Paired-associate Learning Research Articles

Anterior thalamic nuclei: A critical substrate for non-spatial paired-associate memory in rats.

Injury or dysfunction in the anterior thalamic nuclei (ATN) may be the key contributory factor in many instances of diencephalic amnesia. Experimental ATN lesions impair spatial memory and temporal discriminations, but there is only limited support for a more general role in non-spatial memory. To extend evidence on the effects of ATN lesions, we examined the acquisition of biconditional associations between odour and object pairings presented in a runway, either with or without a temporal gap between these items. Intact adult male rats acquired both the no-trace and 10-s trace versions of this non-spatial task. Intact rats trained in the trace version showed elevated Zif268 activation in the dorsal CA1 of the hippocampus, suggesting that the temporal component recruited additional neural processing. ATN lesions completely blocked acquisition on both versions of this association-memory task. This deficit was not due to poor inhibition to non-rewarded cues or impaired sensory processing, because rats with ATN lesions were unimpaired in the acquisition of simple odour discriminations and simple object discriminations using similar task demands in the same apparatus. This evidence challenges the view that impairments in arbitrary paired-associate learning after ATN lesions require the use of multimodal spatial stimuli. It suggests that diencephalic amnesia associated with the ATN stems from degraded attention to stimulus-stimulus associations and their representation across a distributed memory system.

Separation of memory span and learning rate: Evidence from behavior and spontaneous brain activity in older adults.

It is unclear how the ability to initially acquire information in a first learning trial relates to learning rate in subsequent repeated trials. The separation of memory span and learning rate is an important psychological dilemma that remains unaddressed. Given the potential effects of aging on memory and learning, this study investigated the separation of memory span and learning rate from behavior and spontaneous brain activity in older adults. We enrolled a total of 758 participants, including 707 healthy older adults and 51 mild cognitive impairment (MCI) patients. Sixty-five participants out of 707 completed resting-state functional magnetic resonance imaging (fMRI) scanning. Behaviorally, memory span and learning rate were not correlated with each other in the paired-associative learning test (PALT) but were negatively correlated in the auditory verbal learning test (AVLT). This indicated that the relationship between memory span and learning rate for item memory might be differentially affected by aging. Interaction analysis confirmed that these two capacities were differentially affected by test type (associative memory vs. item memory). Additionally, at three progressive brain activity indexes (ALFF, ReHo, and DC), the right brain regions (right inferior temporal gyrus and right middle frontal gyrus) were more negatively correlated with memory span, whereas, the left precuneus was more positively correlated with learning rate. Regarding pathological aging, none of the correlations between memory span and learning rate were significant in either PALT or AVLT in MCI. This study provides novel evidence for the dissociation of memory span and learning rate at behavioral and brain activity levels, which may have useful applications in detecting cognitive deficits or conducting cognitive interventions.

The effect of bilingualism on executive functions when languages are similar: a comparison between Hungarian–Serbian and Slovak–Serbian young adult bilinguals

Among the factors argued to contribute to a bilingual advantage in executive function (EF), the combination of languages spoken by the bilingual is often overlooked. In this study, we explored the role of language similarity on memory and EF task by comparing performance of three groups of young adults—Hungarian–Serbian and Slovak–Serbian early balanced bilinguals, and Serbian-speaking monolinguals. Slovak is typologically related to Serbian, which are both Slavic, in contrast to Hungarian, which is Finno–Ugric. On the computerized tasks from the CANTAB battery (CANTAB Cognition, 2016, www.cantab.com), differences between monolinguals and bilinguals emerged on the EF tasks: Stockings of Cambridge (SOC) and Attentional Set Shifting (AST), but not the memory tasks: Delayed Matching to Sample (DMS), Paired Associate Learning (PAL), Spatial Working Memory (SWM). Both Hungarian–Serbian and Slovak–Serbian bilinguals outperformed the monolinguals on the more difficult SOC tasks, solved using more than a minimally required number of moves. This is in line with reports that bilinguals perform better under more complex conditions that require more monitoring and switching. However, bilinguals speaking Hungarian and Serbian spent less time preparing to execute the simpler SOC tasks, which can be solved in a minimum of two or three moves; they also exhibited reduced local switching cost and were faster overall on AST than both the Slovak–Serbian bilinguals and Serbian monolinguals. The advantageous performance of speakers of the typologically unrelated languages in our study suggests that these bilinguals may have more efficient attention switching and inhibition systems than bilinguals who speak typologically similar languages.

