Learning Trials Research Articles

Assessing learning and memory among patients with pediatric brain tumor (PBT): a comparison of measures

ABSTRACT Patients with pediatric brain tumor (PBT) can have memory deficits due to tumor location, medical complications, and treatment. The main objective of this study was to investigate whether the California Verbal Learning Test-Children’s Version (CVLT-C; 1994) and briefer Child and Adolescent Memory Profile (ChAMP; 2015) similarly identify such deficits. Seventy-five patients with PBT ages 8–16 ( = 13.1 years, SD = 2.1) were administered the ChAMP or CVLT-C. Rote verbal learning, long-term retrieval, and recognition were analyzed using standardized z-scores. Analyses of differences between measures did not reach statistical significance. Both measures indicated significant downward shifts across free retrieval trials from normative means, with scores approximately 1/3 (ChAMP) to 1/2 (CVLT-C) SD below means across learning and long-term retrieval trials. Scores on recognition trials did not differ significantly from the normative mean. Post-hoc analyses using a subset of the sample who received cranial irradiation (n = 45) similarly found no significant differences between memory measures. Additional post-hoc examination of proportion of participants falling within or below the “below average” range (≤8th percentile) revealed comparable performance between the two measures, whereas the proportion of participants falling at or below 1.5 SDs below the mean on retrieval trials was lower using ChAMP Lists as compared to the CVLT-C. Given the ChAMP is less demanding in terms of time and effort and utilizes more updated and representative normative data, this study supports the ChAMP as a useful tool to evaluate learning and memory within this population.

Plasma Aβ42/40 and cognitive variability are associated with cognitive function in Black Americans: Findings from the AA-FAIM cohort.

It is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low-burden disease markers, plasma amyloid beta (Aβ)42/40, and intra-individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults. Two hundred fifty-seven Black participants enrolled in the African Americans Fighting Alzheimer's in Midlife (AA-FAIM) study underwent at least one cognitive assessment visit; a subset of n = 235 had plasma samples. Baseline IICV was calculated as the standard deviation across participants' z scores on five cognitive measures: Rey Auditory Verbal Learning Test Delayed Recall, Trail Making Test Parts A and B (Trails A and B), and Boston Naming Test. Using mixed effects regression models, we compared concurrent and longitudinal models to baseline plasma Aβ42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma Aβ42/40. IICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma Aβ42/40 was unrelated to baseline cognitive performance, but a pattern emerged in interactions with age in longitudinal models of Trails A and B and Rey Auditory Verbal Learning Test total learning trials. Although not significant after correcting for multiple comparisons, low Aβ42/40 was associated with faster cognitive declines over time. Our results are promising as they extend existing findings to an Black American sample using low-cost, low-burden methods that can be implemented outside of a research center, thus supporting efforts for inclusive AD biomarker research.

Learned pseudo-random number generator: WGAN-GP for generating statistically robust random numbers.

Pseudo-random number generators (PRNGs) are software algorithms generating a sequence of numbers approximating the properties of random numbers. They are critical components in many information systems that require unpredictable and nonarbitrary behaviors, such as parameter configuration in machine learning, gaming, cryptography, and simulation. A PRNG is commonly validated through a statistical test suite, such as NIST SP 800-22rev1a (NIST test suite), to evaluate its robustness and the randomness of the numbers. In this paper, we propose a Wasserstein distance-based generative adversarial network (WGAN) approach to generating PRNGs that fully satisfy the NIST test suite. In this approach, the existing Mersenne Twister (MT) PRNG is learned without implementing any mathematical programming code. We remove the dropout layers from the conventional WGAN network to learn random numbers distributed in the entire feature space because the nearly infinite amount of data can suppress the overfitting problems that occur without dropout layers. We conduct experimental studies to evaluate our learned pseudo-random number generator (LPRNG) by adopting cosine-function-based numbers with poor random number properties according to the NIST test suite as seed numbers. The experimental results show that our LPRNG successfully converted the sequence of seed numbers to random numbers that fully satisfy the NIST test suite. This study opens the way for the "democratization" of PRNGs through the end-to-end learning of conventional PRNGs, which means that PRNGs can be generated without deep mathematical know-how. Such tailor-made PRNGs will effectively enhance the unpredictability and nonarbitrariness of a wide range of information systems, even if the seed numbers can be revealed by reverse engineering. The experimental results also show that overfitting was observed after about 450,000 trials of learning, suggesting that there is an upper limit to the number of learning counts for a fixed-size neural network, even when learning with unlimited data.

