Working Memory Errors Research Articles

The longitudinal study of rat hippocampus influenced by stress: Early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats

Epidemiologic studies indicate that early adverse experience is related to learning disabilities in adults, but the neurobiological mechanisms have not yet been identified. We used longitudinal animal experiments to test the hypothesis that early life stress enhances hippocampal vulnerability and working memory deficit in adult rats. The expression of Synaptophysin (SYN) and apoptosis (Apo) in hippocampal CA3 and dentate gyrus (DG) regions were examined to evaluate the effects of environmental factors on the hippocampus. The working memory errors via radial 8-arm maze were studied to evaluate the long-term effect of early stress on rats’ spatial learning ability. Our results indicated that chronic restraint stress in early life and forced cold water swimming stress in adulthood reduced SYN expression and increased Apo levels in rat hippocampus, but the hippocampal damage tended to recover when rats returned to a non-stress environment. In addition, when the rats were exposed to forced cold water swimming stress during adulthood, SYN expression (CA3 and DG regions) and Apo levels (CA3 region) in rat hippocampus showed statistical difference between early restraint stress group and non-early restraint stress group (rats exposed to stress in adulthood only). One month after the two groups of rats returned to non-stress environment, this difference of SYN expression (CA3 and DG regions) and working memory deficit between the two groups was still statistically significant. Our study findings suggested that early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats, and reduces structural plasticity of hippocampus.

Neonatal hippocampal damage impairs specific food/place associations in adult macaques.

This study describes a novel spatial memory paradigm for monkeys and reports the effects of neonatal damage to the hippocampus on performance in adulthood. Monkeys were trained to forage in eight boxes hung on the walls of a large enclosure. Each box contained a different food item that varied in its intrinsic reward value, as determined from food preference testing. Monkeys were trained on a spatial and a cued version of the task. In the spatial task, the boxes looked identical and remained fixed in location whereas in the cued task, the boxes were individuated with colored plaques and changed location on each trial. Ten adult Rhesus macaques (5 neonatal sham-operated and 5 with neonatal neurotoxic hippocampal lesions) were allowed to forage once daily until they preferentially visited boxes containing preferred foods. The data suggest that all monkeys learned to discriminate preferred from nonpreferred food locations, but that monkeys with neonatal hippocampal damage committed significantly more working memory errors than controls in both tasks. Furthermore, following selective satiation, controls altered their foraging pattern to avoid the satiated food, whereas lesioned animals did not, suggesting that neonatal hippocampal lesions prohibit learning of specific food-place associations. We conclude that whereas an intact hippocampus is necessary to form specific item-in-place associations, in its absence, cortical areas may support more broad distinctions between food types that allow monkeys to discriminate places containing highly preferred foods.

Nigella sativaOil Enhances the Spatial Working Memory Performance of Rats on a Radial Arm Maze

Nigella sativa, an established historical and religion-based remedy for a wide range of health problems, is a herbal medicine known to have antioxidant and neuroprotective effects. This present study investigated the effect of Nigella sativa oil (NSO) administration on the spatial memory performance (SMP) of male adult rats using eight-arm radial arm maze (RAM). Twelve Sprague Dawley rats (7–9 weeks old) were force-fed daily with 6.0 μL/100 g body weight of Nigella sativa oil (NSO group; n = 6) or 0.1 mL/100 g body weight of corn oil (control) (CO group; n = 6) for a period of 20 consecutive weeks. For each weekly evaluation of SMP, one day food-deprived rats were tested by allowing each of them 3 minutes to explore the RAM for food as their rewards. Similar to the control group, the SMP of the treated group was not hindered, as indicated by the establishment of the reference and working memory components of the spatial memory. The results demonstrated that lesser mean numbers of error were observed for the NSO-treated group in both parameters as compared to the CO-treated group. NSO could therefore enhance the learning and memory abilities of the rats; there was a significant decrease in the overall mean number of working memory error (WME) in the NSO-treated group.

Impaired interval timing and spatial-temporal integration in mice deficient in CHL1, a gene associated with schizophrenia.

