Biomedical subjects

D Gaffan

Publications and source records attributed to D Gaffan.

At least 19 recordsLinked to original sources

PubMed2001

Visual discrimination learning impairments produced by combined transections of the anterior temporal stem, amygdala and fornix in marmoset monkeys.

Marmoset monkeys (Callithrix jacchus) with bilateral transections of the anterior temporal stem, amygdala and fornix were unable to relearn a 2-choice object discrimination first learnt prior to surgery, and were very severely impaired at relearning a concurrent object discrimination task which they had learnt and relearnt prior to surgery, indicating that they had a dense retrograde amnesia. They also had difficulty learning new visual object discriminations but were only mildly impaired on spatial learning. When tested on new learning of concurrent discriminations 8 to 10 weeks after surgery, three operated monkeys were unable to reach criterion in 400 trials while the remaining two operated monkeys performed within the normal range. The operated monkeys were subsequently shown to be impaired on acquisition of shape discriminations using black objects. These anterograde effects suggest that the impairment runs mainly in the domain of visual analysis. The monkeys also exhibited many of the features of the Klüver-Bucy syndrome. Histological analysis indicated that in addition to cutting some of the subcortical temporal lobe efferent pathways, the surgical procedures had cut the cholinergic afferents to the temporal neocortex, entorhinal cortex, and hippocampus. In a second experiment we found that treatment with the cholinergic agonist pilocarpine, which is effective in monkeys with specific cholinergic lesions, was unable to remediate the lesion-induced impairments. This suggests that transection of the non-cholinergic afferents, or the temporal lobe subcortical efferents, contributed to the behavioural syndrome and the learning and retention deficits seen in these monkeys.

Acetylcholinesterase↗

PubMed2001

Dense amnesia in the monkey after transection of fornix, amygdala and anterior temporal stem.

The traditional explanation of dense amnesia after medial temporal lesions is that the amnesia is caused by damage to the hippocampus and related structures. An alternative view is that dense amnesia after medial temporal lesions is caused by the interruption of afferents to the temporal cortex from the basal forebrain. These afferents travel to the temporal cortex through three pathways, namely the anterior temporal stem, the amygdala and the fornix-fimbria, and all these three pathways are damaged in dense medial temporal amnesia. In four experiments using different memory tasks, we tested the effects on memory of sectioning some or all of these three pathways in macaque monkeys. In a test of scene-specific memory for objects, which is analogous in some ways to human episodic memory, section of fornix alone, or section of amygdala and anterior temporal stem sparing the fornix, each produced a significant but mild impairment. When fornix section was added to the section of anterior temporal stem and amygdala in this task, however, a very severe impairment resulted. In an object recognition memory task (delayed matching-to-sample) a severe impairment was seen after section of anterior temporal stem and amygdala alone, with or without the addition of fornix section; this impairment was significantly more severe than that which was seen in the same task after amygdalectomy leaving the temporal stem intact, with or without fornix section. Animals with combined section of anterior temporal stem, amygdala and fornix were also impaired in object-reward association learning. However, the retention of pre-operatively acquired object-reward associations was at a high level. These results show that the pattern of impairments after section of anterior temporal stem, amygdala and fornix in the monkey, leaving hippocampus intact, resembles human dense amnesia and is different from the effects of hippocampal lesions in the monkey.

Amnesia↗

PubMed2001

Crossed unilateral lesions of the medial forebrain bundle and either inferior temporal or frontal cortex impair object-reward association learning in Rhesus monkeys.

In an accompanying paper we showed that combined transection of the fornix, amygdala and temporal stem in monkeys produced dense amnesia, including an impairment in visual object-reward association learning. We proposed that this combined surgical section had its effect by isolating temporal cortex from the ascending projections of the basal forebrain and midbrain structures. To test this hypothesis, in the present experiment we disconnected the inferior temporal cortex from these basal forebrain and midbrain structures, while sparing cortical white matter, by crossed unilateral lesions of the medial forebrain bundle in one hemisphere and inferior temporal cortex in the opposite hemisphere. The aim of the medial forebrain bundle lesion was to section axons of cells, both those that project to the cortex via the medial forebrain bundle, and those which control the activity of these same structures. A single unilateral lesion alone had no effect on the ability to learn and remember visual object-reward associations, but the crossed unilateral lesions produced an impairment in this task which was equal in severity to the impairment seen earlier after bilateral section of the fornix, amygdala and temporal stem. The impairment was not an effect of interrupting fibres to the cortex from the ventromedial hypothalamus, or of unilateral sensory neglect. This supports the hypothesis that these midbrain and basal forebrain afferents to the inferior temporal cortex are important for new visual learning. Furthermore, an impairment of equal severity was demonstrated in a separate group of animals that received crossed unilateral lesions of the medial forebrain bundle in one hemisphere and of the frontal cortex in the opposite hemisphere. We propose that the frontal cortex acts to modulate basal forebrain activity which in turn reinforces object representations in the inferior temporal cortex during learning.

