Variance In Memory Performance Research Articles

Multi-session tDCS over the posterior parietal cortex and associative memory.

Associative memory (AM) plays a crucial role in our ability to link disparate elements of our experiences, yet it is especially vulnerable to age-related decline and pathological conditions. Non-invasive brain stimulation (NIBS), particularly transcranial direct current stimulation (tDCS), has been investigated as a potential intervention to enhance cognitive functions, including AM. Previous tDCS studies yielded inconsistent results, often due to variations in stimulation sites and protocols. Nonetheless, enough evidence suggests that tDCS over the posterior parietal cortex (PPC) can improve AM performance. This study aimed to investigate the cumulative effects of multiple anodal tDCS over the PPC on AM performance alongside item memory and verbal fluency. In a randomized sham-controlled trial, 59 healthy young adults were assigned to either anodal or sham stimulation group, receiving tDCS (1.5 mA, for 20 minutes, at P3) over three consecutive days. Memory performance was assessed at four timepoints: pretest, immediately after the first session, posttest (Day 5), and follow-up (Day 9). Although tDCS was well tolerated, the anticipated enhancement of memory performance was not observed. We interpret these findings in the light of methodological considerations and propose potential explanations for the observed results emphasizing the large between-participants variability in memory performance as a significant factor that may have hindered the detection of tDCS effects.

Emotional modulation of memorability in mnemonic discrimination

Although elements such as emotion may serve to enhance or impair memory for images, some images are consistently remembered or forgotten by most people, an intrinsic characteristic of images known as memorability. Memorability explains some of the variability in memory performance, however, the underlying mechanisms of memorability remain unclear. It is known that emotional valence can increase the memorability of an experience, but how these two elements interact is still unknown. Hippocampal pattern separation, a computation that orthogonalizes overlapping experiences as distinct from one another, may be a candidate mechanism underlying memorability. However, these two literatures have remained largely separate. To explore the interaction between image memorability and emotion on pattern separation, we examined performance on an emotional mnemonic discrimination task, a putative behavioral correlate of hippocampal pattern separation, by splitting stimuli into memorable and forgettable categories as determined by a convolutional neural network as well as by emotion, lure similarity, and time of testing (immediately and 24-hour delay). We measured target recognition, which is typically used to determine memorability scores, as well as lure discrimination, which taxes hippocampal pattern separation and has not yet been examined within a memorability framework. Here, we show that more memorable images were better remembered across both target recognition and lure discrimination measures. However, for target recognition, this was only true upon immediate testing, not after a 24-hour delay. For lure discrimination, we found that memorability interacts with lure similarity, but depends on the time of testing, where memorability primarily impacts high similarity lure discrimination when tested immediately but impacts low similarity lure discrimination after a 24-hour delay. Furthermore, only lure discrimination showed an interaction between emotion and memorability, in which forgettable neutral images showed better lure discrimination compared to more memorable images. These results suggest that careful consideration is required of what makes an image memorable and may depend on what aspects of the image are more memorable (e.g., gist vs. detail, emotional vs. neutral).

Early visual cortices reveal interrelated item and category representations in aging.

Neural dedifferentiation, the finding that neural representations tend to be less distinct in older adults compared with younger adults, has been associated with age-related declines in memory performance. Most studies assessing the relation between memory and neural dedifferentiation have evaluated how age impacts the distinctiveness of neural representations for different visual categories (e.g., scenes and objects). However, how age impacts the quality of neural representations at the level of individual items is still an open question. Here, we present data from an age-comparative fMRI study that aimed to understand how the distinctiveness of neural representations for individual stimuli differs between younger and older adults and relates to memory outcomes. Pattern similarity searchlight analyses yielded indicators of neural dedifferentiation at the level of individual items as well as at the category level in posterior occipital cortices. We asked whether age differences in neural distinctiveness at each representational level were associated with inter- and/or intraindividual variability in memory performance. While age-related dedifferentiation at both the item and category level related to between-person differences in memory, neural distinctiveness at the category level also tracked within-person variability in memory performance. Concurrently, neural distinctiveness at the item level was strongly associated with neural distinctiveness at the category level both within and across participants, elucidating a potential representational mechanism linking item- and category-level distinctiveness. In sum, we provide evidence that age-related neural dedifferentiation co-exists across multiple representational levels and is related to memory performance.Significance Statement Age-related memory decline has been associated with neural dedifferentiation, the finding that older adults have less distinctive neural representations than younger adults. This has been mostly shown for category information, while evidence for age differences in the specificity of item representations is meager. We used pattern similarity searchlight analyses to find indicators of neural dedifferentiation at both levels of representation (category and item) and linked distinctiveness to memory performance. Both item- and category-level dedifferentiation in the calcarine cortex were related to interindividual differences in memory performance, while category-level distinctiveness further tracked intraindividual variability. Crucially, neural distinctiveness was strongly tied between the item and category levels, indicating that intersecting representational properties of posterior occipital cortices reflect both individual exemplars and categories.