Metabolic and quality of life effects of growth hormone replacement in patients with TBI and AGHD: A pilot study

ObjectiveTraumatic brain injury (TBI), a common cause of adult growth hormone deficiency (AGHD), affects 20% of Veterans returning from Iraq and Afghanistan (OEF/OIF/OND). Growth hormone replacement therapy (GHRT) improves quality of life (QoL) in AGHD but remains unexplored in this population. This pilot, observational study investigates the feasibility and efficacy of GHRT in AGHD following TBI. DesignIn this 6-month study of combat Veterans with AGHD and TBI starting GHRT (N = 7), feasibility (completion rate and rhGH adherence) and efficacy (improvements in self-reported QoL) of GHRT were measured (primary outcomes). Secondary outcomes included body composition, physical and cognitive function, psychological and somatic symptoms, physical activity, IGF-1 levels and safety parameters. It was hypothesized that participants would adhere to GHRT and that QoL would significantly improve after six months. ResultsFive subjects (71%) completed all study visits. All patients administered daily rhGH injections, 6 (86%) of whom consistently administered the clinically-prescribed dose. While QoL demonstrated numeric improvement, this change did not reach statistical significance (p = 0.17). Significant improvements were observed in total lean mass (p = 0.02), latissimus dorsi strength (p = 0.05), verbal learning (Trial 1, p = 0.02; Trial 5, p = 0.03), attention (p = 0.02), short-term memory (p = 0.04), and post-traumatic stress disorder (PTSD) symptoms (p = 0.03). Body weight (p = 0.02) and total fat mass (p = 0.03) increased significantly. ConclusionGHRT is a feasible and well-tolerated intervention for U.S. Veterans with TBI-related AGHD. It improved key areas impacted by AGHD and symptoms of PTSD. Larger, placebo-controlled studies testing the efficacy and safety of this intervention in this population are warranted.

The reliability and validity of the snellen memory test for point‐of‐care detection of Alzheimer’s risk in cognitively unimpaired older adults

AbstractBackgroundEpisodic memory decline is one of the earliest cognitive indicators in Alzheimer’s disease (AD) with impairment in memory in older adults an important indicator of incipient AD. Optometry has potential for population based, point‐of‐care screening as retinal biomarkers can detect both symptomatic and preclinical AD. Here, we aimed to develop and optimize a test of episodic memory for use in clinical optometry/ophthalmology settings alongside retinal imaging methods to detect both preclinical and early symptomatic AD.Method30 cognitively normal (CN) older adults (55‐81 years; 68.5±7) from the Atlas of Retinal Imaging in Alzheimer’s Study (ARIAS) completed the Snellen Memory Test (SMT). Participants completed a a Snellen Eye Chart for three learning trials of 10 seconds exposures, followed by immediate free recall. After a 20‐minute delay, participants completed delayed free recall in which they were asked to recall as many of the letters as they had been shown. This was followed by a recognition test in which participants viewed a mock chart identifying the correct letters and if they were in the correct location as the original chart.ResultAn intraclass correlation coefficient was calculated to determine the inter‐rater reliability among three raters for 10 randomly selected administrations. Overall results indicated good reliability with a mean coefficient of 0.87 (95% CI: 0.71‐1.03). Convergent and divergent validity for the 30 participants was assessed by comparing SMT performance to RBANS indices and the Free and Cued Selective Reminding Test (FCSRT). The SMT significantly correlated with the RBANS Immediate Memory Index (r = 0.38‐0.52), Language Index (r = 0.39‐0.51), and Attention Index (r = 0.39‐0.46) as well as with selective reminding trial 1 and 2 (r = 0.45‐0.78), and free and cued recall for trial 3 (r = 0.45‐0.47).ConclusionThe SMT has potential as an episodic memory test that could be used for point of care detection of preclinical AD. Future work will continue to validate the SMT against reference standard neuropsychological assessments of episodic memory and against AD retinal imaging biomarkers.

