up-to-date-models of the world around us. This process is, however, frequently impaired in stress-related mental disorders resulting in symptoms such as fragmented memories in PTSD. Here, we combined a real life-like narrative-insight task, in which participants learned how initially separate events are linked, with fMRI-based representational similarity analysis to test if and how acute stress interferes with the insight-driven reconfiguration of memories. Our results showed that stress reduced the activity of medial temporal and prefrontal areas when participants gained insight into the link between events. Moreover, stress abolished the insight-related increase in representational dissimilarity for linked events in the anterior part of the hippocampus as well as its association with measures of subsequent memory that we observed in non-stressed controls. However, memory performance, as assessed in a forced-choice recognition test, was even enhanced in the stress group. Our findings suggest that acute stress impedes the neural integration of events into coherent episodes but promotes long-term memory for these integrated narratives and may thus have implications for understanding memory distortions in stress-related mental disorders. [ABSTRACT FROM AUTHOR]

• We tested the influences of temporal variability on alpha oscillations. • Small or large variability in the delay durations was manipulated. • Alpha power during retention varied with duration variability. • Alpha power decreased over the left frontoparietal regions for small variability. • We found a positive relationship between the response times and alpha attenuation. While maintaining information over a delay of time, working memory (WM) also allows individuals to prepare the mnemonic contents for prospective utilisation. However, it remains unclear whether the expectation of the time of WM test could modulate neural responses during the retention interval of WM and subsequent performance. Here, we investigated whether temporal expectations based on the variability of delay duration can modulate 9–13 Hz alpha oscillations during WM retention and whether the expectation-induced alpha activity was associated with WM performance. Participants performed a retro-cueing WM task with magnetoencephalography (MEG) (Experiment 1) and a standard WM task with electroencephalography (EEG) (Experiment 2). The expectation of the timing of the WM test was manipulated by the temporal structure of the tasks with small or large variability in the delay durations. We showed that alpha oscillations during retention interval and WM performance varied with duration variability in both of the MEG and EEG experiments. The novel finding was greater alpha-power attenuation over the left frontal and parietal regions during WM retention when the duration variability was small and the test onset was predictable, compared to when the duration variability was large and the test onset was less predictable. Importantly, we observed a positive relationship in variability difference between the response benefit and alpha-power attenuation in the left posterior parietal regions at both MEG-source and EEG-electrode levels. Finally, we confirmed the behavioural benefit when a condition with a fixed delay-duration was included in a behavioural experiment (Experiment 3). When conjoined, the delay duration enables individuals to anticipate when the relevant information would be put to work, and alpha oscillations track the anticipatory states during WM maintenance. [ABSTRACT FROM AUTHOR]

• Contextual information can be decoded from non-stimulated areas of the early visual cortex even in the absence of line continuations. • Mnemonic content co-exists with contextual information in the early visual cortex. • Mnemonic content is a constituent part of feedback signals in V1 and V2 when it is accessed episodically but not semantically. Efficient processing of the visual environment necessitates the integration of incoming sensory evidence with concurrent contextual inputs and mnemonic content from our past experiences. To examine how this integration takes place in the brain, we isolated different types of feedback signals from the neural patterns of non-stimulated areas of the early visual cortex in humans (i.e., V1 and V2). Using multivariate pattern analysis, we showed that both contextual and time-distant information, coexist in V1 and V2 as feedback signals. In addition, we found that the extent to which mnemonic information is reinstated in V1 and V2 depends on whether the information is retrieved episodically or semantically. Critically, this reinstatement was independent on the retrieval route in the object-selective cortex. These results demonstrate that our early visual processing contains not just direct and indirect information from the visual surrounding, but also memory-based predictions. [ABSTRACT FROM AUTHOR]

The reconsolidation process is the mechanism by which strength and/or content of consolidated memories are updated. Prediction error (PE) is the difference between the prediction made and current events. It is proposed as a necessary condition to trigger the reconsolidation process. Here we analyzed deeply the role of the PE in the associative memory reconsolidation in the crab Neohelice granulata . An incongruence between the learned temporal relationship between conditioned and unconditioned stimuli (CS-US) was enough to trigger the reconsolidation process. Moreover, after a partial reinforced training, a PE of 50% opened the possibility to labilize the consolidated memory with a reminder which included or not the US. Further, during an extinction training a small PE in the first interval between CSs was enough to trigger reconsolidation. Overall, we highlighted the relation between training history and different reactivation possibilities to recruit the process responsible of memory updating. [ABSTRACT FROM AUTHOR]

