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Background Individualized and reliable biomarkers are crucial for diagnosing Alzheimer’s disease (AD). However, lack of accessibility and neurobiological correlation are the main obstacles to their clinical application. Machine learning algorithms can effectively identify personalized biomarkers based on the prominent symptoms of AD. Methods Episodic memory–related magnetic resonance imaging (MRI) features of 143 patients with amnesic mild cognitive impairment (MCI) were identified using a multivariate relevance vector regression algorithm. The support vector machine classification model was constructed using these MRI features and verified in 2 independent datasets (N = 994). The neurobiological basis was also investigated based on cognitive assessments, neuropathologic biomarkers of cerebrospinal fluid, and positron emission tomography images of amyloid-β plaques. Results The combination of gray matter volume and amplitude of low-frequency fluctuation MRI features accurately predicted episodic memory impairment in individual patients with amnesic MCI (r = .638) when measured using an episodic memory assessment panel. The MRI features that contributed to episodic memory prediction were primarily distributed across the default mode network and limbic network. The classification model based on these features distinguished patients with AD from normal control subjects with more than 86% accuracy. Furthermore, most identified episodic memory–related regions showed significantly different amyloid-β positron emission tomography measurements among the AD, MCI, and normal control groups. Moreover, the classification outputs significantly correlated with cognitive assessment scores and cerebrospinal fluid pathological biomarkers' levels in the MCI and AD groups. Conclusions Neuroimaging features can reflect individual episodic memory function and serve as potential diagnostic biomarkers of AD.

Background Deficits in relational episodic memory encoding are characteristic of schizophrenia (SZ), but whole-brain multivariate analyses of these deficits have been lacking. Open science has provided task-based functional magnetic resonance imaging (fMRI) data investigating paired associate encoding in SZ, but it has not yet been mobilized to address this gap in the literature. Therefore, in this study, we use previously unpublished task fMRI data to conduct the first network-level investigation of impaired relational episodic encoding in SZ. Methods Using fMRI data acquired from 40 healthy control participants and 40 age- and sex-matched persons with SZ, we examined the networks involved in successful versus unsuccessful encoding of verbal paired associates using an associative semantic strategy. Results Constrained principal component analysis for fMRI revealed 3 distinct functional networks recruited during encoding: a responding network, a linguistic processing/attention network, and the default mode network. Relative to the healthy control group, the SZ group exhibited aberrant activity in all 3 networks during successful encoding; namely, hypoactivation in the linguistic processing/attention network, lower peak activation in the responding network, and weaker suppression in the default mode network. Independent of group effects, a pattern of stronger anticorrelating linguistic processing/attention–default mode network activity during successful encoding significantly predicted subsequent retrieval of paired associates. Conclusions Together with previous observations of language network hypoactivation during controlled semantic processes, these results suggest that abnormalities in networks representing language and meaning may contribute to difficulties employing deep semantic strategies during relational episodic encoding in SZ.

BackgroundWhile neuroimaging has provided insights into the formation of episodic memories in relation to voluntary memory recall, less is known about neural mechanisms that cause memories to occur involuntarily, for example, as intrusive memories of trauma. Here, we investigated brain activity shortly after viewing distressing events as a function of whether memories for those events later intruded involuntarily. The postencoding period is particularly important because it is a period when clinical interventions could be applied.MethodsA total of 32 healthy volunteers underwent functional magnetic resonance imaging while viewing distressing film clips, interspersed with 5 minutes of awake (postencoding) rest. Voluntary memories of the films were assessed using free recall and verbal and visual recognition tests after a week, while intrusive (involuntary) memories were recorded in a diary throughout that week.ResultsWhen analyzing functional magnetic resonance imaging responses related to watching the films, we replicated findings that those “hotspots” (salient moments within the films) that would later become intrusive memories elicited higher activation in parts of the brain’s salience network. Surprisingly, while the postencoding persistence of multivoxel correlation structures associated with entire film clips predicted subsequent voluntary recall, there was no evidence that they predicted subsequent intrusions.ConclusionsResults replicate findings regarding the formation of intrusive memories during encoding and extend findings regarding the consolidation of information in postencoding rest in relation to voluntary memory. While we provided a first step using a naturalistic paradigm, further research is needed to elucidate the role of postencoding neural processes in the development of intrusive memories.

Resting-state network research is extremely influential, yet the functions of many networks remain unknown. In part, this is due to typical (e.g., univariate) analyses testing the function of individual regions and not the full set of co-activated regions that form a network. Connectivity is dynamic and the function of a region may change based on its current connections. Therefore, determining the function of a network requires assessment at the network-level. Yet popular theories implicating the default mode network (DMN) in episodic memory and social cognition, rest principally upon analyses performed at the level of individual brain regions. Here we use independent component analysis to formally test the role of the DMN in episodic and social processing at the network level. As well as an episodic retrieval task, two independent datasets were employed to assess DMN function across the breadth of social cognition; a person knowledge judgement and a theory of mind task. Each task dataset was separated into networks of co-activated regions. In each, the co-activated DMN, was identified through comparison to an a priori template and its relation to the task model assessed. This co-activated DMN did not show greater activity in episodic or social tasks than high-level baseline conditions. Thus, no evidence was found to support hypotheses that the co-activated DMN is involved in explicit episodic or social processing tasks at a network-level. The networks associated with these processes are described. Implications for prior univariate findings and the functional significance of the co-activated DMN are considered.

Decreased fidelity of mnemonic representations plays a critical role in age-related episodic memory deficits, yet the brain mechanisms underlying such reductions remain unclear. Using functional and structural neuroimaging, we examined how changes in two key nodes of the posterior-medial network, the hippocampus and the angular gyrus (AG), might underpin loss of memory precision in older age. Healthy young and older adults completed a memory task that involved reconstructing object features on a continuous scale. Investigation of blood-oxygen-level-dependent (BOLD) activity during retrieval revealed an age-related reduction in activity reflecting successful recovery of object features in the hippocampus, whereas trial-wise modulation of BOLD signal by graded memory precision was diminished in the AG. Gray matter volume of the AG further predicted individual differences in memory precision in older age, beyond likelihood of successful retrieval. These findings provide converging evidence for a role of functional and structural integrity of the AG in constraining the fidelity of episodic remembering in older age, yielding new insights into parietal contributions to age-related episodic memory decline.

Episodic memory is supported by hippocampal interactions with a distributed network. Aging is associated with memory decline and network de-differentiation. However, the role of de-differentiation in memory decline has not been directly tested. We reasoned that hippocampal network-targeted stimulation could test these theories, as age-related changes in the network response to stimulation would indicate network reorganization, and corresponding changes in memory would suggest that this reorganization is functional. We compared effects of stimulation on fMRI connectivity and memory in younger versus older adults. Theta-burst network-targeted stimulation of left lateral parietal cortex selectively increased hippocampal network connectivity and modulated memory in younger adults. In contrast, stimulation in older adults increased connectivity throughout the brain, without network selectivity, and did not influence memory. These findings provide evidence that network responses to stimulation are de-differentiated in aging and suggest that age-related de-differentiation is relevant for memory. This manuscript is part of the Special Issue entitled "Cognitive Neuroscience of Healthy and Pathological Aging" edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.

