Biomedical subjects

J P Aggleton

Publications and source records attributed to J P Aggleton.

At least 55 records · Page 3Linked to original sources

PubMed1999

The ability of odours to serve as state-dependent cues for real-world memories: can Viking smells aid the recall of Viking experiences?

This study determined the extent to which re-exposure to the unique combination of odours present in a museum (the Jorvik Viking Centre in York) aids the recall of a previous visit to the museum, which had typically taken place several years earlier. To test this, three groups of participants completed questionnaires about the contents of the museum, but in different conditions. One group completed the questionnaire in the presence of exactly the same distinctive odours as those present in the museum at the time of their original visit. Those in two other groups were given either a different (control) set of odours or no odours at all. After a brief delay, the same questionnaire was presented again to participants in all three groups. Those who had initially been given a novel (control) set of odours were now tested in the presence of the genuine Jorvik museum odours, while the group that had received the Jorvik odours were now tested with the control odours. The third group received no odours on either test. Only the novel odour-Jorvik odours condition led to a highly significant improvement in performance. This interaction showed that the museum odours could act as effective retrieval cues for this incidentally acquired, real-world episode.

Adult↗

PubMed1999

Episodic memory, amnesia, and the hippocampal-anterior thalamic axis.

By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an "extended hippocampal system" comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon. These are necessary for the encoding and, hence, the effective subsequent recall of episodic memory. An additional feature of this hippocampal-anterior thalamic axis is the presence of projections back from the diencephalon to the temporal cortex and hippocampus that also support episodic memory. In contrast, this hippocampal system is not required for tests of item recognition that primarily tax familiarity judgements. Familiarity judgements reflect an independent process that depends on a distinct system involving the perirhinal cortex of the temporal lobe and the medial dorsal nucleus of the thalamus. In the large majority of amnesic cases both the hippocampal-anterior thalamic and the perirhinal-medial dorsal thalamic systems are compromised, leading to severe deficits in both recall and recognition.

Amnesia↗

PubMed1998

Neurotoxic lesions of the dorsomedial thalamus impair the acquisition but not the performance of delayed matching to place by rats: a deficit in shifting response rules.

This study examined the acquisition of a T-maze matching to place task by rats with neurotoxic lesions of the thalamic nucleus medialis dorsalis. This test of spatial working memory also entails learning a task rule that is contrary to the animals' innate preference. The rats next performed the same matching task over different retention delays. Finally, they were trained on a reversal of the task rule, i.e., to nonmatch to place. Although the lesions produced a clear acquisition impairment on the matching task, there was no evidence of a loss of working memory. A series of control tasks found no appreciable effect on a conditioned cue preference task or on open field activity. The pattern of results shows that medialis dorsalis lesions lead to a selective increase in perseverative behavior that can retard task acquisition. This perseverative deficit closely resembles that observed after prefrontal damage in rats, strongly indicating dysfunction in a common system.

Animals↗

PubMed1998

Fornix lesions can facilitate acquisition of the transverse patterning task: a challenge for "configural" theories of hippocampal function.

Configural theories of hippocampal function predict that hippocampal dysfunction should impair acquisition of the transverse patterning task, which involves the concurrent solution of three discrimination problems: A+ versus B-; B+ versus C-; and C+ versus A-. The present study tested this prediction in rats using computer-graphic stimuli presented on a touchscreen. Experiment 1 assessed the effects of fornix lesions when the three problems were introduced sequentially (phase 1: A+ vs B-; phase 2: A+ vs B-, B+ vs C-; phase 3: A+ vs B-, B+ vs C-, C+ vs A-). Fornix lesions significantly facilitated acquisition of the complete transverse patterning task (phase 3) but had no effect on the number of sessions or errors required to attain criterion during phase 1 or phase 2. In experiment 2, in which all three problems were presented concurrently from the outset of training, fornix-lesioned animals outperformed control animals during the seventh block of acquisition trials and were not impaired during any stage of acquisition. Importantly, these same animals were significantly impaired on two allocentric spatial tasks: T-maze alternation (experiments 1 and 2) and the Morris Swim Task (experiment 1). These results contradict the predictions of configural theories of hippocampal function and cast doubt on the popular notion that spatial learning is a special case of configural learning.

Animals↗

PubMed1998

An examination of the spatial working memory deficit following neurotoxic medial dorsal thalamic lesions in rats.

