Associate Learning Test Research Articles

Performance on an Associative Memory Test Decreases 8 hr After Cardiovascular Exercise.

This study was designed to assess the effects of acute exercise on performance of a paired associate learning (PAL) test, an operationalization of hippocampal-dependent associative memory. Participants performed a PAL test and then ran on a treadmill (exercise group, n = 52) or solved Sudoku puzzles (control group, n = 54). Participants returned 2, 5, or 8hr later to perform a second, different, PAL test. PAL scores for the control group did not change over time. Similarly, scores on tests taken 2 and 5hr after exercise were not different from baseline or control data. Scores on tests taken 8hr after exercise, however, fell significantly below baseline (by 8.6%) and control (by 9.8%) scores. These data demonstrate that acute exercise can negatively affect the encoding and retrieval of new information even hours after the exercise bout, which should be a consideration when designing exercise programs to enhance, and not hinder, learning.

Could intraoperative magnesium sulphate protect against postoperative cognitive dysfunction?

Although there is much concern about the pathogenesis of postoperative cognitive dysfunction (POCD); no effective prevention strategies are currently described. The aim of this work was to study whether intraoperative magnesium sulphate could have a protective effect against developing POCD and to study its impact on serum level of S100B, a marker of neuronal degeneration. This is a prospective randomized controlled trial carried out on 80 participants undergoing elective laparoscopic cholecystectomy, 40 participants received conventional general anesthesia (conventional anesthesia group) and 40 participants received conventional general anesthesia with extra administration of intraoperative magnesium sulphate (Mg sulphate group). Cognitive assessment for both groups was done preoperatively and 1 week postoperatively using Paired Associate Learning test (PALT) and Benton Visual Retention Test (BVRT). Quantitative determination of serum S100B was done for both groups preoperatively and one week postoperatively by using an enzyme- linked immunoabsorbent assay technique. Postoperative PALT and BVRT were significantly lower than preoperative PALT and BVRT in the conventional anesthesia group (P value =0.043, P value =0.015 respectively), but not in the Mg sulphate group (P value =0.134, P value =0.151 respectively). Postoperative S100B was significantly higher than preoperative S100B in the conventional anesthesia group (P value =0.006), but not in the Mg sulphate group (P value =0.293). Administration of intravenous infusion of magnesium sulphate during conventional general anesthesia can protect against POCD and attenuate the post operative elevation of serum S100B.

OSA and Neurocognitive Impairment in Children With Congenital Heart Disease

Children with congenital heart disease (CHD) have an increased risk of neurocognitive impairment. No prior studies have evaluated the role of OSA, which is associated with neurocognitive impairment in children without CHD. Is OSA is associated with neurocognitive impairment in children with CHD? Children aged 6 to 17 years with corrected moderate to complex CHD without syndromes that may affect neurocognition were recruited from the pediatric cardiology clinic. Participants underwent home sleep testing and neurocognitive testing, including a validated Intellectual Quotient (IQ) test as well as validated tests of memory (Paired Associates Learning test), executive function (Intra-Extra Dimensional set shift test), and attention (Simple Reaction Test) from the CANTAB neurocognitive testing battery. Complete results were available for 30 children. Seventeen children (57%) were found to have OSA. Total IQ was markedly lower in children with CHD and comorbid OSA compared with children with CHD without comorbid OSA (mean, 86 ± 12 vs98 ± 11; P= .01). Children with CHD and OSA did significantly worse on the Paired Associates Learning test, with a median of eight total errors (interquartile range [IQR], 2.25-15) compared with children with CHD without OSA (median total errors, 2, IQR, 1-8; P= .02). Children with CHD and comorbid OSA have impaired neurocognition compared with children with CHD without comorbid OSA. OSA may be a reversible cause of neurocognitive impairment in children with CHD. Further research is needed to evaluate the effects of OSA treatment on neurocognitive impairment in children with CHD.