This paper reviews evidence demonstrating a bidirectional relationship between memory and eating in humans and rodents. In humans, amnesia is associated with impaired processing of hunger and satiety cues, disrupted memory of recent meals, and overconsumption. In healthy participants, meal-related memory limits subsequent ingestive behavior and obesity is associated with impaired memory and disturbances in the hippocampus. Evidence from rodents suggests that dorsal hippocampal neural activity contributes to the ability of meal-related memory to control future intake, that endocrine and neuropeptide systems act in the ventral hippocampus to provide cues regarding energy status and regulate learned aspects of eating, and that consumption of hypercaloric diets and obesity disrupt these processes. Collectively, this evidence indicates that diet-induced obesity may be caused and/or maintained, at least in part, by a vicious cycle wherein excess intake disrupts hippocampal functioning, which further increases intake. This perspective may advance our understanding of how the brain controls eating, the neural mechanisms that contribute to eating-related disorders, and identify how to treat diet-induced obesity.

Importance Cognitive and visual impairments in Parkinson’s Disease Psychosis (PDP) raise the question of whether a specific profile of impaired cognition and visual function is linked to vulnerability to visual hallucinations (VHs). Previous studies have limited sample sizes and only included a sub-sample of tests. This is the first meta-analysis quantifying visuo-cognitive impairments in PDP patients across a spectrum of tests and taking into account potential confounding factors such as levodopa medication, illness duration and general cognitive ability. Objective Compare visual processing and cognitive performance between PD patients with and without VHs (PDVH and PDnoVH). Methods Four databases (PubMed, PsychINFO, Scopus, WebOfScience) were searched for studies on visual and/or cognitive performance of PDnoVH and PDVH published up to 02/2020. For each task, means and SDs were extracted and standardized-mean-differences (SMDs) between-groups calculated. Effect-sizes (Hedges’ g) were calculated for all comparisons and synthesized in random-effects meta-analyses with robust-variance-estimation (accounting for multiple correlated measures within each study per cognitive/visual domain). Publication bias was assessed with funnel plots and Egger intercept. Results N=99 studies including 2508 PDVH patients (mean age 68.4 years) and 5318 PDnoVH (mean age 66.4 years) were included in the seven meta-analyses. PDVH patients performed worse than PDnoVH across all measures of cognition and visual processing, with the greatest between-group effect-sizes in executive functions, attention, episodic memory and visual processing. Study characteristics were not significantly associated with between-group differences in the domains investigated. Age-differences were significantly associated with performance differences in general cognition, working memory and executive functions. Conclusion Models of PDVH need to incorporate a wider range of cognitive and processing domains than currently included. There is a need for studies disentangling the temporal relationship between cognitive/visual deficits and VHs as early identification of risk before the onset of VHs could mitigate later outcomes such as progression to dementia.

Background To examine the association of job strain with cognitive ability and the influence of life-course job strain on later life cognitive decline. Methods Data were derived from six waves of the Survey of Health, Aging, and Retirement in Europe. The study sample consists of 13349 participants aged 50 to 98 years at wave 2 and has been followed up for 12-years. Job strain status across working life was assessed using a short demand-control job strain model containing two core dimensions: job demands and job control collected in wave 3. Cognitive abilities concerning episodic memory was assessed by immediate recall and delayed recall tests, executive function was evaluated by verbal fluency test collected in all waves (waves 2–7) except wave 3. Mixed-effects model was used to estimate working life job strain and its cumulative effect on cognitive decline. Results Both passive and high strain jobs were associated with lower levels of cognitive ability (episodic memory and verbal fluency) in comparison with active job. Long exposure to active- or low strain-job was associated with higher cognitive ability whereas long exposure to passive job or moderate duration of high strain job was associated with lower cognitive ability. The rate of memory decline was positively related to moderate duration of passive job and negatively related to long-term exposure to low strain job. Limitations Information on working conditions was based on self-reported recollections. Conclusions Working life variation in job strain status and their duration may explain individual differences in cognitive ability in later life.

The number of people with dementia worldwide is estimated at 50 million by 2018 and continues to rise mainly due to increasing aging and population growth. Clinical impact of current interventions remains modest and all efforts aimed at the identification of new therapeutic approaches are therefore critical. Previously, we showed that JM-20, a dihydropyridine-benzodiazepine hybrid molecule, protected memory processes against scopolamine-induced cholinergic dysfunction. In order to gain further insight into the therapeutic potential of JM-20 on cognitive decline and Alzheimer's disease (AD) pathology, here we evaluated its neuroprotective effects after chronic aluminum chloride (AlCl3) administration to rats and assessed possible alterations in several types of episodic memory and associated pathological mechanisms. Oral administration of aluminum to rodents recapitulates several neuropathological alterations and cognitive impairment, being considered a convenient tool for testing the efficacy of new therapies for dementia. We used behavioral tasks to test spatial, emotional- associative and novel object recognition memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study revealed that JM-20 prevented memory decline alongside the inhibition of AlCl3 -induced oxidative stress, increased AChE activity, TNF-α and pro-apoptotic proteins (like Bax, caspase-3, and 8) levels. JM-20 also protected against neuronal damage in the hippocampus and prefrontal cortex. Our findings expanded our understanding of the ability of JM-20 to preserve memory in rats under neurotoxic conditions and confirm its potential capacity to counteract cognitive impairment and etiological factors of AD by breaking the progression of key steps associated with neurodegeneration.

Background People with schizophrenia (SZ) exhibit impaired episodic memory when relating objects to each other in time and space. Empirical studies and computational models suggest that low-frequency neural oscillations may be a mechanism by which the brain keeps track of temporal relationships during encoding and retrieval, with modulation of oscillatory power as sequences are learned. It is unclear whether sequence memory deficits in SZ are associated with altered neural oscillations. Methods Using electroencephalography, this study examined neural oscillations in 51 healthy control subjects and 37 people with SZ during a temporal sequence learning task. Multiple 5-object picture sequences were presented across 4 study-test blocks in either fixed or random order. Participants answered semantic questions for each object (e.g., living/nonliving), and sequence memory was operationalized as faster responses for fixed versus random sequences. Differences in oscillatory power between fixed versus random sequences provided a neural index of temporal sequence memory. Results Although both groups showed reaction time differences in late blocks (blocks 3 and 4), this evidence of sequence memory was reduced in people with SZ relative to healthy control subjects. Decreases in globally distributed prestimulus alpha (8–12 Hz) and beta 1 (13–20 Hz) power for fixed versus random sequences in late blocks were also attenuated in people with SZ relative to healthy control subjects. Moreover, changes in oscillatory power predicted individual reaction time differences and fully mediated the relationship between group and sequence memory. Conclusions Disrupted modulation of alpha and beta 1 electroencephalography oscillations is a candidate mechanism of temporal sequence memory deficits in people with SZ.