Interval timing is crucial for decision-making and motor control and is impaired in many neuropsychiatric disorders, including schizophrenia - a neurodevelopmental disorder with a strong genetic component. Several gene mutations, polymorphisms or rare copy number variants have been associated with schizophrenia. L1 cell adhesion molecules (L1CAMs) are involved in neurodevelopmental processes, and in synaptic function and plasticity in the adult brain. Mice deficient in the Close Homolog to L1 (CHL1) adhesion molecule show alterations of hippocampal and thalamo-cortical neuroanatomy as well as deficits in sensorimotor gating and exploratory behavior. We analyzed interval timing and attentional control of temporal and spatial information in male CHL1 deficient (KO) mice and wild type (WT) controls. In a 20-s peak-interval timing procedure (standard and reversed), KO mice showed a maintained leftward shift of the response function relative to WT, indicative of a deficit in memory encoding/decoding. In trials with 2, 5, or 10-s gaps, KO mice shifted their peak times less than WT controls at longer gap durations, suggesting a decreased (attentional) effect of interruptions. In the spatial-temporal task, KO mice made more working and reference memory errors than controls, suggestive of impaired use of spatial and/or temporal information. When the duration spent on the central platform of the maze was manipulated, WT mice showed fewer spatial errors at the trained duration than at shorter or longer durations, indicative of discrimination based upon spatial-temporal integration. In contrast, performance was similar at all tested durations in KO mice, indicative of control by spatial cues, but not by temporal cues. These results suggest that CHL1 KO mice selectively attend to the more relevant cues of the task, and fail to integrate more complex spatial-temporal information, possibly as a result of reduced memory capacity related to hippocampal impairment, and altered temporal-integration mechanisms possibly due to thalamo-cortical anomalies.

The anaesthetic combination of ketamine/midazolam does not alter the acquisition of spatial and motor tasks in adult mice

The ketamine/midazolam association of a dissociative with a sedative agent is used for the induction and maintenance of anaesthesia in laboratory animals. Anaesthesia may interfere with research results through side-effects on the nervous system, such as memory impairment. It is known that ketamine and midazolam affect cognition; however, their effects have not been clarified when used in a context of balanced anaesthesia. Thus, this study evaluated the effects of ketamine/midazolam on the acquisition of motor and of a spatial memory task in adult mice. Twenty-eight C57BL/6 adult male mice were divided into three groups: untreated control, treated with ketamine/midazolam (75 mg/kg / 10 mg/kg) and treated with midazolam (10 mg/kg) groups. Respiratory rate, heart rate and systolic pressure were measured every 5 min in the animals treated with ketamine/midazolam, as this was the only group that exhibited loss of the righting reflex. One day after treatment, animals were tested in the open field, rotarod and radial arm maze. There were no differences between treatments regarding open-field activity, rotarod performance or number of working and reference memory errors in the radial arm maze task. In conclusion, the learning process of spatial and motor tasks was not disrupted by the anaesthetic combination of ketamine/midazolam. These results suggest its safe use in adult mice in projects where acquisition of a spatial and motor task is necessary.

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze.

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

Developmental Effects of Malathion Exposure on Recognition Memory and Spatial Learning in Males Wistar Rats

Most cognitive effects of Organophosphate Pesticides (OP) are induced after exposure to parathion, chlorpyrifos and diazinon, which the usage has been restricted because of overt signs of their toxicities. In this study, we investigate whether developmental exposure to Malathion could impair spatial learning and recognition memory in male rats. Animals exposed by intragastric route, from in utero to young adult stage, to incremental doses of Malathion dissolved in corn oil; 100, 200 and 300 mg/kg of body weight, and one control group are given corn oil. Then, cognitive and behaveioral abilities are assessed using Barnes maze and object recognition memory task. Malathion administration at 300 mg/kg is toxic to pregnant dams, and pups are stillborns. Rats exposed to 200 mg/kg make a significant working memory error, and require more time to find an escape box during the initial training phase of Barnes maze. However, fewer errors are made in rats exposed to 100 mg/kg. For reversal learning task, the high dose group shows great deficits in spatial strategy to locate the new position of the box. With respect to recognition task, both dose 100 and 200 mg/kg impair significant short-term (2 h after habituation phase) object recognition memory, but long-term (24 h after habituation phase) recognition memory is intact in high dose group. The current study also reveals that all treatments induce high significant neocortex acetylcholinesterase (AChE) activity inhibition, but 100 mg/kg dose is not sufficient to disrupt great hippocampal activity alteration. These results suggest that developmental exposure to Malathion, despite low toxicity described, may induce late-emerging spatial learning and recognition memorialterations. Moreover, Cortical and hippocampal area that support strongly these behaviors remain sensitive to incremental doses of Malathion.