VASCULAR RISK FACTORS AND COGNITIVE FUNCTIONS IN THE PATIENTS WITH CEREBROVASCULAR DISEASE

The aim: To assess the severity of cognitive impairment (CI) in patients with cerebrovascular disease (CVD) depending on the number of vascular risk factors (VRF). Materials and methods: The study consisted of five hundred and eighty patients with CVD (247 females and 333 males) aged from 45 to 89 years (mean age: 64,1±8,9 years). The patients were divided into 6 groups (I, II, III, IV, V, VI) depending on the number of VRF. The examination consisted of a standard clinical evaluation, neurological examination, the application of neuropsychological tests (the MMSE; the PALT/The Paired Associates Learning Test; clock drawing test), laboratory tests, MRI of brain. Results: According to ANOVA, the greater the number of VRF the patients had, the lower was their total MMSE score corresponding to more pronounced cognitive decline (F=2,97, p=0,012). A significant negative correlation between patients' age and their MMSE score was detected regardless of their VRF count. The patients of the V and VI groups had substantially lower parameters of immediate, delayed memory and clock drawing test score comparing to the patients of the I group. Conclusions: The presence of 4 and more VRF was related to more pronounced CI in the patients with CVD. Decline of different aspects of memory, attention, spatial orientation, abstract thinking, planning, concentration, executive and visuospatial skills in groups of patients with 4,5 and 6 vascular risk factors was established. Age was substantially associated with cognitive decline in all the group of patients.

Effects of Collagen Hydrolysates on Human Brain Structure and Cognitive Function: A Pilot Clinical Study

This study investigated the effects of collagen hydrolysates (CH) on language cognitive function and brain structure. In this open-label study, 5 g CH was administered once a day for 4 weeks to 30 healthy participants aged 49–63 years. The primary outcome measures were the brain healthcare quotients based on gray matter volume (GM-BHQ) and fractional anisotropy (FA-BHQ). The secondary outcome measures were changes in scores between week 0 and week 4 for word list memory (WLM) and standard verbal paired associate learning (S-PA) tests as well as changes in the physical, mental, and role/social component summary scores of the Short Form-36(SF-36) quality of life instrument. CH ingestion resulted in significant improvements in FA-BHQ (p = 0.0095), a measure of brain structure, as well in scores for the WLM (p = 0.0046) and S-PA (p = 0.0007) tests, which measure cognitive function. There were moderate correlations between the change in WLM score and the change in GM-BHQ (r = 0.4448; Spearman’s rank correlation) and between the change in S-PA score and the change in FA-BHQ (r = 0.4645). Daily ingestion of CH changed brain structure and improved language cognitive function.

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.

Depressive symptoms as predictors of visual memory deficits in middle-age

BackgroundDepression has been known to affect memory and other cognitive domains. The objective of this longitudinal cohort study was to investigate longitudinal associations between depressive symptoms at age 31 years and visual memory and new learning at the age of 46 years. We investigated whether depressive symptoms at age 31 predicted visual memory deficits at age 46 years, and whether changes in depressive symptoms between 31 and 46 years predicted visual memory at age 46. MethodsParticipants were members of the Northern Finland Birth Cohort 1966. Depressive symptoms were assessed with the Symptom Checklist-25 (SCL-25) on both occasions. Visual memory and new learning were assessed using Paired Associative Learning (PAL) test at the age 46 follow-up. PAL total errors adjusted and first trial memory score were used as outcomes and basic educational level, relationship status, physical activity and diet at baseline were considered as confounding factors in linear regression analysis. ResultsA total of 5029 (57% female) participants were included in the main analysis. No associations were found between depressive symptoms or change in depressive symptoms and visual memory and new learning scores. The result did not change following cut-offs 1.55 and 1.75 for depression. LimitationsSCL-25 only measures symptoms during the past week. Only one cognitive domain was assessed. ConclusionsContrary to our hypothesis, neither baseline depressive symptoms nor change in depressive symptoms predicted visual memory scores 15 years later. It appears that sub-clinical depressive symptoms do not effect this cognitive domain in the middle-aged population.