The deep layers of the entorhinal cortex are important for spatial cognition, as well as memory storage, consolidation and retrieval. A long-standing hypothesis is that deep-layer neurons relay spatial and memory-related signals between the hippocampus and telencephalon. We review the implications of recent circuit-level analyses that suggest more complex roles. The organization of deep entorhinal layers is consistent with multi-stage processing by specialized cell populations; in this framework, hippocampal, neocortical, and subcortical inputs are integrated to generate representations for use by targets in the telencephalon and for feedback to the superficial entorhinal cortex and hippocampus. Addressing individual sublayers of the deep entorhinal cortex in future experiments and models will be important for establishing systems-level mechanisms for spatial cognition and episodic memory.

To improve the cognitive ability of the mobile robot in an unknown environment, this paper proposes an episodic memory based self-organizing learning (EM-SOL) framework for robotic experiences learning, cognitive map building and navigation. This EM-SOL framework uses the spatial cells in the hippocampus and entorhinal cortex to path integrate the robotic kinesthetic cues for dead reckoning, and meanwhile extracts the visual cues to activate state neurons for state recognition. By updating the state neurons network, this framework constructs the robotic episodic memory to store these particular experiences created along the exploration process, and achieves the robotic self-organizing learning. The framework based map building method can optimize the cumulative error by introducing the spatial cells phase reset mechanism, and build an episodic-cognitive map that describes not only the topology relationship but also the cognition relationship between these particular experiences in the environment. Furthermore, a combined topological and metric vector navigation method is presented, which can locate the robot relative to its previous experiences in the memory space, anticipate a preferred global path to the target, and guide the mobile robot to navigate to the target accurately. Finally, the proposed EM-SOL framework based methods are evaluated in both the physical environments and the standard KITTI dataset. The results show that the mobile robot can keep on learning to adapt to the changes in an unknown environment, construct valid episodic memory to store these particular learned experiences, build an episodic-cognitive map and execute the target navigation task with high efficiency and accuracy.

We assessed sex differences in amyloid- and tau-PET retention in 119 amyloid positive patients with mild cognitive impairment or Alzheimer’s disease (AD) dementia. Patients underwent 3T-MRI, (11)C-PIB amyloid-PET and (18)F-Flortaucipir tau-PET. Linear ordinary least squares regression models tested sex differences in Flortaucipir-PET SUVR in a summary temporal region of interest as well as global PIB-PET. No sex differences were observed in demographics, Clinical Dementia Rating Sum of Boxes (CDR-SoB), Mini-Mental State Exam (MMSE), raw episodic memory scores, or cortical thickness. Females had higher global PIB SUVR (η(p)(2)=.043, p=.025) and temporal Flortaucipir SUVR (η(p)(2)=.070, p=.004), adjusting for age and CDR-SoB. Sex differences in temporal Flortaucipir-PET remained significant when controlling additionally for PIB SUVR and APOE4 status (η(p)(2)=.055, p=.013), or when using partial volume-corrected data. No sex differences were present in areas of known Flortaucipir off-target binding. Overall, females demonstrated greater AD regional tau-PET burden than males despite clinical comparability. Further characterization of sex differences will provide insight into AD pathogenesis and support development of personalized therapeutic strategies.

Background Supplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations. Objective The objective of this study was to investigate the effects of citicoline (Cognizin®), on memory in healthy elderly populations with age-associated memory impairment (AAMI). Methods A total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons. Results A total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052). Conclusions Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging. This trial was registered at clinicaltrials.gov as NCT03369925.

Better sleep quality has been associated with better episodic memory performance in young adults. However, the strength of sleep-memory associations in aging has not been well characterized. It is also unknown whether factors such as sleep measurement method (e.g., polysomnography, actigraphy, self-report), sleep parameters (e.g., slow wave sleep, sleep duration), or memory task characteristics (e.g., verbal, pictorial) impact the strength of sleep-memory associations. Here, we assessed if the aforementioned factors modulate sleep-memory relationships. Across age groups, sleep-memory associations were similar for sleep measurement methods, however, associations were stronger for PSG than self-report. Age group moderated sleep-memory associations for certain sleep parameters. Specifically, young adults demonstrated stronger positive sleep-memory associations for slow wave sleep than the old, while older adults demonstrated stronger negative associations between greater wake after sleep onset and poorer memory performance than the young. Collectively, these data show that young and older adults maintain similar strength in sleep-memory relationships, but age impacts the specific sleep correlates that contribute to these relationships.

In this review, we focus on the potential role of the γ-aminobutyric acidergic (GABAergic) system in age-related episodic memory impairments in humans, with a particular focus on Alzheimer's disease (AD). Well-established animal models have shown that GABA plays a central role in regulating and synchronizing neuronal signaling in the hippocampus, a brain area critical for episodic memory that undergoes early and significant morphologic and functional changes in the course of AD. Neuroimaging research in humans has documented hyperactivity in the hippocampus and losses of resting state functional connectivity in the Default Mode Network, a network that itself prominently includes the hippocampus-presaging episodic memory decline in individuals at-risk for AD. Apolipoprotein ε4, the highest genetic risk factor for AD, is associated with GABAergic dysfunction in animal models, and episodic memory impairments in humans. In combination, these findings suggest that GABA may be the linchpin in a complex system of factors that eventually leads to the principal clinical hallmark of AD: episodic memory loss. Here, we will review the current state of literature supporting this hypothesis. First, we will focus on the molecular and cellular basis of the GABAergic system and its role in memory and cognition. Next, we report the evidence of GABA dysregulations in AD and normal aging, both in animal models and human studies. Finally, we outline a model of GABAergic dysfunction based on the results of functional neuroimaging studies in humans, which have shown hippocampal hyperactivity to episodic memory tasks concurrent with and even preceding AD diagnosis, along with factors that may modulate this association.

Late-onset Alzheimer's disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether sex influences episodic memory-related brain function in cognitively intact older adults at risk of developing AD. Here we used task-based multivariate partial least squares analysis to examine sex differences in episodic memory-related brain activity and brain activity-behavior correlations in a matched sample of cognitively intact older women and men with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (Mage=63.03±3.78; Meducation=15.41±3.40). We observed sex differences in task-related brain activity and brain activity-behavior correlations during the encoding of object-location associative memories and object-only item memory, and the retrieval of object only item memories. Our findings suggest a generalization of episodic memory-related brain activation and performance in women compared to men. Follow up analyses should test for sex differences in the relationship between brain activity patterns and performance longitudinally, in association with risk factors for AD development. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP .

What are the contents of the infant mind? In the last decade, computational advances in fMRI have allowed researchers access to the internal representations of adults. Applied similarly in infants, fMRI stands to revolutionize our understanding of cognitive development. By measuring representations at their source, infant fMRI overcomes some of the limitations of behavioral measures. We discuss example domains where this approach could be fruitful, including episodic memory, semantic cognition, spatial representations, and theory of mind. In these and other areas, the richness of fMRI data could give new insight into how infants represent the world and potentially help resolve ongoing debates in developmental science.

Background Previous studies show that activity in the posterior default mode network (pDMN), including the posterior cingulate cortex and the precuneus, is correlated with the success of long-term episodic memory retrieval. However, the role of the anterior DMN (aDMN) including the medial prefrontal cortex is still unclear. Some studies show that activating the medial prefrontal cortex improves memory retrieval while other studies show deactivation of the medial prefrontal cortex in successful retrieval of episodic memories, suggesting a possible functional dissociation between the aDMN and pDMN. Objective In the current study, we aim to causally explore this probable dissociation using high-definition transcranial direct current stimulation (HD-tDCS). Methods We perform a randomised double-blinded two-visit placebo-controlled study with 84 healthy young adults. During Visit 1 they learn 75 Swahili-English word-associations. Seven days later, they randomly receive either anodal, cathodal or sham HD-tDCS targeting the pDMN or aDMN while they recall what they have previously learned. Results We demonstrate that anodal stimulation of the pDMN and cathodal stimulation of the aDMN, equally improve the percentage of Swahili-English word-associations recalled 7 days after learning. Conclusions Modulating the activity in the aDMN and pDMN causally affect memory retrieval performance. HD-tDCS of the aDMN and pDMN shows that anodal stimulation of the pDMN and cathodal stimulation of the aDMN increases memory retrieval performance one week after the learning phase. Given consistent evidence, it is highly likely that we are increasing the activity in the pDMN with anodal pDMN stimulation. However, it is not clear if cathodal HD-tDCS targetting aDMN works via decoupling from the pDMN or via indirectly disinhibit pDMN.

Astrocytes play a formative role in memory consolidation during physiological conditions; when dysregulated, astrocytes release glial fibrillary acidic protein (GFAP), which has been linked with negative memory outcomes in animal studies. We examined the association between blood GFAP, memory, and white matter (WM) integrity, accounting for blood markers of AD pathology (i.e., Aβ42) and neurodegeneration (i.e., total tau; neurofilament light chain) in 114 older adults (asymptomatic, n = 69; MCI/AD dementia, n = 45). Higher levels of GFAP were associated with lower memory scores (p0.0001), such that for 1 SD increase in mean GFAP values, the memory composite score decreased on average by 0.49 (Standard error = 0.071). These results remained significant after controlling for diagnostic status and AD-related blood biomarkers. Higher GFAP was also related to lower WM integrity in regions vulnerable to AD pathology; however, WM integrity did not account for the association between GFAP and memory. Study findings suggest that higher blood levels of a marker of astrogliosis may reflect impoverished memory functions and white matter health, independent of markers of amyloid or neurodegeneration.

Retrieval gating refers to the ability to modulate the retrieval of features of a single memory episode according to behavioral goals. Recent findings demonstrate that younger adults engage retrieval gating by attenuating the representation of task-irrelevant features of an episode. Here, we examine whether retrieval gating varies with age. Younger and older adults incidentally encoded words superimposed over scenes or scrambled backgrounds that were displayed in one of three spatial locations. Participants subsequently underwent fMRI as they completed two memory tasks: the background task, which tested memory for the word’s background, and the location task, testing memory for the word’s location. Employing univariate and multivariate approaches, we demonstrated that younger, but not older adults, exhibited attenuated reinstatement of scene information when it was goal-irrelevant (during the location task). Additionally, in younger adults only, the strength of scene reinstatement in the parahippocampal place area during the background task was related to item and source memory performance. Together, these findings point to an age-related decline in the ability to engage retrieval gating.

Decades of neuroscience research in rodents have established an essential role of the hippocampus in the processing of episodic memories. Based on accumulating evidence of functional segregation in the hippocampus along the longitudinal axis, this role has been primarily ascribed to the dorsal hippocampus. More recent findings, however, demonstrate that functional segregation also occurs along transverse axis of the hippocampus, within the hippocampal subfields CA1, CA2, CA3, and the dentate gyrus (DG). Because the functional heterogeneity within CA1 has been addressed in several recent articles, here we discuss behavioral findings and putative mechanisms supporting generation of asymmetrical activity patterns along the transverse axis of DG and CA3. While transverse subnetworks appear to discretely contribute to the processing of spatial, non-spatial, temporal, and social components of episodic memories, integration of these components also occurs, especially in the CA3 subfield and possibly downstream, in the cortical targets of the hippocampus.

Episodic memory of scatter-hoarding animals involves encoding and storage of memories of cached food items, in conjunction with subsequent retrieval or recovery. Although the reward values mediate the interaction of item memory and source memory, whether nonhuman animals divide their spatial memory resources between cached items of different values has never been tested. Here, we used a unique scatter-hoarder/seed system to test our ‘cache value hypothesis’, which proposes that scatter-hoarding animals will preferentially allocate spatial memory resources towards higher-valued caches. By making Edwards's long-tailed rats, Leopoldamys edwardsi, anosmic, using Triton X-100, we showed that L. edwardsi recovered more caches containing large nuts than those containing small ones, although the two kinds of nuts were equivalently cached. Our results therefore support the hypothesis that scatter-hoarding animals allocate more spatial memory resources to caches containing high-valued items. This is one of the few studies to investigate how item memory regulates source memory (order information) in the context of food storing and recovery by animals, especially by scatter-hoarding rodents. That high-valued items were remembered better than low-valued ones in our study suggests that item memory appears to be contextually associated with order information of items in animal memory processes, which is not in agreement with a previous suggestion that order information is independent of content or item information.

INTRODUCTION: Cognitive deficits occur in Parkinson’s disease (PD). Cardiorespiratory fitness (CRF) is associated with better cognitive performance in aging especially in executive function (EF) and memory. The association between CRF and cognitive performance is understudied in people with PD. Brain structures underlying associations also remains unknown. This cross-sectional study examined the associations between CRF and cognitive performance in PD. We also examined associations between CRF and brain structures impacted in PD. Mediation analysis were conducted to examine whether brain structures impacted in PD mediate putative associations between CRF and cognitive performance. METHODS: Individuals with PD (N=33) underwent magnetic resonance imaging (MRI), CRF evaluation (estimated VO(2)max), and neuropsychological assessment. Composite cognitive scores of episodic memory, EF, attention, language, and visuospatial functioning were generated. Structural equation models were constructed to examine whether MRI volume estimates (thalamus and pallidum) mediated associations between CRF and cognitive performance (adjusting for age, education, PD disease duration, sex, MDS-UPDRS motor score, and total intracranial volume). RESULTS: Higher CRF was associated with better episodic memory (Standardized β=0.391; p=0.008), EF (Standardized β=0.324; p=0.025), and visuospatial performance (Standardized β=0.570; p=0.005). Higher CRF was associated with larger thalamic (Standardized β=0.722; p=0.004) and pallidum (Standardized β=0.635; p=0.004) volumes. Thalamic volume mediated the association between higher CRF and better EF (Indirect effect=0.309) and episodic memory (Indirect effect=0.209) performance (p

