Visual Paired Associate Learning Research Articles

A visual paired associate learning (vPAL) paradigm to study memory consolidation during sleep.

Sleep improves the consolidation and long-term stability of newly formed memories and associations. Most research on human declarative memory and its consolidation during sleep uses word-pair associations requiring exhaustive learning. In the present study, we present the visual paired association learning (vPAL) paradigm, in which participants learn new associations between images of celebrities and animals. The vPAL is based on a one-shot exposure that resembles learning in natural conditions. We tested if vPAL can reveal a role for sleep in memory consolidation by assessing the specificity of memory recognition, and the cued recall performance, before and after sleep. We found that a daytime nap improved the stability of recognition memory and discrimination abilities compared to identical intervals of wakefulness. By contrast, cued recall of associations did not exhibit significant sleep-dependent effects. High-density electroencephalography during naps further revealed an association between sleep spindle density and stability of recognition memory. Thus, the vPAL paradigm opens new avenues for future research on sleep and memory consolidation across ages and heterogeneous populations in health and disease.

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.

Computerized paired associate learning performance and imaging biomarkers in older adults without dementia.

This cross-sectional study examined whether performance on the computerized Paired Associate Learning (PAL) task from the Cambridge Neuropsychological Test Automated Battery is associated with amyloid positivity as measured by Positron Emission Tomography, regional volume composites as measured by Magnetic Resonance Imaging, and cognitive impairment. Participants from the BIOCARD Study (N = 73, including 62 cognitively normal and 11 with mild cognitive impairment; M age = 70years) completed the PAL task, a comprehensive clinical and neuropsychological assessment, and neuroimaging as part of their annual study visit. In linear regressions covarying age, sex, years of education and diagnosis, higher PAL error scores were associated with amyloid positivity but not with medial temporal or cortical volume composites. By comparison, standard neuropsychological measures of episodic memory and global cognition were unrelated to amyloid positivity, but better performance on the verbal episodic memory measures was associated with larger cortical volume composites. Participants with mild cognitive impairment demonstrated worse cognitive performance on all of the cognitive measures, including the PAL task. These findings suggest that this computerized visual paired associate learning task may be more sensitive to amyloid positivity than standard neuropsychological tests, and may therefore be a promising tool for detecting amyloid positivity in non-demented participants.

VStore: A Novel Virtual Reality Assessment of Functional Cognition

Background: Cognitive deficits are present in a number of neuropsychiatric disorders including, Alzheimer’s disease, schizophrenia and depression. Assessments used to measure cognition in these disorders are time-consuming, burdensome, and lack ecological validity. To address these limitations, we developed a novel virtual reality shopping task – VStore. This study aims to establish the validity of VStore compared to the established computerised cognitive battery, Cogstate. Methods:104 healthy volunteers aged 20-79 completed the assessments. Main VStore outcomes included: 1) verbal recall of 12 grocery items, 2) time to collect items, 3) time to select items on a self-checkout machine, 4) time to make the payment, 5) time to order coffee, and 6) total completion time. To establish concurrent validity, bivariate correlations were performed between VStore outcomes and Cogstate tasks measuring attention, processing speed, verbal and visual learning, working memory, executive function, and paired associate learning. Construct validity analysis was also performed to examine which cognitive domains best predicted VStore performance. Finally, two ridge regression models were built using VStore outcomes in the first, and Cogstate outcomes in the second model as predictors of biological age to compare their sensitivity to age-related cognitive decline. Findings: We found moderate correlations between VStore and Cogstate outcomes. VStore Total Time was best explained by tasks measuring working memory and paired associate learning, in addition to age and technological familiarity, accounting for 46% of the variance. Finally, with λ = 5·16, the model fitting selected five parameters for VStore when predicting biological age (MSE = 185·8, SE= 19·34). With λ = 9·49 for Cogstate, the model fitting selected eight tasks (MSE = 226·8, SE = 23·48). Interpretation: These findings suggest that VStore is a promising assessment that engages standard cognitive domains and is sensitive to age-related cognitive decline. Funding Statement: Medical Research Council – Doctoral Training Partnership, King’s College London. Declaration of Interests: LP reports non-financial support from Vitae VR Ltd., during the conduct of the study. Authors SSS and EM created VStore, with contributions from LAP and technical development from VitaeVR Ltd. King’s College London has licensed its rights in VStore to VitaeVR Ltd. Authors LAP, EM, and SSS are entitled to a share of any revenues King’s College London may receive from commercialisation of VStore by VitaeVR Ltd. The other authors have no conflict of interest to declare. Ethics Approval Statement: Ethical approval was granted by the Psychiatry, Nursing and Midwifery Research Ethics Committee, King’s College London (LRS-16/17-4540). Informed consent was obtained.