Associations of APOE4 and Alzheimer’s disease biomarkers with cortical reinstatement and episodic memory in clinically unimpaired older adults

AbstractBackgroundCortical reinstatement is a key neural correlate of episodic remembering across the lifespan and explains significant variability in memory performance among older adults. We assessed whether Alzheimer’s disease (AD) risk factors – cerebrospinal fluid (CSF) Aβ42/Aβ40, CSF pTau181, plasma pTau181, and APOE genotype – impact cortical reinstatement in clinically unimpaired older adults.MethodParticipants were 150 clinically unimpaired older adults enrolled in the Stanford Aging and Memory Study (SAMS). APOE genotype was determined from whole‐genome sequencing and participants were classified as ε4 carriers (N = 38) or non‐carriers (N = 112). CSF Aβ42/Aβ40 and pTau181 and plasma pTau181 were quantified using the automated Lumipulse G system. Cortical reinstatement was quantified during successful retrieval of word‐picture associations using fMRI multivoxel pattern analysis (MVPA) in five regions of interest, including parahippocampal gyrus (PHG), ventral temporal cortex (VTC), middle temporal gyrus (MTG), angular gyrus (ANG), and posterior medial cortex (PMC). Regression analyses examined cross‐sectional relationships between regional cortical reinstatement and a) APOE genotype (N = 150), b) CSF Aβ42/Aβ40 and pTau181 (N = 113), and (c) plasma pTau181 (N = 140), as well as associations of these variables with associative memory discrimination (d’). All models included age, sex, and regional MVPA classifier accuracy during memory encoding.ResultAPOE ε4 genotype was negatively associated with reinstatement strength in VTC (β = ‐0.54, p < .005), MTG (β = ‐0.32, p < .05), and ANG (β = ‐0.32, p < .05) and CSF Aβ42/Aβ40 burden was linked to weaker reinstatement in ANG (β = 0.16, p < .05). In VTC, the effect of APOE ε4 on reinstatement remained significant after controlling for CSF Aβ42/Aβ40 (β = ‐0.47, p < .05); a similar pattern was observed in MTG and ANG. Although CSF pTau181 was unrelated to reinstatement strength, both pTau181 and cortical reinstatement explained unique variance in memory performance (pTau181: β = ‐0.26, p < .005, reinstVTC: β = 0.39, p < .001). Analogous findings were observed with plasma pTau181.ConclusionThese results suggest that APOE ε4 impacts cortical reinstatement, and that this effect may be independent of amyloid burden. These effects of APOE ε4 may be distinct from tau‐mediated effects on episodic memory in human aging.

Cognitive reserve in figural and verbal memory in healthy older adults – preliminary results

