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The object recognition task in rats and mice: a simple and rapid model in safety pharmacology to detect amnesic properties of a new chemical entity.

INTRODUCTION: The aim of the present study was to evaluate the potential usefulness of the object recognition learning paradigm to detect the potential amnesic properties of a new drug for use in the characterisation of its safety pharmacology profile. METHODS AND RESULTS: In the first experiment, the time-dependent decay of object recognition memory was characterised in Sprague-Dawley rats and C57Bl/6J mice. Under our experimental conditions, it takes between 3 and 4 post-training hours for the rats and between 1 and 2 post-training hours for the mice to forget the respective value of the objects. In the second experiment, the effects of scopolamine (0.03-1 mg/kg) were investigated in both rats and mice when administered 30 min prior to training in the object recognition task. Memory retention was tested 2 h after training in rats and 1 h after training in mice. Scopolamine impairs the object recognition memory at doses of 0.1, 0.3, and 1 mg/kg in rats and at doses of 0.3 and 1 mg/kg in mice. In the last experiment, effects of two benzodiazepines (alprazolam and diazepam) were assessed in the mouse model of object recognition task. Diazepam and alprazolam were intraperitoneally administered 30 min prior to training and memory retention was tested 10 min and 1 h after training. At 0.2 mg/kg, both benzodiazepines impair object recognition memory when testing is performed 1 h after training. However, when testing is performed 10 min after training, both benzodiazepines at 0.2 mg/kg failed to disrupt memory processes. DISCUSSION: Taken together, these results show that the object recognition task can easily be performed in rats and mice for safety pharmacology studies related to CNS function. Because of the ageing population and the increasing number of drugs prescribed to elderly patients, it becomes important to evaluate the potential side effects of a new chemical entity on memory function during evaluation of its safety profile. The object recognition task, which is simple, rapid, and reliable, should be of great use in safety pharmacology to detect amnesic properties of new compounds.

Alprazolam↗

[Deficit of explicit memory in Parkinson's disease demonstrated by auditory-verbal and visual-design learning tasks].

This study is concerned with explicit memory in both auditory and visual modalities in patients with non-demented(on DSM-III-R) Parkinson's disease. On some explicit memory studies, Parkinsonian patients were compared with normal controls matched for age and education. For assessment of recollection, recall and recognition were assessed using two clinical test batteries, Rey's Auditory-Verbal Learning Test and Rey's Visual-Design Learning Test. In addition to a comparison of recall and recognition, the present research inquired into the serial position data in free recall, analysis by applying a signal detection theory to the recognition data, and metamemory by using self-assessment of recognition. The results showed that the Parkinsonian group was significantly impaired on both tests of free recall compared to the normal controls. By contrast, when given tests of recognition memory for the same lists, their performance was almost identical only in assessment of correct scores(hits). There was a significant correlations between performances on achieved categories of the Wisconsin Card Sorting Test and on free recalls of the auditory-verbal learning test in the patient group. In recall, no qualitative differences of the serial position curves were observed between the two groups, as an increasing pattern of primacy and recency effect was preserved. In addition, the two groups performed equally well on both auditory (digit span) and visual(spatial span) short-term memory assessment. Moreover, on the trial-recall curves, from the first trial to the last two groups showed no significant differences in their learning effect and forgetting. Irrespective of modalities, however, the Parkinsonian group recalled less than the controls in the first trials. The poor performance of recall in the patients could be explained in terms of diminished attentional resources of the central executive system processing information beyond their short-term memory span within the framework of Baddeley's model of working memory which simultaneously controls two functions of encoding and retention. It was suggested that diminished central resources would be strongly associated with basal frontal dysfunction in Parkinson's disease. When recognition memory was further investigated, false alarms but not misses significantly increased despite normal hits in the patients on both tests. Analysis by using a signal detection theory produced significant differences, in that the Parkinsonian patients had lower values of beta and d' on auditory-verbal learning while they had lower tendency of beta on visual-design. The trend that they fell into errors by recognizing a distracter as the target presented previously was likely to be related a dysfunction of the supervisory system of Norman and Shallice's model which was assumed to be in the prefrontal cortex. Moreover, the present research disclosed that metamemory, i.e. the ability to assess their own memory, was disturbed in the Parkinsonian patients. In addition to the problem of recognition mentioned above, it was suggested that the impaired metamemory could be attributed to a deterioration of frontal lobe function.

Female↗

Temporal characteristics of visual memory.

