Paired Associates Research Articles

Episodic recognition memory based on incidental learning of visual associations is largely preserved compared to recall in amnestic mild cognitive impairment and mild Alzheimer’s disease

We investigated preserved episodic recognition memory based on incidental learning of visual associations in Alzheimer’s disease (AD). In a cross-sectional design, we analyzed episodic memory score profiles of patients with amnestic mild cognitive impairment (a-MCI) (n = 42) or mild AD (n = 19) who had hippocampal atrophy, and healthy elderly controls (n = 43). The Visual Association Test-Extended served as a measure of episodic memory. Multiple-choice cued recognition was compared with paired associate recall and free recall within groups. Results showed that patients recognized learned material much better compared to when they had to recall material, resulting in large effect sizes (Cohen’s d) ranging from 1.3 to 3.5. We conclude that episodic recognition memory based on incidental learning of visual associations is largely preserved when compared to recall in a-MCI and mild AD. This suggests that the episodic memory impairment in AD may be characterized as a retrieval impairment rather than a consolidation impairment, indicating that preserved recognition compared to recall may be compatible with AD being the correct diagnosis. Measuring the episodic memory impairment in AD may benefit from using tests that capture different aspects of memory processes such as incidental learning of visual associations.

Relation between vitamin D level and severity, symptomatology and cognitive dysfunction of major depressive disorder—A sample of Egyptian patients

BackgroundVitamin D helps in the regulation of neurotransmission and neuroprotection. Therefore, vitamin D deficiency might lead to inactivated receptors and may result in depression. AimThe 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. MethodsSerum levels of 25-hydroxy vitamin D were measured with electro-chemiluminescence binding assay in 75 patients with MDD. Vitamin D deficiency was described as <20 ng/ml. 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 genital symptoms: decreased libido and menstrual disturbances. There was no statistically significant correlation between level of vitamin D and cognitive functions. ConclusionMDD 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 libido and menstrual disturbances.

Classical density functional theory reveals coexisting short-range structural decay and long-range force decay in ionic liquids

We look into the electrostatic screening in ionic liquids through the calculations of structural profiles and surface forces inside the slit system with varying width. The strong ion-ion correlation is modeled with ion pair association using reaction-based classical density functional theory. The equilibrium densities and ion pair fraction are solved iteratively. For pure ionic liquids, the oscillation of charge density is damped over relatively short range while surface force decays exponentially in the long range. Pair fraction approaches the bulk value asymptotically with growing slit width. Different components of surface force are identified according to various types of interactions.

Semantic diversity in paired-associate learning: Further evidence for the information accumulation perspective of cognitive aging.

Normal aging is often associated with a performance decline on various cognitive tests, including paired associate learning (PAL), where participants are asked to learn and recall arbitrary word pairs. While many studies have taken this as evidence to support the notion of age-related deficits in cognitive processing, Ramscar, Hendrix, Shaoul, Milin, and Baayen (Topics in Cognitive Science, 6(1), 5-42) and Ramscar, Sun, Hendrix, and Baayen (Psychological Science, 28(8), 1171-1179, 2017) posit that the decline in performance on various cognitive tasks can be explained by the accumulation of linguistic knowledge over time. To demonstrate this, Ramscar et al. (2017) found that older bilingual participants outperformed monolingual counterparts on a verbal PAL task, proposed to be due to bilinguals having accumulated less information about the words used in the study. However, comparing bilinguals to monolinguals introduces confounding factors. For example, bilingual's better performance may be due to superior executive functioning. To minimize these between-subject confounds, the current study used a within-subject design in order to examine the influence of linguistic experience on paired associate learning in younger and older adults. Linguistic experience was modeled using a semantic diversity measure of word strength (Jones, Johns, & Recchia, 2012). When frequency is controlled for, high semantic diversity words are associated to a greater number of words and have a higher average strength of association. In the current study, PAL performance of older adults was significantly lower for word pairs involving high semantic diversity words, while their performance did not differ for low semantic diversity words, consistent with the information accumulation perspective of aging.

