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Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type.

Patients with dementia of the Alzheimer type (DAT) received two tests of visual selective attention, together with tests of spatial and visual recognition memory and visuospatial conditional learning previously used to show deficits early in the course of DAT. One set of attentional tests compared visual discrimination learning along intra- and extra-dimensional shifts, using a "total change" design. In the 12 DAT patients capable of attempting the extra-dimensional shift (subgroup 1), performance was equivalent to that of controls. This subgroup was also unimpaired at simple and compound discrimination learning and reversal and an intra-dimensional shift. They were as accurate as controls on a visual search task requiring matching of stimuli on two dimensions with variable numbers of alternatives, but were significantly impaired in the tests of recognition memory and learning. By contrast, the other 13 patients showed marked impairments in the attentional tasks. This subgroup was also significantly worse than subgroup 1 in performance on the visual recognition and conditional learning tasks, and showed greater severity on most of the clinical ratings of dementia. The sparing of attentional shifting in patients early in the course of DAT is contrasted with the impairments previously described in patients with Parkinson's disease with only mild or absent memory loss. The implications of this double dissociation of deficits for understanding the neural bases of the cognitive deficits in these two neurodegenerative diseases are discussed and their significance for the staging of DAT is considered.

Aged↗

The role of stimulus comparison in perceptual learning: an investigation with the domestic chick.

In two experiments an imprinting procedure was used to familiarize chicks with two stimuli, A and B, that subsequently served as the discriminanda in a simultaneous discrimination. On the first day of each experiment, subjects either received presentations of A and B that were intermixed within a session (mixed exposure) or presentations of A in one session and of B in another (separate exposure). For half of the subjects in each of the exposure conditions, A and B differed in both colour and form; for the remainder A and B differed in form alone. On the second day of the experiments, the chicks were placed into a cool test apparatus and given training in which approaching A was rewarded by the delivery of a stream of warm air, but approaching B was not. Acquisition of this discrimination was more rapid when A and B differed in two respects than when they differed in form alone. When A and B differed in both colour and form, the heat-reinforced discrimination was acquired more rapidly after separate exposure than after mixed exposure; but when A and B differed in form alone, discrimination learning was more rapid following mixed exposure than separate exposure. The latter finding, that the opportunity to compare stimuli differing in only one dimension facilitates subsequent discrimination learning, is consistent with earlier suggestions (Gibson, 1969) regarding the conditions that promote perceptual learning.

Animals↗

Naltrexone reverses age-induced cognitive deficits in rats.

We evaluated young (3-4 months) and aged (22-24 months) male Sprague-Dawley rats in an attentional set-shifting procedure that assessed reversal, intradimensional shift (IDS), and extradimensional shift (EDS) discrimination learning tasks within one test session. These aspects of discrimination learning are sensitive to damage to distinct regions of frontal cortex. Compared to young animals, aged rats were significantly impaired on the EDS task and did not demonstrate significant impairment on the reversal or IDS tasks. The opioid antagonist naltrexone (2mg/kg, ip) was administered to young and aged rats prior to testing to assess possible improvements in aged-related cognitive impairments. Naltrexone (2mg/kg) attenuated the impairments in cognitive function in the EDS task for aged animals, but did not alter any task performance in the younger group. These results suggest that normal aging in rats is associated with impaired medial frontal cortex function as assessed by this attentional set-shifting procedure and opioid mediated mechanisms may represent a therapeutic target for drugs to improve cognitive deficits associated with aging.

Aging↗

Lesions of the hippocampus or fornix do not interfere with the relative validity effect on a discrete stimulus or the context.

Two experiments with rats used an appetitively motivated instrumental discrimination procedure to examine whether damage to the hippocampal system would interfere with the relative validity effect in which a partially reinforced stimulus trained in compound acquires a weak conditioned response when concurrently trained CSs are perfect predictors of the presence or absence of the US [A.R. Wagner, F.A. Logan, K. Haberlandt, T. Price, Stimulus selection in animal discrimination learning, J. Exp. Psychol. 76 (1968) 171-180]. The true discrimination (TD) group received training with two compound cues containing a common element. One compound was reinforced and another never reinforced (AX+, BX-). Following TD training the common element (X) failed to acquire a strong conditioned response in comparison to a control, pseudo discrimination (PD) group (AX+/-, BX+/-), in which both compound cues were reinforced 50% of the time. Although (X) was reinforced on a partial reinforcement schedule, (50%) in both groups, conditioning of X was affected by the reinforcement schedules of the accompanying elements (A and B). Neither radio-frequency lesions of the fornix-fimbria (Experiment 1) nor neurotoxic lesions of the hippocampus (Experiment 2) interfered with this effect on X or on the same effect found during the inter trial interval (ITI). Rates of ITI responding were higher in the PD groups than in the TD groups suggesting stronger contextual conditioning following PD training. Furthermore, disruptions to the hippocampal system in Experiment 2 resulted in increased rates of lever pressing for food. These results do not support the notion that the hippocampus is critically involved in selective associations.

