Estradiol or diarylpropionitrile administration to wild type, but not estrogen receptor beta knockout, mice enhances performance in the object recognition and object placement tasks

Cognitive processes mediated by the hippocampus and cortex are influenced by estradiol (E₂); however, the mechanisms by which E₂ has these effects are not entirely clear. As such, studies were conducted to begin to address the role of actions at the β form of the intracellular estrogen receptor (ERβ) for E₂’s cognitive effects in adult female mice. We investigated whether E₂ improved performance of wild type (WT) and ERβ knockout (βERKO) mice in tasks considered to be mediated by the cortex and hippocampus, the object recognition and object placement tasks. WT and βERKO mice were ovariectomized (ovx) and E₂ (0.1 mg/kg), an ERβ selective ER modulator (SERM), diarylpropionitrile (DPN; 0.1 mg/kg), or oil vehicle was administered to mice following training in these tasks. We hypothesized that if E₂ has mnemonic effects, in part, due to its actions at ERβ, then WT mice administered E₂ or DPN would have improved performance compared to vehicle WT controls, which would not be different from βERKO mice administered vehicle, E₂ or DPN. Alternatively, activation of ERα (with E₂, which is a ligand for both ERα and ERβ) may produce opposing effects on cognition and/or the activation of ERα and ERβ vs. either receptor isoform alone may produce a different pattern of effects. Results obtained supported the hypothesis that ERβ activation is important for mnemonic effects. Ovx WT, but not βERKO, mice administered E₂ or DPN had a greater percentage of time exploring a novel object in the object recognition task and a displaced object in the object placement task. Thus, actions at ERβ may be important for E₂ or SERMs to enhance cognitive performance of female mice in the object recognition and placement tasks.     

Forgotten but not gone: Context effects on recognition do not require explicit memory for context

Context effects on recognition memory provide an important indirect assay of associative learning and source memory. Neuropsychological studies have indicated that such context effects may obtain even if the contexts themselves are not remembered—for example, in individuals impaired on direct tests of memory for contextual information. In contrast, a recent study indicated that the effects of temporal context reinstatement on visual recognition obtain only when the contextual information itself was explicitly recollected. Here we report that the effects of reinstatement of spatial-simultaneous context on visual object recognition memory obtain irrespective of whether those context stimuli are explicitly recognized. We suggest that spatial-simultaneous context effects might be based on ensemble unitization of target and context stimuli at encoding, whereas temporal context effects may require recollective processes.     

Infusion of protein synthesis inhibitors in the entorhinal cortex blocks consolidation but not reconsolidation of object recognition memory

Memory consolidation and reconsolidation require the induction of protein synthesis in some areas of the brain. Here, we show that infusion of the protein synthesis inhibitors anisomycin, emetine and cycloheximide in the entorhinal cortex immediately but not 180 min or 360 min after training in an object recognition learning task hinders long-term memory retention without affecting short-term memory or behavioral performance. Inhibition of protein synthesis in the entorhinal cortex after memory reactivation involving either a combination of familiar and novel objects or two familiar objects does not affect retention. Our data suggest that protein synthesis in the entorhinal cortex is necessary early after training for consolidation of object recognition memory. However, inhibition of protein synthesis in this cortical region after memory retrieval does not seem to affect the stability of the recognition trace.     

Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks

Research on how steroid hormones mediate mnemonic processes have focused on effects of 17β-estradiol (E₂); yet, progesterone (P₄) co-varies with E₂ across endogenous hormonal milieu, and itself may influence cognitive processes. We investigated the hypothesis that acute P₄ treatment enhances cognitive performance compared to vehicle. Ovariectomized (OVX) c57/BL6J mice were randomly assigned to be subcutaneously injected with oil vehicle or P₄ (10 mg/kg). Mice were trained in the spontaneous alternation, object recognition, object placement, water maze, or fear conditioning tasks, and injected with vehicle or P₄ before training or immediately post-training, and then were tested 1, 4, or 24 h later. The data obtained from these experiments supported our hypothesis. P₄ increased the percentage of spontaneous alterations made in a T-maze more so than did vehicle. P₄, compared to vehicle, increased the percentage of time spent exploring the novel object in the object recognition task, but did not alter performance in the object placement task. P₄, compared to vehicle, decreased latencies to reach the location in the water maze where the platform had been during training in a probe trial, but did not alter performance in the control, cued trial. Compared to vehicle, P₄ treatment increased freezing in contextual and cued fear testing. Thus, acute P₄ treatment to OVX mice can improve cognitive performance across a variety of tasks.     