In order to infer the temporal relations among iconic, short-term, and long-term components of visual memory, random dot patterns were used as memory stimuli in six recognition memory experiments. Experiment 1 demonstrated that recognition was still above chance for intervals up to 12 s. In Experiments 2 and 3, an intervening masking stimulus was found to be effective only if presented within the first 500 ms of the interval. The remaining three experiments employed a two-target task, with the second target replacing the masking stimulus. Recognition performance with the second target was the same as that in a single-target task, whereas performance with the first target was almost at chance level. Increasing the interval between the targets resulted in a gradual improvement in the recognition of the first target.

Form Perception↗

Alcohol and triazolam: differential effects on memory, psychomotor performance and subjective ratings of effects.

The effects of alcohol (0.80 g/kg) and the benzodiazepine hypnotic triazolam (0.25 mg/70 kg) were compared directly in a double-dummy, double-blind, placebo-controlled, repeated-measures design in 18 healthy volunteers. While alcohol (0.80 g/kg) and triazolam (0.25 mg/70 kg) produced comparable levels of psychomotor performance impairment, a dissociation was observed, such that the magnitude of memory impairment (measured by d', participants' sensitivity in discriminating between old and new words in the recognition memory paradigm) was greater with triazolam than with alcohol, whereas subjective ratings of the overall strength of drug effect were higher with alcohol than with triazolam. Participants also adopted a more conservative response bias in the recognition memory paradigm in the alcohol (0.80 g/kg) condition relative to both placebo and triazolam (0.25 mg/70 kg). In addition to characterizing the adverse effects of two widely used psychoactive substances, the present results may also contribute to the understanding of underlying neurochemical mechanisms.

Adult↗

Hippocampal CA1 spiking during encoding and retrieval: relation to theta phase.

The hippocampal theta rhythm is a prominent oscillation in the field potential observed throughout the hippocampus as a rat investigates stimuli in the environment. A recent computational model [Hasselmo, M. E., Bodelon, C., & Wyble, B. P. (2002a). A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning. Neural Computation, 14, 793-817. Neuromodulation, theta rhythm and rat spatial navigation. Neural Networks, 15, 689-707] suggested that the theta rhythm allows the hippocampal formation to alternate rapidly between conditions that promote memory encoding (strong synaptic input from entorhinal cortex to areas CA3 and CA1) and conditions that promote memory retrieval (strong synaptic input from CA3 to CA1). That model predicted that the preferred theta phase of CA1 spiking should differ for information being encoded versus information being retrieved. In the present study, the spiking activity of CA1 pyramidal cells was recorded while rats performed either an odor-cued delayed nonmatch-to-sample recognition memory test or an object recognition memory task based on the animal's spontaneous preference for novelty. In the test period of both tasks, the preferred theta phase exhibited by CA1 pyramidal cells differed between moments when the rat inspected repeated (match) and non-repeated (nonmatch) items. Also in the present study, additional modeling work extended the previous model to address the mean phase of CA1 spiking associated with stimuli inducing varying levels of retrieval relative to encoding, ranging from novel nonmatch stimuli with no retrieval to highly familiar repeated stimuli with extensive retrieval. The modeling results obtained here demonstrated that the experimentally observed phase differences are consistent with different levels of CA3 synaptic input to CA1 during recognition of repeated items.

Animals↗

CBF gradient changes elicited by visual stimulation and visual memory tasks.

Normal volunteers underwent three successive scans of regional cerebral blood flow (rCBF) using the 133Xe inhalation technique during visual stimulation, a recognition memory task and a resting state defined by high EEG alpha content. Since the stimulation was virtually identical in both non-rest conditions, we were able to separate the CBF pattern resulting from simple stimulation and that resulting from the cognitive (recognition memory) component alone. These turned out to have very nearly opposite effects on the normal anterior-to-posterior resting state gradient: the sensory component diminished the gradient, while the cognitive component exaggerated it. It is suggested that these normative data can be of clinical value in the study of cerebral recovery/reorganization following post-traumatic amnesia.

Adult↗

Lateral asymmetry in testing long-term memory for faces.

Accuracy of recognition memory for faces initially seen in the central visual field was found to be greater 48 hours when previously seen and new faces were presented to the left visual field than when presentation was to for right visual field. It is argued that this result reflects relative specialization for the right hemisphere in storing visual patterns.

Dominance, Cerebral↗

Episodic memory in dementia of the Alzheimer type and in normal ageing: similar impairment in automatic processing.

A perceptual identification task was used to provide an implicit measure for automatic memory processes. The facilitation of word identification on repeated presentation is taken as a measure of the automatic retrieval of an episode. In addition, recognition memory was tested. The recognition task is an explicit test of memory and relies mainly on controlled processing. In the first experiment 11 patients suffering from probable Alzheimer disease and 11 normal age- and sex-matched controls were tested. Both groups exhibited a rather small facilitation effect (ca 7%) but did not differ in the size of the effect. However, when tested explicitly, a difference in recognition memory existed between the two groups. In the second experiment the performance of 11 normal young subjects was compared to that of 11 normal elderly subjects. Whereas the elderly group showed a small facilitation effect similar to that observed in the first experiment, a considerable facilitation effect was found for the young group. Also, the elderly group had poorer recognition memory than the young group.