Effects of Wuling mycelia on pentylenetetrazole-induced epilepsy in rats

To investigate the effects and mechanisms of Wuling mycelia on seizure development and learning ability induced by pentylenetetrazole-kindling epilepsy in rats. SD rats were randomly divided into four groups: pentylenetetrazole-kindling model group (model group), low dose Wuling mycelia (0.3 g*kg(-1)) group (LD-WM group), high dose Wuling mycelia (0.6 g*kg(-1)) group (HD-WM group) and control group. The rats were intraperitoneal injected with a subconvulsive dose (35 mg*kg(-1)) of pentylenetetrazole (saline in control group) every 48 h for 12 times. Wuling mycelia was intragastrically applied 30 min before pentylenetetrazole injection. An 8-arm radial maze ( 4 arms baited) was used to measure the learning ability. Histamine was measured by chemical fluorometric enzyme immunoassay. Compared with the model group, the kindling stage of LD-WM group degraded significantly after 7th injection, the latency to the onset of myoclonic jerks (LTMJ) and the latency to the onset of generalized seizures (LTGS) prolonged after the 6th and 7th injection, respectively (P<0.05). The kindling stage of HD-WM group also degraded markedly after the 6th to 8th injection, and the LTMJ and the LTGS extended after the 8th to 9th and 6th injection, respectively (P<0.05). Compared with the control group, the frequency of working memory error (WME) and reference memory error (RME) of the model group in the 8-arm radial maze increased through 3-d training (P<0.05). The memory tests showed that the impairment induced by pentylenetetrazole was partially reversed by Wuling mycelia. Compared with the control group, brain histamine contents (hippocampus, cortex, thalamus and hypothalamus) were significantly lower in model group (P<0.05). But compared with the model group, hippocampal histamine contents in LD-WM group and hippocampal, thalamic and hypothalamic histamine contents in HD-WM group were elevated (P<0.05). Wuling mycelia can delay the kindling and ameliorate the ability of learning in rats with pentylenetetrazole-induced epilepsy and the enhancement of neuronal histamine activity may be one of possible mechanisms.

Association between Tobacco Smoking and Cognitive Functioning in Young Adults

Tobacco smoking represents a considerable public health burden globally. Smoking in older adults is associated with cognitive impairment and more rapid age-associated cognitive decline, but there is a paucity of studies in younger people. Adults aged 18-29 years were recruited from a longitudinal study investigating impulsivity in young people. Exclusion criteria were presence of any axis-I morbidity or cannabis use. Subjects undertook neurocognitive assessment using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Demographic, clinical, and cognitive differences between smokers (N = 37) and nonsmokers (N = 177) were characterized. Groups were well matched in terms of age, education, income, and gender. In comparison to nonsmokers, nicotine users showed significant cognitive impairments on sustained attention (target detection: p= .005), spatial working memory (errors: p= .023, strategy use: p= .004), executive planning (p= .002), and did not appropriately adjust behavior as a function of risk (Gamble task risk adjustment: p= .004). Smokers were intact on general response speeds and response inhibition. These data, using objective translational paradigms, support an association between tobacco smoking and cognitive problems in young people, with implications for such individuals and for society. Future studies should extend these results longitudinally to explore causality, and evaluate effects of nicotinic agents (including anti-smoking medications) on cognition.

The involvement of Type II Neuregulin-1 in rat visuospatial learning and memory

The cognitive deficits observed in schizophrenia are considered a core feature of the disease. Neuregulin-1 is a risk gene for schizophrenia that is involved in many neurodevelopmental and synaptic plasticity-related processes relevant to schizophrenia. Here, we have utilized a rat model (Nrg1Tn), which is hypomorphic for the neuregulin-1 (Nrg1) gene, to test whether reduced Type II NRG1 in the rat brain leads to cognitive deficits relevant to schizophrenia. Wild-type and homozygous Nrg1Tn male rats were tested in memory tasks that evaluated spatial memory (Morris water maze) and visuospatial working and reference memory (Can Test). Nrg1Tn rats were not impaired on the Morris water maze, but did show a deficit in the appetitive visuospatial discrimination test. Nrg1Tn rats committed more reference and working memory errors in this test. These results indicate that decreased Type II NRG1 in the brain may lead to deficits in visuospatial learning and memory.