AbstractBackgroundCognitive reserve plays an important role in individual trajectories of age‐related memory decline, with education and semantic fluency representing cognitive reserve proxies (CRPs). Higher CR may attenuate well‐known effects of ageing on the brain, such as decreases in grey matter volume (GMV). We hypothesised that the known associations between age‐related GMV and cognition would be (differentially) attenuated by CRPs.MethodWe analysed 3‐Tesla T1‐weighted Multi‐Echo MPRAGE and cognitive data (Verbal Learning and Memory Test (VLMT), Rey Complex Figure Test (RCFT), and Regensburg Verbal Fluency Test (RWT)) from 51 cognitively normal adults (73.2±7.62 years, 31 male) in our new cohort established within the CRC1436 (https://sfb1436.de/). MRI data were pre‐processed and analysed using CAT12. We performed a whole‐brain linear regression to first assess age‐related reductions in GMV (covariates: sex, total intracranial volume (TIV), education), extracting mean betas for significant regions of interest (ROIs). We investigated the relationship between GMV in age‐vulnerable regions and memory using linear regressions in R (covariates: age, sex, TIV), and assessed CRPs as moderators on this relationship. Finally, we tested whether CRPs explained variance in memory performance over and above that of GMV and age. We accounted for multiple testing via Benjamini‐Hochberg‐correction.ResultWhole brain analyses identified bilateral hippocampal GMV as negatively associated with age (Fig.1). Linear regression analyses yielded a significant positive association between bilateral hippocampal GMV and figural memory (Fig.2). However, we observed no significant moderation by CRPs on this relationship. Finally, we observed weak evidence for cognitive reserve when adjusting for GMV and age, with higher variance explained by CRPs (Table 1). Semantic fluency positively predicted a figural memory composite when adjusting for right (p = 0.006) as well as left hippocampal GMV (p = 0.014). Education positively predicted verbal memory when adjusting for right (p<0.001) as well as left hippocampal GMV (p<0.001).ConclusionConsistent with operational definitions, our results provide weak evidence for semantic fluency and for education as CRPs in figural and verbal memory, respectively. However, our findings are preliminary, given the future addition of more participants. Nevertheless, these results provide important first insights into cognitive reserve in this developing cohort.

Robust prediction of memory and neuroticism in men and women using connectome‐based predictive modeling

AbstractBackgroundAlzheimer’s disease (AD) disproportionately impacts women, yet we have little understanding of the differences in brain circuitry that underlie this vulnerability. We explored aspects of brain connectivity that robustly predict memory performance (measured by RAVLT performance) and neuroticism (measured by NEO‐N) in healthy women vs men by leveraging data‐driven machine learning to model the brain connectome in the Lifespan Human Connectome Project Aging (HCP‐A) dataset.MethodWe used functional MRI scans to create whole‐brain connectivity matrices based on 268 regions‐of‐interest for 725 healthy subjects (319 men, 406 women) aged 36 to 100 enrolled in HCP‐A. Before and after separating the subjects by sex, connectome‐based predictive modeling (CPM) was used with a p‐value threshold of 0.01 and split‐half cross‐validation to identify and implement edges that significantly predicted the neurobehavioral scores to train a predictive model for each group. The models were applied to test sets within each group, outputting the predicted behavioral measures and Pearson correlations between predicted and observed scores.ResultAs anticipated, overall performance in HCP‐A was higher for women than men in RAVLT (p < 1x10‐7) and NEO‐N (p = 0.12). Our model predicted the RAVLT measure (Fig. 1) with accuracies ranging from R = 0.2154 (p < 1x10‐4) to R = 0.4293 (p < 1x10‐4). Our sex‐based models also predicted a high variance in the RAVLT measure between sexes (σ2 = 0.015, Fig. 2). While neuroticism predictors were not as robust for short‐term memory, the models were still able to predict a significant amount of variance (σ2 = 0.023, Fig. 2).ConclusionWe successfully implemented CPM to derive robust brain‐based predictors of memory performance and neuroticism. Models derived separately for each sex differ in their ability to explain variance in these measures. Future analyses will pinpoint specific edges within the connectivity matrices that explain variance in memory performance or neuroticism in men vs women. We anticipate these will yield important insights into why women are at higher risk of developing AD.

Hippocampal CA1 volume is associated with higher p‐tau and diminished memory performance in normal older adults