Gender/Sex Differences in the Association of Mild Behavioral Impairment with Cognitive Aging.

While the gender/sex differences in neuropsychiatric symptoms in dementia population are well described, gender/sex differences in mild behavioral impairment (MBI) in dementia-free populations and the relationship to cognitive performance and to subsequent cognitive decline have not been studied. We aimed to explore gender/sex differences in the association of MBI with the level of cognitive performance and its rate of decline in a dementia-free cohort. We studied 8,181 older adults enrolled in the online PROTECT UK Study. MBI was assessed using the MBI Checklist and cognition was measured by digit span, paired associate learning, spatial working memory, and verbal reasoning. Statistical analysis was conducted using linear regression models and linear mixed-effects models. Out of 8,181 individuals (median age 63 years, 73% females), 11% of females and 14% of males had MBI syndrome. Females exhibited less often symptoms of decreased motivation (45% versus 36% in males), impulse dyscontrol (40% versus 44% in males; p = 0.001) and social inappropriateness (12% versus 15%; p < 0.001), while they showed more often symptoms of emotional dysregulation (45% versus 36%; p < 0.001). The associations of MBI domains with some measures of cognitive performance and decline were stronger in males than females, with the exception of the association of emotional dysregulation with the rate of cognitive decline in verbal reasoning, which was present exclusively in females. MBI may influence cognition to a greater extent in males than in females. We propose that predictors and biomarkers of dementia should consider gender/sex as an effect modifier.

Relationship between neuropsychological test scores and hippocampal atrophy in non-demented Japanese older adults

BackgroundIt is essential to detect morphological changes in the brain prior to the onset of cognitive decline. Although hippocampal volumes have been reported to be correlated with scores on neuropsychological tests, this relationship is still unclear among Japanese non-demented older adults. Thus, this exploratory retrospective study aimed to identify neuropsychological tests that correlate with the degree of hippocampal atrophy in Japanese non-demented older adults. MethodsThirteen non-demented Japanese older adults aged 71.2 ± 5.2 years were included. Hippocampal atrophy was evaluated by assessing the participants’ MRI scans using the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) software. Spearman’s partial correlation analyses were conducted to reveal relationships between VSRAD scores and neuropsychological test scores, including Raven’s Colored Progressive Matrices test (RCPM), the Standard Verbal Paired Associate Learning test (SP-A), and the Trail Making Test (TMT) scores by controlling for age, sex, and years of education. ResultsThe Spearman’s partial correlation analysis results revealed that there were significant correlations between the degree of hippocampal atrophy and RCPM (rho = -0.691, p = 0.027), TMT part B (rho = 0.823, p = 0.003), and the related SP-A test scores (rho = -0.663, p = 0.027). ConclusionsOur results indicate that neuropsychological tests, particularly the TMT part B, might be used in assessing the degree of hippocampal atrophy in non-demented Japanese elderly individuals and should be studied further in the future to develop screening methods to detect brain atrophy.

System alignment supports cross-domain learning and zero-shot generalisation

Recent findings suggest conceptual relationships hold across modalities. For instance, if two concepts occur in similar linguistic contexts, they also likely occur in similar visual contexts. These similarity structures may provide a valuable signal for alignment when learning to map between domains, such as when learning the names of objects. To assess this possibility, we conducted a paired-associate learning experiment in which participants mapped objects that varied on two visual features to locations that varied along two spatial dimensions. We manipulated whether the featural and spatial systems were aligned or misaligned. Although system alignment was not required to complete this supervised learning task, we found that participants learned more efficiently when systems aligned and that aligned systems facilitated zero-shot generalisation. We fit a variety of models to individuals' responses and found that models which included an offline unsupervised alignment mechanism best accounted for human performance. Our results provide empirical evidence that people align entire representation systems to accelerate learning, even when learning seemingly arbitrary associations between two domains.