Disrupted parahippocampal and midbrain function underlie slower verbal learning in adolescent-onset regular cannabis use

RationaleProlonged use of cannabis, the most widely used illicit drug worldwide, has been consistently associated with impairment in memory and verbal learning. Although the neurophysiological underpinnings of these impairments have been investigated previously using functional magnetic resonance imaging (fMRI), while performing memory tasks, the results of these studies have been inconsistent and no clear picture has emerged yet. Furthermore, no previous studies have investigated trial-by-trial learning.ObjectivesWe aimed to investigate the neural underpinnings of impaired verbal learning in cannabis users as estimated over repeated learning trials.MethodsWe studied 21 adolescent-onset regular cannabis users and 21 non-users using fMRI performed at least 12 h after last cannabis use, while they performed a paired associate verbal learning task that allowed us to examine trial-by-trial learning. Brain activation during repeated verbal encoding and recall conditions of the task was indexed using the blood oxygen level-dependent haemodynamic response fMRI signal.ResultsThere was a significant improvement in recall score over repeated trials indicating learning occurring across the two groups of participants. However, learning was significantly slower in cannabis users compared to non-users (p = 0.032, partial eta-squared = 0.108). While learning verbal stimuli over repeated encoding blocks, non-users displayed progressive increase in recruitment of the midbrain, parahippocampal gyrus and thalamus (p = 0.00939, partial eta-squared = 0.180). In contrast, cannabis users displayed a greater but disrupted activation pattern in these regions, which showed a stronger correlation with new word-pairs learnt over the same blocks in cannabis users than in non-users.ConclusionsThese results suggest that disrupted medial temporal and midbrain function underlie slower learning in adolescent-onset cannabis users.

HIPPOCAMPAL GLUTAMATE MODULATION DURING MEMORY ENCODING: ASSOCIATION WITH AGE AND SUBFIELD VOLUMES

Hippocampal glutamatergic activity plays a pivotal role in memory consolidation, including the ability to form novel associations that declines with age. To test whether glutamatergic dysfunction may underpin age-related memory declines, we examined in vivo age differences in hippocampal glutamate modulation during encoding of associations, and its relationship with hippocampal subfield volumes. Proton functional magnetic resonance spectroscopy was performed on 32 young (25.1±2.8 years; 18 females) and 16 older (65.9±2.7 years; 7 females) adults to measure changes in hippocampal (randomly assigned right or left) glutamate during an object-location paired association learning task (with 12 cycles of encoding-retrieval epochs). Volumes of the dentate gyrus&CA3, CA1, subiculum, and entorhinal cortex were manually measured from T2-weighted MRI images. Memory performance differed between the age-groups [F(1, 46)=8.56, p<.01], with the older attaining a lower asymptote [t(46)=2.93, p<.05] compared to the younger. Age differences in glutamate were observed only during encoding (age-group x epoch: F(3,137)=5.28, p<.01), and varied over the epochs. Young adults showed increased glutamate during the first four encoding epochs of each cycle, with levels remaining high thereafter. Old adults evidenced a decrease in glutamate during the first four epochs, and a slow, sustained ramping-up afterwards. Including both age-groups, the maximum change in glutamate, calculated using the maximum and minimum levels during encoding, was positively associated with CA1 [F(2,39)=4.28, p<.05] and the dentate gyrus&CA3 volume [F(2,39)=4.4, p<.05], after correcting for multiple comparisons. Glutamate modulation specific to encoding may underlie age-related memory declines and be related to selected hippocampal subfield volumes.