An adapted version of the Three Words Three Shapes Test (3W3S) to old Brazilian adults

AbstractBackgroundAn adapted version of the Three Words Three Shapes Test (3W3S) is conducted for old Brazilian adults. This study describes the translation, back‐translation, and pilot study of 3W3S‐Br senior Brazilian adults' adaptation process.MethodThe 3W3S administration and scoring procedures were translated to Brazilian Portuguese by three independent translators. Concomitantly, a panel of specialists selected 18 abstract, regular nouns with the same amount of letters of the original format. The selected words must have had medium to high frequency in Brazilian Portuguese. They should also relate semantically and phonetically to the original ones. A final version was established and back‐translated. The 3W3S‐Br was then applied to 24 participants, divided into two groups, according to forms, of 12 members each (Form A (FA) and Form B (FB)). Inclusion criteria were age between 60‐80 years in the absence of depression, cognitive and functional impairment. The 3W3S‐Br has 5 conditions: 1) Copy (C); 2) Incidental Recall (IR); 3) Learning Trials total (LT), presented in three attempts; 4) Delayed Recall (DR); 5) Recognition (R). Correlations were verified by Pearson coefficient and differences between groups were compared by the Mann‐Whitney test. The analysis was performed by SPSS 28.0 or Windows.ResultThere were no significant associations between age (mean: 67±5), education (11±5), and sex(42%female) in all conditions of this instrument (p<0,05). Significant positive associations were demonstrated between MMSE and 3W3S‐Br in C (r = 0,481), LT (r = 0,455), DR (r = 0,407), R (r = 0,773). The comparison between alternate forms did not reveal differences in the 5 conditions of the test (p < 0,05). The groups also did not show significant differences between age, education, gender, and occurence of COVID‐19 infection.ConclusionAge, education, and sex did not correlate with 3W3S‐Br, whereas MEEM demonstrated correlations in most of its conditions. Alternate forms did not differ in this group of old Brazilian adults. The first steps of the adaptation process were completed and led to evidence of its clinical utility, granting further investigations. Further studies will be conducted to test psychometric properties and finalize the adaptation process.

Learning and laterality in wild-caught Namaqua rock mice (Micaelamys namaquensis)

Individuals often exhibit differences in cognition and/or preferences for one side over the other. Such differences have been attributed to the mating system and lateralization of the brain hemispheres that can differ between the sexes, respectively. Despite the hypothesized significant effects on fitness, only a limited number of rodent studies addresses sex differences in laterality and most focus on laboratory rodents. Here we examined whether wild-caught Namaqua rock mice (Micaelamys namaquensis), a rodent widespread in sub-Saharan Africa, exhibit sex differences in learning and laterality in a T-maze. Food-deprived animals entered the maze significantly faster over subsequent learning trials, suggesting that the sexes learned to find the food reward at the end of the maze arms equally. Although we could not confirm a side preference at the population level, the animals were strongly lateralized at an individual level. When the sexes were considered separately, females exhibited a preference for the right maze arm while the opposite was observed in males. The lack of comparable studies of sex-specific lateralization patterns in rodents makes the generalization of our results challenging and highlights the need for more such studies in rodents at both the individual and population levels.

Multifocal hypometabolic correlates to deficits of verbal memory in mesial temporal lobe epilepsy