Animals↗

Severe learning impairment caused by combined immunotoxic lesion of the cholinergic projections to the cortex and hippocampus in monkeys.

Monkeys with immunotoxic lesions of both the basal nucleus of Meynert and the vertical limb of the diagonal band of Broca (NBM+VDB) lost cholinergic innervation throughout the cortex and hippocampus. They were impaired at learning discriminations between objects differing in either few, or many, attributes and at learning visuospatial conditional discriminations. Monkeys with immunotoxic lesions of the NBM lost cholinergic innervation of the neocortex only. Initially, they were unable to learn a simple visual discrimination where the stimuli differed in a limited number of attributes but they were unimpaired at learning discriminations between objects that differed in more attributes. They were mildly impaired at learning a visuospatial conditional task. The impairment exhibited by monkeys with lesions of the NBM alone ameliorated with time but that following NBM+VDB lesions did not. Previous experiments have shown that monkeys with immunotoxic lesions of the VDB alone are impaired at learning visuospatial conditional discriminations but are unimpaired at learning simple visual discriminations. When monkeys with NBM lesions were given excitotoxic lesions of the CA1 field of the hippocampus the learning impairment on discriminations between objects which differed in few attributes was reinstated. Pretreatment with a cholinergic agonist improved learning ability on visual discrimination learning in all monkeys but this improvement was significantly greater in monkeys with lesions of the NBM. On conditional discrimination learning, which is particularly sensitive to hippocampal damage, pilocarpine produced a significant improvement in monkeys with NBM+VDB lesions (where the hippocampal dysfunction was cholinergic) but not in monkeys with NBM+CA1 lesions (where the hippocampal damage was structural).

Acetylcholine↗

Facilitated stimulus-response associative learning and long-term memory in mice lacking the NTAN1 amidase of the N-end rule pathway.

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Inactivation of the NTAN1 gene encoding the asparagine-specific N-terminal amidase in mice results in impaired spatial memory [26]. The studies described here were designed to further characterize the effects upon learning and memory of inactivating the NTAN1 gene. NTAN1-deficient mice were found to be better than wild-type mice on black-white and horizontal-vertical discrimination learning. They were also better at 8-week Morris maze retention testing when a reversal trial was not included in the testing procedures. In all three tasks NTAN1-deficient mice appeared to use a strong win-stay strategy. It is concluded that inactivating the asparagine-specific branch of the N-end rule pathway in mice results in impaired spatial learning with concomitant compensatory restructuring of the nervous system in favor of non-spatial (stimulus-response) learning.

Amidohydrolases↗

Early colour deprivation in the pigeon.

When cats and monkeys are deprived of specific stimuli during an early sensitive period the development of their visual system is known to be affected. In pigeons, pattern discrimination learning has been shown to be affected by monocular deprivation [2]. Our study was set up to examine whether colour discrimination learning could be affected by colour deprivation. Young pigeons were reared under restricted colour illumination for at least 3 months after hatching so as to obtain a group bred under red illumination, one bred under blue illumination and a control group. After this period several psychophysical tests were used to test the pigeons' sense of colour. No significant difference was found between the 'deprived' birds and the controls. The spectral sensitivity, determined with the help of the ERG, did not differ for the three groups. We conclude that early colour deprivation does not affect visual development in the pigeon.

Animals↗

Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down's syndrome.