The present study examined the performance of rats with neurotoxic lesions centred in the thalamic nucleus medialis dorsalis on standard and modified versions of the eight arm radial maze test. In Experiment 1, the thalamic lesions produced a borderline deficit in acquisition of the standard task, but subsequently had no effect when a delay was interposed after the first four arms had been entered. The same lesions had no effect on T-maze alternation, but they did impair radial-arm maze performance when intramaze and extramaze cues were set against each other. In Experiment 2, lesions of the dorsomedial thalamus impaired acquisition of the standard radial-arm maze task, but combining the results from Experiments 1 and 2 showed that this acquisition deficit was confined to those animals in which bilateral damage extended into the adjacent anterior thalamic nuclei. In addition, lesions of the dorsomedial thalamus disrupted radial-arm maze performance when the task was modified to compare working memory and reference memory and increased activity and exploration. These changes were not associated with anterior thalamic damage. Finally, the thalamic lesions did not affect performance on a test of spontaneous object recognition. It is concluded that lesions of medialis dorsalis do not disrupt spatial memory but do affect other processes that can interact with task performance. These include a failure of extramaze cues to overshadow intramaze cues, a change in activity and exploration levels and deficits in with-holding spatial responses.

Animals↗

PubMed1998

Recognition memory in rats--I. Concepts and classification.

Recognition is the process by which a subject is aware that a stimulus has been previously experienced. It requires that the characteristics of events are perceived, discriminated, identified and then compared (matched) against a memory of the characteristics of previously experienced events. Understanding recognition memory, its underlying neuronal mechanisms, its dysfunction and alleviation of the latter by putative cognition enhancing drugs is a major research target and has triggered a wealth of animal studies. One of the most widely used animals for this purpose is the rat, and it is the rat's recognition memory which is the focus of this review. In this first part, concepts of recognition memory, stages of mnemonic processing and paradigms for the measurement of the rat's recognition memory will be discussed. In two subsequent articles (parts II and III) we will focus on the neuronal mechanisms underlying recognition memory in rats. Three major points arise from the comparison of paradigms that have in the past been used to assess recognition memory in rats. First, it should be realized that some tasks which, at face value, can all be considered to measure recognition memory in rats, may not assess recognition memory at all but may, for example, be based on recall rather than recognition. Second, it is evident that different types of recognition memory can be distinguished and that tasks differ in the type of recognition memory taxed. Some paradigms, for example, measure familiarity, whereas others assess recency. Furthermore, paradigms differ as to whether spatial stimuli or items are employed. Third, different processes, ranging from stimulus-response learning to the formation of concepts, may be involved to varying extent in different tasks. These are important considerations and question the predictive validity of the results obtained from studies examining, for example, the effects of putative cognition enhancing drugs.

Animals↗

PubMed1998

Recognition memory in rats--II. Neuroanatomical substrates.

A discussion of the neuroanatomical systems thought to be of importance for the mediation of recognition memory in the rat warrants consideration of different, but not necessarily exclusive concepts. An important concept is the hypothesis that a dichotomy in the neural systems mediating spatial and non-spatial (item) memory exists in the rat. We have adopted a model of recognition memory suggesting that information about previously encountered items is stored in a dynamic pattern of neural activity and not in a localized representation. These patterns are features of distributed neuronal networks and different networks may process different forms of recognition memory. Two parallel-distributed neuronal networks are proposed in the rat. Network 1 is essential for the processing of non-spatial/item recognition memory processes and incorporates the cortical association areas such as TE1, TE2 and TE3, the rhinal cortices, the mediodorsal thalamic nucleus and prefrontal cortical areas. Network 2 comprises the hippocampus, mamillary bodies, anterior thalamic nuclei and medial prefrontal areas, especially the prelimbic cortex, and is suggested to be pivotal for the processing of spatial recognition memory.

Animals↗

PubMed1998

Recognition memory in rats--III. Neurochemical substrates.