Animals↗

PubMed2000

Perceptual and mnemonic matching-to-sample in humans: contributions of the hippocampus, perirhinal and other medial temporal lobe cortices.

Two questions were addressed by the present study. The first was whether the previously reported item recognition deficit which is shown by amnesic patients may be due to a perceptual rather than a memory deficit. To address this question a group of amnesic patients were tested on a 14-choice forced-choice visual item recognition test which included a "simultaneous" condition in which the sample remained visible during the matching decision and a zero second delay. Eacott, Gaffan and Murray (1994) have reported an impairment in simultaneous matching-to-sample following perirhinal damage in monkeys. In our amnesic patients, a deficit was found only after filled delays of 10 seconds or longer and this was also the case for a subgroup of patients whose damage included the perirhinal cortex. The second question, which arose from the model of Aggleton and Brown (1999), was whether performance on the DMS task would remain intact following selective damage to the hippocampus. We tested a patient with bilateral damage to the hippocampus on the 14-choice DMS task and found that her performance was not significantly impaired at delays of up to 30 seconds.

Adult↗

PubMed2000

Comparison of perirhinal cortex ablation and crossed unilateral lesions of the medial forebrain bundle from the inferior temporal cortex in the rhesus monkey: effects on learning and retrieval.

Seven monkeys learned new object-reward associations and scene problems and were overtrained on 100 problems of each type. Four monkeys received crossed lesions of the medial forebrain bundle (MFB) and inferior temporal cortex, with the later addition of a fornix section ipsilateral to the MFB lesion. The remaining 3 monkeys received bilateral perirhinal cortex ablation. Disconnection of the MFB from the inferior temporal cortex impaired postoperative new learning, but the retrieval of problems overtrained preoperatively was relatively preserved. Subjects with perirhinal cortex ablation were severely impaired in new learning and at the retrieval of scene problems, but retention of object-reward associations was relatively well preserved. The results support the hypothesis that isolation of the inferior temporal cortex from basal forebrain and midbrain afferents results in dense anterograde amnesia, whereas the role of the perirhinal cortex in learning is dependent on the perceptual difficulty of the task.

Amygdala↗

PubMed2000

Differential cognitive effects of colloid cysts in the third ventricle that spare or compromise the fornix.

A series of twelve cases, all of whom had received surgery for the removal of a colloid cyst in the third ventricle, was examined on a series of memory tests. The only consistent predictor of poor memory performance that could be detected from MRIs was the presence of bilateral interruption of the fornix, which occurred in three of the subjects. Although these three cases were poor on tests of learning and recall, there was evidence that recognition was less impaired. The subjects were also tested on a set of recognition and concurrent discriminations that closely matched tests given to non-human primates. Clear parallels were found between the apparent effects of fornix damage in these clinical cases and those observed following more selective surgery in non-human primates. These findings not only indicate that fornix damage is sufficient to induce anterograde amnesia but also support the validity of recent animal tests that are thought to capture aspects of episodic memory.

Adult↗

PubMed2000

Mediodorsal thalamic function in scene memory in rhesus monkeys.

Three monkeys were trained preoperatively in a scene memory task which is analogous, in some ways, to human episodic memory. The same animals were also trained in object-reward association memory. Following bilateral ablations of almost the entire magnocellular division of the mediodorsal thalamic nucleus, the animals were impaired both in scene memory and in object-reward association memory. These results, combined with recent results in object recognition memory from monkeys with mediodorsal thalamic lesions, show that the impairment produced by this lesion is more general, affecting a broader range of memory tasks, than the impairment which is produced in monkeys by lesions restricted to the hippocampus-fornix-mamillary system. It is also more severe than the effect of lesions limited to the medial part of the magnocellular division of the mediodorsal thalamic nucleus. These findings extend the evidence that the magnocellular division of the mediodorsal thalamic nucleus has an important and general role in memory, and they are consistent with the proposal that lesions of the magnocellular division of that nucleus have their effect by disrupting the function of prefrontal cortex.