Methylphenidate (MPH) is the first-choice pharmacological treatment for treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) across the lifespan. However, it is unclear whether MPH affects cognitive development, while recent (pre-) clinical studies suggest effects on the developing brain. The present randomized, placebo-controlled trial aims to determine whether MPH has short-term, age-dependent effects on cognitive performance in ADHD after a 1-week washout. Effects of 16 weeks MPH treatment were assessed after a one-week washout on cognitive functioning. Boys (age=10-12) and men (age=23-40) with ADHD were assigned to MPH treatment (boys n=25, men n=24) or placebo (boys n=25, men n=24). Outcome measures were working memory, response inhibition, response speed, episodic memory, and delay aversion. Differences in task performances over time (pre-, mid-, and post-treatment, following a 1-week wash-out) were compared between age and treatment conditions with mixed ANOVAs. MPH improved working memory and response speed, but only during treatment. No lasting age*treatment effects were observed post intervention. Overall, the results from the present randomized, placebo-controlled trial show that the effects of MPH on cognition do not extend past treatment in children or adults. While treatment with MPH improves cognition during treatment, these effects appear transient after 16-weeks of treatment. (Title trial: "Effects of methylphenidate on the developing brain"; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3103).

Working memory (WM) maintains task-relevant information in a state ready for processing. While traditional theories assume that sustained neuronal activity is responsible for WM, the Activity Silent WM (ASWM) account proposes that maintenance can also be supported by short-term synaptic weight changes. Here, we argue that the evidence for ASWM can be explained more parsimoniously by the involvement of episodic memory (EM) in WM tasks. Like ASWM, EM relies on rapid synaptic modification that is also activity silent; however, while ASWM posits transient synaptic modifications, EM traces persist over longer time periods. We discuss how, despite this difference, well-established EM mechanisms can account for the key findings attributed to ASWM, and describe predictions of this account.

The precise role played by the hippocampus in supporting cognitive functions such as episodic memory and future thinking is debated, but there is general agreement that it involves constructing representations comprised of numerous elements. Visual scenes have been deployed extensively in cognitive neuroscience because they are paradigmatic multi-element stimuli. However, questions remain about the specificity and nature of the hippocampal response to scenes. Here, we devised a paradigm in which we had participants search pairs of images for either colour or layout differences, thought to be associated with perceptual or spatial constructive processes respectively. Importantly, images depicted either naturalistic scenes or phase-scrambled versions of the same scenes, and were either simple or complex. Using this paradigm during functional MRI scanning, we addressed three questions: 1. Is the hippocampus recruited specifically during scene processing? 2. If the hippocampus is more active in response to scenes, does searching for colour or layout differences influence its activation? 3. Does the complexity of the scenes affect its response? We found that, compared to phase-scrambled versions of the scenes, the hippocampus was more responsive to scene stimuli. Moreover, a clear anatomical distinction was evident, with colour detection in scenes engaging the posterior hippocampus whereas layout detection in scenes recruited the anterior hippocampus. The complexity of the scenes did not influence hippocampal activity. These findings seem to align with perspectives that propose the hippocampus is especially attuned to scenes, and its involvement occurs irrespective of the cognitive process or the complexity of the scenes.

The hippocampus is essential for some types of memory, but its specific role remains conjectural. While studies on place cells have supported the hypothesis that the hippocampus provides a spatial substrate for episodic memory, recent engram studies have shown that optogenetic activation of a subset of hippocampal neurons that lack a temporal structure of the spike sequences can also induce memory-associated behavior. In this short review, I discuss the various lines of research that have led to different views of the role of the hippocampus in memory and propose a plausible interpretation of the findings that incorporates two influential theories.

Much of the rich internal world constructed by humans is derived from, and experienced through, visual mental imagery. Despite growing appreciation of visual exploration in guiding episodic memory processes, extant theories of prospection have yet to accommodate the precise role of visual mental imagery in the service of future-oriented thinking. We propose that the construction of future events relies on the assimilation of perceptual details originally experienced, and subsequently reinstantiated, predominantly in the visual domain. Individual differences in the capacity to summon discrete aspects of visual imagery can therefore account for the diversity of content generated by humans during future simulation. Our integrative framework provides a novel testbed to query alterations in future thinking in health and disease.

Background and Objectives Computerized cognitive interventions (CCIs) have been increasingly implemented among older adults with mild cognitive impairment (MCI). However, older individuals’ attitudes toward technology may limit CCI engagement. This exploratory-developmental study examined whether a “multi-functional interactive computer system” (MICS), which provides pleasurable activities via computer, would improve attitudes toward computers and in turn increase the efficacy of a subsequent CCI. Research Design and Methods A phase one double-blind trial randomized 49 seniors with MCI to a MICS + CCI condition or a CCI-only condition. Attitudes toward technology use was assessed using The Attitudes Toward Computers Questionnaire (ATCQ), and cognition was assessed using episodic memory and executive function composite scores at baseline, the ends of MICS and CCI phases, and 3-month follow-up. Results The MICS + CCI group did not show significantly greater improvement in cognition than the CCI only group. Secondary analyses indicated that improvement in executive function from baseline occurred in both groups. Participants who did show improved attitudes toward computers, whether through MICS or simply computer exposure itself, showed improvement in executive function. Discussion and Implication Participants in the MICS + CCI group used MICS less than expected. A more structured and supervised approach may be needed to facilitate MICS exposure. Improved attitudes toward computers regardless of MICS exposure may benefit candidates for CCI.

The entorhinal cortex is subdivided into anterolateral entorhinal cortex (alERC) and posteromedial entorhinal cortex (pmERC) subregions, which are theorized to support distinct cognitive roles. This distinction is particularly important as the alERC is one of the earliest cortical regions affected by Alzheimer's pathology and related neurodegeneration. The relative associations of alERC/pmERC with neuropsychological test performance have not been examined. We examined how alERC/pmERC volumes differentially relate to performance on 1) the Modified Rey Auditory Learning Test (ModRey), a verbal memory test designed to assess normal/preclinical populations, 2) the Montreal Cognitive Assessment (MoCA), and 3) the National Alzheimer's Coordinating Center neuropsychological battery. We also examined whether alERC/pmERC volumes correlate with Alzheimer's disease cerebrospinal fluid (CSF) biomarkers. In 65 cognitively healthy (CDR = 0) older adults, alERC, but not pmERC, volume was associated with ModRey memory retention. Only alERC volume differentiated between participants who scored above and below the MoCA cutoff score for impairment. Evaluating the MoCA subdomains revealed that alERC was particularly associated with verbal recall. On the National Alzheimer's Coordinating Center battery, both alERC and pmERC volumes were associated with Craft story recall and Benson figure copy, but only alERC volume was associated with Craft story retention and semantic fluency. Neither alERC nor pmERC volume correlated with CSF levels of amyloid or tau, and regression analyses showed that alERC volume and CSF amyloid levels were independently associated with ModRey retention performance. Taken together, these results suggest that the alERC is important for memory performance and that alERC volume differences are related to a pattern of neuropsychological test performance (i.e., impairments in episodic memory and semantic fluency) typically seen in clinical Alzheimer's disease.