Aged↗

Age differences in picture memory with resemblance and discrimination tasks.

Previous research on recognition memory has examined age-related effects on knowledge of the difference between lures and input items (e.g., false alarm rate), but has not examined age-related effects on knowledge of the resemblance between lures and input items. In the present experiment, subjects in two age groups (means = 19.3 years and 63.8 years) saw a list of scenic pictures, followed by a recognition test containing same-photo items, each a copy of an input picture, same-scene items, each from the same original scene as an input picture, and different-scene items. The task was to categorize each test picture as same-photo, same-scene or different-scene. There were no reliable age differences on standard recognition measures of hits and false alarms. However, younger subjects were better than older subjects at detecting the resemblance between same-scene items and input items, although this age difference was less apparent when the initial encoding provided experience with resemblance detection. The results have implications regarding age effects in picture memory and in recognition memory generally.

Adolescent↗

The effect of visual and interaction fidelity on spatial cognition in immersive virtual environments.

Accuracy of memory performance per se is an imperfect reflection of the cognitive activity (awareness states) that underlies performance in memory tasks. The aim of this research is to investigate the effect of varied visual and interaction fidelity of immersive virtual environments on memory awareness states. A between groups experiment was carried out to explore the effect of rendering quality on location-based recognition memory for objects and associated states of awareness. The experimental space, consisting of two interconnected rooms, was rendered either flat-shaded or using radiosity rendering. The computer graphics simulations were displayed on a stereo head-tracked Head Mounted Display. Participants completed a recognition memory task after exposure to the experimental space and reported one of four states of awareness following object recognition. These reflected the level of visual mental imagery involved during retrieval, the familiarity of the recollection, and also included guesses. Experimental results revealed variations in the distribution of participants' awareness states across conditions while memory performance failed to reveal any. Interestingly, results revealed a higher proportion of recollections associated with mental imagery in the flat-shaded condition. These findings comply with similar effects revealed in two earlier studies summarized here, which demonstrated that the less "naturalistic" interaction interface or interface of low interaction fidelity provoked a higher proportion of recognitions based on visual mental images.

Adult↗

New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment.

Although thousands of new neurons are continuously produced in the dentate gyrus of rodents each day, the function of these newborn cells remains unclear. An increasing number of reports have provided correlational evidence that adult hippocampal neurogenesis is involved in learning and memory. Exposure of animals to an enriched environment leads to improvement of performance in several learning tasks and enhances neurogenesis specifically in the hippocampus. These data raise the question of whether new neurons participate in memory improvement induced by enrichment. To address this issue, we have examined whether the increase in the number of surviving adult-generated cells following environmental enrichment contributes to improved memory function. To this end, neurogenesis was substantially reduced throughout the environmental enrichment period using the antimitotic agent methylazoxymethanol acetate (MAM). Recognition memory performance of MAM-treated enriched rats was evaluated in a novel object recognition task and compared with that of naive and nontreated enriched rats. Injections of 5-bromo-2'-deoxyuridine were used to label dividing cells, together with double immunofluorescent labelling using glial or neuronal cell-specific markers. We found that enrichment led to improved long-term recognition memory and increased hippocampal neurogenesis, and that MAM treatment during environmental enrichment completely prevented both the increase in neurogenesis and enrichment-induced long-term memory improvement. These results establish that newborn cells in the dentate gyrus contribute to the expression of the promnesic effects of behavioural enrichment, and they provide further support for the idea that adult-generated neurons participate in modulating memory function.

Animals↗

Four easy memory tests for older adults.

This report describes four short memory tests which have been developed for use with older adults. Three of these tests are recognition memory tests; one is verbal, one is visual, and one is predominantly visual, but likely to involve some verbal mediation. The fourth task is a verbal paired-associate learning test which uses two sets of six high frequency words. Normative data obtained from 107 subjects aged 64-81 on all four tests are provided. A ceiling effect was obtained, indicating that these tests are relatively easy. A validation study was carried out, in which a group of patients with a cortical degenerative condition was assessed on the easy tests, and performance on published recognition memory tests could be compared with performance on the easy tests. Several patients who had scored at chance on the published version not only obtained measurable scores on the easy version, but also obtained discrepancy scores. Possible uses for the four short memory tests are suggested.

Aged↗

[Implicit and explicit memories of odors].

