Biomedical subjects

D Gaffan

Publications and source records attributed to D Gaffan.

At least 19 recordsLinked to original sources

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↗

PubMed1997

Hemifield-specific visual recognition memory impairments in patients with unilateral temporal lobe removals.

Recent evidence on visual neglect suggests that each hemisphere maintains a retinotopically organized representation of the visual world contralateral to the current fixation point and that this representation is based not only on analysis of the current retinal input but, equally importantly, on information retrieved from memory. This idea predicts that unilateral damage to memory systems should produce a lateralized impairment of memory for the retinotopically contralateral visual world. To test this prediction we examined visual recognition memory performance in the left and right visual hemifields of patients who had undergone partial unilateral temporal lobe removals for the relief of epilepsy, either in the left hemisphere (n = 5) or the right (n = 5). The patients were given complex artificial scenes to remember, constructed of independent left and right halves, and were then tested for recognition of the left and the right halves separately. Stimuli were exposed tachistoscopically throughout and fixation was maintained on a central position. Patients made significantly more errors with half-scenes in the hemifield contralateral to their removal than in the ipsilateral hemifield, an increase of 50% in the error rate on average. The effect was seen equally in patients with left and right removals. This finding supports the idea that visual memory retrieval is retinotopically organized.

Adult↗

PubMed1997

Monkeys can associate visual stimuli with reward delayed by 1 s even after perirhinal cortex ablation, uncinate fascicle section or amygdalectomy.

In the present experiment monkeys learned concurrent associations of two-dimensional objects (presented on a computer screen) with delayed reward. Hypothetical mechanisms of associative memory, such as long-term potentiation (LTP), required coincidental activation of two population of neurons: one representing the object and the other signalling the reward. In monkeys neurons in area TE of temporal cortex show object-specific activity during object presentation but only fraction of those neurons remain active after stimulus offset. In a delayed reward condition the majority of object-specific neurons in TE cease firing before reward is given and can be detected. In the present study the rate of learning with 1000 ms delay of reward was no slower than learning with immediate reward. This indicates that information about the object is somehow retained across the delay, possibly somewhere outside TE. In the present study we tested that assumption. Area TE projects to the perirhinal cortex and, via uncinate fascicle, to the prefrontal cortex. In our hands, ablations of perirhinal cortex or disconnection of prefrontal cortex from TE (by transection of uncinate fascicle) did not impair learning with delayed reward. Ablation of amygdala, a structure involved in reward-learning, slowed down learning equally with and without delay. We conclude that retaining information about the visually perceived objects across a delay does not exclusively depend upon integrity of perirhinal cortex, or uncinate fascicle, or amygdala. Parallel involvement of those structures remains a possibility and establishment of the role of residual activity of TE neurons requires further neurophysiological investigation.

Amygdala↗

PubMed1997

Impairment of visual object-discrimination learning after perirhinal cortex ablation.

Eight cynomolgus monkeys learned preoperatively 20 concurrent visual discriminations between pairs of colored shapes presented on a touch screen with 24-hr intertrial intervals. Three then received bilateral perirhinal cortex ablation, and 5 remained controls. The ablated monkeys were severely impaired in reacquiring the preoperatively acquired set, whereas postoperative learning of 20 new discriminations was not significantly affected. The task was then made more difficult. First, the number of foils from which the stimulus had to be selected was increased to 2, 4, 7, and then 14. Second, larger sets of 40, 80, and 160 problems were presented. Both manipulations revealed some significant but relatively mild impairments in the monkeys with ablations. It is suggested that perirhinal cortex ablation impairs the monkey's capacity to identify individual objects, which leads to deficits in both visual-object recognition memory and discrimination learning.

Animals↗

PubMed1997

Visual neglect in the monkey. Representation and disconnection.

Macaque monkeys were trained preoperatively in a visual search task. Neglect after a unilateral lesion was measured as the tendency to make errors (choices of non-target stimuli) ipsilateral to the lesion. Neglect was observed after optic tract section combined with forebrain commissurotomy (n = 6) and after parietal leucotomy, i.e. unilateral section of the white matter between the fundus of the intraparietal sulcus and the lateral ventricle (n = 3). Neglect was not observed after optic tract section alone, or forebrain commissurotomy alone, or posterior parietal cortical ablation, or posterior parietal ablation plus frontal eyefield ablation, or after frontal lobectomy plus forebrain commissurotomy (n = 3 in each of these groups). We propose that the cortex of each hemisphere maintains a retinotopically organized representation of the visible halfworld that is contralateral to the animal's current point of fixation, and that this representation is based not only on analysis of the current retinal input but also on memory. Visual neglect reflects an impairment in this representation. According to this proposal, the fact that neglect is not caused by optic tract section alone is explained by the ability of the blind hemisphere to build a memory-based representation of what is contralateral to the current point of fixation, using memories of visual information which arrived from the ipsilateral visual field in previous fixations that were directed contralateral to the current fixation point. However, neglect does follow when unilateral optic tract section is combined with forebrain commissurotomy, even though the cortex is intact, because then the blind hemisphere is not only deprived of information arriving from the contralateral field but it is also cut off from information arriving from the ipsilateral visual field, and therefore cannot build a memory-based representation of the currently contralateral visible world.