Prevalence, Influence Factors and Cognitive Characteristics of Mild Cognitive Impairment in Type 2 Diabetes Mellitus.

Background: Type 2 diabetes mellitus (T2DM) is considered as an independent risk factor for mild cognitive impairment (MCI). This study was performed to investigate the prevalence, influencing factors and cognitive characteristics of MCI in elderly patients with T2DM in China.Methods: In the cross-sectional study, we performed cluster random sampling of 3,246 people age 60 years and older across the country. All participants were interviewed and screened for T2DM and MCI. A total of 341 subjects were diagnosed of MCI according to the criteria of Petersen, and a total of 256 subjects were diagnosed of T2DM by using the American Diabetes Association criteria Among the 256 T2DM people, 56 were also diagnosed with MCI. Logistic regression analyses were performed to evaluate risk and protective factor for MCI with T2DM. We also assessed their cognitive function by using the Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Digit span, Associative Learning Test (ALT), Visual Identification Test (VIT), Verbal Fluency (VF), Wechsler Adult Intelligence Scale (WAIS)-III Block Design, WAIS-III picture completion and Auditory Verbal Learning Test (AVLT).Results: Among the 256 T2DM patients, 56 were diagnosed with MCI, and the prevalence of MCI in T2DM was 21.8%. Multivariate logistic regression analyses showed that depression (p = 0.002, OR = 6.220, 95% CI: 2.005–19.290) was a risk factor for MCI among T2DM patients, while education (p < 0.001, OR = 0.869, 95% CI: 0.805–0.983) was a protective one. All the scores of neuropsychological tests (except for MMSE) in T2DM patients with MCI were lower than those without MCI (p < 0.05), but there was no statistical difference (p > 0.05) in neuropsychological tests between T2DM-MCI group and No-T2DM-MCI group. Linear regression analysis showed that the drug treatment of diabetes was positively correlated (t = 2.263, p = 0.025) with the total score of auditory word tests.Conclusions: The present study suggests a high prevalence of MCI among Chinese T2DM patients. Depression is a risk factor for MCI, while education is a protective one. T2DM patients with MCI often show comprehensive cognitive impairment, and the drug treatment of diabetes might help to improve cognitive function.

Odour conditioning of positive affective states: Rats can learn to associate an odour with being tickled.

Most associative learning tests in rodents use negative stimuli, such as electric shocks. We investigated if young rats can learn to associate the presence of an odour with the experience of being tickled (i.e. using an experimenter’s hand to mimic rough-and-tumble play), shown to elicit 50 kHz ultrasonic vocalisations (USVs), which are indicative of positive affect. Male, pair-housed Wistar rats (N = 24) were all exposed to two neutral odours (A and B) presented in a perforated container on alternate days in a test arena. Following 60s of exposure, the rats were either tickled on days when odour A (n = 8) or odour B (n = 8) was present, or never tickled (n = 8). When tickled, rats produced significantly more 50 kHz USVs compared to the days when not being tickled, and compared to control rats. The level of anticipatory 50 kHz USVs in the 60s prior to tickling did not differ significantly between the tickled and control rats. As a retrieval test following the odour conditioning, rats were exposed successively in the same arena to three odours: an unknown neutral odour, extract of fox faeces, and either odours A or B. Compared to controls, 50 kHz USVs of tickled rats increased when exposed to the odour they had previously experienced when tickled, indicating that these rats had learned to associate the odour with the positive experience of being tickled. In a test with free access for 5 min to both arms of a T-maze, each containing one of the odours, rats tickled with odour A spent more time in the arm with this odour. This work is the first to test in a fully balanced design whether rats can learn to associate an odour with tickling, and indicates that positive odour conditioning has potential to be used as an alternative to negative conditioning tests.

