Detection of a deficit in visual discrimination of pattern following lesions of anterior cortex: role of type of motivation.

6 albino rats were trained under appetitive motivation to perform diametrically opposed visual discriminations of pattern via opposite eyes. Small lesions were subsequently placed unilaterally in anterior neocortex. Following a period of post-surgical recovery, subjects were re-trained on the diammetrically opposed discriminations in alternating 10-trial blocks. Every subject made more post-surgical errors on the discrimination mediated by the eye contralateral to the lesion. Since albino rats have virtually complete decussation of the visual system, this indicates selective impairment in mediation of performance of pattern discrimination in the part of the lesioned hemispheres. Thus, findings previously obtained in studies involving aversive motivation are general to appetitively motivated tasks.     

The effects of lesions to the rat hippocampus or rhinal cortex on olfactory and spatial memory: retrograde and anterograde findings

The role of the hippocampal system in retrograde and anterograde amnesia was investigated by using a novel olfactory-guided paradigm and a traditional test of spatial learning. In the retrograde study, rats were trained on a sequence of two-choice olfactory discriminations in the weeks prior to receiving neurotoxic lesions of the hippocampus or aspiration lesions of the perirhinal-entorhinal cortex. Memory tests for preoperatively learned discriminations revealed no statistical impairment for subjects with damage to the hippocampus on a problem learned remote in time from surgery (i.e., 4 weeks +) or on the two recently learned discriminations (i.e., 1–3 weeks prior to surgery). The performance of subjects with perirhinal-entorhinal damage provided an important comparison for subjects with specific hippocampal lesions. Despite showing intact memory for the remotely learned problem, perirhinalentorhinal damage resulted in numerically (although not significantly) weaker performance on postoperative tests of retention for the discriminations learned in the 3 weeks prior to surgery. In the anterograde portion of the study, long-term memory for newly acquired discriminations was spared in subjects with damage to the hippocampus, whereas subjects in the perirhinal-entorhinal lesion group again showed the weakest memory performance on these tests of 5-day retention. Postoperative water maze learning was uniformly impaired in subjects with damage to the hippocampus and perirhinalentorhinal cortex, thus confirming the effect of these lesions and supporting the involvement of these brain areas in spatial processes. These findings further dissociate the specific involvement of the hippocampus in tasks of a spatial-relational nature versus nonrelational tasks, such as discrimination learning and recognition memory (e.g., Duva et al., 1997; Eichenbaum, 1997; Eichenbaum, Schoenbaum, Young, & Bunsey, 1996). Moreover, the results suggest that damage to the hippocampus itself does not contribute to retrograde or anterograde memory impairments for all types of information, whereas the data suggest a more important role for the perirhinal-entorhinal cortex in recognition memory, irrespective of modality.     

Perirhinal cortex lesions impair feature-negative discrimination

The role of the perirhinal cortex in inhibitory eyeblink conditioning was examined. In Experiment 1, rats were given lesions of the perirhinal cortex or control surgery and subsequently trained with a feature-negative discrimination procedure followed by summation and retardation tests for conditioned inhibition. Perirhinal cortex lesions impaired, but did not prevent acquisition of feature-negative discrimination. Results from the summation test showed that rats with perirhinal cortex lesions could not generalize feature-negative discrimination to a new stimulus. There were no group differences during the retardation test. Experiment 2 showed that lesions of the perirhinal cortex did not impair simple excitatory conditioning. Experiment 3 showed that perirhinal cortex lesions had no effect on acquisition of a simple tone-light discrimination. The results suggest that the perirhinal cortex plays a role in eyeblink conditioning when using discrimination procedures involving overlapping stimuli.     

Pitch and timing abilities in adult left-hemisphere-dysphasic and right-hemisphere-damaged subjects

The production and perception of pitch and rhythm were tested in patients with acquired unilateral left-hemisphere (LH) lesions (and subsequent motor dysphasia, n = 13), patients with unilateral right-hemisphere (RH) lesions (n = 14), and normal age-matched controls. While the LH dysphasic subjects were not generally impaired on the production or perception of pitch, they were grossly impaired on the production and perception of rhythm. The RH subjects, in contrast, were impaired on measures of pitch perception and production, including the discrimination and production of single notes and of melodies. It is concluded that the two hemispheres differ in their specialization for the perception and production of pitch and rhythm.     

Conditioned taste aversions support drug discrimination learning at low dosages of morphine.