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).

Postretrieval Relearning Strengthens Hippocampal Memories via Destabilization and Reconsolidation.

Memory reconsolidation is hypothesized to be a mechanism by which memories can be updated with new information. Such updating has previously been shown to weaken memory expression or change the nature of the memory. Here we demonstrate that retrieval-induced memory destabilization also allows that memory to be strengthened by additional learning. We show that for rodent contextual fear memories, this retrieval conditioning effect is observed only when conditioning occurs within a specific temporal window opened by retrieval. Moreover, it necessitates hippocampal protein degradation at the proteasome and engages hippocampal Zif268 protein expression, both of which are established mechanisms of memory destabilization-reconsolidation. We also demonstrate a conceptually analogous pattern of results in human visual paired-associate learning. Retrieval-relearning strengthens memory performance, again only when relearning occurs within the temporal window of memory reconsolidation. These findings link retrieval-mediated learning in humans to the reconsolidation literature, and have potential implications both for the understanding of endogenous memory gains and strategies to boost weakly learned memories.SIGNIFICANCE STATEMENT Memory reconsolidation allows existing memories to be updated with new information. Previous research has demonstrated that reconsolidation can be manipulated pharmacologically and behaviorally to impair problematic memories. In this article, we show that reconsolidation can also be exploited to strengthen memory. This is shown both in rats, in a fear memory setting, and in a human declarative memory setting. For both, the behavioral conditions necessary to observe the memory strengthening match those that are required to trigger memory reconsolidation. There are several behavioral approaches that have previously been shown convincingly to strengthen memory. The present demonstration that reconsolidation can underpin long-lasting memory improvements may both provide an underlying mechanism for such approaches and provide new strategies to boost memories.

Individual differences in the shape bias in preschool children with specific language impairment and typical language development: theoretical and clinical implications.

We investigated whether preschool children with specific language impairment (SLI) exhibit the shape bias in word learning: the bias to generalize based on shape rather than size, color, or texture in an object naming context ('This is a wek; find another wek') but not in a non-naming similarity classification context ('See this? Which one goes with this one?'). Fifty-four preschool children (16 with SLI, 16 children with typical language [TL] in an equated control group, and 22 additional children with TL included in individual differences analyses but not group comparisons) completed a battery of linguistic and cognitive assessments and two experiments. In Experiment 1, children made generalization choices in object naming and similarity classification contexts on separate days, from options similar to a target object in shape, color, or texture. On average, TL children exhibited the shape bias in an object naming context, but children with SLI did not. In Experiment 2, we tested whether the failure to exhibit the shape bias might be linked to ability to detect systematicities in the visual domain. Experiment 2 supported this hypothesis, in that children with SLI failed to learn simple paired visual associations that were readily learned by children with TL. Analyses of individual differences in the two studies revealed that visual paired-associate learning predicted degree of shape bias in children with SLI and TL better than any other measure of nonverbal intelligence or standard assessments of language ability. We discuss theoretical and clinical implications.

Effect of cholinergic neurotransmission modulation on visual spatial paired associate learning in healthy human adults

Use of cross-species neuropsychological paradigms such as visual-spatial paired associate learning (PAL) may allow for a better understanding of underlying neural substrates of memory. Such paradigms, which are often used to guide models of memory in animals, can then be carried forward into humans to provide a basis for evaluation of pharmacologic compounds designed to ameliorate learning and memory impairments in neurologic and psychiatric morbidities. This double-blind, randomized, crossover trial investigated effects of donepezil, an acetylcholinesterase (AChE) inhibitor, in attenuating scopolamine-induced cognitive impairment using a novel, "process-based" computerized measure of visual-spatial PAL. In healthy male volunteers, scopolamine (0.6mg) induced a time-dependent reduction in visual-spatial PAL, with the greatest impairment (Cohen's d = 1.37) observed 2h after dosing. Cotreatment with donepezil (10mg) significantly ameliorated scopolamine-induced impairment at the 2-h time point (Cohen's d = 0.66). Process-based analyses revealed a significant impairment in both memory (Cohen's d = 1.37 to 0.50) and executive (Cohen's d = 1 .21 to 0.62) aspects of visual-spatial PAL performance following acute scopolamine challenge, and these reductions were ameliorated by donepezil. Acute scopolamine challenge can produce large and robust deficits in visual-spatial PAL, which reflect impairments in both memory and executive processes. Coadministration of a single dose of donepezil can ameliorate these deficits. These results provide support for the use of a visual-spatial PAL test as a pharmacodynamic cognitive marker of central nervous system (CNS)-mediating compounds in humans.