Postoperative cognitive dysfunction and the possible underlying neurodegenerative effect of anaesthesia

Introduction: There is alarming evidence about the involvement of general anaesthesia in the development of postoperative cognitive dysfunction.Aim: To clarify the impact of general anaesthesia on cognitive function and to study the possible effect of general anaesthesia on serum S100B, the marker of neuronal degeneration.Methods: This is a prospective randomised controlled study carried out on 50 patients undergoing elective laparoscopic cholecystectomy under conventional general anaesthesia. Cognitive assessment for selected patients was done preoperative and 1 week postoperative using Paired Associate Learning test (PALT) for assessment of verbal memory and Benton Visual Retention test (BVRT) for assessment of visual memory. Quantitative determination of serum S100B was done for all patients in the basal sample and postoperative sample by applying an enzyme- linked immunoabsorbent assay technique on am automated ELISA platform.Results: Regarding cognitive tests, there was a statistically significant difference between the mean value of preoperative PALT and postoperative PALT (p-value = .012). There was also a statistically significant difference between the mean value of preoperative BVRT and postoperative BVRT (p-value = .011). Regarding S100B, there was a statistically significant difference between preoperative and postoperative serum level (p-value = .002). There was also a statistically significant negative correlation between postoperative S100B serum level and the postoperative scores of both PALT and BVRT.Conclusion: General anaesthesia is incriminated in the development of postoperative verbal and visual memory impairment and in the postoperative increase in serum S100B, the markers of neuronal degeneration.

A Key Role for Subiculum-Fornix Connectivity in Recollection in Older Age.

Individual differences in memory during aging are associated with the microstructure of the fornix, a bidirectional tract connecting the hippocampus with the diencephalon, basal forebrain and cortex. To investigate the origin of alterations in fornix microstructure, measurement of hippocampal subfield volumes was combined with diffusion MRI and cognitive evaluation in a new sample of 31 healthy human participants aged 50–89 years. The fornix, uncinate and parahippocampal cingulum were reconstructed using diffusion MRI tractography. Episodic memory was assessed with free and cued verbal recall, visual recognition and paired associate learning tests. Recall performance was associated with fornix microstructure and hippocampal subfield volumes. Subiculum and CA1 volumes remained positively associated with fornix microstructure when controlling for other volumes. Subiculum volume was also associated with fornix microstructure independent of age. Regression analyses showed that subiculum-fornix associations explained more variation in recall than that of CA1-fornix associations. In a multivariable regression model, age and subiculum volume were independent predictors of free recall whilst fornix microstructure and CA1 volume were not. These results suggest that age-related changes in a network that includes the subiculum and fornix are important in cognitive change in healthy aging. These results match anatomical predictions concerning the importance of hippocampal – diencephalic projections for memory.

Examining Validity of the Standardized Verbal Paired Associates Learning Test

本研究では標準言語性対連合学習検査 (S-PA) の標準化に際して収集したデータをもとに, S-PA の正答数と他の神経心理学的検査の成績との関連を分析し, S-PA の併存的妥当性について検討を行った。 S-PA 開発の際に収集した健常者データ 758 名分, および脳損傷例データ 48 名分を分析対象とした。 S-PA との関連をみる他の検査として健常者データに関しては, 言語流暢性検査 (WFT) および WAIS-III の数唱問題と類似問題を分析に用いた。脳損傷例データに関しては WFT および WAIS-III と WMS-R の全検査結果を分析に用いた。分析の結果, S-PA の正答数は WMS-R の言語性記憶指標や言語性対連合の成績と高い相関を示し, 言語性記憶検査として S-PA の併存的妥当性が確認された。一方で S-PA と WMS-R の論理的記憶の成績との相関はやや低く, S-PA は物語の記銘とは異なる側面を測定している検査であると考えられた。また, S-PA の成績には語彙の豊富さや単語の共通点を探す能力, 視覚的イメージの操作や処理の素早さも関連する可能性が示唆された。

Effect of local anesthesia (with lidocaine vs bupivacaine) on cognitive function in patients undergoing elective cataract surgery.