Background and ObjectivesNeuropsychological research on mesial temporal lobe epilepsy (MTLE) often highlights material-specific memory deficits, but a lesion-focused model may not accurately reflect the underlying networks that support episodic memory in these patients. Our study evaluated the pathophysiology behind verbal learning/memory deficits as revealed by hypometabolism quantified through 18-fluorodeoxyglucose positron emission tomography (FDG-PET). MethodsThis retrospective study included thirty presurgical patients with intractable unilateral MTLE who underwent interictal FDG-PET and verbal memory assessment (12 females, mean age: 38.73 years). Fluorodeoxyglucose-positron emission tomography mapping was performed with voxel-based mapping of glucose utilization to a database of age-matched controls to derive regional Z-scores. Neuropsychological outcome variables included scores on learning and recall trials of two distinct verbal memory measures validated for use in epilepsy research. Pearson’s correlations evaluated relationships between clinical variables and verbal memory. Linear regression was used to relate regional hypometabolism and verbal memory assessment. Post hoc analyses assessed areas of FDG-PET hypometabolism (threshold Z ≤ −1.645 below mean) where verbal memory was impaired. ResultsVerbal memory deficits correlated with hypometabolism in limbic structures ipsilateral to language dominance but also correlated with hypometabolism in networks involving the ipsilateral perisylvian cortex and contralateral limbic and nonlimbic structures. DiscussionWe conclude that traditional models of verbal memory may not adequately capture cognitive deficits in a broader sample of patients with MTLE. This study has important implications for epilepsy surgery protocols that use neuropsychological data and FDG-PET to draw conclusions about surgical risks.

Intricate covariation between exploration and avoidance learning in a generalist predator

Abstract Many predators avoid unprofitable prey by learning to use visual features of the prey as reliable indicators of quality. However, individual variation in avoidance learning is rarely examined in detail. It has been hypothesized that better avoidance learning ability might correlate with faster exploration tendency, but available data are limited in both quantity and scope. In this study, we examined the covariation between exploration, foraging decisions, and avoidance learning in a generalist lizard Eutropis multifasciata to test the prediction that faster explorers are also better avoidance learners. We also examined how sex, population, and color of unpalatable prey might mediate the exploration-avoidance learning covariation. We collected data on exploration and foraging behavior in individuals from two allopatric populations and quantified changes in foraging decisions over five daily learning trials, in which individuals were presented with normal- and bitter-tasting prey that differed consistently in color. Even though bitter prey elicited strong negative responses, lizards overall did not avoid consuming fewer such prey with learning. Instead, they learned to prioritize on palatable prey as the experiment progressed. In concordance with our prediction, we found that faster explorers were generally better avoidance learners, even though sex, population, and prey color were also important. Our study represents a rare experimental test of the exploration-avoidance learning covariation, especially in non-avian systems. Our results suggest that unpalatability might be an ineffective defense against generalist predators such as E. multifasciata and that faster explorers might impose stronger selection for the evolution of warning signals in unprofitable prey.

Using Bidirectional Associative Memory Neural Networks to Solve the N-bit Task

Nowadays, artificial neural networks can easily solve the N-bit parity problem. However, each time a different level must be learned, the network must be retrained. This, combined with the exponential increase of learning trials required as N grows, make these models too different from how their biological counterpart solves them. This is because humans learn to recognize patterns, count, and determine if numbers are odd or even. Once they have learned these tasks, they can have them interact to solve any level without further training. This behavior is akin to performing multiple associations of different tasks. Therefore, it is proposed that by using bidirectional associative memory neural networks, it would be possible to solve the N-bit parity problem in a similar fashion to humans. To achieve this, two networks interacted; one served as a task Identifier and the other as a memory Extractor, giving the desired behavior influenced by the Identifier. Results showed that the model could solve the 2- to 9-bit in linear time once the associations were learned. Moreover, this was possible with 97% fewer inputs and no retraining. In addition, because of the recurrent nature of the model, it could also solve the tasks even under high noise levels.

Hierarchical categorization learning is associated with representational changes in the dorsal striatum and posterior frontal and parietal cortex.

Learning and recognition can be improved by sorting novel items into categories and subcategories. Such hierarchical categorization is easy when it can be performed according to learned rules (e.g., "if car, then automatic or stick shift" or "if boat, then motor or sail"). Here, we present results showing that human participants acquire categorization rules for new visual hierarchies rapidly, and that, as they do, corresponding hierarchical representations of the categorized stimuli emerge in patterns of neural activation in the dorsal striatum and in posterior frontal and parietal cortex. Participants learned to categorize novel visual objects into a hierarchy with superordinate and subordinate levels based on the objects' shape features, without having been told the categorization rules for doing so. On each trial, participants were asked to report the category and subcategory of the object, after which they received feedback about the correctness of their categorization responses. Participants trained over the course of a one-hour-long session while their brain activation was measured using functional magnetic resonance imaging. Over the course of training, significant hierarchy learning took place as participants discovered the nested categorization rules, as evidenced by the occurrence of a learning trial, after which performance suddenly increased. This learning was associated with increased representational strength of the newly acquired hierarchical rules in a corticostriatal network including the posterior frontal and parietal cortex and the dorsal striatum. We also found evidence suggesting that reinforcement learning in the dorsal striatum contributed to hierarchical rule learning.