Sildenafil provides sustained neuroprotection in the absence of learning recovery following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats

In this study, we tested whether the phosphodiesterase-5 inhibitor sildenafil protects against neurodegeneration and facilitates recovery from learning deficits examined long after chronic cerebral hypoperfusion (CCH) induced by the 4-vessel occlusion/internal carotid artery (4-VO/ICA) model in middle-aged rats. Male Wistar rats (12-15 months of age) were subjected to permanent 3-stage 4-VO/ICA with an interstage interval of 4 days. Sildenafil (3 mg/kg, p.o.) was administered at one dose per day for 10 days, beginning soon after the first occlusion stage. Three months later, learning in a non-food-rewarded, eight-arm radial maze task was tested. Learning performance is expressed as the latency to find a goal box and the number of reference or working memory errors. Histological examination was performed 1-3 days after behavioral testing. In the vehicle-treated group, permanent 4-VO/ICA markedly disrupted learning performance and caused moderate-to-severe neurodegeneration in the CA1-CA4 subfields of the hippocampus (56.2%), dentate gyrus (DG; 19.2%), retrosplenial cortex (RS cortex; 47.4%), and parietal association cortex (PtA cortex; 38.2%). Sildenafil treatment did not prevent 4-VO/ICA-induced learning deficits, whereas neurodegeneration was significantly reduced in the CA1-CA4 subfields (30.5%), DG (7.2%), RS cortex (11.8%), and PtA cortex (6.5%). Advancing previous findings from our laboratory, this study suggests that while sildenafil can provide important neuroprotection in different brain regions of middle-aged rats subjected to CCH, such histological effect does not translate into cognitive recovery.

Pharmacological effects of cannabinoids on the reference and working memory functions in mice

Evidence indicates cannabinoid receptor agonists impair performance in procedures to assess memory that may also be confounded by motivational or motor effects, both of which occur with cannabinoids. Thus, convergence of evidence from a variety of procedures that differ in motivation, attention, arousal and response requirements, but share a common reliance on memory, is required. There are no current reports on cannabinoid effects on mice tested in the radial arm maze. The objective was to determine the effects of the cannabinoid agonist CP 55940 and the dependence of any such effects on the CB1 receptor using the CB1 receptor antagonist SR 141716A on two strains of mice in the eight-arm radial maze procedure. Male C57BL/6J (N = 36) and C3H/HEJ (N = 12) mice were trained to a criterion and then were treated (IP) with vehicle + vehicle, SR 141716A + vehicle, vehicle + CP 55940 and SR 141716A + CP 55940 in a fully balanced mixed design prior to further tests in the maze. Reference (long-term) and working (short-term) memory were assessed. CP 55940 impaired performance of the reference memory task in the C57BL/6J strain but not the C3H/HEJ strain; SR 141716A reversed the effect of CP 55940 on these measures. CP 55940 also increased working memory errors in the C57BL/6J mice only, which was not affected by SR 141716A. The present study provides evidence for a strain-specific effect of a dose of CP 55940 on reference memory. While the cannabinoid agonist also impaired working memory in one strain, this effect was apparently not mediated by CB1 receptors.