PurposePostoperative cognitive dysfunction has gained much attention over the last years. Multiple clinical trials have attempted to differentiate the effect of local vs general anesthesia on postoperative cognitive function. The aim of this work was to study the effect of local anesthesia with lidocaine vs bupivacaine on cognitive functionPatients and methodsThis was a prospective randomized trial carried out on 61 patients undergoing elective cataract surgery by phacoemulsification under local anesthesia. Twenty-eight patients received lidocaine 2% and 33 patients received bupivacaine 0.5%. Cognitive assessment for all patients was done preoperatively and 1 week postoperatively using paired associate learning test (PALT) and category verbal fluency (VF) test (animal category).ResultsRegarding cognitive assessment of patients in lidocaine group, there was a statistically significant difference between the mean value of preoperative PALT and postoperative PALT (P-value =0.004), and between the mean value of preoperative VF and postoperative VF (P-value =0.002). As for bupivacaine group, there was a statistically significant difference between the mean value of preoperative PALT and postoperative PALT (P-value =0.021), and between the mean value of preoperative VF and postoperative VF (P-value =0.037). On comparing lidocaine and bupivacaine groups in pre and postoperative PALT & VF scores, there was no statistically significant difference between both groupsConclusionBoth lidocaine and bupivacaine caused postoperative cognitive impairment. Lidocaine was found to have a worse effect on cognitive function than bupivacaine, but the difference was not statistically significant.

Influence of visual cues on oviposition site searching and learning behavior in the parasitic beetle Dastarcus helophoroides (Fairmaire) (Coleoptera: Bothrideridae)

Color cues play a key role in the location of hosts and host habitats; learning behavior can allow parasitoids to explore different hosts and reduce environmental uncertainty. However, it remains unclear whether the parasitic beetle Dastarcus helophoroides (Fairmaire) uses and learns visual cues to locate oviposition sites. In this study, we investigated the ability of females to respond to colors and associate the presence of a simulated oviposition site—wood with a trough—with colored substrates after training. Two sets of experiments were conducted: (i) investigating the innate preference for substrate coloration and (ii) investigating the ability to learn to associate substrate color with the presence of simulated oviposition sites, with the beetles being trained to respond to different substrate colors with simulated oviposition sites in sessions on 10 consecutive days. The parasitic beetles displayed an innate preference for the black substrate, but this preference changed after the beetles were trained on substrates of different colors. In the associative learning tests, these beetles laid more eggs on the reward-conditioned substrates than on the black substrate after being trained. Our results suggest that visual cues are learned and used by D. helophoroides during their search for and selection of oviposition sites.

T2 Relaxometry and Diffusion Tensor Indices of the Hippocampus and Entorhinal Cortex Improve Sensitivity and Specificity of MRI to Detect Amnestic Mild Cognitive Impairment and Alzheimer's Disease Dementia.

Quantitative T2 and diffusion MRI indices inform about tissue state and microstructure, both of which may be affected by pathology before tissue atrophy. To evaluate the capability of both volumetric and quantitative MRI (qMRI) of the hippocampus and entorhinal cortex (EC) for classification of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). Retrospective cross-sectional study. Consecutive cohorts of healthy age-matched controls (n = 62), aMCI patients (n = 25), and ADD patients (n = 14). 3T using T1-weighted imaging, T2-weighted imaging, T2 relaxometry and diffusion tensor imaging (DTI). Montreal Cognitive Assessment and paired associate learning tests for cognitive state. Hippocampal subfield volumes by the automated segmentation of hippocampal subfields system from structural brain images. T2 relaxation time and DTI indices quantified for hippocampal subfields. The fraction of voxels with high T2 values (>20 ms above subfield median) was calculated and regionalized for hippocampus and EC. Support vector machine and receiver operating characteristic analyses from cognitive and MRI data. qMRI classified aMCI and ADD with excellent sensitivity (79.0% and 94.5%, respectively) and specificity (85.6% and 86.1%, respectively), superior to volumes alone (70.0% and 84.5% for respective sensitivities; 82.2 and 91.1 for respective specificities) and similar to cognitive tests (61.7% and 87.5% for respective sensitivities; 88.2% and 90.7% for respective specificities). Regions of high T2 are dispersed throughout each hippocampal subfield in aMCI and ADD with higher concentration than controls, and was most pronounced in the EC. No other individual qMRI marker than EC volume can separate aMCI from ADD, however. DATA CONCLUSION: qMRI markers of hippocampal and entorhinal tissue states are sensitive and specific classifiers of aMCI and ADD. They may serve as markers of a neurodegenerative state preceding volume loss. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:445-455.