Investigating the causal effect of cannabis use on cognitive function with a quasi-experimental co-twin design

BackgroundIt is unclear whether cannabis use causes cognitive decline; several studies show an association between cannabis use and cognitive decline, but quasi-experimental twin studies have found little support for a causal effect. Here, we evaluate the association of cannabis use with general cognitive ability and executive functions (EFs) while controlling for genetic and shared environmental confounds in a longitudinal twin study. MethodsWe first examined the phenotypic associations between cannabis initiation, frequency, and use disorder with cognitive abilities, while also controlling for pre-use general cognitive ability and other substance involvement. We tested the concurrent association between the cannabis use variables and cognitive abilities in late adolescence and young adulthood and the longitudinal association between cannabis use variables during adolescence and young adulthood cognitive abilities. Next, we used multilevel models to test whether these relations reflect between- and/or within-twin pair associations. ResultsPhenotypically, cannabis use was related to poorer cognitive functioning, although most associations were negligible after accounting for other substance use. Nevertheless, there were few significant within-family twin-specific associations, except that age 17 cannabis frequency was associated with worse age 23 Common EF and general cognitive ability. ConclusionsWe found little support for a potential causal effect of cannabis use on cognition, consistent with previous twin studies. Results suggest that cannabis use may not cause decline in cognitive ability among a normative sample of cannabis users.

Memory response and neuroimaging correlates of a novel cognitive rehabilitation program for memory problems in epilepsy: A pilot study.

Memory deficits are very common in epilepsy, but no standard of care exists to effectively manage them. We assessed effectiveness of cognitive rehabilitation (CR) on memory and neural plasticity in people with epilepsy (PWE) reporting memory impairments. Nine PWE completed 6 weekly sessions adapted from 2 generic CR programs enriched with information regarding epilepsy. Participants completed neuropsychological, mood, and quality of life (QOLIE-31) measures prior and after completion of CR; 5/9 participants also completed pre- and post-CR fMRI while performing a verbal paired associates learning task. FMRI data were analyzed using group spatial independent components analysis methods; paired t-tests compared spatial activations for pre-/post-CR. Improvements were seen in immediate recall in Rey Auditory Verbal Learning Task, QOLIE-31, and read word recognition in paired associates task (all p's≤0.05). FMRI changes comparing pre-to-post CR were noted through increased activation in the left inferior frontal gyrus (IFG) and anterior cingulate and decreased activation in the left superior temporal gyrus; also noted were decreased activations in the default mode network (DMN), right cingulate, right middle temporal gyrus, right supramarginal gyrus, and increased DMN activation in the left cuneus. This study demonstrates feasibility of conducting CR program in PWE with fMRI as a mechanistic biomarker. Improvements in cognition and cortical plasticity await confirmation in larger samples.

Visual-verbal paired associate memory in mild cognitive impairment: A neuropsychological and brain volumetric study

Visual-verbal paired associate memory in mild cognitive impairment: A neuropsychological and brain volumetric study

Visual paired associate learning deficits associated with elevated beta-amyloid in cognitively normal older adults.

Previous studies have shown that paired associate learning (PAL), a type of episodic memory, is impaired in early Alzheimer's disease (AD). Such tasks require that a set of associations (e.g., pattern-location) be learned over several trials, and the objective is to reduce errors with each trial. Currently, the nature and magnitude of impairment and decline on PAL measures in cognitively normal (CN) older adults with elevated levels of beta-amyloid (Aβ+) is unknown. This study examined PAL errors in Aβ+ and Aβ - CN older adults, both within a single assessment and over time. Participants (210 Aβ - CN, 146 Aβ + CN) from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study underwent three assessments over 36-months (baseline, and 18- and 36-month follow-ups) using a computerized paired associate learning task (CPAL). Aβ status was determined by positron emission tomography (PET) neuroimaging. No significant group differences in PAL were evident at baseline. Significant groupxtime interactions were observed, with the Aβ - CN group, but not the Aβ + CN group, evidencing improvement over time (Cohen's d = 0.30 [0.08, 0.51]). Despite this, no group differences were evident at 36-months. Results suggest that PAL dysfunction is evident over time in Aβ + CNs. This indicates a lack of benefit from repeated exposure to the task over time associated with Aβ+, which is not the case for Aβ - CNs. Further, results suggest that assessing change in Aβ+ related cognition over time, rather than at a single assessment, provides greater understanding of dysfunction in early AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A Mendelian randomization study of IL6 signaling in cardiovascular diseases, immune-related disorders and longevity