Predictors of virtual radial arm maze performance in adolescent Italian children

BackgroundComparisons between animal and human neurotoxicology studies are a foundation of risk assessment, but are hindered by differences in measured behaviors. The radial arm maze (RAM), a rodent visuospatial learning and memory task, has a computerized version for use in children, which may help improve comparisons between animal and human studies. ObjectiveTo describe the characteristics and correlates of the virtual radial arm maze (VRAM) in 255 children age 10–15 years from Italy. MethodsWe administered the VRAM using a laptop computer and measured children's performance using the latency, distance, and working/reference memory errors during eight trials. Using generalized linear mixed models, we described VRAM performance in relation to demographic factors, child activities, and several standard neuropsychologic tests (Italian translations), including the Conners Parent Rating Scales-Short Version (CPRS), California Verbal Learning Test (CVLT), Wechsler Intelligence Scales for Children, finger tapping speed, reaction time, and motor skills. ResultsChildren's VRAM performance tended to improve between trials 1 and 6 and then plateaued between trials 6 and 8. Males finished the task 14s faster (95% confidence interval [CI]: −20, −9) than females. Children who played 2+h of video games per day finished 16s faster (CI: −26, −6) and with 34% (CI: 5, 54%) fewer working memory errors than children who reported not playing video games. Higher IQ and better CVLT scores were associated with better VRAM performance. Higher cognitive/inattention CPRS scores were associated with more working (11%; CI: 1, 22) and reference memory errors (7%; CI: 1, 12). ConclusionsConsistent with animal studies, VRAM performance improved over the course of test trials and males performed better than females. Better VRAM performance was related to higher IQ, fewer inattentive behaviors, and better verbal memory. The VRAM may help to improve the integration and comparison between animal and epidemiological studies of environmental neurotoxicants.

High serum androstenedione levels correlate with impaired memory in the surgically menopausal rat: a replication and new findings

After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle-depleted ovaries. In two independent studies, in rodents that had undergone ovarian follicular depletion, we found that higher endogenous serum androstenedione levels correlated with increased working memory errors. This led to the hypothesis that higher androstenedione levels impair memory. The current study directly tested this hypothesis, examining the cognitive effects of exogenous androstenedione administration in rodents. Middle-aged ovariectomised rats received vehicle or one of two doses of androstenedione. Rats were tested on a spatial working and reference memory maze battery including the water-radial arm maze, Morris water maze (MM) and delay match-to-sample task. Androstenedione at the highest dose impaired reference memory as well as the ability to maintain performance as memory demand was elevated. This was true for both high temporal demand memory retention of one item of spatial information, as well as the ability to handle multiple items of spatial working memory information. We measured glutamic acid decarboxylase (GAD) protein in multiple brain regions to determine whether the gamma-aminobutyric acid (GABA) system relates to androstenedione-induced memory impairments. Results showed that higher entorhinal cortex GAD levels were correlated with worse MM performance, irrespective of androstenedione treatment. These findings suggest that androstenedione, the main hormone produced by the follicle-depleted ovary, is detrimental to working memory, reference memory and memory retention. Furthermore, while spatial reference memory performance might be related to the GABAergic system, it does not appear to be altered with androstenedione administration, at least at the doses used in the current study.

Competition increases binding errors in visual working memory

When faced with maintaining multiple objects in visual working memory, item information must be bound to the correct object in order to be correctly recalled. Sometimes, however, binding errors occur, and participants report the feature (e.g., color) of an unprobed, non-target item. In the present study, we examine whether the configuration of sample stimuli affects the proportion of these binding errors. The results demonstrate that participants mistakenly report the identity of the unprobed item (i.e., they make a non-target response) when sample items are presented close together in space, suggesting that binding errors can increase independent of increases in memory load. Moreover, the proportion of these non-target responses is linearly related to the distance between sample items, suggesting that these errors are spatially specific. Finally, presenting sample items sequentially decreases non-target responses, suggesting that reducing competition between sample stimuli reduces the number of binding errors. Importantly, these effects all occurred without increases in the amount of error in the memory representation. These results suggest that competition during encoding can account for some of the binding errors made during VWM recall.

Effect of beef consumption on body iron and cognitive function in iron‐deficient women

Iron depletion is associated with cognitive impairment in women of reproductive age. This project investigates the effect of moderate beef intake on total body iron and cognitive function in university undergraduate women. At baseline, women (n=17) were classified by body iron tertile and randomly assigned to a beef or nonbeef meat lunch group (85 g, 3x weekly) for 16 weeks. Computerized neurocognitive tests were administered at baseline and week 16. Changes in calculated body iron and cognitive performance from baseline to endpoint were analyzed using generalized linear models and Spearman correlations. Women in the 1st (lowest) vs. 2nd and 3rd iron tertile responded to either lunch intervention with significant increases in body iron (ANOVA, P&lt;0.01) and significant improvements in tests of spatial working memory (decrease in errors and improvement in strategy, P&lt;0.05). Change in body iron was inversely associated with change in spatial working memory error rate (r=−0.49; P&lt;0.05). These preliminary findings suggest that working memory improves in association with increased iron status in iron‐deficient women consuming moderate amounts of beef or nonbeef meat. Funded by the Idaho Beef Council.