Semantic relatedness retroactively boosts memory and promotes memory interdependence across episodes.

Two fundamental issues in memory research concern when later experiences strengthen or weaken initial memories and when the two memories become linked or remain independent. A promising candidate for explaining these issues is semantic relatedness. Here, across five paired-associate learning experiments (N=1000), we systematically varied the semantic relatedness between initial and later cues, initial and later targets, or both. We found that learning retroactively benefited long-term memory performance for semantically related words (vs. unshown control words), and these benefits increased as a function of relatedness. Critically, memory dependence between initial and later pairs also increased with relatedness, suggesting that pre-existing semantic relationships promote interdependence for memories formed across episodes. We also found that modest retroactive benefits, but not interdependencies, emerged when subjects learned via studying rather than practice testing. These findings demonstrate that semantic relatedness during new learning retroactively strengthens old associations while scaffolding new ones into well-fortified memory traces.

Relation between Vitamin D level and severity, symptomatology and cognitive dysfunction of Major Depressive Disorder - A sample of Egyptian patients

IntroductionVitamin D helps in the regulation of neurotransmission and neuroprotection. Therefore, vitamin D deficiency might lead to inactivated receptors and may result in depression.ObjectivesThe study assessed the relation between serum level of vitamin D and severity, symptomatology and cognitive dysfunction of Major Depressive Disorder (MDD) in a sample of Egyptian patients.Methods Serum levels of 25-hydroxy vitamin D were measured with electro-chemiluminescence binding assay technique in 75 patients with major depressive disorder. Patients were recruited from Psychiatry and Addiction Hospital, Kasr Al Ainy outpatient clinic. Patients were subjected to the Structured Clinical Interview for DSM-IV Axis I Disorders(SCID), Hamilton depression scale (HAM-D), Mini-mental status examination (MMSE), Wechsler memory subtests (story A and paired associate learning test (PALT) ), Benton visual retention test (BVRT) and Trail B test.Results94.6% of patients had vitamin D deficiency. There was no significant correlation between levels of vitamin D and severity of depression according to HAM-D. Regarding symptoms of depression, there was a statistically significant difference between levels of vitamin D, being more deficient with decreased concentration, decreased libido and menstrual disturbances. There was no statistically significant correlation between level of vitamin D and cognitive functions tests.Conclusions Major depressive disorder was associated with vitamin D deficiency but no statistical significant correlation could be established neither between levels of vitamin D and severity of depression nor between levels of vitamin D and cognitive dysfunction. Vitamin D level was statistically correlated with decreased concentration, decreased libido and menstrual disturbances.DisclosureNo significant relationships.

1312-P: Impaired Beta-Cell Function in Older Patients Corresponds to Changes in Salience Network Connectivity

The salience network (anterior cingulate cortex (ACC) —insula) plays an important role in regulating attention and memory in the context of decision making and has also been shown to be highly responsive to changes in peripheral glucose levels. Increased age is also associated with changes in glucose homeostasis and the salience network. To investigate these relationships, 40 healthy, cognitively normal, non-diabetic subjects (20 Young (age mean 28±1 years, BMI 28.1 ±1.1 kg/m2, HbA1c 5.3±0.1%) and 20 Old (age mean of 73±2 years, BMI 26.9±0.9 kg/m2, HbA1c 5.5±0.1%)) underwent an OGTT, resting state functional connectivity (FC) MRI brain scanning, and cognitive assessments (Cambridge Neuropsychological Test Automated Battery) . Despite similar BMI, HbA1C, and fasting glucose levels, older individuals had lower disposition index (young: 9±2, old: 3.3±0.4, p=0.005) indicating impaired β-cell function. There were no differences in measures of insulin sensitivity (HOMA-IR (p=0.38) or Matsuda index (p=0.70) . A seed-based analysis using a predefined cubic voxel in the ACC showed differences in FC between the ACC and the left insula (Main Effect by group, P&amp;lt;0.001) with lower connectivity values in Old compared to Young subjects. This connectivity value also correlated with errors on the Paired Associate Learning task, which tests attention and memory (r=-0.5, P=0.001) . Moreover, the connectivity values correlated with the disposition index in older subjects (r=0.49, P=0.03) but not younger subjects (P=0.9) . Thus, in our cohort of healthy, cognitively normal older subjects, impairments in beta-cell function are associated with altered functional connectivity within the salience network. These findings highlight the need for future investigations to determine whether mild age-related changes in glycemic control contribute to neurocognitive changes in older patients. Disclosure J.Deajon-jackson: None. C.Lacadie: None. C.Watt: None. D.Scheinost: None. J.J.Hwang: None. Funding Claude D. Pepper Older Americans Independence Center at Yale School of Medicine (P30AG021342)