AbstractBackgroundPrior work has demonstrated that elevated CSF biomarkers in older adults are associated with diminished performance across several hippocampally‐dependent memory tasks. It is unknown whether early structural changes in medial temporal lobe subfields (1) may be impacted by elevated p‐tau181, and (2) mediate the effect of p‐tau181 on memory performance in older adults.MethodThe current study draws on a cohort of 147 cognitively unimpaired older adults (Stanford Aging and Memory Study) that completed both 3T MRI and lumbar punctures. To examine memory performance, participants completed two hippocampally dependent tasks: a paired associate cued recall task and a mnemonic discrimination task (MST) that examined discrimination between previously studied “old” objects, novel “foil” objects and perceptually similar “lure” objects. Lure trials were binned in five difficulty levels, ranging from low to high similarity compared to previously presented stimuli. Hippocampal subregions (CA1, CA3/DG, subiculum) were manually delineated on T2*weighted images following Carr et al., (2017). CSF was processed with Lumipulse to measure Ab42:Ab40 ratio and p‐tau181. Multiple regression was used to assess the associative memory d’ from the paired associate task. Given the repeated measures design of the MST task, linear mixed models were conducted to understand the association between hippocampal subfields and p‐tau181 on performance as a function of similarity strength (Trelle et al., 2021). Age, sex, and education were controlled in all models.ResultP‐tau181 was correlated with reduced left CA1 volume (partial r2=0.043, p = 0.01), but not with volume in other hippocampal subfields. Increased CA1 volume was positively associated with better memory performance, including higher associative memory recall and old‐lure discrimination. After controlling for p‐tau181, CA1 volume was no longer associated with performance on the associative memory task but remained significantly correlated with old/lure discrimination. Notably, increased CA1 volume improved overall discrimination for old/lure trials, independent of the difficulty level, while the association between p‐tau181 and performance was strongest at the lower similarity level.ConclusionReduced CA1 volume and p‐tau explain unique variance in memory performance in older adults. This combination of biofluid biomarkers and high‐resolution MRI has the potential to understand mechanisms underlying age‐related memory decline.

Transfer learning for cognitive reserve quantification

Cognitive reserve (CR) has been introduced to explain individual differences in susceptibility to cognitive or functional impairment in the presence of age or pathology. We developed a deep learning model to quantify the CR as residual variance in memory performance using the Structural Magnetic Resonance Imaging (sMRI) data from a lifespan healthy cohort. The generalizability of the sMRI-based deep learning model was tested in two independent healthy and Alzheimer's cohorts using transfer learning framework. Structural MRIs were collected from three cohorts: 495 healthy adults (age: 20-80) from RANN, 620 healthy adults (age: 36-100) from lifespan Human Connectome Project Aging (HCPA), and 941 adults (age: 55-92) from Alzheimer's Disease Neuroimaging Initiative (ADNI). Region of interest (ROI)-specific cortical thickness and volume measures were extracted using the Desikan-Killiany Atlas. CR was quantified by residuals which subtract the predicted memory from the true memory. Cascade neural network (CNN) models were used to train RANN dataset for memory prediction. Transfer learning was applied to transfer the T1 imaging-based model from source domain (RANN) to the target domains (HCPA or ADNI). The CNN model trained on the RANN dataset exhibited strong linear correlation between true and predicted memory based on the T1 cortical thickness and volume predictors. In addition, the model generated from healthy lifespan data (RANN) was able to generalize to an independent healthy lifespan data (HCPA) and older demented participants (ADNI) across different scanner types. The estimated CR was correlated with CR proxies such education and IQ across all three datasets. The current findings suggest that the transfer learning approach is an effective way to generalize the residual-based CR estimation. It is applicable to various diseases and may flexibly incorporate different imaging modalities such as fMRI and PET, making it a promising tool for scientific and clinical purposes.

Structural and functional connectivity uniquely contribute to explained variance in episodic memory performance in cognitively normal older adults

AbstractBackgroundGiven mounting evidence that AD‐related neuropathological changes may be present in cognitively normal individuals, there is a need to examine brain biomarkers related to variability in cognition that may precede cognitive decline. Although prior studies demonstrate age‐related changes in structural connectivity (SC) and functional connectivity (FC) separately (Contreras et al., 2015), few have adopted a multimodal approach to test the potential interplay between SC and FC, and their relative associations with cognition. Here, we examined the independent contributions of SC and FC to individual differences in episodic memory performance in cognitively normal older adults.MethodThis cross‐sectional study included 107 cognitively normal participants from the BIOCARD study. SC was indexed using radial diffusivity (RD) and mean diffusivity (MD) of two limbic white matter tracts (fornix and hippocampal cingulum), as measured by diffusion‐weighted MRI. FC within five large‐scale brain networks (control, default, limbic, dorsal attention, and salience/ventral attention) was derived using resting state fMRI. Hierarchical linear regression was utilized to directly compare the relative contributions of SC and FC to individual variability in a composite delayed episodic memory score, while also accounting for age, sex, cerebrospinal fluid (CSF) Aß42 and total tau, and gray matter volumes of the entorhinal cortex and hippocampus.ResultsWhen all five FC networks were included in the regression, only the salience network emerged as a significant FC predictor. Therefore, we performed a follow‐up analysis with salience network connectivity as the only FC measure of interest. In this model, the addition of both SC and FC measures (but not CSF or gray matter volumes) significantly increased the proportion of explained variance in memory performance, and all three measures (fornix/hippocampal cingulum microstructure, and salience network connectivity) were significant independent predictors of memory performance.ConclusionThese findings demonstrate that both connectivity modalities make unique contributions to episodic memory performance, but CSF and gray mater volumes do not. Furthermore, the highest proportion of explained variance was achieved when both modalities were included in the model, suggesting that the combination of SC and FC markers best accounts for individual variability in episodic memory in cognitively normal older adults.