GLUTAREDOXIN1 OVEREXPRESSION AMELIORATES EARLY F-ACTIN LOSS AND COGNITIVE DEFICITS SEEN IN ALZHEIMER’S DISEASE MOUSE MODEL

Fibrillar actin (F-actin) is the key cytoskeletal protein that is highly enriched at dendritic spines and defines spine morphology. We recently demonstrated that synaptosomal F-actin levels were significantly decreased in APP/PS1 mice as early as 1 month of age. APP/PS1 mice also showed recall deficit upon contextual fear conditioning (cFC) at 2 months, which was reversed by F-actin stabilizing agent, jasplakinolide. Reactive oxygen species (ROS) generated by β-amyloid (Aβ) has been implicated in Alzheimer's disease (AD) pathogenesis. However, it is unclear whether ROS contributes to F-actin loss in synaptosomes, in vivo, in mice. Therefore, we investigated whether altered redox signaling could contribute to F-actin loss and behavioral deficits seen early in AD. We used age matched WT and APPswe/PS1ΔE9 mice for our experiments. Associative learning and memory test was assessed by cFC. Highly enriched F-Actin and G-Actin fractions were isolated from WT and APP/PS1 mice. We also used AMS-derivatization approach to determine reduced form of F-actin. AAV-glutaredoxin1 viral particles were delivered into hippocampus of mouse brain using stereotaxic injections. Statistical comparisons were performed using unpaired t-tests or ANOVA followed by post-hoc test. Reduced form of F-actin was significantly decreased but not reduced form of G-actin in synaptosomes of APP/PS1 mice as early as 1 month and this loss was sustained until 9 months, when overt symptoms are observed. S-glutathionylation of synaptosomal actin, which is known to hinder F-actin stabilization, was significantly increased in one month APP/PS1 mice. To determine the role of Aβ mediated endogenous ROS levels on F-actin loss and behavioural deficits in APP/PS1 mice we over-expressed glutaredoxin1 in hippocampus of the mouse brain. Remarkably, we found that cFC behavioral deficits seen in APP/PS1 mice was restored by over expression of glutaredoxin1 in AD mice. We demonstrate that Aβ induced ROS-mediated glutathionylation of actin as one of the mechanisms hindering F-actin stabilization in synaptic compartments leading to behavioral deficits in APP/PS1 mice, which can be reversed by over expression of glutaredoxin1. Our findings provide evidence that F-actin loss through oxidative modification at the synapse plays a critical role in synaptic dysfunction in AD pathogenesis.

Developing an Ethically Acceptable Virtual Fencing System for Sheep.

Simple SummaryVirtual fencing has the potential to be implemented in animal management systems where conventional fencing cannot be applied. Previous work has been conducted on cattle with virtual fencing technology that uses a collar that emits a warning audio when an animal approaches a GPS set boundary. If the animal continues walking towards the boundary an electric stimulus is applied. Less research has been conducted on sheep virtual fencing, so alternatives need to be explored to test the proof of concept on the application of virtual fencing with sheep. Using manually controlled training collars, 30 crossbred sheep were trained to respond to an audio cue in order to avoid receiving a low-level electrical stimulus.To ensure animal welfare isn’t compromised when using virtual fencing, animals must be able to associate a benign conditioned stimulus with an aversive stimulus. This study used an associative learning test to train 30, four-year-old, Merino x Suffolk ewes, to associate an audio cue with an electric stimulus. Collars manually controlled by a GPS hand-held unit were used to deliver the audio and electric stimuli cues. For the associative learning, when sheep approached an attractant at a distance of three m from the trough, an audio cue was applied for one s. If the sheep stopped or changed direction, the audio cue ceased immediately and no electrical stimulus was applied. If the sheep did not respond to the audio cue it was followed by a low-level electrical stimulus. Approaches to the attractant significantly decreased from day one to day two. It took a mean of three pairings of the audio cue and electrical stimulus for a change in behaviour to occur, after which sheep that approached the attractant had a 52% probability of avoiding the electrical stimulus and responding to the audio cue alone. Further research is required to determine whether sheep can be trained to associate an audio cue with a negative stimulus for use in group grazing situations.