Growing evidence suggests that inflammation is a significant contributor to different cardiovascular diseases (CVDs). Mendelian randomization (MR) was performed to assess the causal inference between plasma soluble IL6 receptor (sIL6R), a negative regulator of IL6 signaling, and different cardiovascular and immune-related disorders. Cis-MR with multiple instrumental variables showed an inverse association of sIL6R with rheumatoid arthritis, atrial fibrillation, stroke, coronary artery disease, and abdominal aortic aneurysm. However, genetically-determined sIL6R level was positively associated with atopic dermatitis and asthma. Also, sIL6R level was associated with longevity, as evaluated by parental age at death, a heritable trait. Gene-based association analysis with S-PrediXcan by using tissues from GTExV7 showed that IL6R tissue expression-disease pair associations were consistent with the directional effect of IL6 signaling identified in MR. Genetically-determined reduced IL6 signaling lowers the risk of multiple CVDs and is associated with increased longevity, but at the expense of higher atopic risk.

Interplay of the long axis of the hippocampus and ventromedial prefrontal cortex in schema-related memory retrieval.

When new information is relevant to prior knowledge or schema, it can be learned and remembered better. Rodent studies have suggested that the hippocampus and ventromedial prefrontal cortex (vmPFC) are important for processing schema-related information. However, there are inconsistent findings from human studies on the involvement of the hippocampus and its interaction with the vmPFC in schema-related memory retrieval. To address these issues, we used a human analog of the rodent spatial schema task to compare brain activity during immediate retrieval of paired associations (PAs) in schema-consistent and schema-inconsistent conditions. The results showed that the anterior hippocampus was more involved in retrieving PAs in the schema-consistent condition than in the schema-inconsistent condition. Connectivity analyses showed that the anterior hippocampus had stronger coupling with the vmPFC when the participants retrieved newly learned PAs successfully in the schema-consistent (vs. schema-inconsistent) condition, whereas the coupling of the posterior hippocampus with the vmPFC showed the opposite. Taken together, the results shed light on how the long axis of the hippocampus and vmPFC interact to serve memory retrieval via different networks that differ by schema condition.

Therapy Dogs Improve Student Affect but Not Memory

ABSTRACTWhile students are increasingly struggling with anxiety and depression, the effects of therapy dogs on student stress has only recently been explored. This study was conducted to investigate whether therapy dogs can improve student affect and to determine if these benefits extend to cognition in the form of enhanced ability to remember information. Forty-four college students were randomly assigned to interact with a therapy dog or not during both learning (session 1) and testing (session 2) in a paired-associates procedure. Arousal, stress, and mood were measured at the beginning and end of each session. As predicted, therapy dogs increased happiness and decreased stress and arousal. However, there was no difference in recognition memory for the paired associates between the therapy dog and control conditions. Mood was a significant predictor of memory, such that decreased happiness in session 2 predicted better recognition performance. These findings indicate that the benefits of therapy dogs are primarily affective and not cognitive.

Overnight sleep benefits both neutral and negative direct associative and relational memory.

Strong evidence suggests that sleep plays a role in memory consolidation, which involves both stabilizing memory into long-term storage as well as integrating new information into existing stores. The current study investigated consolidation, across a day of wakefulness or night of sleep, of emotional and neutral directly learned visual paired associates (A-B/B-C pairs) as well as formation of memory for relational pairs formed via overlapping learned components (A-C pairs). Participants learned 40 negative and 40 neutral face-object pairs followed by a baseline test in session 1 either in the morning or evening. They then spent a 12-hour retention period during which participants either went about their normal day or spent the night in the sleep lab. During session 2, participants completed a surprise test to assess their memory for relational pairs (A-C) as well as memory for direct associates (A-B/B-C). As hypothesized, the results demonstrated that a 12-hour retention period predominantly spent asleep, compared to awake, benefited memory for both relational and direct associative memory. However, contrary to the hypothesis that emotional salience would promote preferential consolidation, sleep appeared to benefit both negative and neutral information similarly for direct associative and relational memories, suggesting that sleep may interact with other factors affecting encoding (e.g., depth of encoding) to benefit direct and relational associative memory. As one of the few studies examining the role of nocturnal sleep and emotion on both direct and relational associative memory, our findings suggest key insights into how overnight sleep consolidates these different forms of memory.