Medial temporal lobe white matter pathway variability is associated with individual differences in episodic memory in cognitively normal older adults

Significant evidence demonstrates that aging is associated with variability in cognitive performance, even among individuals who are cognitively normal. In this study, we examined measures from magnetic resonance imaging and cerebrospinal fluid (CSF) to investigate which measures, alone or in combination, were associated with individual differences in episodic memory performance. Using hierarchical linear regressions, we compared the ability of diffusion tensor imaging (DTI) metrics, CSF measures of amyloid and tau, and gray matter volumes to explain variability in memory performance in a cohort of cognitively normal older adults. Measures of DTI microstructure were significantly associated with variance in memory performance, even after accounting for the contribution of the CSF and magnetic resonance imaging gray matter volume measures. Significant associations were found between DTI measures of the hippocampal cingulum and fornix with individual differences in memory. No such relationships were found between memory performance and CSF markers or gray matter volumes. These findings suggest that DTI metrics may be useful in identifying changes associated with aging or age-related diseases.

Prefrontal working memory activity predicts episodic memory performance: A neuroimaging study

Working memory (WM) and long term memory (LTM) are different neuropsychological processes, although distinction between these domains is an area of debate. LTM is thought to rely on hippocampal circuitry. Cognitive neuroscience models imply that WM processing may at least partially support LTM within regions of the prefrontal cortex (PFC). We sought to determine the association between PFC based WM processing and LTM in the visuospatial domain. In contrast to prior work, we aimed to query if WM was involved in learning and free recall trials as measured by standard neuropsychological tests of LTM. Forty-three older adults (24 with a diagnosis of amnestic Mild Cognitive Impairment and 19 elderly controls) were included in the analysis. Patients completed a fMRI task of visuospatial maintenance WM in which they were required to match a previously studied complex shape with one of two probes. Extent of activity in the right PFC during the WM task was tabulated for each patient. Hippocampal volume was quantified from T1 scans. On a separate day patients completed neuropsychological testing, including the Brief Visuospatial Memory Test- Revised (BVMT-R), which includes learning trials (total recall), delayed free recall, and recognition. Right PFC activity was associated with performance on BVMT-R total recall and delayed recall. Results from multiple regression showed that PFC activity explained an additional 9 % of the variance in memory performance above right hippocampal volume. These findings suggest that PFC processing that supports WM (including stimuli maintenance, retrieval, and selection) are also involved in LTM learning and recall.

AMYLOID AND TAU BURDEN IMPROVE RESIDUAL APPROACHES TO COGNITIVE RESERVE QUANTIFICATION IN AD

Cognitive reserve (CR) is a construct describing resistance to brain pathology. Residual cognitive performance, after accounting for the effect of relevant variables such as brain pathology, has been employed as a measure of CR. Most prior studies, however, have not accounted for the influence of amyloid and tau burden in modeling pathology. We extended the CR framework to include PET biomarkers of AD neuropathology. 363 participants from ADNI were analyzed, including 129 cognitively normal, 84 with significant memory concerns, 74 with early MCI, 44 with late MCI, and 32 with AD. We assessed the relationship between groups of related variables comparable to those previously delineated by Reed et al (2010) and episodic memory using multiple linear regression (MLR). We report the relationship between memory and sex, race, ethnicity, and education as MEM-D (demographic); memory and cortical volume, hippocampal volume, and white matter hyperintensities as MEM-B (brain MRI); and, memory and amyloid (mean cortical [18F]Florbetapir SUVR), tau (mean lateral temporal lobe [18F]Flortaucipir SUVR), and MEM-B variables, as MEM-B+. Combinations of these models are denoted as MEM-DB and MEM-DB+. MLR was used to assess the relation of CR, defined as unstandardized residuals from the above models, to functional outcomes including FAQ and CDR sum-of-boxes (CDRsb). Including amyloid and tau significantly improved the fit for models MEM-B+ (R2=.334, p<.001) relative to MEM-B (R2=.237, p<.001) and MEM-DB+ (R2=.423, p<.001) relative to MEM-DB (R2=.317, p<.001). As expected, associations between memory performance and groups of related variables strengthened with the inclusion of amyloid and tau measures. This was similarly reflected in the weakened associations between residual performance from these models and functional measures (FAQ/CDRsb) after the inclusion of biomarkers, though the relationships remained significant (p<.001). Amyloid and tau pathology explain a statistically significant proportion of variance in memory performance beyond structural brain measures and subject demographics. The current findings in a large ADNI sample are consistent with a recent report in a smaller sample. Future studies using residual approaches to CR quantification will have increased validity after accounting for amyloid and tau pathology.