Differential associations of visual memory with hippocampal subfields in subjective cognitive decline and amnestic mild cognitive impairment

BackgroundAlthough previous studies have demonstrated that the hippocampus plays a role in verbal memory, the role of hippocampal subfields in visual memory is uncertain, especially in those with preclinical Alzheimer's disease (AD). This study aimed to examine relationships between hippocampal subfield volumes and visual memory in SCD (subjective cognitive decline) and aMCI (amnestic mild cognitive impairment).MethodsThe study sample included 47 SCD patients, 62 aMCI patients, and 51 normal controls (NCs) and was recruited from Shanghai Jiao Tong University Affiliated Sixth People's Hospital. Visual memory was measured by the subtests of BVMT-R (Brief Visuospatial Memory Test-Revised), PLT (Pictorial Learning Test), DMS (Delayed Matching to Sample), and PAL (Paired Associates Learning). Hippocampal subfield volumes were estimated using FreeSurfer software (version 6.0). We modeled the association between visual memory and relative hippocampal subfield volumes (dividing by estimated total intracranial volume) using Pearson's correlation and linear regression.ResultsCompared with the NC group, patients with SCD did not find any relative hippocampal subregion atrophy, and the aMCI group found atrophy in CA1, molecular layer, subiculum, GC-ML-DG, CA4, and CA3. After adjusting for covariates (age, sex, and APOE ε4 status) and FDR (false discovery rate) correction of p (q values) < 0.05, in NC group, DMS delay matching scores were significant and negatively associated with presubiculum (r = -0.399, FDR q = 0.024); in SCD group, DMS delay matching scores were negatively associated with CA3 (r = -0.378, FDR q = 0.048); in the aMCI group, BVMT-R immediate recall scores were positively associated with CA1, molecular layer, subiculum, and GC-ML-DG (r = 0.360–0.374, FDR q < 0.036). Stepwise linear regression analysis confirmed the association.ConclusionsOur results indicate a different and specific correction of visual memory with relative hippocampal subfield volumes between SCD and aMCI. The correlations involved different and more subfields as cognitive decline. Whether these associations predict future disease progression needs dynamic longitudinal studies.

No-think, No drink? Assessing the ability of reconsolidation interference by intentional forgetting to suppress alcohol memories in hazardous drinkers

Memory reconsolidation offers an opportunity to modify previously consolidated memories by first reactivating them. The process is triggered by the presentation of retrieval cues (reminders of the memory to be reactivated). However, reconsolidation is not universally triggered upon retrieval. Here we investigate one boundary condition thought to constrain memory reactivation: retrieval length. We also investigate the effects of a novel post-retrieval manipulation: intentional suppression. We assessed this with the think/no-think (TNT) task, in a clinically relevant sample of hazardous drinkers, using alcohol-related paired associate learning. 73 participants took part in four online sessions. On the first session participants were required to learn 36 image-word pairs. On the second session participants received 0, 4, 18 or 36 retrieval cues followed by the TNT task. The recall of the pairs was assessed 2 and 7 days after the retrieval + TNT procedure. The 4-trial retrieval procedure was the most consistent with triggering memory reconsolidation. This group showed greater practice effects and was the only group in which suppression-induced forgetting was observed at test. However, suppression-induced forgetting of alcohol cues was lower than in normative samples, indicating that intentional forgetting effects may depend upon population, salience of material and time between suppression and retrieval.