Individual differences in forced-choice recognition memory: Partitioning contributions of recollection and familiarity

In forced-choice recognition memory, two different testing formats are possible under conditions of high target–foil similarity: Each target can be presented alongside foils similar to itself (forced-choice corresponding; FCC), or alongside foils similar to other targets (forced-choice noncorresponding; FCNC). Recent behavioural and neuropsychological studies suggest that FCC performance can be supported by familiarity whereas FCNC performance is supported primarily by recollection. In this paper, we corroborate this finding from an individual differences perspective. A group of older adults were given a test of FCC and FCNC recognition for object pictures, as well as standardized tests of recall, recognition, and IQ. Recall measures were found to predict FCNC, but not FCC performance, consistent with a critical role for recollection in FCNC only. After the common influence of recall was removed, standardized tests of recognition predicted FCC, but not FCNC performance. This is consistent with a contribution of only familiarity in FCC. Simulations show that a two-process model, where familiarity and recollection make separate contributions to recognition, is 10 times more likely to give these results than a single-process model. This evidence highlights the importance of recognition memory test design when examining the involvement of recollection and familiarity.     

Neurophysiology of sustained attention in early infancy: Investigating longitudinal relations with recognition memory outcomes

The ability to sustain attention is a critical cognitive domain that emerges in infancy and is predictive of a multitude of cognitive processes. Here, we used a heart rate (HR) defined measure of sustained attention to assess corresponding changes in frontal electroencephalography (EEG) power at 3 months of age. Second, we examined how the neural underpinnings of HR-defined sustained attention were associated with sustained attention engagement. Third, we evaluated if neural or behavioral sustained attention measures at 3-months predicted subsequent recognition memory scores at 9 months of age. Seventy-five infants were included at 3 months of age and provided usable attention and EEG data and 25 infants returned to the lab at 9 months and provided usable recognition memory data. The current study focuses on oscillatory power in the theta (4–6 Hz) frequency band during phases of HR-defined sustained attention and inattention phases. Results revealed that theta power was significantly higher during phases of sustained attention. Second, higher theta power during sustained attention was positively associated with proportion of time in sustained attention. Third, longitudinal analyses indicated a significant positive association between theta power during sustained attention on 9-month visual paired comparison scores such that higher theta power predicted higher visual paired comparison scores at 9-months. These results highlight the interrelation of the attention and arousal systems which have longitudinal implications for subsequent recognition memory processes.     

Chronic oral methylphenidate induces post-treatment impairment in recognition and spatial memory in adult rats

Recent pre-clinical research has indicated that chronic treatment with methylphenidate (Ritalin^®) in young animals can result in lasting and potentially detrimental alterations in brain function that can persist into adulthood. Chronic methylphenidate-induced neuronal alterations may result in behavior and cognitive deficits that include increases in behavioral responses and impairment in recognition memory. This study compared the cognitive consequences following chronic treatment with two doses (5 and 10 mg/kg) of methylphenidate on recognition and spatial memory in adult male Long-Evans rats using an established oral dosing procedure. The animals were then tested in the Object Recognition test at 14 days post treatment and the Object Placement test at 21 days post treatment. The results indicate that repeated exposure to oral methylphenidate impaired the performance of rats in these tests. The current findings add to recent research demonstrating negative consequences in rats pre-treated with methylphenidate, and extend previous findings to include deficits in spatial recognition memory.     

Emotion and memory: A recognition advantage for positive and negative words independent of arousal

Much evidence indicates that emotion enhances memory, but the precise effects of the two primary factors of arousal and valence remain at issue. Moreover, the current knowledge of emotional memory enhancement is based mostly on small samples of extremely emotive stimuli presented in unnaturally high proportions without adequate affective, lexical, and semantic controls. To investigate how emotion affects memory under conditions of natural variation, we tested whether arousal and valence predicted recognition memory for over 2500 words that were not sampled for their emotionality, and we controlled a large variety of lexical and semantic factors. Both negative and positive stimuli were remembered better than neutral stimuli, whether arousing or calming. Arousal failed to predict recognition memory, either independently or interactively with valence. Results support models that posit a facilitative role of valence in memory. This study also highlights the importance of stimulus controls and experimental designs in research on emotional memory.     