P2‐422: PRESERVED FUNCTIONAL CONNECTIVITY IN THE DEFAULT MODE AND SALIENCE NETWORKS IS ASSOCIATED WITH YOUTHFUL MEMORY IN SUPERAGING

9Superagers9 are older adults who, despite their advanced age, maintain youthful memory. Previous morphometry studies revealed multiple default mode network (DMN) and salience network (SN) regions whose cortical thickness is preserved in superagers and correlates with memory performance. In this study, we examined the intrinsic functional connectivity within DMN and SN in 41 young (24.5 ± 3.6 years old) and 40 elderly adults (66.9 ± 5.5 years old). As in prior studies, superaging was defined as youthful performance on a memory recall task, the California Verbal Learning Test (CVLT). Participants underwent a resting state fMRI scan and performed a separate visual-verbal recognition memory task. As predicted, within both DMN and SN, superagers had stronger connectivity compared to typical older adults and similar connectivity compared to young adults. Superagers also performed similarly to young adults and better than typical older adults on the recognition task, demonstrating youthful episodic memory that generalized across memory tasks. Stronger connectivity within each network independently predicted better performance on both the CVLT and recognition task in older adults. Variation in intrinsic connectivity explained unique variance in memory performance, above and beyond preserved neuroanatomy. A post-hoc analysis revealed that DMN and SN nodes were more strongly inversely correlated in superagers than in typical older adults but were similarly correlated in superagers and young adults. Stronger between-network inverse correlations also predicted better memory performance in the entire sample of older adults. These results extend our understanding of the neural basis of superaging as a model of successful aging.

Stronger Functional Connectivity in the Default Mode and Salience Networks Is Associated With Youthful Memory in Superaging.

"Superagers" are older adults who, despite their advanced age, maintain youthful memory. Previous morphometry studies revealed multiple default mode network (DMN) and salience network (SN) regions whose cortical thickness is greater in superagers and correlates with memory performance. In this study, we examined the intrinsic functional connectivity within DMN and SN in 41 young (24.5 ± 3.6 years old) and 40 older adults (66.9 ± 5.5 years old). Superaging was defined as youthful performance on a memory recall task, the California Verbal Learning Test (CVLT). Participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and performed a separate visual-verbal recognition memory task. As predicted, within both DMN and SN, superagers had stronger connectivity compared with typical older adults and similar connectivity compared with young adults. Superagers also performed similarly to young adults and better than typical older adults on the recognition task, demonstrating youthful episodic memory that generalized across memory tasks. Stronger connectivity within each network independently predicted better performance on both the CVLT and recognition task in older adults. Variation in intrinsic connectivity explained unique variance in memory performance, above and beyond youthful neuroanatomy. These results extend our understanding of the neural basis of superaging as a model of successful aging.

The influence of perceptual similarity and individual differences on false memories in aging

Previous false memory research has suggested that older adults' false memories are based on an overreliance on gist processing in the absence of item-specific details. Yet, false memory studies have rarely taken into consideration the precise role of item-item similarity on the cognitive and neural mechanisms underlying perceptual false memories in older adults. In addition, work in our laboratory has suggested that when investigating the neural basis of false memories in older adults, it is equally as critical to take into account interindividual variability in behavior. With both factors in mind, the present study was the first to examine how both controlled, systematic differences in perceptual relatedness between targets and lures and individual differences in true and false recognition contribute to the neural basis of both true and false memories in older adults. Results suggest that between-subject variability in memory performance modulates neural activity in key regions associated with false memories in aging, whereas systematic differences in perceptual similarity did not modulate neural activity associated with false memories.