Fractal dimensionality (FD) measures the complexity within the folds and ridges of cortical and subcortical structures. We tested the degree that FD might provide a new perspective on the atrophy-compensation hypothesis: age or disease-related atrophy causes a compensatory neural response in the form of increased brain activity in the prefrontal cortex to maintain cognition. Brain structural and functional data were collected from 63 middle-aged and older adults and 18 young-adult controls. Two distinct patterns of FD were found that separated cortical from subcortical structures. Subcortical FD was more strongly negatively correlated with age than cortical FD, and cortical FD was negatively associated with brain activity during memory retrieval in medial and lateral parietal cortices uniquely in middle-aged and older adults. Multivariate analyses revealed that the lower FD/higher brain activity pattern was associated with poorer cognition-patterns not present in young adults, consistent with compensation. Bayesian analyses provide further evidence against the modal interpretation of the atrophy-compensation hypothesis in the prefrontal cortex-a key principle found in some neurocognitive theories of aging.

Post-retrieval monitoring is associated with engagement of anterior cingulate and dorsolateral prefrontal cortex. Recent fMRI studies reported age-invariant monitoring effects in these regions and an age-invariant correlation between these effects and memory performance. The present study examined monitoring effects during associative recognition (difference in activity elicited by ‘rearranged’ and ‘intact’ test pairs) under single and dual (tone detection) task conditions in young and older adults (Ns = 28 per group). It was predicted that, for the older adults only, dual tasking would attenuate memory performance and monitoring effects and weaken their correlation. Consistent with this prediction, in the older group imposition of the secondary task led to lower memory performance and elimination of the relationship between monitoring effects and performance. However, the size of the effects did not differ between single and dual task conditions. The findings suggest that the decline in older adults' memory performance in the dual task condition resulted not from impaired monitoring, but from a different cause that also weakened the dependence of performance on monitoring.

International audience; Background: Cognitive impairment is important to consider in the assessment of multiple sclerosis (MS) patients. A short battery of cognitive assessment, the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), has been developed to address the need for rapid assessment by combining 3 tests assessing the main cognitive spheres reached in MS. Objectives: To establish regression-based norms of the BICAMS in French speaking healthy subjects (HS) and validate its use in persons with multiple sclerosis (PwMS). Methods: In all, 123 PwMS including 40 with relapsing-remitting MS, 41 patients with secondary progressive MS and 42 with primary progressive MS and 276 HS were evaluated by the BICAMS including 3 tests, the Symbol Digit Modalities Test (SDMT), the French Verbal learning test (FVLT) a French-adapted memory test, (or the California Verbal Learning Test (CVLT) at retesting) and the Brief Visuo-Spatial Memory Test (BVMT-R). The standards for these tests were established in the healthy population using a multiple regression technique. Validity in MS was measured. Results: Regression-based norms of BICAMS tests have been established in the HS population. 50.4% of PwMS have impairment for at least one BICAMS test (-1.5SD on the Z-score). The most common pathological test was the FVLT altered in 36.6% of patients, followed by the SDMT and the BVMT-R. The re-test reliability was good for the various BICAMS tests, 0.891 for SDMT, 0.781 for FVLT/CVLT and 0.669 for BVMT-R. Conclusion: This study establishes the validity of the BICAMS as a short and easy to apply battery for a brief assessment of the speed of information processing and episodic memory in MS.

Pattern separation is a basic principle of neuronal coding that precludes memory interference in the hippocampus. Its existence is supported by numerous theoretical, computational, and experimental findings in different species. However, I argue that recent evidence from single-neuron recordings suggests that pattern separation may not be present in the human hippocampus and that memories are instead coded by the coactivation of invariant and context-independent engrams. This alternative model prompts a reassessment of the definition of episodic memory and its distinction from semantic memory. Furthermore, I propose that a lack of pattern separation in memory coding may have profound implications that could explain cognitive abilities that are uniquely developed in humans, such as our power of generalization and of creative and abstract thinking.

Reactivation refers to the phenomenon wherein patterns of neural activity expressed during perceptual experience are re-expressed at a later time, a putative neural marker of memory. Reactivation of perceptual content has been observed across many cortical areas and correlates with objective and subjective expressions of memory in humans. However, because reactivation emphasizes similarities between perceptual and memory-based representations, it obscures differences in how perceptual events and memories are represented. Here, we highlight recent evidence of systematic differences in how (and where) perceptual events and memories are represented in the brain. We argue that neural representations of memories are best thought of as spatially transformed versions of perceptual representations. We consider why spatial transformations occur and identify critical questions for future research.

Introduction The serial clinical failures of novel cognitive enhancer candidates point out the lack of predictive power in the preceding animal experimentation. For a more predictive profiling of putative procognitive drugs in rodents, we recently elaborated a methodical approach which consists of three fundamental steps: 1. teaching various learning tasks representing different cognitive domains to the same cohort of animals with the aim to create a population with ‘widespread knowledge’. 2. Applying a cognitive deficit-inducing intervention to transform this cohort of animals to a ‘patient population’. 3. Testing putative procognitive drugs with a ‘clinical trial-like’ design on the wide spectrum of cognitive (dys)functions in the actual ‘patient population’. The present study has been the first trial to test the feasibility and utility of the proposed system. Methods The population with ‘widespread knowledge’ consisted of 2 year old male Long-Evans rats with a learning history in five-choice serial reaction time task (5-CSRTT, attentional paradigm), Morris water maze (MWM, spatial learning), a cooperative task carried out in pairs (social learning), and a skill-learning task, „pot-jumping”. For inducing cognitive deficit, thus creating a ‘patient population’ we increased the difficulty of the tasks. For the cognitive enhancer mechanism to test in the system we chose a serotonin 5-HT6 receptor antagonist compound, RO4368554. Animals were randomly assigned to vehicle- and drug treated groups based on their baseline learning performance and their response in a pilot test of increase in task difficulty. During the 13-day long treatment with 3 mg/kg ip. RO4368554 all the learning paradigms were repeatedly run with increased difficulty supplemented with a novel object recognition test (NOR, episodic memory). Results In the 5-CSRTT, reducing the stimulus duration from 1 s to 0.25 s caused a significant decrease in the percentage of correct responses (from 52 % to 31 % in the control group) which was not affected by the 5-HT6 receptor antagonist treatment (correct responses decreased from 58 % to 31 %). In the MWM, replacing the escape platform to a new location did not mean a hard challenge for the rats. Members of both groups could find it within a relatively short time: mean escape latencies were 83 s and 65 s at the first replacement trial and 58 s and 74 s at the second one in the control and drug-treated groups, respectively. In the cooperation paradigm, where the rats had to perform simultaneous nose-pokes to get a reward, task difficulty was increased by requiring two consecutive simultaneous nose-poking from the animals. This caused a fall in the percentage of successful trials in both groups (from 48 % to 12 % and from 50 % to 20 % in the saline – and drug-treated group, respectively), however, by the end of the treatment RO4368554-treated animals showed significantly higher performance (29 %) than saline treated rats (2%). The NOR test, carried out with a 5 -h delay, revealed poor recognition memory in both groups (discrimination index (DI) values were 0.13 and 0.06 for saline and RO4368554, respectively). Performance in the pot jumping test was also not improved by the drug-treatment. Conclusions The applied study design allowed parallel measurements of the action of the test compound on several cognitive functions and to follow its time course. RO4368554 did not show notable effects on impaired attention and visual recognition; nor did it affect spatial and procedural learning, but it exerted beneficial effect on cooperative behaviour. The revealed activity pattern highlight the cognitive domain most sensitive to the particular drug effect and may give hints for further target validating and clinical studies.