Mice with segmental trisomy of chromosome 16 (Ts65Dn) have been used as a model for Down's syndrome. These mice are born with a normal density of basal forebrain cholinergic neurons but, like patients with Down's syndrome, undergo a significant deterioration of these neurons later in life. The time course for this degeneration of cholinergic neurons has not been studied, nor is it known if it correlates with the progressive memory and learning deficits described. Ts65Dn mice that were 4, 6, 8, and 10 months old were sacrificed for evaluation of basal forebrain morphology. Separate groups of mice were tested on visual or spatial discrimination learning and reversal. We found no alterations in cholinergic markers in 4-month-old Ts65Dn mice, but thereafter a progressive decline in density of cholinergic neurons, as well as significant shrinkage of cell body size, was seen. A parallel loss of staining for the high-affinity nerve growth factor receptor, trkA, was observed at all time points, suggesting a biological mechanism for the cell loss involving this growth factor. Other than transient difficulty in learning the task requirements, there was no impairment of trisomic mice on visual discrimination learning and reversal, whereas spatial learning and reversal showed significant deficits, particularly in the mice over 6 months of age. Thus, the loss of ChAT-immunoreactive neurons in the basal forebrain was coupled with simultaneous deficits in behavioral flexibility on a spatial task occurring for the first time around 6 months of age. These findings suggest that the loss of cholinergic function and the simultaneous decrease in trkA immunoreactivity in basal forebrain may directly correlate with cognitive impairment in the Ts65Dn mouse

Animals↗

The role of binocular neurons in the cat striate cortex in combining information from the two eyes.

Cats were raised under conditions of daily alternating monocular exposure, so that each eye received normal input, but the animals were never allowed to use both eyes simultaneously. With single cell recording techniques it could be shown that this led to a severe disturbance of the normal binocularity of cortical neurons. The cats were trained by operant techniques in a two-choice box to discriminate with each eye non-retinotopic stimulus pairs. To test the ability to combine binocular signals it was tested whether the learned discrimination would transfer to red/green colored stimuli which were viewed dichoptically through appropriately colored contract lenses. The arrangement was such that the positive stimulus could be distinguished from the negative stimuli only when the signals from both eyes were combined and used simultaneously. All cats showed immediate transfer, from the monocularly learned discrimination task to the dichoptic paradigm. This indicates that the presence of a normal population of binocular cortical cells in area 17 is not a prerequisite for the ability to use binocular cues for the solution of a pattern discrimination task.

Animals↗

Deficits in visual learning produced by posterior temporal lesions in cats.

Eight cats with lesions in the posterior temporal (PT) cortex, seven cats with lesions in the basolateral amygdala (BLA), and eight intact controls were observed on eight tests of visual discrimination learning and of spontaneous responses to salient visual stimuli. The effects of the two lesions were somewhat dissociable. The PT lesions were accompanied by a severe deficit in pattern discrimination learning but no loss in visual tracking or orientation to the silhouette of a threatening cat. The BLA lesions produced a milder and less consistent loss in pattern discrimination but serious defects in tracking and reponse to the cat silhouette. Both operated groups performed well on the visual cliff. The deficit from PT lesions appeared independent of damage to the geniculocortical system. The parallel of symptoms from PT lesions in cats and inferotemporal lesions in monkeys is discussed.

Amygdala↗

A comparison of the effects of fornix transection and sulcus principalis ablation upon spatial learning by monkeys.

In each of three experiments with Cynomolgus monkeys (Macaca fascicularis), there was a group of normal control animals, a group with bilateral cortical ablations in the principal sulcus, and a group with fornix transection. In Expt. 1, half of each group learned problems in which the position of a pair of visual stimuli, to the monkey's left or right, indicated which of the visual stimuli was the correct (rewarded) one. The other animals learned problems in which visual stimuli indicated, irrespective of their own spatial position, whether reward was to be found on the monkey's left or on the right. The animals with fornix transection were impaired in both tasks. The animals with sulcus principalis ablation were also impaired in both tasks. The impairment caused by fornix transection was more severe than that caused by sulcus principalis ablation. Within each of the two operated groups, the degree of impairment in the two tasks was equal, when assessed in proportion to the difficulty of each task for control animals. Expt. 2 showed that neither of the operated groups was impaired in visual discrimination learning with spatial position irrelevant. Expt. 3 tested spatial discrimination learning (acquisition and reversal of a left-right discrimination) with irrelevant visual cues. Here the fornix-transected group was impaired but the group with sulcus principalis ablations was normal. It is suggested, on the basis of these findings and previous results, that fornix transection produces a general deficit in remembering the spatial arrangement of whole scenes, while sulcus principalis ablation produces a deficit in high-order integration involving spatial information.