Early Detection of Learning Difficulties when Confronted with Novel Information in Preclinical Alzheimer's Disease Stage 1.

We employed a highly demanding experimental associative learning test (the AFE-T) to explore memory functioning in Preclinical Alzheimer's Disease stage 1 (PreAD-1) and stage 2 (PreAD-2). The task consisted in the learning of unknown object/name pairs and our comprehensive setup allowed the analysis of learning curves, immediate recall, long-term forgetting rates at one week, three months, and six months, and relearning curves. Forty-nine cognitively healthy subjects were included and classified according to the presence or absence of abnormal CSF biomarkers (Control, n = 31; PreAD-1, n = 14; PreAD-2, n = 4). Control and PreAD-1 performances on the experimental test were compared by controlling for age and education. These analyses showed clear learning difficulties in PreAD-1 subjects (F = 6.98; p = 0.01). Between-group differences in long-term forgetting rates were less notable, reaching statistical significance only for the three-month cued forgetting rate (F = 4.83; p = 0.03). Similarly, relearning sessions showed only statistical trends between the groups (F = 3.22; p = 0.08). In the whole sample, significant correlations between CSF Aβ42/tau ratio and the AFE-T were found, both in the total learning score (r = 0.52; p < 0.001) and in the three-month cued forgetting rate (r = -0.38; p < 0.01). Descriptive subanalyses involving PreAD-2 suggested greater learning and recall difficulties in these subjects when compared with the PreAD-1 group. The present results suggest that explicit learning difficulties when binding information could be one of the earliest signs of the future emergence of episodic memory difficulties on the Alzheimer's disease continuum. Our findings indicate that the AFE-T is a sensitive test, capable of detecting subtle memory difficulties in PreAD-1.

Cerebral Blood Flow Change by the Miyake's Paired Verbal Associate Learning Test with Android PC Application

Cerebral Blood Flow Change by the Miyake's Paired Verbal Associate Learning Test with Android PC Application

Ovariectomy increases the age-induced hyperphosphorylation of Tau at hippocampal CA1.

One of the main hallmarks of Alzheimer's disease includes the neurofibrillary tangles formation produced by hyperphosphorylation of the Tau protein, whose expression is putatively regulated by the ovarian hormones estradiol and progesterone. Hippocampus is a brain region that participates in many functions related to learning and memory; in addition, it is abundant in both estradiol and progesterone receptors. In this study, we explore the expression of Tau hyperphosphorylation at hippocampus and the performance of rats in an autoshaping learning task at 5, 10 and 15months after the ovaries removal. In these animals, ovariectomy was performed at 3months of age. These data were compared with those derived from intact rats at 8, 13 and 18months old. A clear decrease in the number of conditioned responses of both intact and ovariectomized rats in the autoshaping learning task was observed. The interaction of both factors confirms that, in this test, learning varies depending on aging and the presence or absence of ovaries. A progressive increase in hippocampal Tau phosphorylation at Ser-396 was observed in either intact or ovariectomized rats. Interestingly, an interaction between the analyzed factors shows that such hyperphosphorylation was potentiated by the absence of ovaries. These results emphasize the importance of aging and the lack of ovarian hormones for an associative learning test and for the expression of one of the most important hallmarks of Alzheimer's disease.