AMD has been linked to memory deficits, with no established neural mechanisms. In order to describe how resting-state, brain network functional connectivity relates to memory and AMD status in older adults without dementia, we collected resting-state brain fMRI and standardized verbal recall tests from 42 older adults with AMD and 41 age-matched controls. We used seed-based whole brain analysis to quantify the strength of functional connectivity between hubs of the default mode network (DMN) and a network of medial temporal regions relevant for memory. Our results indicated neither memory performance nor network connectivity differed by AMD status. However, the AMD participants exhibited stronger relationships than the controls between memory performance and connectivity from the memory network hub (left parahippocampal) to two other regions: the left temporal pole and the right superior/middle frontal gyri. Also, the connectivity between the medial prefrontal cortex and posterior cingulate cortex of DMN correlated more strongly with memory performance in AMD compared to control. We concluded that stronger brain-behavior correlation in AMD may suggest a role for region-specific connectivity in supporting memory in the context of AMD.

Today, based on brain imaging analyses, we can consider the brilliant metaphor about event discreteness of the conscious process by William James (1890) to be an experimental fact. Such events compose sequences: linguistic, episodic memory, motor behavior, etc., whose dynamics are robust, reproducible, and sensitively react to incoming informational signals. The human mind is able to process, understand and predict time-dependent information about the environment and about ourselves, and generate corresponding commands to control behavior. Many experiments have indicated that the mind relies on sequential dynamics to carry out these tasks. Based on brain imaging experiments, we discuss here a set of key principles and their instantiation in nonlinear differential equations to form a dynamical theory of consciousness and creativity. General hierarchical models of consciousness and creativity include coupled low-dimensional equations that govern cooperative variables for several cognitive modalities: episodic (semantic) memory, working memory, attention, emotion, perception and their sequential interaction. In the phase spaces spanned by variables of these models, the joint transient dynamics of cognitive modalities is represented by coupled heteroclinic networks which share complex metastable states. The interaction of such states is responsible for the robustness of transient neural dynamics involved in the generation of thoughts and in the programming of behavior. In the framework of the analyzed dynamical models, we discuss the interaction of cognitive processes and the generation of new information in creativity.

Despite advances in understanding the consequences of age-related episodic memory decline for future simulation, much remains unknown regarding changes in the neural underpinnings of future thinking with age. We used a repetition suppression paradigm to explore age-related changes in the neural correlates of emotional future simulation. Younger and older adults simulated positive, negative, and neutral future events either two or five times. Reductions in neural activity for events simulated five versus two times (i.e., repetition suppression) identifies brain regions responsive to the specific emotion of simulated events. Critically, older adults showed greater repetition suppression than younger adults in the temporal pole for negative simulations, and the cuneus for positive simulations. These findings suggest that older adults distance themselves from negative future possibilities by thinking about them in a more semantic way, consistent with the view that older adults down-regulate negative affect and up-regulate positive affect. More broadly this study increases our understanding of the impact of aging on the neural underpinnings of episodic future simulation.

Background There is a need to determine why prior concussion has been associated with adverse outcomes in some retired and active athletes. We examined whether serum inflammatory markers moderate the associations of prior concussion with hippocampal volumes and neurobehavioral functioning in active high school and collegiate athletes. Methods Athletes (N=201) completed pre-season clinical testing and serum collection (C-reactive protein [CRP]; Interleukin-6 [IL]-6; IL-1 receptor antagonist [RA]) and in-season neuroimaging. Linear mixed-effects models examined associations of prior concussion with inflammatory markers, self-reported symptoms, neurocognitive function, and hippocampal volumes. Models examined whether inflammatory markers moderated associations of concussion history and hippocampal volume and/or clinical measures. Results Concussion history was significantly associated with higher symptom severity, p=0.012, but not hippocampal volume or inflammatory markers (ps>0.05). A significant interaction of prior concussion and CRP was observed for hippocampal volume, p=0.006. Follow-up analyses showed that at high levels of CRP, athletes with two or more prior concussions had smaller hippocampal volume compared to athletes without prior concussion, p=0.008. There was a significant interaction between prior concussion and levels of IL-1RA on memory scores, p=0.044, i.e., at low levels of IL-1RA, athletes with two or more concussions had worse memory performance than those without prior concussion (p=0.014). Conclusion Findings suggest that certain markers of systemic inflammation moderate the association between prior concussion and hippocampal volume and episodic memory performance. Current findings highlight potential markers for predicting at-risk individuals and identify therapeutic targets for mitigating the long-term adverse consequences of cumulative concussion.

Contains fulltext : 219603.pdf (Publisher’s version ) (Closed access) Speakers and listeners usually interact in larger discourses than single words or even single sentences. The goal of the present study was to identify the neural bases reflecting how the mental representation of the situation denoted in a multi-sentence discourse (situation model) is constructed and shared between speakers and listeners. An fMRI study using a variant of the ambiguous text paradigm was designed. Speakers (n=15) produced ambiguous texts in the scanner and listeners (n=27) subsequently listened to these texts in different states of ambiguity: preceded by a highly informative, intermediately informative or no title at all. Conventional BOLD activation analyses in listeners, as well as inter-subject correlation analyses between the speakers' and the listeners' hemodynamic time courses were performed. Critically, only the processing of disambiguated, coherent discourse with an intelligible situation model representation involved (shared) activation in bilateral lateral parietal and medial prefrontal regions. This shared spatiotemporal pattern of brain activation between the speaker and the listener suggests that the process of memory retrieval in medial prefrontal regions and the binding of retrieved information in the lateral parietal cortex constitutes a core mechanism underlying the communication of complex conceptual representations. 16 p.