Animals↗

PubMed1998

Perirhinal cortex ablation impairs visual object identification.

Impairments in both recognition memory and concurrent discrimination learning have been shown to follow perirhinal cortex ablation in the monkey. The pattern of these impairments is consistent with the hypothesis that the perirhinal cortex has a role in the visual identification of objects. In this study we compared the performance of a group of three cynomolgus monkeys with bilateral perirhinal cortex ablation with that of a group of three normal controls in two tasks designed to test this hypothesis more directly. In experiment 1 the subjects relearned a set of 40 familiar concurrent discrimination problems; the stimuli in each trial were digitized images of real objects presented in one of three different views. After attaining criterion they were tested on the same problems using similar, but previously unseen, views of the objects. In experiment 2 the subjects were tested on their ability to perform 10 of these familiar discriminations with each problem presented in the unfamiliar context of a digitized image of a unique complex scene. The subjects with ablations were significantly impaired on both tasks. These results demonstrate that the role of the perirhinal cortex is not restricted to memory, and they support the hypothesis that the perirhinal cortex is involved in visual object identification. We suggest that the perirhinal cortex is crucially involved in processing coherent concepts of individual objects. A deficit of this nature could underlie the pattern of impairments that follow perirhinal cortex damage in both visual object recognition memory and visual associative memory.

Animals↗

PubMed1998

Idiothetic input into object-place configuration as the contribution to memory of the monkey and human hippocampus: a review.

Memory for object-place configurations appears to be a common function of the hippocampus in the human and monkey brain. The nature of the spatial information which enters into these object-configural memories in the primate, and the location of the memories themselves, have remained obscure, however. In the rat, much evidence indicates that the hippocampus processes idiothetic spatial information, an estimate of the animal's current environmental location derived from path integration. I propose that in primates the hippocampus provides idiothetic information about the environmental location of body parts, and that the main function of this information in the primate brain is to become configured with object-identity information provided by temporal lobe cortex outside the hippocampus.

Animals↗

PubMed1998

Memory after frontal/temporal disconnection in monkeys: conditional and non-conditional tasks, unilateral and bilateral frontal lesions.

Seven Cynomolgus monkeys (Macaca fascicularis) learned a series of reward-visual conditional discrimination problems, in which the arrival or non-arrival of a food pellet at the beginning of each trial acted as an instruction cue, signalling which of two visually distinct stimulus objects the animal should choose on that trial in order to obtain a further food pellet reward. Following surgical removal of the ventrolateral prefrontal cortex in one hemisphere and the inferior temporal cortex in the contralateral hemisphere, combined with forebrain commissurotomy, the four operated animals were severely impaired at relearning this task. They were not impaired, however, in non-conditional visual discrimination learning. Extending the unilateral frontal lesion to include the ventromedial prefrontal cortex had no detrimental effect, nor did complete unilateral removal of the frontal cortex. In a third experiment, the operated animals underwent a further surgery to remove either ventrolateral, ventral or complete frontal cortex similar to that in the opposite hemisphere. Compared to their previous level of performance, the animals with bilateral ventrolateral prefrontal lesions were now mildly impaired and the animals with the bilateral lesion extended to the ventromedial cortex more severely impaired on the non-conditional visual discrimination task. The bilaterally lobectomized animals were unable to relearn the task. We suggest that behaviour in visual learning tasks is controlled by cortical convergence upon subcortical structures, possibly by striatal efferents from both the visual cortex and frontal cortex, and that intrahemispheric convergence of these two efferents within the corpus striatum of one hemisphere could allow detailed control of visual choices by non-visual information, while subcortical interhemispheric transfer allows only less detailed, more general control.

Animals↗

PubMed1998

Perirhinal cortex ablation impairs configural learning and paired-associate learning equally.