Animals↗

PubMed1997

Temporo-frontal disconnection impairs visual-visual paired association learning but not configural learning in Macaca monkeys.

Cynomolgus monkeys were tested in two computer-controlled visual associative memory tasks. The monkeys chose between visual objects on a screen by touching one. In the configural learning task one correct object and one wrong object were presented in each trial. Each of these two objects was composed of two coloured alphanumeric characters abutted together. The designation of the objects as 'correct' or 'wrong' followed a configural rule: e.g. if AB and CD are correct objects then AD and CB are wrong. In the paired association learning task in each trial three spatially separate objects (single alphanumeric characters) were presented. The central object was an instruction cue and the designation of the side objects as 'correct' or 'wrong' choices followed a paired association rule: e.g. if A, C and B are presented (C in the centre) then A is correct and B is wrong; however, if A, D and C are presented then C is correct and A is wrong. Disrupting the direct cortico-cortical interaction between the inferior temporal cortex and the prefrontal cortex by uncinate fascicle transection led to a learning deficit in the paired association task but not in the configural task. These results suggest that the uncinate fascicle facilitates visual-visual associative learning only in the specific case where a visual object acts as an instruction cue to guide the conditional choice of another, spatially separate object, and they support the evidence for a specific role of the uncinate fascicle in the learning of conditional tasks with visual instruction cues.

Animals↗

PubMed1997

The recognition memory deficit caused by mediodorsal thalamic lesion in non-human primates: a comparison with rhinal cortex lesion.

Two earlier studies found that rhinal cortex ablations in the monkey (Macaca fascicularis) impaired delayed matching-to-sample (DMS) when the stimuli in the experiment came from a large population of possible stimuli, but not when the stimulus population was small, while uncinate fascicle section had no effect on DMS whatever the stimulus population size. The mediodorsal thalamus receives a large projection from the rhinal cortex, and has been implicated in recognition memory performance. We trained monkeys preoperatively in delayed matching-to-sample with large and small stimulus populations, exactly as in the earlier studies, then examined the effect of bilaterally ablating the medial portion of the mediodorsal thalamic nucleus. Mediodorsal lesion impaired postoperative delayed matching-to-sample performance with a large stimulus set, but had no effect on performance of DMS with a small stimulus population. In comparison with the earlier data from rhinal cortex lesions with the same methods, wherever a deficit was seen in the rhinal-lesioned animals the mediodorsal thalamic nucleus-lesioned animals showed a smaller deficit. We conclude that other efferents from the rhinal cortex, possibly those to the adjacent inferior temporal cortex, enable better performance in the mediodorsal thalamic nucleus-lesioned animals than in the animals with rhinal cortex ablation.

Animals↗

PubMed1997

Functional double dissociation between two inferior temporal cortical areas: perirhinal cortex versus middle temporal gyrus.

There is both anatomic and cytoarchitectural evidence for dorsal-ventral subdivisions of the inferior temporal cortex. Despite this, there has been only limited evidence of corresponding functional subdivisions and no evidence that two adjacent cortical areas within the inferior temporal cortex, namely area TE and the perirhinal cortex, have distinctly different roles in vision and memory. We assessed the color discrimination abilities of cynomolgus monkeys with either bilateral ablation of the perirhinal cortex or bilateral ablation of the middle temporal gyrus. The stimuli were isoluminant colored squares presented on a touch screen. In each trial the subject had to learn to discriminate and select the correct choice (green) from among a maximum of eight other foils, each varying in either hue or saturation. Relative to unoperated controls, monkeys with middle temporal gyrus lesions were severely impaired in the color discrimination task, whereas monkeys with perirhinal lesions were unimpaired on this task. We also assessed the visual recognition abilities, as measured by a basic delayed nonmatching-to-sample task with trial-unique objects presented in a Wisconsin General Test Apparatus, of rhesus monkeys with bilateral middle temporal gyrus lesions. We then tested the monkeys' postoperative performance on a delayed nonmatching-to-sample task with delays and extended list lengths. The results from this experiment were compared with those from two other groups of rhesus monkeys, an unoperated control group and a group with bilateral perirhinal cortex lesions, both of which had performed the identical tasks in a previous experiment. Relative to unoperated controls, monkeys with perirhinal cortex lesions were severely impaired both in relearning the basic delayed nonmatching-to-sample task and on the postoperative performance test. In contrast, monkeys with middle temporal gyrus lesions were only mildly affected in relearning the basic nonmatching task and were unimpaired on the postoperative performance test. Thus our data demonstrate a clear functional double dissociation between the perirhinal cortex and the middle temporal gyrus. This result gives strong support to the hypothesis that the perirhinal cortex and the adjacent area TE have distinctly different roles in visual learning and memory.

Analysis of Variance↗