In the first part of three overviews on recognition memory in the rat, we discussed the tasks employed to study recognition memory. In the second part, we discussed the neuroanatomical systems thought to be of importance for the mediation of recognition memory in the rat. In particular, we delineated two parallel-distributed neuronal networks, one that is essential for the processing of non-spatial/item recognition memory processes and incorporates the cortical association areas such as TE1, TE2 and TE3, the rhinal cortices, the mediodorsal thalamic nucleus and prefrontal cortical areas (Network 1), the other comprising of the hippocampus, mamillary bodies, anterior thalamic nuclei and medial prefrontal areas (Network 2), suggested to be pivotal for the processing of spatial recognition memory. The next step will progress to the level of the neurotransmitters thought to be involved. Current data suggest that the majority of drugs have non-specific, i.e. delay-independent effects in tasks measuring recognition memory. This may be due to attentional, motivational or motoric changes. Alternatively, delay-independent effects may result from altered acquisition/encoding rather than from altered retention. Furthermore, the neurotransmitter systems affected by these drugs could be important as modulators rather than as mediators of recognition memory per se. It could, of course, also be the case that systemic treatment induces non-specific effects which overshadow any specific, delay-dependent, effect. This possibility receives support from lesion experiments (for example, of the septohippocampal cholinergic system) or studies employing local intracerebral infusion techniques. However, it is evident that those delay-dependent effects are relatively subtle and more readily seen in delayed response paradigms, which tax spatial recognition memory. One interpretation of these results could be that some neurotransmitter systems are more involved in spatial than in item recognition memory processes. However, performance in delayed response tasks can be aided by mediating strategies. Drugs or lesions can alter those strategies, which could equally explain some of the (delay-dependent) drug effects on delayed responding. Thus, it is evident that neither of the neurotransmitter systems reviewed (glutamate, GABA, acetylcholine, serotonin, dopamine and noradrenaline) can be viewed as being directly and exclusively concerned with storage/retention. Rather, our model of recognition memory suggests that information about previously encountered items is differentially processed by distinct neural networks and is not mediated by a single neurotransmitter type.

Animals↗

PubMed1998

Comparing the effects of selective cingulate cortex lesions and cingulum bundle lesions on water maze performance by rats.

The ability of rats to learn the location of a hidden platform in a swim maze was compared in animals with excitotoxic lesions of the anterior or posterior (retrosplenial) cingulate cortex or radiofrequency lesions of the cingulum bundle or fimbria-fornix. Performance of this allocentric spatial task was unaffected by the posterior cingulate cortex lesions, while anterior cingulate cortex damage produced only a mild acquisition deficit. Transection of the fornix and lesions of the cingulum bundle produced similar patterns of impairment on initial acquisition, but the cingulum bundle lesions had less effect on reversal of the task. The results from the water maze, and from a subsequent T-maze alternation task, indicate that cingulum bundle lesions can produce a spatial deficit that is similar, but milder, to that observed after fornix transection. The results of the excitotoxic lesions suggest that previous studies examining conventional cingulate lesions may have been influenced by damage to adjacent fibre tracts, such as the cingulum bundle.

Animals↗

PubMed1997

Differential activation of the rat hippocampus and perirhinal cortex by novel visual stimuli and a novel environment.

Two groups of rats were shown individual novel visual objects. One group had been familiarised to the environmental context within which the objects were shown, the other experienced the situation for the first time. The activation of neurones in perirhinal cortex and the hippocampal formation was determined by counts of nuclei stained for products of the immediate early gene c-fos. The ratio of counts in the hippocampal formation to that in perirhinal cortex was compared for the two groups: the ratio was significantly higher (4.2:1) in the group experiencing the environment for the first time. Thus, whereas perirhinal neurones are activated by novel rather than familiar objects, hippocampal neurones are preferentially activated by a novel rather than a familiar environment.

Animals↗

PubMed1997

Impaired auditory recognition of fear and anger following bilateral amygdala lesions.

The amygdalar complex is a medial temporal lobe structure in the brain which is widely considered to be involved in the neural substrates of emotion. Selective bilateral damage to the human amygdala is rare, offering a unique insight into its functions. There is impairment of social perception after amygdala damage, with defective recognition of facial expressions of emotion. Among the basic emotions, the processing of fear and anger has been shown to be disrupted by amygdala damage. Although it remains puzzling why this not found in all cases, the importance of the amygdala in negative emotion, and especially fear, has been confirmed by conditioning, memory and positron emission tomography (PET) experiments. Central to our understanding of these findings is the question of whether the amygdala is involved specifically in the perception of visual signals of emotion emanating from the face, or more widely in the perception of emotion in all sensory modalities. We report here a further investigation of one of these rare cases, a woman (D.R.) who has impaired perception of the intonation patterns that are essential to the perception of vocal affect, despite normal hearing. As is the case for recognition of facial expressions, it is recognition of fear and anger that is most severely affected in the auditory domain. This shows that the amygdala's role in the recognition of certain emotions is not confined to vision, which is consistent with its being involved in the appraisal of danger and the emotion of fear.