A process‐based approach to characterizing the effect of acute alprazolam challenge on visual paired associate learning and memory in healthy older adults

Alprazolam is a benzodiazepine that, when administered acutely, results in impairments in several aspects of cognition, including attention, learning, and memory. However, the profile (i.e., component processes) that underlie alprazolam-related decrements in visual paired associate learning has not been fully explored. In this double-blind, placebo-controlled, randomized cross-over study of healthy older adults, we used a novel, "process-based" computerized measure of visual paired associate learning to examine the effect of a single, acute 1-mg dose of alprazolam on component processes of visual paired associate learning and memory. Acute alprazolam challenge was associated with a large magnitude reduction in visual paired associate learning and memory performance (d = 1.05). Process-based analyses revealed significant increases in distractor, exploratory, between-search, and within-search error types. Analyses of percentages of each error type suggested that, relative to placebo, alprazolam challenge resulted in a decrease in the percentage of exploratory errors and an increase in the percentage of distractor errors, both of which reflect memory processes. Results of this study suggest that acute alprazolam challenge decreases visual paired associate learning and memory performance by reducing the strength of the association between pattern and location, which may reflect a general breakdown in memory consolidation, with less evidence of reductions in executive processes (e.g., working memory) that facilitate visual paired associate learning and memory.

Examining the nature of impairment in visual paired associate learning in amnestic mild cognitive impairment.

Visual spatial learning is impaired in mild cognitive impairment (MCI) although the nature of this impairment is not clear. This study investigated the nature and magnitude of errors made by adults with amnestic MCI (aMCI) when learning pattern-location paired associations in a continuous manner. Visual associate learning was measured using the Continuous Paired Associate Learning (CPAL) task in which 30 adults who met clinical criteria for aMCI and 30 matched controls were required to learn a set of associations between patterns and locations across increasing memory loads (two, four, six, and eight). As hypothesized, the aMCI group made more total errors than controls for all memory loads above two. However, the rate of increase in errors with memory load in the aMCI group was approximately twice that for controls. In controls, errors on the CPAL task reflected almost exclusively difficulty in memory. In the aMCI group, errors on the CPAL reflected limitations in associative learning but also in short-term memory and response monitoring. These results suggest that impairments in specific aspects of executive function and working memory might contribute to poor performance on visual paired associate learning in aMCI.

Understanding failure of visual paired associate learning in amnestic mild cognitive impairment

Impairment in visual paired associate learning occurs often in with amnestic mild cognitive impairment (aMCI), a condition considered to be an early stage of Alzheimer's disease (AD). To date, studies of aMCI have characterized impaired visual paired associate learning only in terms of summary scores such as total errors or total trials to criterion. The aim of this study was to determine the nature and magnitude of errors made on a continuous paired associate learning (CPAL) task designed to allow analysis of the component processes involved in paired associate learning. Twenty-one individuals with aMCI and 54 healthy age-matched older adults (HC) performed the CPAL task in which they had to learn six pattern–location pairings over six trials. Results suggested that aMCI patients performed significantly worse on the CPAL, both in learning rate and in error accumulation. Qualitative analyses of CPAL performance revealed that in aMCI there were significantly more errors on all indices except perseverative errors. When expressed as a percentage of total errors, abnormalities occurred only for within-search and exploratory errors. These findings suggest that poor performance on visual paired associate learning tasks in aMCI reflects impairments in both learning and executive function.