Modeling the function of episodic memory in spatial learning.

Episodic memory has been studied extensively in the past few decades, but so far little is understood about how it drives future behavior. Here we propose that episodic memory can facilitate learning in two fundamentally different modes: retrieval and replay, which is the reinstatement of hippocampal activity patterns during later sleep or awake quiescence. We study their properties by comparing three learning paradigms using computational modeling based on visually-driven reinforcement learning. Firstly, episodic memories are retrieved to learn from single experiences (one-shot learning); secondly, episodic memories are replayed to facilitate learning of statistical regularities (replay learning); and, thirdly, learning occurs online as experiences arise with no access to memories of past experiences (online learning). We found that episodic memory benefits spatial learning in a broad range of conditions, but the performance difference is meaningful only when the task is sufficiently complex and the number of learning trials is limited. Furthermore, the two modes of accessing episodic memory affect spatial learning differently. One-shot learning is typically faster than replay learning, but the latter may reach a better asymptotic performance. In the end, we also investigated the benefits of sequential replay and found that replaying stochastic sequences results in faster learning as compared to random replay when the number of replays is limited. Understanding how episodic memory drives future behavior is an important step toward elucidating the nature of episodic memory.

Electroconvulsive Therapy Impact on Memory Performance in Patients With Depression

IntroductionThe safety of electroconvulsive therapy has improved greatly over the last decades, making the potentially adverse effects on memory and other neurocognitive functions the main clinical aspect of concern in the present. In Colombia, the general population and healthcare professionals (even some psychiatrists) seem to have mostly negative opinions towards electroconvulsive therapy treatment, but maybe this could be reconsidered if more information is provided; therefore, the aim of the present study was to evaluate the changes in memory and the severity of the symptoms in a group of patients with severe depression before and after electroconvulsive therapy. MethodsTwenty-three patients ranging in age from 23 to 70 years from the electroconvulsive therapy service at the San Juan de Dios Clinic (Manizales, Colombia) were recruited in order to assess the effect of electroconvulsive therapy on memory in patients with severe depression. Depressive symptoms and memory were assessed with the Hamilton Depression Scale (HAMD) and Rey Auditory Verbal Learning Test (RAVLT), respectively. The assessment was administered to participants before the initial treatment of electroconvulsive therapy series (0-1 day) and 2 days after their last treatment. ResultsElectroconvulsive therapy resulted in significant improvement in the rating of depression. There were no significant differences in the five learning trials, delayed recall, learning and forgetting scores from pre-treatment to post-treatment. Significant pre-treatment/post-treatment differences were found in the delayed recognition trial. ConclusionsPre- and post- electroconvulsive therapy cognitive assessment is a feasible and useful procedure. In general, memory performance does not worsen after electroconvulsive therapy in patients with depression. Only delayed recognition is affected a few days following electroconvulsive therapy, particularly in patients with low educational level and bitemporal (BT) electrode placement.

Abstract P507: Pre-Statistical Harmonization of Cognitive Measures Across Eight Population-Based NIH Cohorts in the Collaborative Cohort of Cohorts for COVID-19 Research (C4R)