A male advantage for spatial and object but not verbal working memory using the n-back task

Sex-related differences have been reported for performance and neural substrates on some working memory measures that carry a high cognitive load, including the popular n-back neuroimaging paradigm. Despite some evidence of a sex effect on the task, the influence of sex on performance represents a potential confound in neuroimaging research. The present study investigated sex-related differences in verbal, spatial, and common object versions of the high cognitive load "n-back" working memory task. Eighteen male and 18 female undergraduates completed all 3 versions of the task. A mixed ANOVA, with Sex (male and female) as the between-subjects factor and Condition (verbal, spatial, and object) as the within-subjects repeated measure revealed that males were significantly more accurate than females on the spatial and object versions of the n-back task and performed equivalently to females on the verbal version of the task. Although the expected female advantage for verbal working memory was not found using this effortful n-back task, these results support a male advantage for high cognitive load spatial and object working memory. Future research should take into account the influence of sex on performance of the n-back task, and examine sex-related differences in working memory using other paradigms.     

No sex differences in spatial location memory for abstract designs

Previous research has demonstrated a female advantage, albeit imperfectly, on tests of object location memory where object identity information is readily available. However, spatial and visual elements are often confounded in the experimental tasks used. Here spatial and visual memory performance was compared in 30 men and 30 women by presenting 12 abstract designs in a spatial array for recall and recognition (visual memory) and spatial location ("object" location memory). Object location memory was measured via a sensitive absolute displacement score defined as the distance in mms between the position assigned to the object during recall and the actual position it originally occupied. There were no sex differences in either the visual or spatial location tests. Controlling for age and estimated IQ scores made no impact on the results. These data suggest an absence of a sex difference in purely visual and spatial aspects of object location memory.     

Sexual orientation and spatial position effects on selective forms of object location memory

Prior research has demonstrated robust sex and sexual orientation-related differences in object location memory in humans. Here we show that this sexual variation may depend on the spatial position of target objects and the task-specific nature of the spatial array. We tested the recovery of object locations in three object arrays (object exchanges, object shifts, and novel objects) relative to veridical center (left compared to right side of the arrays) in a sample of 35 heterosexual men, 35 heterosexual women, and 35 homosexual men. Relative to heterosexual men, heterosexual women showed better location recovery in the right side of the array during object exchanges and homosexual men performed better in the right side during novel objects. However, the difference between heterosexual and homosexual men disappeared after controlling for IQ. Heterosexual women and homosexual men did not differ significantly from each other in location change detection with respect to task or side of array. These data suggest that visual space biases in processing categorical spatial positions may enhance aspects of object location memory in heterosexual women.     

The contribution of familiarity to recognition memory is a function of test format when using similar foils

Patient Y.R., who suffered hippocampal damage that disrupted recollection but not familiarity, was impaired on a yes/no (YN) object recognition memory test with similar foils. However, she was not impaired on a forced-choice corresponding (FCC) version of the test that paired targets with corresponding similar foils (Holdstock et al., 2002). This dissociation is explained by the Complementary Learning Systems (CLS) neural-network model (Norman & O'Reilly, 2003) if recollection is impaired but familiarity is preserved. The CLS model also predicts that participants relying exclusively on familiarity should be impaired on forced-choice noncorresponding (FCNC) tests, where targets are presented with foils similar to other targets. The present study tests these predictions for all three test formats (YN, FCC, FCNC) in normal participants using two variants of the remember/know procedure. As predicted, performance using familiarity alone was significantly worse than standard recognition on the YN and FCNC tests, but not on the FCC test. Recollection in the form of recall-to-reject was the major process driving YN recognition. This adds support to the interpretation of patient data, according to which hippocampal damage causes a recollection deficit that leads to poor performance on the YN test relative to FCC.     

Repeated checking causes distrust in memory but not in attention and perception

Repeated checking to reduce memory distrust seems to be counterproductive: it increases memory distrust. Obsessive-compulsive (OC) patients tend to be uncertain about other cognitive domains as well, like attention and perception. In an experiment with 70 healthy participants, we tested whether perseverative checking induces distrust not only in memory, but also in attention and perception. Participants were administered a computer task in which they had to activate, deactivate, and check threat-irrelevant stimuli, and rate their confidence in memory, attention, and perception in a pre-test and post-test. In between these tests, the relevant checking group performed 20 checks of the same stimuli used in the pre- and post-test. The irrelevant checking group performed 20 checks of different stimuli. Although memory accuracy improved in both groups, repeated checking reduced confidence in memory, vividness, and detail in the relevant checking group, but not in the irrelevant checking group. A trend was found towards a decline in attentional confidence in the relevant checking group only. Perception was not affected by repetitive checking. A replication study revealed similar results of relevant checking on meta-memory, however, the trend for attentional distrust was not confirmed. The results suggest that perseveration may be domain specific, i.e., only the cognitive processes that are subject to perseveration are affected.     