Visual paired-associate learning: In search of material-specific effects in adult patients who have undergone temporal lobectomy

The mesial temporal lobes are important for learning arbitrary associations. It has previously been demonstrated that left mesial temporal structures are involved in learning word pairs, but it is not yet known whether comparable lesions in the right temporal lobe impair visually mediated associative learning. Patients who had undergone left (n=16) or right (n=18) temporal lobectomy for relief of intractable epilepsy and healthy controls (n=13) were administered two paired-associate learning tasks assessing their learning and memory of pairs of abstract designs or pairs of symbols in unique locations. Both patient groups had deficits in learning the designs, but only the right temporal group was impaired in recognition. For the symbol location task, differences were not found in learning, but again a recognition deficit was found for the right temporal group. The findings implicate the mesial temporal structures in relational learning. They support a material-specific effect for recognition but not for learning and recall of arbitrary visual and visual–spatial associative information.

Assessment of memory function: the relation between daily observation and neuropsychological test performance

The aim of the study was to explore the value of a daily observation scale in the assessment of patients' memory function by nurses on a geriatric ward. An observational study of 50 geriatric inpatients was carried out. The relationship between the memory items of the Nurses' Behavioral Rating Scale for Geriatric Inpatients (GIP) and four types of neuropsychological memory tests was examined: visual paired-associate learning (Visual Association Test, VAT), word-list learning (Eight Word Test, 8WT from the Amsterdam Dementia Screening, ADS), and the subtests Route Recall and Story Recall from the Rivermead Behavioural Memory Test (RBMT). Correlations with the overall measures assessing level of dementia such as the Mini-mental State Examination (MMSE), Clinical Dementia Rating scale (CDR) and the 15-item Geriatric Depression Scale (GDS-15) were examined as well. The Pearson's correlation coefficients between GIP and the four memory tests were between 0.45 and 0.71 (p < 0.01). The GIP correlations with the MMSE and CDR were 0.63 and 0.46, respectively (p < 0.01). No significant correlation was found with the GDS-15. Statistically significant differences in GIP memory scores between patients with dementia and non-demented patients were found (p < 0.01). Results indicate that an observation scale of memory function may have value for providing information about the underlying memory impairment. The results of nurses' observations may be used in triage contributing to the diagnostic process by selecting patients requiring further neuropsychological assessment.

The early diagnosis and differential diagnosis of Alzheimer’s disease with clinical methods

Alzheimer's disease is a progressive and fatal neurodegenerative disorder in which the novel drugs can slow down the progression in the early phase. Our purpose was to find biological markers, which would detect neuropathology in the prodromal and early phase of Alzheimer's disease. Beside the routine diagnostic methods, neuropsychological test, auditory event related potential and special laboratory tests were performed among subjects with Alzheimer's disease, vascular dementia, mild cognitive impairment and major depression compared to a healthy control group. Visual Paired Associate Learning was impaired in all patient groups, in major depression it seemed to be reversible. In amnestic mild cognitive impairment and in dementia a longer latency of late component of auditory evoked potential, P300, was found. Reduced paraoxonase activity in the serum and increased Nepsilon(gamma-glutamyl)lysine isodipeptide concentration in the cerebrospinal fluid were detected in both dementia groups. Characteristic changes of Visual Paired Associate Learning and P300 might predict the conversion to Alzheimer's disease in mild cognitive impairment. The paraoxonase activity and the isodipeptide concentration can be sensitive markers of the pathomechanism of neurodegeneration. A combined use of the above-mentioned methods can help in the early prediction and diagnosis of Alzheimer's disease.

Word, nonword, and visual paired associate learning in Dutch dyslexic children

Verbal and non-verbal learning were investigated in 21 8–11-year-old dyslexic children and chronological-age controls, and in 21 7–9-year-old reading-age controls. Tasks involved the paired associate learning of words, nonwords, or symbols with pictures. Both learning and retention of associations were examined. Results indicated that dyslexic children had difficulty with verbal learning of both words and nonwords. In addition, analysis of the errors made during nonword learning showed that both phonological errors and general learning errors were distributed similarly for the reading groups. This suggests that nonword learning in dyslexics is slower, but not qualitatively different from normal readers. Furthermore, no differences were found between the dyslexics and age-matched normal readers on non-verbal learning. Long-term retention of the learned visual–verbal associations (both words and nonwords) was not impaired in dyslexic children as compared to normal readers. Finally, phonological awareness ability was assessed. Dyslexics performed worse than age-matched normal readers, but similar to reading-age controls.