Background Borderline personality disorder (BPD) is associated with subjective reports of forgetfulness and deficits on tests of memory performance. However, it is not yet known whether individuals with BPD show different patterns of activation in the hippocampus during episodic memory encoding, especially for materials that are not emotionally-valenced. Methods Participants with BPD (n = 20) and non-psychiatric controls (n = 21) completed a memory encoding task in which they viewed scenes without emotional content during functional magnetic resonance imaging scans. Subsequently, they completed a recognition memory test outside of the scanner and neural activation during the presentation of successfully remembered scenes was contrasted with scenes that were subsequently forgotten. Results Controls exhibited significant left hippocampal activation during successful memory encoding, displaying greater activity during the presentation of subsequently remembered versus forgotten scenes, and the strength of this activation was related to their recognition memory performance. Although hippocampal activation was observed for the BPD group during successful memory encoding, it did not reach significance when implementing a non-parametric statistical approach. Additionally, individual hippocampal recruitment was not significantly correlated with recognition memory performance in the BPD group. The strength of this correlation, but not the overall magnitude of hippocampal activation, was significantly different between the groups. Limitations Participants with BPD had comorbid psychiatric diagnoses and varied treatment histories. Whether patients and controls differentially perceived emotional content in the neutral scene memoranda was not tested. Conclusions Memory problems in BPD may be partially explained by a disrupted relationship between hippocampal activation and successful memory encoding.

Remembering associations between encoded items and their contextual setting is a feature of episodic memory. Although this ability generally deteriorates with age, there is substantial variability in how older individuals perform on episodic memory tasks. A current topic of debate in the cognitive neuroscience of aging literature revolves around whether this variability may stem from genetic and/or environmental factors related to reserve, allowing some individuals to compensate for age-related decline through differential recruitment of brain regions. In this fMRI study spanning a large adult lifespan sample (N = 154), we tested whether higher cognitive reserve was associated with better task-fMRI context memory performance, and functional compensatory activity patterns in the aging brain. We used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of cognitive reserve [i.e., a composite score consisting of years of education (EDU) and crystallized IQ], impacted brain activity during the encoding and retrieval of spatial and temporal contextual details. The results indicated that age-related increases in encoding activity within anterior and lateral frontal, inferior parietal, occipito-temporal and medial temporal cortices, was correlated with better subsequent memory performance; and may be indicative of age-related functional compensation at encoding. Interestingly this compensatory pattern was not correlated with our proxy measure of cognitive reserve but was associated with total brain volume (a measure of brain reserve). However, cognitive reserve was associated with age-invariant and task-general activity in superior temporal, occipital, and left inferior frontal regions. We conclude that the relationship between cognitive reserve, brain reserve and age-related functional compensation is complex, and that EDU and IQ may not fully account for individual differences in cognitive reserve when studying well educated, healthy aging cohorts.

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative brain disorders, primarily affecting the frontal and/or temporal lobes. Three main subtypes are recognised, each with distinct clinical and cognitive profiles: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). Subtype-specific cerebellar grey matter atrophy has been associated with cognitive dysfunction in FTD; however, the extent and severity of structural abnormalities in the cerebro-cerebellar circuits in these disorders has not been investigated. This study aimed to identify patterns of cerebellar white matter changes and their relations to cognitive deficits in the main FTD subtypes. Results revealed bilateral cerebellar white matter changes in all FTD subtypes compared with controls, with greater cerebellar white matter changes in bvFTD than SD and PNFA. Both afferent and efferent cerebellar pathways were associated with cognition. The profiles of the involvement of cerebellar pathways in cognition varied across FTD syndromes. In bvFTD, the output pathway of the cerebellum was only associated with measures of episodic memory. The input pathway was associated with measures of attention, working memory, visuospatial, episodic memory, executive function, and emotion. In SD, both the output and input pathways were associated with measures of working memory, language, and emotion. Finally, in PNFA, both the output and input pathway of the cerebellum were associated with attention, language, and executive function. Additionally, the input pathway was associated with working memory, visuospatial, and emotion. This study is the first to identify patterns of cerebellar white matter changes across FTD syndromes, which in turn relate to cognitive deficits. These findings extend our understanding of the cerebro-cerebellar networks and provide new insight into the role of cerebellar white matter in cognition.

Artificial neural networks experience serious catastrophic forgetting (or interference) when information is learned sequentially. A significant effort in the machine learning community is devoted to the solution of this problem. Many approaches to overcome the catastrophic interference (CI) find parallels with an organization of the human memory system. In this paper, we provide a review of biologically inspired approaches for CI prevention. The main emphasis is made on the development of methods inspired by generative properties of the brain. We developed and tested several methods for preventing CI using an artificial dataset generated on the base of previous experience of neural network. The proposed methods include the activation maximization approach, the method based on Bayesian learning, and the method based on generative neural networks. The methods based on a combination of episodic memory (several stored samples) and semantic memory (sampling of posterior probability function) show superiority compared to other recent methods devoted to CI prevention. Based on generative approaches, the biologically plausible mechanisms of active forgetting and memory reconsolidation are also demonstrated. The proof of concept experiments were performed on several publicly available datasets.

The anterior temporal lobe (ATL) is involved in a wide range of cognitive processes but its functional specialization remains unclear. In this review, we synthesize evidence from cytoarchitecture, anatomical and functional connectivity, and functional activation to elucidate how subregions in the ATL contribute to various cognitive processes. Two complementary meta-analyses were conducted. We first constructed a comprehensive functional preference profile for all subregions through large-scale neuroimaging meta-analysis, and then employed a coordinate-based activation likelihood estimation analysis to examine such functional preferences by input types. We identified two subregions in the dorsal aspect of the ATL (i.e., superior dorsal, inferior dorsal) and two other subregions (lateral, ventromedial) in the ventral aspect of the ATL, all have distinct anatomical and functional preferences. We proposed sensory, language, and socioemotion as the three dimensions that jointly capture the cognitive components cutting across the four ATL subregions: the superior dorsal ATL was associated with auditory sensory, language (phonological production aspects), and emotion; the inferior dorsal ATL with auditory sensory and language (phonological perception and production aspects); the lateral ATL with visual sensory, language (semantic and episodic aspects), and social processing; and the ventromedial ATL with visual sensory, episodic memory, and emotion. The various functions associated with the ATL can be clustered into subregions, which provides sourceful basis for testing hypothesis-driven cognitive framework.

Two vital memory functions — remembering specific experiences and generalizing across many experiences — are in tension with each other. In the complementary-learning-systems model, the hippocampus allows for fast learning of unique episodic memories while the cortex slowly extracts regularities from overlapping representations. Whereas episodic memories undergo consolidation over protracted time periods, many questions remain about how memory generalization evolves over time. Sleep’s role in consolidating individual memories has been convincingly demonstrated using targeted memory reactivation, a method whereby memories can be selectively strengthened through the unobtrusive presentation of learning-related stimuli during sleep. In this review, we argue that targeted memory reactivation can help advance understanding of memory transformation and the contrast between specificity and generalization.