Intracranial self-stimulation improves memory consolidation in rats with little training

Post-training intracranial electrical self-stimulation can improve learning and memory consolidation in rats. However, the molecular mechanisms involved are not known yet. Since previous paradigms of this kind of facilitation are relatively unsuitable to try a molecular approach, here we develop a single and short model of learning and memory facilitation by post-training self-stimulation that could make easier the research of its neural and molecular basis. Thus, three consecutive experiments were carried out to ascertain whether post-training self-stimulation is able to facilitate memory when learning consists of only a brief (5 trials) two-way active avoidance conditioning session. The results of Experiment 1 showed that it is actually possible, and that 48 h after the acquisition session is a very good time to observe the memory improvement. As a way to probe the retroactive effect of self-stimulation, in Experiment 2 we observed that the same self-stimulation treatment given to the subjects not post-training but 48 h before a single two-way active avoidance session does not improve the acquisition of conditioning. In Experiment 3, we showed that the SS facilitative effect observed 48 h after the acquisition session in Experiment 1 was still maintained one week later. We concluded that post-training intracranial self-stimulation can consistently improve memory consolidation even when little acquisition training is given to the animals in a single training session.     

Sex differences in object location memory and spatial navigation in Long-Evans rats

In both humans and rodents, males typically excel on a number of tasks requiring spatial ability. However, human females exhibit advantages in memory for the spatial location of objects. This study investigated whether rats would exhibit similar sex differences on a task of object location memory (OLM) and on the watermaze (WM). We predicted that females should outperform males on the OLM task and that males should outperform females on the WM. To control for possible effects of housing environment, rats were housed in either complex environments or in standard shoebox housing. Eighty Long-Evans rats (40 males and 40 females) were housed in either complex (Complex rats) or standard shoebox housing (Control rats). Results indicated that males had superior performance on the WM, whereas females outperformed males on the OLM task, regardless of housing environment. As these sex differences cannot be easily attributed to differences in cognitive style related to linguistic processing of environmental features or to selection pressures related to the hunting gathering evolutionary prehistory of humans, these data suggest that sex differences in spatial ability may be related to traits selected for by polygynous mating strategies.     

Susceptibility to induction of long-term depression is associated with impaired memory in aged Fischer 344 rats

The current study employed aged and young male Fischer 344 rats to examine the relationship between long-term depression (LTD), age, and memory. Memory performance was measured on two tasks that are sensitive to hippocampal function; inhibitory avoidance and spatial discrimination on the Morris water maze. The slope of the extracellular excitatory postsynaptic field potential was recorded from CA3-CA1 synapses in hippocampal slices. Low frequency stimulation (LFS) induced a modest LTD only in aged animals under standard recording conditions. The decrease in synaptic transmission examined only in aged animals correlated with memory scores on the spatial task and LTD was not observed in aged animals with the highest memory scores. LTD induction was facilitated by increasing the Ca(2+)/Mg(2+) ratio of the recording medium or employing a paired-pulse stimulation paradigm. Age differences disappeared when LFS was delivered under conditions of elevated Ca(2+)/Mg(2+) in the recording medium. Using multiple induction episodes under conditions which facilitate LTD-induction, no age-related difference was observed in the maximum level of LTD. The results indicate that the increased susceptibility to LTD induction is associated with impaired memory and results from a shift in the induction process. The possible relationship between LTD and memory function is discussed.     

Post-encoding emotional arousal enhances consolidation of item memory,but not reality-monitoring source memory

The current study examined whether the effect of post-encoding emotional arousal on item memory extends to reality-monitoring source memory and, if so, whether the effect depends on emotionality of learning stimuli and testing format. In Experiment 1, participants encoded neutral words and imagined or viewed their corresponding object pictures. Then they watched a neutral, positive, or negative video. The 24-hour delayed test showed that emotional arousal had little effect on both item memory and reality-monitoring source memory. Experiment 2 was similar except that participants encoded neutral, positive, and negative words and imagined or viewed their corresponding object pictures. The results showed that positive and negative emotional arousal induced after encoding enhanced consolidation of item memory, but not reality-monitoring source memory, regardless of emotionality of learning stimuli. Experiment 3, identical to Experiment 2 except that participants were tested only on source memory for all the encoded items, still showed that post-encoding emotional arousal had little effect on consolidation of reality-monitoring source memory. Taken together, regardless of emotionality of learning stimuli and regardless of testing format of source memory (conjunction test vs. independent test), the facilitatory effect of post-encoding emotional arousal on item memory does not generalize to reality-monitoring source memory.