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Biomedical subjects

Timothy J Bussey

Publications and source records attributed to Timothy J Bussey.

At least 19 recordsLinked to original sources
PubMed2006

Why does brain damage impair memory? A connectionist model of object recognition memory in perirhinal cortex.

Object recognition is the canonical test of declarative memory, the type of memory putatively impaired after damage to the temporal lobes. Studies of object recognition memory have helped elucidate the anatomical structures involved in declarative memory, indicating a critical role for perirhinal cortex. We offer a mechanistic account of the effects of perirhinal cortex damage on object recognition memory, based on the assumption that perirhinal cortex stores representations of the conjunctions of visual features possessed by complex objects. Such representations are proposed to play an important role in memory when it is difficult to solve a task using representations of only individual visual features of stimuli, thought to be stored in regions of the ventral visual stream caudal to perirhinal cortex. The account is instantiated in a connectionist model, in which development of object representations with visual experience provides a mechanism for judgment of previous occurrence. We present simulations addressing the following empirical findings: (1) that impairments after damage to perirhinal cortex (modeled by removing the "perirhinal cortex" layer of the network) are exacerbated by lengthening the delay between presentation of to-be-remembered items and test, (2) that such impairments are also exacerbated by lengthening the list of to-be-remembered items, and (3) that impairments are revealed only when stimuli are trial unique rather than repeatedly presented. This study shows that it may be possible to account for object recognition impairments after damage to perirhinal cortex within a hierarchical, representational framework, in which complex conjunctive representations in perirhinal cortex play a critical role.

Brain Injuries↗
PubMed2006

Paradoxical facilitation of object recognition memory after infusion of scopolamine into perirhinal cortex: implications for cholinergic system function.

The cholinergic system has long been implicated in learning and memory, yet its specific function remains unclear. In the present study, we investigated the role of cortical acetylcholine in a rodent model of declarative memory by infusing the cholinergic muscarinic receptor antagonist scopolamine into the rat perirhinal cortex during different stages (encoding, storage/consolidation, and retrieval) of the spontaneous object recognition task. Presample infusions of scopolamine significantly impaired object recognition compared with performance of the same group of rats on saline trials; this result is consistent with previous reports supporting a role for perirhinal acetylcholine in object information acquisition. Scopolamine infusions directly before the retrieval stage had no discernible effect on object recognition. However, postsample infusions of scopolamine with sample-to-infusion delays of up to 20 h significantly facilitated performance relative to postsample saline infusion trials. Additional analysis suggested that the infusion episode could cause retroactive or proactive interference with the sample object trace and that scopolamine blocked the acquisition of this interfering information, thereby facilitating recognition memory. This is, to our knowledge, the first example of improved recognition memory after administration of scopolamine. The overall pattern of results is inconsistent with a direct role for cortical acetylcholine in declarative memory consolidation or retrieval. Rather, the cholinergic input to the perirhinal cortex may facilitate acquisition by enhancing the cortical processing of incoming stimulus information.

Acetylcholine↗
PubMed2006

Abnormal categorization and perceptual learning in patients with hippocampal damage.

Prevailing theory holds that the medial temporal lobe (MTL) subserves declarative memory exclusively, whereas nondeclarative memory is independent of this brain region. Recent studies in patients with amnesia, however, have shown that performance on declarative memory tasks may not always be dependent on a single MTL memory system, instead highlighting the critical role of anatomically distinct structures in processing different stimulus types. In particular, the hippocampus has been implicated in spatial memory, whereas perirhinal cortex seems critical for object memory. To assess whether stimulus type would also be a key dimension in nondeclarative memory, patients with selective hippocampal lesions were tested on simple categorization and perceptual learning of faces and virtual reality scenes. The patients demonstrated preserved categorization and perceptual learning of faces but abnormal performance when the stimuli to be discriminated were virtual reality scenes. These findings imply that stimulus type may be a more critical predictor of performance on memory tasks (declarative and nondeclarative) than previously thought. They also suggest that reports of good nondeclarative memory after MTL damage may, in some cases, simply reflect the use of stimuli that fail to tap the processes dependent on structures in this region, such as spatial processing in the case of the hippocampus.

Adult↗
PubMed2006

Genetic and dopaminergic modulation of reversal learning in a touchscreen-based operant procedure for mice.