Schema‐like learning and memory consolidation acting through myelination

Memory is a dynamic brain function that is continually processed after encoding. Although psychologic concepts of mental schema are now well established, they have rarely been considered in animal studies. We used a behavior paradigm of multiple flavor-place paired associates (PAs) and showed that memory schema facilitates fast acquisition of new PAs in a single trial. The hippocampus is necessary for the encoding of new PAs and for memory retrieval within a certain time window—24 h following new PA consolidation. Whereas the anterior cingulate cortex (ACC) plays a critical role for dynamic PA learning and consolidation during training sessions, ACC is essential in schema representation and activation. New myelin generation is essential for learning. Neural activity in the cortical regions impacts myelination by regulating oligodendrocyte (OL) proliferation, differentiation, and myelin formation. Here, we show that newly formed OL progenitor cells and mature OLs are increased following repeated PA learning and that establishment of the memory schema is associated with enhanced myelin strength in the ACC region. Furthermore, to ensure that myelination is necessary for the acquisition of paired-associate learning, ACC lysolecithin-induced demyelination revealed impaired PA learning associated with decrease in ACC θ band power and reduced spike-field coherence and phase-locking in ACC.—Hasan, M., Kanna, M. S., Jun, W., Ramkrishnan, A. S., Iqbal, Z., Lee, Y., Li, Y. Schema-like learning and memory consolidation acting through myelination.

Optimizing the Spacing of Retrieval Practice to Improve Pharmacy Students’ Learning of Drug Names

Objective. To optimize student pharmacists' long-term retention of brand and generic drug names through spacing and modification of quiz format. Methods. In three experiments, student pharmacists learned brand and generic names for the Top 200 medications taught in a self-paced course. The students completed two spaced quizzes on the course content, a final examination, and a measure of long-term retention administered several weeks after the course was completed. Experiment 1 examined the spacing of quiz 2 relative to quiz 1 and the final examination. Experiment 2 examined whether providing hints such as giving the first 3 letters of the paired associate impacted learning. Experiment 3 examined whether providing more elaborate context improved student retention. Results. When quiz 2 was administered closer to quiz 1 but further from the final examination (expanding practice), students' long-term knowledge retention was greatest. When the first three letters of the paired associate were provided, students' long-term retention decreased. When more elaborative context was provided within the quizzes, students' long-term retention was unaffected despite higher final examination performance. Conclusion. Making retrieval of concepts easier reduces pharmacy students' long-term knowledge retention, albeit only a small effect was seen in this study. In addition, providing more elaborative context in terms of drug class and indication during retrieval did not improve students' learning.

Study of encoding and storage in memorization among patients with Alzheimer's disease

Memorization comprises three stages: encoding, storage, and retrieval. Using neuropsychological tests, we investigated the stage at which encoding and storage are retained in Alzheimer's disease (AD) patients with progressive memory disorder. The target patients were an amnestic mild cognitive impairment (MCI) group (21 cases) and FAST 4 (37 cases), 5 (10 cases), and 6 (4 cases) AD groups. The neuropsychological tests performed were the Rivermead behavioral memory test and Wechsler memory scale-revised. These were carried out in the MCI group as well as in each AD stage group. We investigated the delayed recall (free recall and cued recall) based on the disease stage and raw score of the sub-items in delayed recognition. The MCI group had 48% (median 0 point) correct respondents (providing ≥1 correct answer) for free recall, whereas FAST 4 and 5 groups had ≤14% correct respondents. In the verbal paired associates II evaluated in cued recall, the MCI group had 90% correct respondents, and the FAST 4, 5, and 6 groups had rates of 51%, 60%, and 50%, respectively. For the pictures and photos in the delayed recognition tasks, there were no significant differences in the percentage of correct respondents between the MCI group (100%) and the FAST 4 and 5 groups (70%-90%). Given that retrieval is impossible if encoding and storage are impaired, we inferred that the encoding and retrieval abilities were retained even in moderately advanced AD.