Effects of Olanzapine and Clozapine on Radial Maze Performance in Naive and MK-801-Treated Mice

Attention, working memory and long-term memory dysfunctions are the most commonly seen cognitive impairments in schizophrenic patients. Conflicting results exist regarding the effects of antipsychotics on cognitive abnormalities. The aim of this study was to investigate the effects of atypical antipsychotic drugs olanzapine (0.4, 0.8 and 1.25 mg/kg, i.p.) and clozapine (0.5 and 1 mg/kg, i.p.) on spatial working memory in naive and MK-801 (0.2 mg/kg, i.p.) treated BALB-c mice in an 8-arm radial arm maze (RAM) task. None of the antipsychotic drugs studied altered number of errors in naive mice, whereas MK-801 significantly increased working memory errors in RAM test. Olanzapine and clozapine potently reversed MK-801 induced increasement of working memory errors. Olanzapine and clozapine prolonged latency of the animals in naive mice. The MK-801-induced enhancement in the speed of mice in performing the RAM task was blocked by olanzapine but not clozapine. Our study shows that atypical antipsychotics olanzapine and clozapine might improve cognitive deficits in schizophrenic patients.

Chronic stress impairs prefrontal cortex-dependent response inhibition and spatial working memory.

Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, the fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague-Dawley rats were first trained on the RAWM and subsequently trained on FMI. After acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when sucrose reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing imprecision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher's r-to-z transformation revealed no significant differences between control and stress groups with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been directly compared within the same animals after chronic stress, using FMI, an appetitive task, and RAWM, a nonappetitive task.

425: Improved detection of anomalies by CVS with fish analysis prior to multifetal reduction (MFPR)