Event-Related Potential Correlates of Acquisition and Retrieval of Verbal Associations in Schizophrenics and Controls

Abstract Reduced amplitudes of event-related potentials (ERP) have often been reported for schizophrenic patients. Positive ERPs were examined in 16 schizophrenic patients and 16 controls in a visual paired-associate learning task, in which successful learning of word pairs was evidenced by recognition of “old” versus “new” word pairs. Patients performed significantly poorer than controls. During acquisition the to-be-associated word pairs evoked a P2 and positive Slow Wave (SW) of similar amplitude in both groups. Although the recognition of items as “old” induced larger positive ERPs in controls, ERPs did not vary with recognition in patients. The presentation of the word pairs (50% old, 50% new combinations) evoked a pronounced posterior positive SW in patients but an anterior negative SW in controls. This pattern is identical to the one obtained from a previous paired-associate learning task with cue-recall and suggests that schizophrenic patients are capable of producing large amplitude positive waves under conditions different from those typical for P300 evocation in normals. The larger positive SW may indicate increased effort to compensate for deficient acquisition or association formation.

Induction of BDNF mRNA during visual paired associate learning: Quantitative analysis using split-brain monkeys

Induction of BDNF mRNA during visual paired associate learning: Quantitative analysis using split-brain monkeys

Neurological and cognitive abnormalities associated with chronic petrol sniffing.

Substance abuse through the deliberate inhalation of petrol (petrol sniffing or gasoline sniffing) is prevalent in inner-urban and remote rural communities. Although acute toxic encephalopathy is a well-documented consequence of petrol sniffing, the neurological and cognitive effects of chronic petrol sniffing are unknown. A structured neurological examination and the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess neurological and cognitive function in 33 current-sniffers (individuals who had sniffed petrol for >6 months), 30 ex-sniffers (individuals who had sniffed petrol in the past but had abstained for 6 months) and 34 matched non-sniffers (individuals who had never sniffed petrol). No subject was, or had been, encephalopathic from petrol sniffing and all were residing in their community. Blood lead and hydrocarbon levels and information about petrol sniffing behaviour were obtained from each subject. When compared with non-sniffers, current-sniffers showed higher rates of abnormal tandem gait, rapid alternating hand movements, finger to nose movements, postural tremor, bilateral palmomental reflexes and brisk deep reflexes. Cognitive deficits occurred in the areas of visual attention, visual recognition memory and visual paired associate learning. Ex-petrol sniffers showed higher rates of abnormal tandem gait and bilateral palmomental reflexes and cognitive deficits in the areas of visual recognition memory and pattern-location paired associate learning. Blood lead levels and length of time of petrol sniffing correlated significantly with the magnitude of neurological and cognitive deficits. Blood hydrocarbon levels were not related to neurocognitive deficits, although this may have been due to methodological difficulties in obtaining hydrocarbon levels. These results suggest that subtle neurological and cognitive abnormalities do occur in individuals who abuse petrol but who do not have acute toxic encephalopathy and that the severity of these abnormalities is reduced with abstinence.

Perirhinal cortex ablation impairs configural learning and paired–associate learning equally

Combined damage to the perirhinal and entorhinal cortex has been implicated in the formation of stimulus–stimulus associative memories. We show in this article that relative to three normal controls three cynomolgus monkeys with ablations restricted to the perirhinal cortex were impaired on a visual paired–associate learning task in which subjects had to learn which of two visual stimuli were associated with a cue stimulus. The subjects with perirhinal cortex ablations also showed an impairment of a similar magnitude on a visual configural learning task in which they had to learn which of two configurations of visual stimuli were associated with food-reward. The stimuli in both tasks were comprised of alphanumeric characters presented upon a touch-screen. Both groups made fewer errors on the configural learning task than on the paired–associate learning task. We suggest that performance on both tasks relies critically on the perirhinal cortex due to the specialization of the perirhinal cortex in processing knowledge about objects. We argue that the specializations of this system and of other memory systems such as the hippocampal-fornix spatial\\episodic memory system, are conferred by the specialization of their anatomical connections to other structures. We reject the notion that there are specific memory processes such as the hippocampal based configural associative system that was proposed to be critical for configural associative learning.

Detection of transcriptional activation during visual paired associate learning in split-brain macaques

Detection of transcriptional activation during visual paired associate learning in split-brain macaques