Amygdala↗

PubMed1997

Spontaneous object recognition and object location memory in rats: the effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix.

The first experiment assessed the effects of neurotoxic lesions in either the anterior cingulate cortex (ACc) or the retrosplenial cortex (RSc) on a test of object recognition. Neither lesion affected performance on this task, which takes advantage of the rat's normal preference to spend more time investigating novel rather than familiar stimuli. In response to this negative result, a second experiment assessed the effects of much more extensive cingulate lesions (Cg) on both object recognition and object location memory. The latter task also used a preference measure, but in this case it concerned preference for a novel location. For comparison purposes this second study included groups of rats with lesions in closely allied regions: the fornix (Fx), the cingulum bundle (CB) and the medial prefrontal cortex (Pfc). Comparisons with sham-operated control rats showed that none of the four groups (Cg, Fx, CB, Pfc) was impaired on the object recognition task, adding further weight to the view that these structures are not necessary for assessing stimulus familiarity. The Fx and Cg groups were, however, impaired on the object location task, suggesting that these regions are necessary for remembering other attributes of a stimulus (spatial location).

Animals↗

PubMed1997

Assessing the magnitude of the allocentric spatial deficit associated with complete loss of the anterior thalamic nuclei in rats.

The behavioural effects of complete lesions of the anterior thalamic nuclei (ANT), the anterior thalamic nuclei plus the lateral dorsal nucleus (ANT + LD), and fornix (FX) were compared using a series of tests of spatial memory. ALl three lesion groups were found to have an equally severe and long-lasting impairment in the acquisition of a T-maze alternation task when compared with the control animals (COMB SHAM). In Experiment 2, the control animals were able to perform the alternation task when the test trial was started from a different location to the sample trial, so demonstrating that they were able to use allocentric cues in order to differentiate the most recently visited arm. In contrast, all the lesion groups performed close to chance level. In fact, for this condition the ANT / LD group was significantly worse than the FX group. In contrast, none of the lesion groups was impaired on an egocentric discrimination and subsequent reversal task (Experiment 3). The control animals came from two different control procedures, a surgical control sub-group (SHAM) and a group of animals that received injections of N-methyl-D-aspartic (NMDA) into the fornix (NMDA SHAM). There were no differences in the performance levels of the NMDA SHAM group compared with the surgical control group in any of the experiments conducted, so showing that the anterior thalamic lesion effects were not due to non-specific damage to the fornix by NMDA. This series of experiments demonstrated that complete lesions of the anterior thalamic region impair the ability to process allocentric information, and provide evidence for a contribution from the lateral dorsal thalamic nucleus.

Animals↗

PubMed1997

The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat.

The effects of lesions centred in the perirhinal cortex region (Prh) or in both the perirhinal cortex region and the fornix (Prh + Fx) were assessed in two different working memory tasks, one spatial the other nonspatial. For the spatial task the rats were tested in an eight arm radial maze, using a standard procedure in which they were rewarded for avoiding previously visited arms. The Prh + Fx, but not the Prh, rats produced significantly more errors (re-entries) and these started significantly earlier in each session when compared with a surgical control group. The nonspatial task was a test of spontaneous object recognition in which rats were tested on their ability to discriminate between a familiar and a novel object. For the initial tests the Prh group failed to discriminate between the objects, but the Prh + Fx group showed a clear preference for the novel object. Observation of the test showed, however, that the Prh + Fx group were spending a greater length of time initially exploring the sample (familiar) object. When the amount of exposure to the sample object was limited to either 20 or 40 s (i.e. was the same for all three groups), the Prh + Fx group now failed to discriminate between the two objects. This change was especially evident for shorter sample duration (20 s). The Prh group did, however, show an amelioration of their deficit with this further testing. The present results support previous dissociation between spatial and nonspatial working memory, and indicate that there may be some recovery of function following perirhinal cortical damage.