Neurobehavioral mechanisms underlying the effects of physical exercise break on episodic memory during prolonged sitting

Background and objectiveEpisodic memory is the ability that enables individuals to recall and re-experience previous events and usually includes information concerning the spatial and temporal context. This study examined the effects of a physical exercise break during a period of prolonged sitting on episodic memory. Furthermore, we aimed to investigate whether alterations of functional connectivity patterns might contribute to the exercise-induced changes in episodic memory. MethodsSixty healthy male college students were randomly assigned (1:1 ratio) to a prolonged-sitting group (PS group) or a physical-exercise-break group (PE group). The face-name paired-associate learning task was used to probe episodic memory. During the task, cortical hemodynamics in the prefrontal cortex were recorded using functional near-infrared spectroscopy (fNIRS). Changes in cortical hemodynamics were used to determine functional connectivity using graph-theoretical network analysis. ResultsThere was no between-group difference in neurobehavioral outcomes at the pretest assessment. During the posttest assessment, compared with the PS group, higher nodal efficiency in the anterior prefrontal cortex (orbitofrontal and frontopolar cortices) was observed during the encoding phase (FDR corrected p values = 0.039), and higher nodal efficiency and degree centrality of orbitofrontal cortex were observed in the retrieval phase in the PE group (FDR corrected p values = 0.035). Moreover, the PE group showed closer temporal correlational interactions between the dorsolateral prefrontal cortex and the anterior prefrontal cortex in the left hemisphere during the episodic memory encoding phase (FDR corrected p values = 0.043), when compared to the PS group. Neither significant between-group difference in accuracy nor correlations between neural and behavioral outcomes were observed after the intervention. ConclusionOur findings suggest that a physical exercise break during a prolonged sitting period has neither a beneficial nor a detrimental effect on behavioral performance concerning episodic memory. However, physical breaks do facilitate functional connectivity patterns of the prefrontal cortex while performing a episodic memory task.

Feasibility and Validity of Cambridge Neuropsychological Test Automated Battery in Mild Cognitive Impairment Screening for Patients with Atrial Fibrillation.

Background Atrial fibrillation (AF) is associated with the worsening of cognitive function. Strategies that are both convenient and reliable for cognitive screening of AF patients remain underdeveloped. We aimed to analyze the sensitivity and specificity of computerized cognitive screening strategies using subtests from Cambridge Neuropsychological Test Automated Battery (CANTAB) in AF patients. Methods The Multitasking Test (MTT), Rapid Visual Information Processing (RVP), and Paired Associates Learning (PAL) subtests from CANTAB were performed in 105 AF patients. Traditional standard neuropsychological tests were used as a reference standard. Cognitive screening models using different CANTAB subtests were established using multivariable logistic regression. Further stepwise regression using the Akaike Information Criterion (AIC) was applied to optimize the models. Receiver operating characteristic curve analyses were used to study the sensitivity and specificity of these models. Results Fifty-eight (55%) patients were diagnosed with mild cognitive impairment (MCI). MTT alone had reasonable sensitivity (82.8%) and specificity (74.5%) for MCI screening, while RVP (sensitivity 72.4%, specificity 70.2%) and PAL (sensitivity 70.7%, specificity 57.4%) were less effective. Stepwise regression of all available variables revealed that a combination of MTT and RVP brought about higher specificity (sensitivity 82.8%, specificity 85.8%), while PAL was not included in the optimal model. Moreover, adding education to the models did not result in improved validity for MCI screening. Conclusion The CANTAB subtests are feasible and effective strategies for MCI screening among AF patients independent of patients' education levels. Hence, they are practical for cardiologists or general practitioners.

Lateral Fluid Percussion Injury Causes Sex-Specific Deficits in Anterograde but Not Retrograde Memory.