Combined damage to the perirhinal and entorhinal cortex has been implicated in the formation of stimulus-stimulus associative memories. We show in this article that relative to three normal controls three cynomolgus monkeys with ablations restricted to the perirhinal cortex were impaired on a visual paired associate learning task in which subjects had to learn which of two visual stimuli were associated with a cue stimulus. The subjects with perirhinal cortex ablations also showed an impairment of a similar magnitude on a visual configural learning task in which they had to learn which of two configurations of visual stimuli were associated with food-reward. The stimuli in both tasks were comprised of alphanumeric characters presented upon a touch-screen. Both groups made fewer errors on the configural learning task than on the paired associate learning task. We suggest that performance on both tasks relies critically on the perirhinal cortex due to the specialization of the perirhinal cortex in processing knowledge about objects. We argue that the specializations of this system and of other memory systems such as the hippocampal-fornix spatial/episodic memory system, are conferred by the specialization of their anatomical connections to other structures. We reject the notion that there are specific memory processes such as the hippocampal based configural associative system that was proposed to be critical for configural associative learning.

Animals↗

PubMed1998

Lesions of the primate rhinal cortex cause deficits in flavour-visual associative memory.

Three Cynomolgus monkeys (Macaca fascicularis) learned a flavour-visual conditional discrimination problem, in which one of two possible food items was presented at the beginning of each trial, and acted as an instruction cue to signal which of two visually distinct stimulus objects the animal must displace on that trial in order to obtain a further food reward. The task was learned first in light then in dark conditions. Following rhinal cortex ablation the animals were unable to use the flavour properties of the food items to guide visual choices, performing at close to chance levels. Postoperative performance on a food preference test showed that their problem in associating a flavour cue with a visual object in the conditional learning task also extended to aberrant choice of foods based on their visual appearance.

Animals↗

PubMed1998

Learning and transfer of object-reward associations and the role of the perirhinal cortex.

Perirhinal cortex ablation has previously been shown only to impair new postoperative object discrimination learning with large stimulus set sizes (> or = 40 problems). In this study, 3 cynomolgus monkeys (Macaca fascicularis) with bilateral perirhinal cortex ablations were impaired relative to 3 normal controls on concurrent discrimination learning tasks with only 10 problems with the objects presented in different orientations in each trial to increase the demands placed on object identification. This supports the hypothesis that perirhinal cortex damage impairs the ability to identify multiple individual objects. Fewer errors were made to digitized images of objects than toward real objects. Both groups subsequently transferred specific object-reward associations from real objects to digitized images of the respective objects and vice versa, providing evidence that cynomolgus monkeys can recognize photographic representations of objects with experience.

Animals↗

PubMed1998

Monkeys with rhinal cortex damage or neurotoxic hippocampal lesions are impaired on spatial scene learning and object reversals.

Rhesus monkeys (Macaca mulatta) with lesions of the rhinal cortex or parahippocampal gyrus (made by aspiration) or hippocampus (made with ibotenic acid) and unoperated controls were tested on object discrimination and reversal, place discrimination and reversal, and spatial scene learning to determine the contribution of these temporal lobe structures to these forms of learning and memory. Rhinal cortex lesions produced a severe deficit in object reversal learning; hippocampal lesions produced a milder deficit. Monkeys with rhinal cortex removals and those with hippocampal lesions were equally impaired on spatial scene learning. None of the lesions impaired place discrimination or reversal. These results argue against the idea that the mnemonic contributions of the rhinal cortex and hippocampus are limited to object and spatial domains, respectively.

Animals↗

PubMed1998

Interaction of frontal and perirhinal cortices in visual object recognition memory in monkeys.

Monkeys were trained preoperatively in visual object recognition memory. The task was delayed matching-to-sample with lists of trial-unique randomly generated visual stimuli in an automated apparatus, and the stimuli were 2D visual objects made from randomly generated coloured shapes. We then examined the effect of either: (i) disconnecting the frontal cortex in one hemisphere from the perirhinal cortex in the contralateral hemisphere by crossed unilateral ablations; (ii) disconnecting the magnocellular portion of the mediodorsal (MDmc) thalamic nucleus in one hemisphere from the perirhinal cortex in the contralateral hemisphere; or (iii) bilaterally ablating first the amygdala, then adding fornix transection, then finally perirhinal cortex ablation. We found that both frontal/perirhinal and MDmc/perirhinal disconnection had a large effect on visual object recognition memory, whereas both amygdalectomy and the addition of fornix transection had only a mild effect. We conclude that the frontal lobe needs to interact with the perirhinal cortex within the same hemisphere for visual object recognition memory, but that routes through the amygdala and hippocampus are not of primary importance.

Amygdala↗

PubMed1997

Amnesia and neglect: beyond the Delay-Brion system and the Hebb synapse.