Introduction: Long-term neurological consequences (eg, stroke, impaired cognition) have been linked to SARS-CoV-2 infection and severity. There are limited data from studies with racial, ethnic, socioeconomic, and geographic diversity. C4R is a prospective study of adults from 14 cohorts that aims to link pre-COVID phenotyping, including cognition (8 studies), to COVID related illness and sequelae. We aimed to conduct pre-statistical harmonization of cognitive tests administered in English and Spanish from 8 cohorts: ARIC, CARDIA, FHS, HCHS/SOL-INCA, MESA, NOMAS, REGARDS, and SHS (Table). Methods: We conducted extensive item-level review of administration, scoring, and coding procedures and score distributions for 84 tests administered in English (all studies) and Spanish (NOMAS, MESA, HCHS/SOL-INCA). Results: Orientation to time and 3-word registration and recall spanned all studies and both languages. Word list recall and verbal fluency (animal; letter) spanned 7 studies (Table). There was variability in the structure, content, administration, scoring, and data coding procedures for items across cohorts and between Spanish and English. Word lists varied by number of words (9-16) and learning trials (3-5). Animal naming varied by time (30 vs. 60 seconds), animal type (4-legged vs. any animal), and scoring (allowing mythical/imaginary animals). Letter fluency varied by whether both Spanish and English words were permitted. Other tests differed by version, study-specific adaptations, prompts/cues, and specificity of scoring rules across cohorts. Conclusions: Cognitive test harmonization requires detailed review of administration, scoring, coding, translation, and procedural differences. Accounting for this variability is essential to cognitive data interpretation. Our pre-statistical harmonization will inform data augmentation and formal harmonization to yield harmonized measures of cognition to clarify population-level differences in cognitive outcomes linked to SARS-CoV-2 infection.

Association of infection with Toxoplasma gondii and Toxocara on cognitive function among US adults aged 60 and over, NHANES 2011–2014

BackgroundToxoplasma gondii and Toxocara are common parasites that infect humans globally. Our aim was to examine the relationship between T. gondii and Toxocara infection and cognition.MethodsMultivariate logistic regression was used...

Interplay between Learning and Voluntary Wheel Running in Male C57BL/6NCrl Mice.

Exercise is shown to improve cognitive function in various human and animal studies. Laboratory mice are often used as a model to study the effects of physical activity and running wheels provide a voluntary and non-stressful form of exercise. The aim of the study was to analyze whether the cognitive state of a mouse is related to its wheel-running behavior. Twenty-two male C57BL/6NCrl mice (9.5 weeks old) were used in the study. The cognitive function of group-housed mice (n = 5-6/group) was first analyzed in the IntelliCage system followed by individual phenotyping with the PhenoMaster with access to a voluntary running wheel. The mice were divided into three groups according to their running wheel activity: low, average, and high runners. The learning trials in the IntelliCage showed that the high-runner mice exhibited a higher error rate at the beginning of learning trials but improved their outcome and learning performance more compared to the other groups. The high-runner mice ate more compared to the other groups in the PhenoMaster analyses. There were no differences in the corticosterone levels between the groups, indicating similar stress responses. Our results demonstrate that high-runner mice exhibit enhanced learning capabilities prior to access to voluntary running wheels. In addition, our results also show that individual mice react differently when introduced to running wheels, which should be taken into consideration when choosing animals for voluntary endurance exercise studies.

Increasing Motivation to Learn English Through The Total Physical Response (TPR) Method

The importance of English in this modern era does not guarantee that students have the motivation to learn English. Most students have low motivation to learn English. It also happened in SMP Ibrahimy 1 Sukorejo. According to the results of the study, the teachers used the lecture method in the learning process. Many students feel bored when learning because the method is less effective. So that many students do not have the motivation to learn English, the researcher used a classroom action research (CAR) approach. CAR consists of three cycles, each cycle consisting of planning, implementation, observation, and reflection. The method used is the Total Physical Response method. The data collection technique used was the Observation Method, Interview Method, Documentation Method, and filling out questionnaires conducted by students. The data analysis technique used was the analysis of increasing motivation through the test again. Based on the learning trials conducted using the total physical response (TPR) method, it was obtained that students' motivation and learning achievement had increased. The increase in motivation to learn English through TPR method was quite large, wherein the Pre-cycle average grade of the class was only 60. In the first cycle 71, the second cycle 81, and the third cycle 92. Seen the results of the N-Gain test recapitulation between pre-cycle and Cycle I, it can be explained that there was an increase in the average N-Gain of 0.27 with low criteria. Furthermore, between cycle, I and cycle II the average increase in N-Gain were 0.31 with moderate criteria, and the last one was the recapitulation of N-Gain test results between cycle II and cycle III of 0.54 with moderate criteria