Cognitive impairment is a common symptom after traumatic brain injury (TBI). Memory, in particular, is often disrupted during chronic post-injury recovery. To understand the sex-specific effects of brain injury on retrograde and anterograde memory, we examined paired associate learning (PAL), spatial learning and memory, and fear memory after lateral fluid percussion TBI. We hypothesized that male and female mice would display unique memory deficits after TBI. PAL task acquisition was initiated via touchscreen operant conditioning 22 weeks before sham injury or TBI. Post-injury PAL testing occurred 7 weeks post-injury. Barnes maze and fear conditioning were completed at 14- and 15-weeks post-injury, respectively. Contrary to our expectations, behavioral outcomes were not primarily influenced by TBI. Instead, sex-specific differences were observed in all tasks which exposed task-specific trends in male TBI mice. Male mice took longer to complete the PAL task, but this was not affected by TBI and did not compromise the ability to make a correct choice. Latency to reach the goal box decreased across testing days in Barnes maze, but male TBI mice lagged in improvement compared to all other groups. Use of two learning indices revealed that male TBI mice were deficient in transferring information from 1 day to the next. Finally, acquisition and contextual retention of fear memory were similar between all groups. Cued retention of the tone-shock pairing was influenced by both injury and sex. Male sham mice displayed the strongest cued retention of fear memory, evidenced by increased freezing behavior across the test trial. In contrast, male TBI mice displayed reduced freezing behavior with repetitive tone exposure. An inverse relationship in freezing behavior to tone exposure was detected between female sham and TBI mice, although the difference was not as striking. Together, these studies show that retrograde memory is intact after lateral TBI. However, male mice are more vulnerable to post-injury anterograde memory deficits. These behaviors were not associated with gross pathological change near the site injury or in subcortical brain regions associated with memory formation. Future studies that incorporate pre- and post-injury behavioral analysis will be integral in defining sex-specific memory impairment after TBI.

A Novel Virtual Reality Assessment of Functional Cognition: Validation Study.

BackgroundCognitive deficits are present in several neuropsychiatric disorders, including Alzheimer disease, schizophrenia, and depression. Assessments used to measure cognition in these disorders are time-consuming, burdensome, and have low ecological validity. To address these limitations, we developed a novel virtual reality shopping task—VStore.ObjectiveThis study aims to establish the construct validity of VStore in relation to the established computerized cognitive battery, Cogstate, and explore its sensitivity to age-related cognitive decline.MethodsA total of 142 healthy volunteers aged 20-79 years participated in the study. The main VStore outcomes included verbal recall of 12 grocery items, time to collect items, time to select items on a self-checkout machine, time to make the payment, time to order coffee, and total completion time. Construct validity was examined through a series of backward elimination regression models to establish which Cogstate tasks, measuring attention, processing speed, verbal and visual learning, working memory, executive function, and paired associate learning, in addition to age and technological familiarity, best predicted VStore performance. In addition, 2 ridge regression and 2 logistic regression models supplemented with receiver operating characteristic curves were built, with VStore outcomes in the first model and Cogstate outcomes in the second model entered as predictors of age and age cohorts, respectively.ResultsOverall VStore performance, as indexed by the total time spent completing the task, was best explained by Cogstate tasks measuring attention, working memory, paired associate learning, and age and technological familiarity, accounting for 47% of the variance. In addition, with λ=5.16, the ridge regression model selected 5 parameters for VStore when predicting age (mean squared error 185.80, SE 19.34), and with λ=9.49 for Cogstate, the model selected all 8 tasks (mean squared error 226.80, SE 23.48). Finally, VStore was found to be highly sensitive (87%) and specific (91.7%) to age cohorts, with 94.6% of the area under the receiver operating characteristic curve.ConclusionsOur findings suggest that VStore is a promising assessment that engages standard cognitive domains and is sensitive to age-related cognitive decline.