Spermine and spermidine are natural polyamines that are produced mainly via decarboxylation of l -ornithine and the sequential transfer of aminopropyl groups from S -adenosylmethionine to putrescine by spermidine synthase and spermine synthase. Spermine and spermidine interact with intracellular and extracellular acidic residues of different nature, including nucleic acids, phospholipids, acidic proteins, carboxyl- and sulfate-containing polysaccharides. Therefore, multiple actions have been suggested for these polycations, including modulation of the activity of ionic channels, protein synthesis, protein kinases, and cell proliferation/death, within others. In this review we summarize these neurochemical/neurophysiological/morphological findings, particularly those that have been implicated in the improving and deleterious effects of spermine and spermidine on learning and memory of naïve animals in shock-motivated and nonshock-motivated tasks, from a historical perspective. The interaction with the opioid system, the facilitation and disruption of morphine-induced reward and the effect of polyamines and putative polyamine antagonists on animal models of cognitive diseases, such as Alzheimer’s, Huntington, acute neuroinflammation and brain trauma are also reviewed and discussed. The increased production of polyamines in Alzheimer’s disease and the biphasic nature of the effects of polyamines on memory and on the NMDA receptor are also considered. In light of the current literature on polyamines, which include the description of an inborn error of the metabolism characterized by mild-to moderate mental retardation and polyamine metabolism alterations in suicide completers, we can anticipate that polyamine targets may be important for the development of novel strategies and approaches for understanding the etiopathogenesis of important central disorders and their pharmacological treatment. [ABSTRACT FROM AUTHOR]

Translational assays of cognition that are similarly implemented in both lower and higher-order species, such as rodents and primates, provide a means to reconcile preclinical modeling of psychiatric neuropathology and clinical research. To this end, Pavlovian conditioning has provided a useful tool for investigating cognitive processes in both lab animal models and humans. This review focuses on trace conditioning, a form of Pavlovian conditioning typified by the insertion of a temporal gap (i.e., trace interval) between presentations of a conditioned stimulus (CS) and an unconditioned stimulus (US). This review aims to discuss pre-clinical and clinical work investigating the mnemonic processes recruited for trace conditioning. Much work suggests that trace conditioning involves unique neurocognitive mechanisms to facilitate formation of trace memories in contrast to standard Pavlovian conditioning. For example, the hippocampus and prefrontal cortex (PFC) appear to play critical roles in trace conditioning. Moreover, cognitive mechanistic accounts in human studies suggest that working memory and declarative memory processes are engaged to facilitate formation of trace memories. The aim of this review is to integrate cognitive and neurobiological accounts of trace conditioning from preclinical and clinical studies to examine involvement of working and declarative memory. [ABSTRACT FROM AUTHOR]

The anterior and lateral thalamus has long been considered to play an important role in spatial and mnemonic cognitive functions; however, it remains unclear whether each region makes a unique contribution to spatial information processing. We begin by reviewing evidence from anatomical studies and electrophysiological recordings which suggest that at least one of the functions of the anterior thalamus is to guide spatial orientation in relation to a global or distal spatial framework, while the lateral thalamus serves to guide behavior in relation to a local or proximal framework. We conclude by reviewing experimental work using targeted manipulations (lesion or neuronal silencing) of thalamic nuclei during spatial behavior and single-unit recordings from neuronal representations of space. Our summary of this literature suggests that although the evidence strongly supports a working model of spatial information processing involving the anterior thalamus, research regarding the role of the lateral thalamus is limited and requires further attention. We therefore identify a number of major gaps in this research and suggest avenues of future study that could potentially solidify our understanding of the relative roles of anterior and lateral thalamic regions in spatial representation and memory. [ABSTRACT FROM AUTHOR]

Novel activities and experiences shape the brain's structure and organisation and, hence, our behaviour. However, evidence from structural plasticity studies remains mixed and the neural correlates of learning and practice are still poorly understood. We conducted a robustly designed study into grey matter plasticity following 2 months of working memory training. We generated a priori hypotheses regarding the location of plastic effects across three cognitive control networks (executive, anterior salience and basal ganglia networks), and compared the effects of adaptive training ( n = 20) with a well-matched active control group ( n = 20) which differed in training complexity and included extensive cognitive assessment before and after the training. Adaptive training relative to control activities resulted in a complex pattern of subtle and localised structural changes: Training was associated with increases in cortical thickness in right-lateralised executive regions, notably the right caudal middle frontal cortex, as well as increases in the volume of the left pallidum. In addition the training group showed reductions of thickness in the right insula, which were correlated with training-induced improvements in backward digit span performance. Unexpectedly, control activities were associated with reductions in thickness in the right pars triangularis . These results suggest that the direction of activity-induced plastic changes depend on the level of training complexity as well as brain location. These observations are consistent with the view that the brain responds dynamically to environmental demands by focusing resources on task relevant networks and eliminating irrelevant processing for the purpose of energy reduction. [ABSTRACT FROM AUTHOR]