Abstract TP215: Prenatal Alcohol Exposure Impairs Long-term Behavioral Recovery Following Ischemic Stroke In Sprague Dawley Rats

Background and Purpose: Early life adversity is an important risk factor for cardiometabolic diseases in adulthood. There is very little information on prenatal insults and adult stroke outcomes. The present study tested the hypothesis that prenatal alcohol exposure (PAE) impedes long-term recovery from ischemic stroke in rats. Methods: Pregnant Sprague Dawley rats (in-house bred) were exposed to 10% alcohol or air, for 1 hour from gestational day 8 through 18 using the rodent alcohol inhalation system. Adult offspring (5-6 mo old) were subjected to endothelin-1 induced MCAo and outcomes were evaluated after 180 days. Long-term cognitive outcomes were determined using the Barnes maze and fear conditioning/extinction test. Results: In the Barnes maze test, control males showed shorter latency to reach the goal box over 3-day learning period (p=0.002), as assessed by the slope of the curve (-27.66, significantly different from 0; p=0.005). In contrast, the latency over the 3-day learning period did not improve in PAE males (-9.674, not significantly different from 0; p=0.22). In females, the latency to escape box during the learning trials was not different between the control and PAE. The fear conditioning data indicate that percent freezing over trials was similar in control and PAE-males. However, the PAE females exhibited a diminished freezing response as compared to control females (p=0.01). In the context of fear extinction, control males showed a reduction in freezing response to repeated tones over the trial blocks (p=0.004) compared to PAE-males. The control and PAE females showed similar freezing responses with repeated tones. Conclusions: The present findings support the hypothesis that PAE modifies long-term cognitive changes after stroke, and further show that different cognitive domains are affected by PAE in males and females.

Theta oscillations in anterior cingulate cortex and orbitofrontal cortex differentially modulate accuracy and speed in flexible reward learning.

Flexible reward learning relies on frontal cortex, with substantial evidence indicating that anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) subregions play important roles. Recent studies in both rat and macaque suggest theta oscillations (5-10 Hz) may be a spectral signature that coordinates this learning. However, network-level interactions between ACC and OFC in flexible learning remain unclear. We investigated the learning of stimulus-reward associations using a combination of simultaneous in vivo electrophysiology in dorsal ACC and ventral OFC, partnered with bilateral inhibitory DREADDs in ACC. In freely behaving male and female rats and using a within-subject design, we examined accuracy and speed of response across distinct and precisely defined trial epochs during initial visual discrimination learning and subsequent reversal of stimulus-reward contingencies. Following ACC inhibition, there was a propensity for random responding in early reversal learning, with correct vs. incorrect trials distinguished only from OFC, not ACC, theta power differences in the reversal phase. ACC inhibition also hastened incorrect choices during reversal. This same pattern of change in accuracy and speed was not observed in viral control animals. Thus, characteristics of impaired reversal learning following ACC inhibition are poor deliberation and weak theta signaling of accuracy in this region. The present results also point to OFC theta oscillations as a prominent feature of reversal learning, unperturbed by ACC inhibition.

Observational learning in rats: Interplay between demonstrator and observer behavior

BackgroundObservational learning is a vital skill for survival. This form of learning has been seen in humans and certain non-human animals. However, the neural circuitry underlying this form of learning is still poorly understood. New methodTo better understand the factors underlying successful observation in rats, we employed a task where an observer must base its behavior on that of a demonstrator rat to identify a reward location. A comparison was made of behavior during a social and non-social observation condition. ResultsObservers oriented more, responded faster and omitted less responses in the social compared to the non-social condition. Observer performance was also linked to initial orientation, proximity, and the manner in which the demonstrator rat performed the task. Comparison with existing methodPrevious work on observational learning encompassed multiple exposures to a single solution over days or weeks. The current method provides data from multiple individual novel observational learning trials, leading to much faster and more robust social learning. This method provides a clearly defined interval in which observation must take place. Allowing for precise tracking of both the observer and demonstrator behavior during the learning period. ConclusionsThis study highlights observer and demonstrator interplay in successful observational learning and provides a novel method for analyzing social behavior in rodents.