Cortico-cognition coupling in treatment resistant schizophrenia

BackgroundBrain structural alterations and cognitive dysfunction are independent predictors for poor clinical outcome in schizophrenia, and the associations between these domains remains unclear. We employed a novel, multiblock partial least squares correlation (MB-PLS-C) technique and investigated multivariate cortico-cognitive patterns in patients with treatment-resistant schizophrenia (TRS) and matched healthy controls (HC). MethodForty-one TRS patients (age 38.5 ± 9.1, 30 males (M)), and 45 HC (age 40.2 ± 10.6, 29 M) underwent 3T structural MRI. Volumes of 68 brain regions and seven variables from CANTAB covering memory and executive domains were included. Univariate group differences were assessed, followed by the MB-PLS-C analyses to identify group-specific multivariate patterns of cortico-cognitive coupling. Supplementary three-group analyses, which included 23 non-affected first-degree relatives (NAR), were also conducted. ResultsUnivariate tests demonstrated that TRS patients showed impairments in all seven cognitive tasks and volume reductions in 12 cortical regions following Bonferroni correction. The MB-PLS-C analyses revealed two significant latent variables (LVs) explaining > 90% of the sum-of-squares variance. LV1 explained 78.86% of the sum-of-squares variance, describing a shared, widespread structure-cognitive pattern relevant to both TRS patients and HCs. In contrast, LV2 (13.47% of sum-of-squares variance explained) appeared specific to TRS and comprised a differential cortico-cognitive pattern including frontal and temporal lobes as well as paired associates learning (PAL) and intra-extra dimensional set shifting (IED). Three-group analyses also identified two significant LVs, with NARs more closely resembling healthy controls than TRS patients. ConclusionsMB-PLS-C analyses identified multivariate brain structural-cognitive patterns in the latent space that may provide a TRS signature.

Changes in cognitive function after carotid artery revascularization: Clinical significance of Standard Verbal Paired-Associate Learning Test (S-PA)

Changes in cognitive function after carotid artery revascularization: Clinical significance of Standard Verbal Paired-Associate Learning Test (S-PA)

A Preclinical Model of Computerized Cognitive Training: Touchscreen Cognitive Testing Enhances Cognition and Hippocampal Cellular Plasticity in Wildtype and Alzheimer's Disease Mice.

With the growing popularity of touchscreen cognitive testing in rodents, it is imperative to understand the fundamental effects exposure to this paradigm can have on the animals involved. In this study, we set out to assess hippocampal-dependant learning in the APP/PS1 mouse model of Alzheimer’s disease (AD) on two highly translatable touchscreen tasks – the Paired Associate Learning (PAL) task and the Trial Unique Non-Matching to Location (TUNL) task. Both of these tests are based on human tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and are sensitive to deficits in both mild cognitive impairment (MCI) and AD. Mice were assessed for deficits in PAL at 9–12 months of age, then on TUNL at 8–11 and 13–16 months. No cognitive deficits were evident in APP/PS1 mice at any age, contrary to previous reports using maze-based learning and memory tasks. We hypothesized that daily and long-term touchscreen training may have inadvertently acted as a cognitive enhancer. When touchscreen-tested mice were assessed on the Morris water maze, they showed improved task acquisition compared to naïve APP/PS1 mice and wild-type (WT) littermate controls. In addition, we show that touchscreen-trained WT and APP/PS1 mice show increased cell proliferation and immature neuron numbers in the dentate gyrus compared to behaviorally naïve WT and APP/PS1 mice. This result indicates that the touchscreen testing paradigm could improve cognitive performance, and/or mask an impairment, in experimental mouse models. This touchscreen-induced cognitive enhancement may involve increased neurogenesis, and possibly other forms of cellular plasticity. This is the first study to show increased numbers of proliferating cells and immature neurons in the hippocampus following touchscreen testing, and that touchscreen training can improve cognitive performance in maze-based spatial navigation tasks. This potential for touchscreen testing to induce cognitive enhancement, or other phenotypic shifts, in preclinical models should be considered in study design. Furthermore, touchscreen-mediated cognitive enhancement could have therapeutic implications for cognitive disorders.