Mice are uniquely suited as experimental subjects for various approaches to the study of the molecular and genetic basis of behavior, and there has been a corresponding explosion in the use of mice in behavioral neuroscience. Rats and monkeys, however, remain the preferred species for high-order cognitive models largely due to the unavailability of valid, reliable and translatable endpoint measures of behavior in the mouse. Here we present further development and validation of a touchscreen-based operant method for measuring cognition that is comparable to methods used in other species and human patients. C57BL/6J mice were found to show good performance on visual discrimination and reversal learning using this method. Demonstrating the sensitivity of the paradigm to genetic factors, C57BL/6J and DBA/2J mice exhibited marked differences in discrimination and reversal learning. Systemic treatment with the selective D1-like agonist, SKF81297, produced an impairment in the early phase of reversal learning, but did not alter visual discrimination, in C57BL/6J mice. The same treatment impaired spatial working memory on the T-maze delayed alternation task, but did not alter control measures of behavior including motivation and locomotor activity. These data demonstrate the sensitivity of visual discrimination and reversal learning measured by this method to genetic factors and pharmacological challenge, and thereby provide an extension and further validation of the method for measuring cognition in mice. When combined with emerging molecular techniques uniquely suited to this species such as genetic engineering and RNA modification this paradigm could provide a powerful new tool for behavioral neuroscience.

Analysis of Variance↗
PubMed2006

Impairment and facilitation of transverse patterning after lesions of the perirhinal cortex and hippocampus, respectively.

We have recently suggested that certain effects of perirhinal cortex removals in monkeys can be attributed to the lesion compromising complex configural representations of visual stimuli. On this view, monkeys with perirhinal cortex lesions will be impaired on acquisition of discrimination problems that possess high "feature ambiguity," that is, those in which many of the same features belong to both rewarded and unrewarded stimuli. A subclass of feature-ambiguous problems includes "configural" discrimination problems in which all features are ambiguous. In the present study, we tested control monkeys and monkeys with bilateral lesions of perirhinal cortex on a configural discrimination problem, the transverse-patterning task (i.e., A+ vs. B-, B+ vs. C-, C+ vs. A-), using complex 2-dimensional visual stimuli. In addition, we investigated the effects of lesions to another structure that has been implicated in configural learning, the hippocampus. Monkeys with perirhinal cortex lesions were impaired, whereas monkeys with selective hippocampal lesions were facilitated, on acquisition of the transverse-patterning task. These data do not provide support for mass action theories of medial temporal lobe function, which cannot account for the opposing effects of the 2 lesions. These results are, however, compatible with a view that perirhinal cortex, and not the hippocampus, contains complex configural representations of visual stimuli critical to the solution of the transverse-patterning task.

Animals↗
PubMed2006

No effect of hippocampal lesions on perirhinal cortex-dependent feature-ambiguous visual discriminations.

Previous studies have shown that perirhinal cortex lesions in monkeys impair visual discriminations with a high degree of "feature ambiguity," a property of visual discriminations that can emerge when features are a part of both rewarded and unrewarded stimuli. The effects of damage to the hippocampus on these perirhinal-dependent feature-ambiguous tasks are, however, unknown. Prominent theories of medial temporal lobe function predict similar effects of perirhinal cortex and hippocampal lesions on cognitive tasks. In contrast, our hypothesis is that perirhinal cortex, and not the hippocampus, is important for nonspatial complex feature-ambiguous discriminations. We sought to distinguish between these competing theories in a straightforward way, by testing rhesus monkeys with hippocampal lesions on the same feature-ambiguous tasks shown previously to depend on perirhinal cortex. It was found that hippocampal lesions had no effects on any of these tasks. The findings support the perceptual-mnemonic/feature conjunction model of perirhinal cortex function, and provide further evidence for heterogeneity of function within the putative medial temporal lobe memory system.

Agnosia↗
PubMed2005

Object memory and perception in the medial temporal lobe: an alternative approach.

The medial temporal lobe (MTL) includes several structures--the hippocampus, and the adjacent perirhinal, entorhinal and parahippocampal cortices--that have been associated with memory for at least the past 50 years. These components of the putative 'MTL memory system' are thought to operate together in the service of declarative memory--memory for facts and events--having little or no role in other functions such as perception. Object perception, however, is thought to be independent of the MTL, and instead is usually considered to be the domain of the ventral visual stream (VVS) or 'what' pathway. This 'textbook' view fits squarely into the prevailing paradigm of anatomical modularisation of psychological function in the brain. Recent studies, however, question this view, indicating that first, the MTL is functionally heterogeneous, and second, structures in the MTL might have a role in perception. Furthermore, the specific contributions of the individual structures within the MTL are being elucidated. These new findings indicate that it might no longer be useful to assume a strict functional dissociation between the MTL and the VVS, and that psychological functions might not be modularised in the way usually assumed. We propose an alternative approach to understanding the functions of these brain regions in terms of what computations they perform, and what representations they contain.