Animals↗

Lesions of orbitofrontal cortex and basolateral amygdala complex disrupt acquisition of odor-guided discriminations and reversals.

Recent work indicates that both orbitofrontal cortex (OFC) and the basolateral complex of the amygdala (ABL) are involved in processes by which cues are associated with predicted outcomes. To examine the respective roles of these structures in discrimination learning, rats with bilateral sham or neurotoxic lesions of either OFC or ABL were trained on a series of four 2-odor discrimination problems in a thirst-motivated go, no-go task. After acquisition of the series of odor problems, the rats were trained on serial reversals of the final odor problem. Performance on each problem was assessed by monitoring accuracy of choice behavior, and also by measuring latency to respond for fluid outcomes after odor sampling. During discrimination learning, rats in both lesioned groups had similar deficits, failing to show normal changes in response latency during learning, while at the same time exhibiting normal choice behavior relative to controls. Choice behavior was affected only during the reversal phase of training, in which OFC and ABL lesions produced distinctive deficits. Rats with ABL lesions were impaired on the first reversal (S1-/S2+), but were unimpaired at acquiring a reversal back to the original odor-outcome contigencies (S1+/S2-), whereas rats with OFC lesions were impaired on both types of reversals. These findings suggest that OFC and ABL serve partially overlapping roles in the use of incentive information that supports normal discrimination performance.

Amygdala↗

The anterior cingulate and reward-guided selection of actions.

Macaques were taught a reward-conditional response selection task; they learned to associate each of two different actions to each of two different rewards and to select actions that were appropriate for particular rewards. They were also taught a visual discrimination learning task. Cingulate lesions significantly impaired selection of responses associated with different rewards but did not interfere with visual discrimination learning or performance. The results suggest that 1) the cingulate cortex is concerned with action reward associations and not limited to just detecting when actions lead to errors and 2) that the cingulate cortex's function is limited to action reinforcer associations and it is not concerned with stimulus reward associations.

Animals↗

The effects of fading procedures on discrimination shifts.

Human discrimination learning is frequently characterized as a "two-link process" consisting of an instrumental response and a covert dimensional attention or mediation response. In subsequent conceptual shift problems, reversal shift facilitation is attributed to partial reinforcement of the covert response in the original problem. Unlike standard trial and error learning conditions, a fading design eliminated the partial reinforcement of covert responding and, consistent with the hypothesis, reduced reversal shift facilitation. Although fading procedures facilitate discrimination learning, they may retard subsequent trial and error learning, a cost that warrants further exploration. Trial and error conditions produced the expected reversal facilitation.

Color Perception↗

Transfer between views of conspecific faces at different ages or in different orientations by sheep.

Sheep are able to discriminate photographs of conspecific faces. The present study investigates adult ewe's recognition of faces of the same animal between different ages or between different orientations. Twelve adult sheep were first trained to discriminate between faces of two unfamiliar animals, one of which was associated with a food reward. Transfer of discrimination from this pair to the same pair but at a different age, or in a different orientation, was then evaluated (transfer test), and compared with a new pair of the same condition (control test). Learned discrimination of a frontal view of unfamiliar 3-month-old lambs' faces improved subsequent discrimination of the same pair when they were 1-month-old in comparison to discrimination of new 1-month-old faces. Moreover, sheep that were trained to discriminate frontal views of unfamiliar adult individuals discriminated profile views of the same animals more accurately than that of novels. However, learned discrimination of the profile view of unfamiliar adult faces had no effect on subsequent discrimination of the frontal view of that same pair. These results suggest that to some extent sheep recognise faces of unfamiliar animals at different ages and in different orientations.

Animals↗

[Structural descriptions. Discrimination and learning of these descriptions].

In order for the computer to learn about objects, the user must first provide a good description language for these objects. In this paper we present a new description language which is structural. Structural descriptions portray objects as composite structures consisting of various components. Structural descriptions can be contrasted with attribute descriptions, which specify only global properties of an object. Attribute descriptions can be expressed using propositional logic. Structural descriptions, however, must be expressed in first-order logic. We present how this language works, why it is suitable for biochemical objects and how one can discriminate on structural descriptions. Finally, we present an application on learning about tRNA which has yielded very good results brings evident of feasibility.

Base Sequence↗