The present experiments explore whether there may be some forms of implicit memory for odors. In the first experiment, the elaborateness of olfactory encoding was varied at presentation. For (explicit) recognition memory testing we found positive effects of labeling responses to odors at encoding. Implicit memory measures (temporal and preference judgments) did not reveal reliable effects of prior odor presentation, however. The second experiment corroborated effects of levels of processing on r recognition memory. Again, perceptual or affective judgments remained insensitive for prior odor exposures. Implicit memory could only be detected with verbal measures at the testing stage (labeling accuracy or latency). These results are consistent with the proposal that odor information is represented at different levels of processing that are even with implicit memory measures only partly accessible.

Adult↗

Differing neuropsychological and neuroanatomical correlates of abnormal reading in early-stage semantic dementia and dementia of the Alzheimer type.

Individuals with semantic dementia (SD) were differentiated neuropsychologically from individuals with dementia of the Alzheimer type (DAT) at very mild-to-mild stages (clinical dementia rating 0.5 or 1). A picture naming and recognition memory experiment provided a particularly useful probe for early identification, with SD individuals showing preserved picture recognition memory and impaired naming, and DAT individuals tending to show the reverse dissociation. The identification of an early SD group provided the opportunity to inform models of reading by exploring the influence of isolated lexical semantic impairment on reading regular words. Results demonstrated prolonged latency in both SD and DAT group reading compared to a control group but exaggerated influence of frequency and length only for the SD group. The SD reading pattern was associated with focal atrophy of the left temporal pole. These cognitive-neuroanatomical findings suggest a role for the left temporal pole in lexical/semantic components of reading and demonstrate that cortical thickness differences in the left temporal pole correlate with prolonged latency associated with increased reliance on sublexical components of reading.

Aged↗

The effects of inferotemporal cortex lesions on Konorski delayed pair comparison in monkeys.

Rhesus monkeys were trained on a pair comparison recognition memory task, running concurrently with a signal detection (attention) problem. The animals were given bilateral posterior or anterior inferotemporal cortex lesions once satisfactory performance had been reached. The former group sustained attentional but only transient mnemonic impairments. Anterior lesions impaired visual learning and memory, but not attention. We confirm that inferotemporal cortex is sub-divided into at least two distinct regions, serving visual attention and other cognitive processes. The role of inferotemporal cortex in recognition memory is discussed, and it is concluded that task-related problems do not permit an unambiguous resolution of this question.

Animals↗

Fos imaging reveals differential neuronal activation of areas of rat temporal cortex by novel and familiar sounds.

To provide information about the possible regions involved in auditory recognition memory, this study employed an imaging technique that has proved valuable in the study of visual recognition memory. The technique was used to image populations of neurons that are differentially activated by novel and familiar auditory stimuli, thereby paralleling previous studies of visual familiarity discrimination. Differences evoked by novel and familiar sounds in the activation of neurons were measured in different parts of the rat auditory pathway by immunohistochemistry for the protein product (Fos) of the immediate early gene c-fos. Significantly higher counts of stained neuronal nuclei (266 +/- 21/mm2) were evoked by novel than by familiar sounds (192 +/- 17/mm2) in the auditory association cortex (area Te3; AudA). No such significant differences were found for the inferior colliculus, primary auditory cortex, postrhinal cortex, perirhinal cortex (PRH), entorhinal cortex, amygdala or hippocampus. These findings are discussed in relation to the results of lesion studies and what is known of areas involved in familiarity discrimination for visual stimuli. Differential activation is produced by novel and familiar individual stimuli in sensory association cortex for both auditory and visual stimuli, whereas the PRH is differentially activated by visual but not auditory stimuli. It is suggested that this latter difference is related to the nature of the particular auditory and visual stimuli used.

Acoustic Stimulation↗

Remembering and knowing: two means of access to the personal past.

The nature of recollective experience was examined in a recognition memory task. Subjects gave "remember" judgments to recognized items that were accompanied by conscious recollection and "know" judgments to items that were recognized on some other basis. Although a levels-of-processing effect (Experiment 1) and a picture-superiority effect (Experiment 2) were obtained for overall recognition, these effects occurred only for "remember" judgments, and were reversed for "know" judgments. In Experiment 3, targets and lures were either preceded by a masked repetition of their own presentation (thought to increase perceptual fluency) or of an unrelated word. The effect of perceptual fluency was obtained for overall recognition and "know" judgments but not for "remember" judgments. The data obtained for confidence judgments using the same design (Experiment 4) indicated that "remember"/"know" judgments are not made solely on the basis of confidence. These data support the two-factor theories of recognition memory by dissociating two forms of recognition, and shed light on the nature of conscious recollection.

Adult↗