Hippocampal damage in people causes impairments of episodic memory, but in rats it causes impairments of spatial learning. Experiments in macaque monkeys show that these two kinds of impairment are functionally similar to each other. After any lesion that interrupts the Delay-Brion system (hippocampus, fornix, mamillary bodies and anterior thalamus) monkeys are impaired in scene-specific memory, where an event takes place against a background that is specific to that event. Scene-specific memory in the monkey corresponds to human episodic memory, which is the memory of a unique event set in a particular scene, as opposed to scene-independent human knowledge, which is abstracted from many different scenes. However, interruption of the Delay-Brion system is not sufficient to explain all of the memory impairments that are seen in amnesic patients. To explain amnesia the specialized function of the hippocampus in scene memory needs to be considered alongside the other, qualitatively different functional specializations of other memory systems of the temporal lobe, including the perirhinal cortex and the amygdala. In all these specialized areas, however, including the hippocampus, there is no fundamental distinction between memory systems and perceptual systems. In explaining memory disorders in amnesia it is also important to consider them alongside the memory disorders of neglect patients. Neglect patients fail to represent in memory the side of the world that is contralateral to the current fixation point, in both short- and long-term memory retrieval. Neglect was produced experimentally by unilateral visual disconnection in the monkey, confirming the idea that visual memory retrieval is retinotopically organized; patients with unilateral medial temporal-lobe removals showed lateralized memory impairments for half-scenes in the visual hemifield contralateral to the removal. Thus, in scene-memory retrieval the Delay-Brion system contributes to the retrieval of visual memories into the retinotopically organized visual cortex. This scene memory interpretation of hippocampal function needs to be contrasted with the cognitive-map hypothesis. The cognitive-map model of hippocampal function shares some common assumptions with the Hebb-synapse model of association formation, and the Hebb-synapse model can be rejected on the basis of recent evidence that monkeys can form direct associations in memory between temporally discontiguous events. Our general conclusion is that the primate brain encompasses widespread and powerful memory mechanisms which will continue to be poorly understood if theory and experimentation continue to concentrate too much, as they have in the past, on the hippocampus and the Hebb synapse.

Amnesia↗

PubMed1997

Excitotoxic lesions of the amygdala fail to produce impairment in visual learning for auditory secondary reinforcement but interfere with reinforcer devaluation effects in rhesus monkeys.

Aspiration lesions of the amygdala were found previously to produce a severe impairment in visual discrimination learning for auditory secondary reinforcement in rhesus monkeys (Gaffan and Harrison, 1987). To determine whether excitotoxic amygdala lesions would also produce this effect, we trained four naive rhesus monkeys on the same task. The monkeys were required to learn 40 new visual discrimination problems per session in a situation in which visual choices were guided by an auditory secondary reinforcer that had been previously associated with food reward. Bilateral excitotoxic lesions of the amygdala had no effect on the rate of learning visual discrimination problems for auditory secondary reinforcement. We also tested the amygdalectomized monkeys on a reinforcer devaluation task and compared their performance with a group of three normal monkeys. The monkeys first learned to discriminate 60 pairs of objects, baited with two different food rewards. Each of the food rewards was then devalued by selective satiation in two separate experimental sessions. Normal controls tended to avoid displacing objects that covered the devalued food to a significantly greater degree than did the amygdalectomized monkeys, indicating that the excitotoxic amygdala damage interfered with reinforcer devaluation effects. Our results are consistent with the idea that the amygdala is necessary for learning the association between stimuli and the value of particular food rewards; however, the amygdala is not necessary for maintaining the value of secondary reinforcers, once they have been learned.

Acoustic Stimulation↗

PubMed1997

The effect of anterior thalamic and cingulate cortex lesions on object-in-place memory in monkeys.

Six Macaque monkeys (Macaca mulatta) were trained in an object-in-place memory task, designed to capture the 'whole scene' nature of episodic memory. In this task the correct, rewarded, response in each scene was to a particular object of a pair, which always occupied a particular position in a unique background which had been generated using randomly chosen colours and shapes. In each session, the monkey learned a new list of these unique scenes. The animals then underwent surgical ablation of either the anterior thalamic nuclei or the cingulate cortex. It was found that the animals with anterior thalamic lesions showed a substantial impairment, whereas the monkeys with cingulate cortex ablations were not significantly impaired at the task. These results confirm the importance of the anterior thalamic nuclei in episodic memory, and suggest that the cingulate gyrus is not a region which is crucial in the type of episodic memory task used in the present experiment.

Animals↗