The present experiment shows that a conditioned taste aversion procedure can support discrimination learning at dosages of morphine comparable to those required to produce motivational effects. Sprague-Dawley rats were injected with 4.0 mg/kg morphine sulfate prior to a saccharin-lithium chloride pairing, and physiological saline prior to a saccharin-saline pairing. The rats avoided the saccharin solution following the administration of morphine and consumed significantly more saccharin following saline administration after four discrimination cycles. After this initial discrimination the subjects were trained with progressively lower doses of morphine. Discrimination learning was apparent at doses of 2.0, 1.5, 1.0, 0.75 and 0.5 mg/kg. Animals initially trained with 1.0 mg/kg morphine also learned the discrimination but required 10 training cycles. After this initial discrimination the subjects were trained with progressively lower dosages of morphine and showed a discrimination at a dosage of 0.5 mg/kg.     

Development of paw preference in rats following unilateral cortical ablations in infancy.

Rats which received unilateral anterior cortical lesions in infancy manifested a preference for the paw contralateral to the intact hemisphere when tested at 5 wk. and at 10 wk. of age. That this effect was locus specific and was not due to a change in the over-all balance of activity between the hemispheres was indicated by the fact that similar lesions made in the posterior cortex did not influence which paw the animals subsequently preferred. The posterior lesions, however, may have lowered the frequency of ambidexterity, a finding interpreted in terms of theoretical arguments concerning bilateral symmetry and the discrimination and memory of left and right.     

Hemispheric Asymmetries: Attention to Visual and Auditory Primitives

A computational theory of hemispheric asymmetries in perception (double filtering by frequency) is described. Its central tenet is that the cerebral hemispheres first perform symmetric filtering of visual and auditory information. Functional hemispheric asymmetry arises from a second filtering stage (containing filters skewed in different directions in the two hemispheres). The first stage selects a range of task-relevant spatial or auditory frequencies from the absolute values. This range is passed to the asymmetric filters. In this way, the hemispheric difference becomes one of relative rather than absolute information. Behavioral deficits due to unilateral lesions in neurological patients and neuroimaging and electrophysiological measures in normal subjects implicate posterior cortex in these hemispheric differences.     

Control of responding by the location of sound: role of binaural cues.

In auditory localization experiments, where the subject observes from a fixed position, both relative sound intensity and arrival time at the two ears determine the extent of localization performance. The present experiment investigated the role of binaural cues in a different context, the sound-position discrimination task, where the subject is free to move and interact with the sound source. The role of binaural cues was investigated in rats by producing an interaural imbalance through unilateral removal of the middle auditory ossicle (incus) prior to discrimination training. Discrete trial go-right/go-left sound-position discrimination of unilaterally incudectomised rats was then compared with that of normal rats and of rats with the incus of both sides removed. While bilateral incus removal affected binaural intensity and arrival times, the symmetry of sound input between the two ears was preserved. Percentage of correct responses and videotaped observations of sound approach and exploration showed that the unilateral rats failed to localize the sounding speaker. Rats with symmetrical binaural input (normal and bilaterally incudectomised rats) accurately discriminated sound position for the duration of the experiment. Previously reported monaural localization based upon following the intensity gradient to the sound source was not observed in the unilaterally incudectomised rats of the present experiment. It is concluded that sound-position discrimination depends upon the use of binaural cues.     

The behavioral effects of enriched housing are not altered by serotonin depletion but enrichment alters hippocampal neurochemistry

To assess a possible role for serotonin in the mediation of the behavioral changes induced by enriched housing conditions (EC), adult female Long-Evans rats sustaining a serotonin depletion (150 microg of 5,7-dihydroxytryptamine, icv) and sham-operated rats were housed postoperatively for 30 days in enriched (12 rats/large cage containing various objects) or standard housing conditions (2 rats/standard laboratory cage). Thereafter, anxiety responses (elevated plus-maze), locomotor activity (in the home-cage), sensori-motor capabilities (beam-walking task), and spatial memory (eight-arm radial maze) were assessed. Monoamine levels were subsequently measured in the frontoparietal cortex and the hippocampus. Overall, EC reduced anxiety-related responses, enhanced sensori-motor performance and improved the memory span in the initial stage of the spatial memory task. Despite a substantial reduction of serotonergic markers in the hippocampus (82%) and the cortex (74%), these positive effects of EC were not altered by the lesion. EC reduced the serotonin levels in the ventral hippocampus (particularly in unlesioned rats: -23%), increased serotonin turnover in the entire hippocampus (particularly in lesioned rats: +36%) and augmented the norepinephrine levels in the dorsal hippocampus (+68% in unlesioned and +49% in lesioned rats); no such alterations were found in the frontoparietal cortex. Our data suggest that an intact serotonergic system is not a prerequisite for the induction of positive behavioral effects by EC. The neurochemical changes found in the hippocampus of EC rats, however, show that the monoaminergic innervation of the hippocampus is a target of EC.     