Measuring the developmental relationship between memory ability and organization of a functional brain network vulnerable to Alzheimer’s disease: Preliminary findings from the PRANK study

AbstractBackgroundThe hallmark memory impairments of typically presenting Alzheimer’s disease (AD) are associated with pathological changes of the hippocampus. While it is known that the hippocampus is necessary for normal relational memory performance, the development of functional brain networks associated with the hippocampus is not well characterized, particularly in the periadolescent epoch. The development of the hippocampus and its associated functional brain network may be influenced by genetic, environmental, or other risk factors for AD, potentially creating vulnerabilities to AD in later life. This project explores the neurodevelopment of this hippocampal network to determine how individual differences in functional connectivity impact relational memory abilities during the periadolescent epoch. Here, we utilized preliminary data from the NIA‐funded Polygenic Risk of Alzheimer’s Disease in Nebraska Kids (PRANK) study, which aims to improve insight regarding how brain and cognitive development is affected by polygenic risk for Alzheimer’s disease. Our continuing study is recruiting healthy periadolescent individuals (8‐13 years of age). Here we report preliminary cross‐sectional findings from the PRANK study exploring how individual differences in hippocampal resting‐state functional connectivity (RSFC) covary with declarative/relational memory ability.MethodAnalyses were conducted on preliminary data from healthy periadolescent participants (n=40). Declarative/relational memory performance was measured with Cambridge Cognition’s Paired Associates Learning (PAL) task. Resting‐state functional MRI data was analyzed using a seed‐based approach with the bilateral hippocampus as the seed region of interest. RSFC data were analyzed to determine their covariance with relational memory ability (operationalized as PAL performance).ResultOur analysis revealed patterns of hippocampal RSFC that were broadly consistent with prior work, sharing the territory of the default mode network (DMN). We also observed regional covariance between hippocampal RSFC and performance on the PAL task.ConclusionThe present work describes preliminary findings of the ongoing PRANK study. Our preliminary observations are consistent with the perspective that hippocampal RSFC covaries with hippocampal‐dependent declarative/relation memory ability among periadolescent children. To understand whether this hippocampal network development is susceptible to genetic risk factors for AD, future work from the PRANK study will utilize participants’ AD polygenic risk scores to determine whether those scores are related to individual differences of hippocampal RSFC.

TasTest: Moving towards a digital screening test for pre‐clinical Alzheimer’s disease

AbstractBackgroundThere is urgent need to develop population‐level digital biomarkers that can detect Alzheimer’s disease (AD) across the continuum, including the preclinical phase. This would allow risk stratification for specialist tests and early recruitment to clinical trials. Motor function declines in the preclinical phase but there has been little exploration of digital motor biomarkers. We have developed ‘TasTest’, an online test that assesses multiple cognitive domains, including movement. The aim of this study was to compare performance on TasTest with subtests of the Cambridge Neuropsychological Test Battery (CANTAB), a validated digital measure of cognitive decline, and determine how performance on the TasTest items varies with age in a large community sample of older adults.MethodThe TasTest items include measures of motor control (speed and coordination of keyboard tapping), processing speed (single and choice reaction time), attention and visual perception (identification of an animal in a distorted image), and visuospatial memory (identifying features from delayed recall of a complex figure). A total of 510 adults aged over 50 years (30% male; mean 65.5 years; SD 7.36), performed TasTest and CANTAB online assessments in their homes. We compared performance on TasTest items to performance on the Paired Associates Learning (PAL) task, which has been previously validated as predictive of accelerated cognitive decline (Barnett et al. 2015, Current Topics in Behavioral Neurosciences, vol 28, Springer, Cham).ResultAll TasTest items were significantly associated with PAL scores except the total number of correct responses on the reaction time tasks (Table 1). Several TasTest items had stronger correlations with age than the PAL, these included the keyboard tapping tasks, the number of correctly identified animals on the distorted image, and both simple and choice reaction times (Figure 1).ConclusionOlder people were able to readily complete TasTest tasks remotely from their homes, and performance on most items was significantly associated with scores on a previously validated test of cognition, and correlated with age. TasTest shows potential as a non‐invasive, scalable dementia screening tool.