Casein haplotype diversity in seven dairy goat breeds.

Selection, drift, gene flow and breeding have extensively shaped the genomic variability of domestic animals. In goat species, several mutations identified within the casein genes have been shown to affect the level of gene expression of milk production traits. The four casein genes – CSN1S1, CSN2, CSN1S2 and CSN3 – are organized in a cluster of 250 kb located in chromosome 6, and due to tight linkage, their genetic variability is well depicted by haplotypes which are transmitted to the progeny. Thirty single nucleotide polymorphisms (SNPs) located within the casein gene cluster were used to characterize the haplotype variability of six southern Italian goat breeds (Girgentana, Maltese, Rossa Mediterranea, Argentata dell'Etna, Messinese, Capra dell'Aspromonte). A representative sample of the Norwegian dairy goat breed (Norsk melkegeit) has been used as an out-group to obtain a weighted measure of genetic diversity in the metapopulation. A total of 54 haplotypes were detected among the seven breeds: 26, 9, 8 and 11 haplotypes were found at CSN1S1, CSN2, CSN1S2 and CSN3 respectively. The number of haplotypes per breed was 14 (Norwegian), 26 (Messinese), 27 (Rossa Mediterranea and Girgentana) and 31 (Maltese, Argentata dell'Etna and Capra dell'Aspromonte). The Maltese breed showed the highest number of private haplotypes, whereas the Norwegian goat recorded the highest number of shared haplotypes. The linkage disequilibrium analysis showed higher levels of association for the SNP pairs within casein loci than SNP pairs between casein loci, likely reflecting low levels of intra-genic recombination. The highest linkage disequilibrium values were found in CSN1S1 and CSN2 genes in all the breeds, except for Argentata dell'Etna and Rossa Mediterranea. The resolution of the haplotype diversity at the casein cluster can be exploited both for selective and conservative plans.

Neural evidence for age-related differences in representational quality and strategic retrieval processes

Mounting behavioral evidence suggests that declines in both representational quality and controlled retrieval processes contribute to episodic memory decline with age. The present study sought neural evidence for age-related change in these factors by measuring neural differentiation during encoding of paired associates and changes in regional blood oxygenation level–dependent activity and functional connectivity during retrieval conditions that placed low (intact pairs) and high (recombined pairs) demands on controlled retrieval processes. Pattern similarity analysis revealed age-related declines in the differentiation of stimulus representations at encoding, manifesting as both reduced pattern similarity between closely related events and increased pattern similarity between distinct events. During retrieval, both groups increased recruitment of areas within the core recollection network when endorsing studied pairs, including the hippocampus and angular gyrus. In contrast, only younger adults increased recruitment of, and hippocampal connectivity with, lateral prefrontal regions during correct rejections of recombined pairs. These results provide evidence for age-related changes in representational quality and in the neural mechanisms supporting memory retrieval under conditions of high, but not low, control demand.

Retrieval practice decreases processing load of recall: Evidence revealed by pupillometry

Retrieval practice is an effective long-term learning strategy. Items practiced through repeated retrieval are resistant to interference, stress, and secondary load, which attributes also characterize automatization in skill learning. In two experiments, we investigated whether retrieval practice is associated with decrease in processing load, which is a further attribute of automatization. Participants first learned paired associates, and then they practiced the items either by repeatedly studying or engaging in retrieval practice. Then their memory was assessed after either five minutes (Experiment 1) or one week (Experiment 2). Processing load was measured by assessing task-evoked pupil dilation during both retrieval practice and later recall. The pattern of results was similar in both experiments. During retrieval practice, processing load decreased during consecutive practice cycles. Moreover, during the final recall test, the retrieval of previously retrieval practiced items required less processing resources, as compared to the retrieval of previously restudied items. Our results suggest that repeated retrieval reduces processing load as well as attentional control involvement during practice and later recall.