Individual differences in associative memory among older adults explained by hippocampal subfield structure and function

Older adults experience impairments in episodic memory, ranging from mild to clinically significant. Given the critical role of the medial temporal lobe (MTL) in episodic memory, age-related changes in MTL structure and function may partially account for individual differences in memory. Using ultra-high-field 7T structural MRI and high-resolution 3T functional MRI (hr-fMRI), we evaluated MTL subfield thickness and function in older adults representing a spectrum of cognitive health. Participants performed an associative memory task during hr-fMRI in which they encoded and later retrieved face-name pairs. Motivated by prior research, we hypothesized that differences in performance would be explained by the following: (i) entorhinal cortex (ERC) and CA1 apical neuropil layer [CA1-stratum radiatum lacunosum moleculare (SRLM)] thickness, and (ii) activity in ERC and the dentate gyrus (DG)/CA3 region. Regression analyses revealed that this combination of factors significantly accounted for variability in memory performance. Among these metrics, CA1-SRLM thickness was positively associated with memory, whereas DG/CA3 retrieval activity was negatively associated with memory. Furthermore, including structural and functional metrics in the same model better accounted for performance than did single-modality models. These results advance the understanding of how independent but converging influences of both MTL subfield structure and function contribute to age-related memory impairment, complementing findings in the rodent and human postmortem literatures.

The role of executive functioning in memory performance in pediatric focal epilepsy.

Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]). Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal). Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval.

Age-related individual variability in memory performance is associated with amygdala-hippocampal circuit function and emotional pattern separation

While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala-lateral entorhinal cortex-DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging.

An investigation of the efficiency of the mini-Kingston standardized cognitive assessment-revised in classifying patients according to DSM-5 major and mild neurocognitive disorders due to possible Alzheimer's disease

The aim of this study was to examine the efficiency of the mini-Kingston standardized cognitive assessment-revised (mini-KSCAr) in classifying patients according to DSM-5 major and mild neurocognitive disorders (NCD) due to possible Alzheimer's disease (AD). Files of 85 individuals who were tested on the Kingston standardized cognitive assessment-revised were reviewed and scores were calculated for the mini-KSCAr. Medical history, psychiatric and physical status, basic and instrumental activities of daily living, as well as scores on the Cambridge cognitive examination-revised (CAMCOG-R), and the clinical dementia rating (CDR) scale were used to establish DSM-5 diagnoses of major or mild neurocognitive disorders (NCD) due to possible AD or no cognitive decline. All participants were tested on the Mini-Mental State Examination (MMSE) and the clock drawing test (CDT), and a subset (N = 28) were also tested on three well-known memory tasks. Scores on the MMSE, CDT, and mini-KSCAr differed across groups, but only the mini-KSCAr significantly distinguished each group from the other two. The mini-KSCAr showed better sensitivity, specificity, and likelihood ratios (LRs) than did the MMSE and the CDT. A regression analysis revealed that the mini-KSCAr accounted for almost half of the variance in memory performance, whereas the MMSE and the CDT contributed nothing to this prediction once the mini-KSCAr was used. The mini-KSCAr is an efficient instrument for the diagnosis of DSM-5 major and mild NCD due to possible AD in a specialized psychogeriatric setting, and its utility is greater than that of the MMSE and the CDT.

KIBRA gene polymorphism has no association with verbal or visual episodic memory performance.

Inter-individual variability in memory performance has been suggested to result, in part, from genetic differences in the coding of proteins involved in long-term potentiation (LTP). The present study examined the effect of a single-nucleotide polymorphism (SNP) in the KIBRA gene (rs17070145) on episodic memory performance, using multiple measures of verbal and visual episodic memory. A total of 256 female and 130 male healthy, older adults (mean age = 60.86 years) were recruited from the Tasmanian Healthy Brain Project (THBP), undergoing both neuropsychological and genetic testing. The current study showed no significant effect of the KIBRA polymorphism on performance on the Rey Auditory Verbal Learning Task, Logical Memory test, Paired Associates Learning test or Rey Complex Figure Task. The results suggest there is little to no functional significance of KIBRA genotype on episodic memory performance, regardless of modality.