Whether the capacity of visual working memory is better characterized by an item-based or a resource-based account continues to be keenly debated. Here, we propose that visual working memory is a flexible resource that is sometimes deployed in a slot-like manner. We develop a computational model that can either encode all items in a memory set, or encode only a subset of those items. A fixed-capacity mnemonic resource is divided among the items in memory. When fewer items are encoded, they are each remembered with higher fidelity, but at the cost of having to rely on an explicit guessing process when probed about an item that is not in memory. We use the new model to test the prediction that participants will more often encode the entire set of items when the demands on memory are predictable. [ABSTRACT FROM AUTHOR]

Classic computational theories of the mnemonic functions of the hippocampus ascribe the processes of pattern separation to the dentate gyrus (DG) and pattern completion to the CA3 region. Until the last decade, the large majority of single-unit studies of the hippocampus in behaving animals were from the CA1 region. The lack of data from the DG, CA3, and the entorhinal inputs to the hippocampus severely hampered the ability to test these theories with neurophysiological techniques. The past ten years have seen a major increase in the recordings from the CA3 region and the medial entorhinal cortex (MEC), with an increasing (but still limited) number of experiments from the lateral entorhinal cortex (LEC) and DG. This paper reviews a series of studies in a local–global cue mismatch (double-rotation) experiment in which recordings were made from cells in the anterior thalamus, MEC, LEC, DG, CA3, and CA1 regions. Compared to the standard cue environment, the change in the DG representation of the cue-mismatch environment was greater than the changes in its entorhinal inputs, providing support for the theory of pattern separation in the DG. In contrast, the change in the CA3 representation of the cue-mismatch environment was less than the changes in its entorhinal and DG inputs, providing support for a pattern completion/error correction function of CA3. The results are interpreted in terms of continuous attractor network models of the hippocampus and the relationship of these models to pattern separation and pattern completion theories. Whereas DG may perform an automatic pattern separation function, the attractor dynamics of CA3 allow it to perform a pattern separation or pattern completion function, depending on the nature of its inputs and the relative strength of the internal attractor dynamics. [ABSTRACT FROM AUTHOR]

Pattern separation describes the orthogonalization of similar inputs into unique, non-overlapping representations. This computational process is thought to serve memory by reducing interference and to be mediated by the dentate gyrus of the hippocampus. Using ultra-high in-plane resolution diffusion tensor imaging (hrDTI) in older adults, we previously demonstrated that integrity of the perforant path, which provides input to the dentate gyrus from entorhinal cortex, was associated with mnemonic discrimination, a behavioral outcome designed to load on pattern separation. The current hrDTI study assessed the specificity of this perforant path integrity–mnemonic discrimination relationship relative to other cognitive constructs (identified using a factor analysis) and white matter tracts (hippocampal cingulum, fornix, corpus callosum) in 112 healthy adults (20–87 years). Results revealed age-related declines in integrity of the perforant path and other medial temporal lobe (MTL) tracts (hippocampal cingulum, fornix). Controlling for global effects of brain aging, perforant path integrity related only to the factor that captured mnemonic discrimination performance. Comparable integrity–mnemonic discrimination relationships were also observed for the hippocampal cingulum and fornix. Thus, whereas perforant path integrity specifically relates to mnemonic discrimination, mnemonic discrimination may be mediated by a broader MTL network. [ABSTRACT FROM AUTHOR]