Animals↗

PubMed1997

Extensive cytotoxic lesions involving both the rhinal cortices and area TE impair recognition but spare spatial alternation in the rat.

Rats with cytotoxic lesions of the perirhinal, postrhinal, and TE cortices (Rh+TE, n = 7) were compared with surgical control animals (n = 7) on a series of spontaneous object recognition tests. The Rh+TE group was associated with a failure to select the novel object. This recognition deficit contrasted with the apparently normal ability of the same animals to learn and perform a spatial working memory test (T-maze alternation). The animals were also tested on the acquisition of an automated visual discrimination task in which the stimuli were presented on a visual display unit (VDU) equipped with a touch screen. The animals with Rh+TE lesions showed only a borderline deficit on this task. These findings are consistent with other evidence implicating the rhinal region in recognition memory. More importantly, they also provide a dissociation between spatial working memory and object recognition and, hence, show that extensive rhinal lesions are not sufficient to disconnect the hippocampus functionally.

Animals↗

PubMed1997

Evidence for the involvement of the mammillary bodies and cingulum bundle in allocentric spatial processing by rats.

Comparisons were made between the behavioural effects of lesions in three inter-related limbic structures: the mammillary bodies, the fornix and the cingulum bundle/cingulate cortex. Cytotoxic lesions of the mammillary nuclei produced a marked deficit on reinforced T-maze alternation, but performance gradually improved with practice. Subsequent tests in a cross-maze and a radial-arm maze showed that the animals with mammillary body lesions failed to use allocentric cues, but were able to perform normally in an egocentric discrimination. Three groups of rats with different patterns of either crossed or unilateral radio frequency lesions of the cingulate region were given the same tasks. The profile of results indicated that disruption of those fibres in the cingulum bundle connecting the anterior thalamic nuclei with the hippocampal/retrohippocampal region was responsible for the observed impairments to T-maze alternation and radial-arm maze performance. There was also evidence that disconnection of frontal connections in the cingulum bundle might affect perseverative behaviour, but not allocentric processing. The results add support to the notion of a functional circuit that involves projections from the hippocampus to the mammillary bodies and anterior thalamic nuclei, and from there back to hippocampal/retrohippocampal regions via the cingulum bundle. This circuit appears to be vital for normal allocentric processing.

Animals↗

PubMed1996

Mapping visual recognition memory through expression of the immediate early gene c-fos.

To study brain regions involved in familiarity discrimination, rats were shown sets of novel and familiar objects. On each trial two objects were shown simultaneously to a rat so that one eye saw a novel object while the other saw a familiar object. Thus novel and familiar objects were seen with the same conditions of alertness and eye movements. Activated neurones were revealed by staining for products of the immediate early gene c-fos. Familiar stimuli activated significantly fewer neurones than novel stimuli in perirhinal cortex and area TE of temporal cortex, and the ventral lateral geniculate nucleus of the thalamus, but not in the hippocampus or other areas sampled. These findings are discussed in relation to recognition memory.

Animals↗

PubMed1996

Amnesia and recognition memory: a re-analysis of psychometric data.

The present study compared the recognition memory deficit in different groups of amnesics using scores from a standard test. The data, taken from a literature search, came from 33 studies reporting the performance of amnesic subjects on the recognition memory test (RMT) [77]. A total of 112 amnesic subjects were grouped according to their pathology. In addition, the analysis included subjects with schizophrenia, amygdala damage, or frontal lobe damage. Of these three nonamnesic groups, only the frontal lobe subjects were impaired on both RMT subtests, while the schizophrenics showed a disproportionate impairment for the recognition of faces. The amygdala subjects were also poor at face recognition. Among the amnesic groups, those subjects likely to have multiple sites of pathology (e.g. Korsakoff amnesics, post-encephalitics) were found to be the most impaired on the RMT. In contrast, those amnesics with more focal, limbic lesions in the hippocampus, fornix, or mamillary body region showed much milder deficits on the RMT task, some performing at normal levels. Despite their apparent sparing of recognition, the overall severity of amnesia in those subjects with limbic lesions appeared comparable to that in the remaining amnesics. These findings indicate that deficits on both subtests of the RMT are a frequent but not inevitable component of anterograde amnesia. They also point to a distinct subgroup of amnesias associated with selective damage in the hippocampus or its diencephalic targets, in which there is a relative sparing of recognition under certain test conditions.

Adolescent↗