Animals↗
PubMed2005

Functional specialization in the human medial temporal lobe.

Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recall-based memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of "feature ambiguity," a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL.

Aged↗
PubMed2005

Glutamate receptors in perirhinal cortex mediate encoding, retrieval, and consolidation of object recognition memory.

Object recognition is consistently impaired in human amnesia and animal models thereof. Results from subjects with permanent brain damage have revealed the importance of the perirhinal cortex to object recognition memory. Here, we report evidence from rats for interdependent but distinct stages in object recognition memory (encoding, retrieval, and consolidation), which require glutamate receptor activity within perirhinal cortex. Transient blockade of AMPA receptor-mediated synaptic transmission within perirhinal cortex disrupted encoding for short- and long-term memory as well as retrieval and consolidation. In contrast, transient NMDA receptor blockade during encoding affected only long-term object recognition memory; NMDA receptor activity was also necessary for consolidation but not retrieval. These results further demonstrate the importance of perirhinal cortex for object recognition memory and suggest that, as in the hippocampus, AMPA and NMDA receptors mediate synaptic transmission and activity-dependent synaptic plasticity, respectively, in several stages of memory processing.

2-Amino-5-phosphonovalerate↗
PubMed2005

Transient inactivation of perirhinal cortex disrupts encoding, retrieval, and consolidation of object recognition memory.

Damage to perirhinal cortex (PRh) impairs object recognition memory in humans, monkeys, and rats when tested in tasks such as delayed nonmatching to sample, visual paired comparison, and its rodent analog, the spontaneous object recognition task. In the present study, we have capitalized on the discrete one-trial nature of the spontaneous object recognition task to investigate the role of PRh in several distinct stages of object recognition memory. In a series of experiments, transient inactivation of PRh was accomplished with bilateral infusions of lidocaine directly into PRh immediately before the sample phase (encoding), immediately before the choice phase (retrieval), or within the retention delay after the sample phase (storage-consolidation). Compared with performance on trials in which they received saline infusions, rats were significantly impaired when lidocaine was infused before the sample phase, regardless of the length of the retention delay. Similarly, delay-independent deficits were observed after immediate pre-choice infusions of lidocaine. Finally, PRh inactivation immediately and 20 min after the sample phase, but not 40, 60, or 80 min after, also disrupted subsequent object recognition when the retention delay was sufficiently long to ensure the dissipation of the actions of lidocaine during the choice phase. The effects of pre-sample and pre-choice inactivation indicate involvement of PRh in encoding and retrieval stages of object recognition, and the time course of post-sample inactivation effects suggests a role for PRh in the maintenance of the object trace during memory consolidation.

Animals↗
PubMed2005

Specialization in the medial temporal lobe for processing of objects and scenes.

There has been considerable debate as to whether the hippocampus and perirhinal cortex may subserve both memory and perception. We administered a series of oddity tasks, in which subjects selected the odd stimulus from a visual array, to amnesic patients with either selective hippocampal damage (HC group) or more extensive medial temporal damage, including the perirhinal cortex (MTL group). All patients performed normally when the stimuli could be discriminated using simple visual features, even if faces or complex virtual reality scenes were presented. Both patient groups were, however, severely impaired at scene discrimination when a significant demand was placed on processing spatial information across viewpoint independent representations, while only the MTL group showed a significant deficit in oddity judgments of faces and objects when object viewpoint independent perception was emphasized. These observations provide compelling evidence that the human hippocampus and perirhinal cortex are critical to processes beyond long-term declarative memory and may subserve spatial and object perception, respectively.

Aged↗
PubMed2005

Conditional motor learning in the nonspatial domain: effects of errorless learning and the contribution of the fornix to one-trial learning.