The hippocampal memory system is thought to alternate between two opposing processing states: encoding and retrieval. When present experience overlaps with past experience, this creates a potential tradeoff between encoding the present and retrieving the past. This tradeoff may be resolved by memory integration —that is, by forming a mnemonic representation that links present experience with overlapping past experience. Here, we used fMRI decoding analyses to predict when – and establish how – past and present experiences become integrated in memory. In an initial experiment, we alternately instructed subjects to adopt encoding, retrieval or integration states during overlapping learning. We then trained across-subject pattern classifiers to ‘read out’ the instructed processing states from fMRI activity patterns. We show that an integration state was clearly dissociable from encoding or retrieval states. Moreover, trial-by-trial fluctuations in decoded evidence for an integration state during learning reliably predicted behavioral expressions of successful memory integration. Strikingly, the decoding algorithm also successfully predicted specific instances of spontaneous memory integration in an entirely independent sample of subjects for whom processing state instructions were not administered. Finally, we show that medial prefrontal cortex and hippocampus differentially contribute to encoding, retrieval, and integration states: whereas hippocampus signals the tradeoff between encoding vs. retrieval states, medial prefrontal cortex actively represents past experience in relation to new learning. [ABSTRACT FROM AUTHOR]

• Active navigational decision-making is contrasted with passive following. • Increased theta power in midfrontal channels during active vs. passive exploration. • Speed and movement were equated, controlling for that potential factor. • Results suggest theta is involved with exploration and memory processes. • Potential reinforcement learning mechanisms are involved in active learning. Active navigation seems to yield better spatial knowledge than passive navigation, but it is unclear how active decision-making influences learning and memory. Here, we examined the contributions of theta oscillations to memory-related exploration while testing theories about how they contribute to active learning. Using electroencephalography (EEG), we tested individuals on a maze-learning task in which they made discrete decisions about where to explore at each choice point in the maze. Half the participants were free to make active decisions at each choice point, and the other half passively explored by selecting a marked choice (matched to active exploration) at each intersection. Critically, all decisions were made when stationary, decoupling the active decision-making process from movement and speed factors, which is another prominent potential role for theta oscillations. Participants were then tested on their knowledge of the maze by traveling from object A to object B within the maze. Results show an advantage for active decision-making during learning and indicate that the active group had greater theta power during choice points in exploration, particularly in midfrontal channels. These findings demonstrate that active exploration is associated with theta oscillations during human spatial navigation, and that these oscillations are not exclusively related to movement or speed. Results demonstrating increased theta oscillations in prefrontal regions suggest communication with the hippocampus and integration of new information into memory. We also found evidence for alpha oscillations during active navigation, suggesting a role for attention as well. This study finds support for a general mnemonic role for theta oscillations during navigational learning. [ABSTRACT FROM AUTHOR]

[Display omitted] • Inhibition of hippocampal mRNA synthesis 6 h post-training hinders LTM consolidation. • Inhibition of hippocampal mRNA synthesis 6 h post-test hinders LTM reconsolidation. • The effect of mRNA synthesis blockade on LTM reconsolidation is structure dependent. It has already been shown that both consolidation and reconsolidation of long-term memories require protein synthesis and de novo gene transcription immediately after training or mnemonic trace reactivation sessions. A few studies have also shown that consolidation of long-term memories also requires a late second wave of de novo gene transcription. Does such a requirement also occur for reconsolidation? By using two different mRNA synthesis inhibitors, we show that blockade of hippocampal late gene expression during a restricted post-training or postretrieval time window hinders the retention of long-term spatial memory for the Morris water maze task without affecting the functionality of the hippocampus. Our results indicate that spatial memory consolidation induces the activation of the late hippocampal genes transcriptional machinery and suggests a late gene expression-dependent reconsolidation process that operates in the dorsal hippocampus to stabilize the reactivated mnemonic trace. [ABSTRACT FROM AUTHOR]

We introduce a deep recursive octree network for general-purpose 3D voxel data processing. Our network compresses a voxel grid of any size down to a very small latent space in an autoencoder-like network. We show results for compressing 3 2 3 , 6 4 3 and 12 8 3 grids down to just 80 floats in the latent space. We demonstrate the effectiveness and efficiency of our proposed method on several publicly available datasets with four experiments: 3D shape classification, 3D shape reconstruction, shape generation and semantic segmentation. Experimental results show that our algorithm maintains accuracy while consuming less memory with shorter training times compared to existing methods, especially in 3D reconstruction tasks. [Display omitted] • This is the first method to explore the combination of volumetric octree and recursive networks. • Proven effectiveness on 3D shape classification, reconstruction, generation and segmentation. • Near state-of-the-art recognition on ModelNet40. • State-of-the-art computational and memory consumption efficiency. • State-of-the-art reconstruction accuracy on ShapeNet-Corev2 database. [ABSTRACT FROM AUTHOR]