fish analysis prior to multifetal reduction (MFPR) Mara Rosner, Eugene Pergament, Stephanie Andriole, Pe’er Dar, Rachel Greenbaum, Mark Evans Montefiore Medical Center/Albert Einstein College of Medicine, Obstetrics & Gynecology and Women’s Health, Bronx, NY, Northwestern Reproductive Genetics PC, Genetics, Chicago, IL, Comprehensive Genetics, Genetic Counseling, New York, NY, Albert Einstein College of Medicine/ Montefiore Medical Center, Obstetrics & Gynecology and Women’s Health, Bronx, NY, Comprehensive Genetics, Ultrasound, New York, NY, Comprehensive Genetics & Mt. Sinai School of Medicine, Obstetrics & Gynecology, New York, NY OBJECTIVE: Over 50% of patients undergoing IVF in the USA are 35 years of age. When multiples, PGD, and ICSI are added, over 70% are at increased risk, yet most patients are not offered CVS prior to MFPR. We routinely offer CVS prior to MFPR. STUDY DESIGN: We retrospectively reviewed our last 470 CVS/MFPR patients. Abnormalities were categorized as structural, FISH, and abnormal karyotype. Our approach is generally not to test fetuses that are clearly abnormal and reduced such that the overall cytogenetic abnormality rate is artificially lowered. RESULTS: 94/470(20%) pregnancies and 96/1339(7.2%) fetuses had anomalies. 62/94(66%) were referred in the 1st trimester of which 24/62(39%) were identified or suggested by ultrasound(US). 27/ 62(43.5%) had an abnormal FISH that dictated MFPR. 21/27(77.7%) of the cytogenetic abnormalities had normal US. 5/21(24%) were T21, 2/21(10%) were T18/13, 13/21(62%) were sex chromosome mosaics, and one was a trisomy 13 mosaic. When final karyotype was available, FISH agreed with the karyotype in 702/728(96.4%) fetuses. Of the 26 discrepancies between FISH and karyotype, 18/26(69%) were sex chromosomes suggesting cross contamination or known innocuous findings such as tetraploidy or inherited inversions. Ultimately, there were 8/728(1%) potentially concerning karyotypic abnormalities discordant from FISH which included mosaic trisomies, one trisomy 8 and one chromosome 15p 7/8 of which were confined placental mosaicisms. Final karyotype and subsequent amniocentesis confirmed one 46XX/46XY mosaic not seen on FISH. CONCLUSION: In our cohort, US alone identified only 39% of 1st trimester anomalies before MFPR. FISH identified another 32.8% and added value beyond US for 15/351 (4.3%) patients. 8/728(1%) required follow up amniocentesis for discrepancies. Given the risks of carrying multiples and published mistakes in reducing the wrong fetus by waiting for karyotype, our data suggest CVS, next day FISH and then MFPR as the optimal strategy. As a by-product, patients can then consider fetal sex when there are no other abnormalities. 426 Adolescent cognitive and anxiety behavior in offspring following in utero exposure to increased trans unsaturated fatty acids through maternal diet Mark Alanis, Claudia Umphlet, Heather Boger, Ann-Charlotte Granholm Medical University of South Carolina, Obstetrics and Gynecology, Charleston, SC, MUSC, Neurosciences, Charleston, SC OBJECTIVE: The developing brain is potentially susceptible to inflammatory diets, such as trans unsaturated fatty acids (TFA). STUDY DESIGN: Fisher 344 virgin rats were randomized to isocaloric experimental (TFA) or study (AIN93) diets for 4 weeks, mated, and then maintained on their study diets until weaning. On postnatal day 23 (P23) offspring were further randomized into 1 of 4 prenatal/postnatal dietary arms (N 16 litters): TFA/TFA, TFA/AIN, AIN/AIN, and AIN/TFA. Adolescent male and female rats (P36-38) underwent anxiety assessment using the elevated plus maze paradigm. Decreased % time and entry into open arms indicate increased anxiety. Adolescent male rats (P40-45) underwent cognitive behavioral performance testing using the water radial arm maze (WRAM) over 12 consecutive days. Spatial working and reference memory errors were averaged across litters during learning (days 1-3) and asymptotic phases (days 4-7, 6-9, and 10-12). Group comparisons were performed using 2-way analysis of variance (ANOVA) with repeated measures. Equality of variance was assessed by the F-test. Two-tailed p values .05 were considered significant. RESULTS: Females demonstrated greater anxiety than males based on the number of entries into open arms (10.5 0.9 versus 16.9 1.6, p .001), but not % open time (40% versus 53% open time, respectively, p .05). Diet did not demonstrate a significant relationship with anxiety (p .52). Rats in all 4 diet arms showed similar improvement over the 12 day WRAM test (Figure). When collapsing the analysis to 2 groups (prenatal TFA versus AIN), prenatal TFA rats committed more total working memory errors compared to prenatal AIN rats during the day 10-12 phase (6.1 .6 vs. 3.3 1.2 errors, respectively; p .03). Variance was not significantly different between the 4 groups (p .05 for all F-tests). CONCLUSION: Prenatal and postnatal dietary exposure of TFA did not demonstrate a major impact on either anxiety or hippocampal-dependent cognitive behavior, which may be explained by a true absence of effect or variance in the sample set (Type II error).

Spatial memory deficits in a virtual reality eight-arm radial maze in schizophrenia

Learning and memory impairments are present in schizophrenia (SZ) throughout the illness course and predict psychosocial function. Abnormalities in prefrontal and hippocampal function are thought to contribute to SZ deficits. The radial arm maze (RAM) is a test of spatial learning and memory in rodents that relies on intact prefrontal and hippocampal function. The goal of the present study was to investigate spatial learning in SZ using a virtual RAM. Thirty-three subjects with SZ and thirty-nine healthy controls (HC) performed ten trials of a virtual RAM task. Subjects attempted to learn to retrieve four rewards each located in separate arms. As expected, subjects with SZ used more time and traveled more distance to retrieve rewards, made more reference (RM) and working memory (WM) errors, and retrieved fewer rewards than HC. It is important to note that the SZ group did learn but did not reach the level of HC. Whereas RM errors decreased across trials in the SZ group, WM errors did not. There were no significant relationships between psychiatric symptom severity and maze performance. To our knowledge, use of a virtual 8-arm radial maze task in SZ to assess spatial learning is novel. Impaired virtual RAM performance in SZ is consistent with studies that examined RAM performance in animal models of SZ. Results provide further support for compromised prefrontal and hippocampal function underlying WM and RM deficits in SZ. The virtual RAM task could help bridge preclinical and clinical research for testing novel drug treatments of SZ.