Conditional motor learning contributes importantly to behavioral flexibility. In previous work, the authors found that fornix transections impaired the ability of macaque monkeys (Macaca mulatta) to learn conditional motor associations between the nonspatial features of visual stimuli and nonspatially differentiated responses. In the present study, they found that significant 1-trial learning of such associations also depended on the fornix. Furthermore, removal of the hippocampus, subiculum, and subjacent parahippocampal cortex, added to fornix transection, had no effect, thus demonstrating that fornix transections eliminated the contribution of the hippocampal system. In addition, the authors examined the effect of errorless learning and found, in control monkeys, that errors made prior to the 1st correct response retarded 1-trial learning.

Animals↗
PubMed2005

Discrimination of multidimensional visual stimuli by mice: intra- and extradimensional shifts.

A visual discrimination protocol similar to that used with monkeys was adapted to measure attentional set-shifting in mice. An automated touchscreen procedure with compound visual stimuli was used to train mice to attend to 1 of 2 stimulus dimensions (lines or shapes). On a 2nd problem with new stimuli, the mice were required to attend to the same dimension (intradimensional [ID] shift) or switch to the previously irrelevant dimension (extradimensional [ED] shift). Mice readily learned the initial compound discrimination and following shift problem, but there was no ID-ED difference. The fact that mice can be tested with stimuli and task sequences similar to those used with primates suggests that this method can be used to directly compare higher cognitive functions in diverse species.

Animals↗
PubMed2005

Removal of cholinergic input to perirhinal cortex disrupts object recognition but not spatial working memory in the rat.

The perirhinal cortex of the temporal lobe has a crucial role in object recognition memory. Cholinergic transmission within perirhinal cortex also seems to be important for this function, as the muscarinic receptor antagonist scopolamine disrupts object recognition performance when administered systemically or directly into perirhinal cortex. In the present study, we directly assessed the contribution of cholinergic basal forebrain input to perirhinal cortex in object recognition. Selective bilateral removal of the cholinergic basal forebrain inputs to perirhinal cortex was accomplished by injecting the immunotoxin 192 IgG-saporin directly into perirhinal cortex in rats. These animals were significantly impaired relative to vehicle-injected controls in a spontaneous object recognition task despite intact spatial alternation performance. These results are consistent with recent reports of object recognition impairment following acute cholinergic receptor blockade and extend these findings by demonstrating that chronic removal of cholinergic basal forebrain input to an otherwise intact perirhinal cortex causes a severe object recognition deficit similar to that associated with more extensive cell body lesions of perirhinal cortex.

Animals↗
PubMed2004

Double dissociation between the effects of peri-postrhinal cortex and hippocampal lesions on tests of object recognition and spatial memory: heterogeneity of function within the temporal lobe.

It is widely believed that declarative memory is mediated by a medial temporal lobe memory system consisting of several distinct structures, including the hippocampus and perirhinal cortex. The strong version of this view assumes a high degree of functional homogeneity and serial organization within the medial temporal lobe, such that double dissociations between individual structures should not be possible. In the present study, we tested for a functional double dissociation between the hippocampus and peri-postrhinal cortex in a single experiment. Rats with bilateral excitotoxic lesions of either the hippocampus or peri-postrhinal cortex were assessed in tests of spatial memory (radial maze) and object recognition memory. For the latter, the spontaneous object recognition task was conducted in a modified apparatus designed to minimize the potentially confounding influence of spatial and contextual factors. A clear functional double dissociation was observed: rats with hippocampal lesions were impaired relative to controls and those with peripostrhinal cortex lesions on the spatial memory task, whereas rats with peri-postrhinal lesions were impaired relative to the hippocampal and control groups in object recognition. These results provide strong evidence in favor of heterogeneity and independence of function within the temporal lobe.

Animals↗
PubMed2003

Role of the anterior cingulate cortex in the control over behavior by Pavlovian conditioned stimuli in rats.

To investigate the contribution of the anterior cingulate cortex (ACC) to stimulus-reward learning, rats with lesions of peri- and postgenual ACC were tested on a variety of Pavlovian conditioning tasks. Lesioned rats learned to approach a food alcove during a stimulus predicting food, and responded normally for conditioned reinforcement. They also exhibited normal conditioned freezing and Pavlovian-instrumental transfer, yet were impaired at autoshaping. To resolve this apparent discrepancy, a further task was developed in which approach to the food alcove was under the control of 2 stimuli, only 1 of which was followed by reward. Lesioned rats were impaired, approaching during both stimuli. It is suggested that the ACC is not critical for stimulus-reward learning per se, but is required to discriminate multiple stimuli on the basis of their association with reward.

Amphetamine↗