Memory for Duration: Role of Hippocampus and Medial Prefrontal Cortex

In this task rats had to learn that a three-dimensional object stimulus (a rectangle) that was visible for 2 s would result in a positive (go) reinforcement for one object (a ball) and no reinforcement (no go) for a different object (a bottle). However, if the rectangle stimulus was visible for 8 s then there would be no reinforcement for the ball (no go), but a reinforcement for the bottle (go). After rats learned this conditional discrimination by responding differentially in terms of latency to approach the object, they received large (dorsal and ventral) lesions of the hippocampus, lesions of the medial prefrontal cortex (anterior cingulate and precentral cortex), lesions of the cortex dorsal to the dorsal hippocampus, or served as sham-operated controls. Following recovery from surgery they were retested. The results indicate that there were major impairments following hippocampal lesions, in contrast to cortical control and medial prefrontal cortex lesions, as indicated by smaller latency differences between positive and negative trials on postsurgery tests. In order to ensure that the deficits observed with hippocampal lesions were not due to a discrimination problem, new rats were trained in an object (gray cylinder) duration discrimination task. In this go/no go procedure, the rats were reinforced for a 2-s exposure (duration) of the gray cylinder, but not a 10-s duration, or vice versa. The results indicate that after hippocampal lesions, there was an initial deficit followed by complete recovery. There were no significant changes for the medial prefrontal, cortical control, or sham-operated animals. It appears that the hippocampus, but not the medial prefrontal cortex, is actively involved in representing in short-term memory temporal attribute information based on the use of markers for the beginning and end of the presence (duration) of a stimulus (object).     

Effects of Unilateral Entorhinal Cortex Lesion on Retention of Water Maze Performance

In a previous study, adult male Sprague-Dawley rats with unilateral, electrolytic entorhinal cortex lesions showed significant deficits in acquisition of a water maze task that measured working memory. The 10 days of testing used two trials per day with an intertrial interval of 1 h, and the rats with entorhinal damage were impaired in total distance to the platform in both trials. In the present retention study, rats who learned the same task prior to injury and were then retested for 5 days after lesion showed only a first day deficit in total distance to platform in the second trial. Analysis of swim patterns indicated that rats with unilateral entorhinal lesions used an altered strategy in retention testing to find the platform in the second trial of each day and incorporated the use of headings appropriate for Trial 1 only. This altered or compensatory strategy was not the optimum choice for problem solution. Although the rats then were able to switch headings and find the platform without significant impairment in total distance to platform on days 2–5 of testing, the use of an initial incorrect strategy indicated subtle residual deficits in cue integration and use of working memory.     

The role of R-S1 expectancy in discrimination and discrimination reversal learning

Four experiments assessed the role of response-reinforcement (R-S¹) expectancy as rats either learned a discrimination or a discrimination reversal. Experiment 1 showed that the higher the percentage of reinforcement during nondiscriminative pretraining the more quickly a subsequent discrimination is learned. Experiment 2 demonstrated that the overlearning reversal effect (ORE) can be obtained even though the overtraining phase consists of responses to a single neutral card. In Experiment 3 subjects were again overtrained on a single neutral stimulus under conditions of varying reinforcement. ORE was apparent under reinforcement of a high percentage of responses but was not apparent under reinforcement of a low percentage. Experiment 4 revealed that the fewer errors a subject makes prior to reversal the better its reversal performance is. Results of these studies were discussed in terms of generalized attention theories and the expectancy notions of Bolles (Psychological Review, 1972, 79(5), 394–409.     

Place learning in scopolamine-treated rats: the roles of distal cues and catecholaminergic mediation

Experiments 1 and 2 tested the hypothesis that cholinergic receptor antagonists impair place learning in a water maze by interfering with the processing of distal, visual cues. Extramaze cues were offered to rats in the form of geometrical patterns arranged on the inner circumference of a curtain surrounding the water maze. In Experiment 1 the animals were offered both the distal cues and proximal cues in the form of pingpong balls in fixed positions on the surface of the water while only distal cues were present in Experiment 2. Animals were injected with either scopolamine (0.5 mg/kg body wt) or saline 20 min prior to the daily place learning sessions. Upon reaching criterion level performance the animals were tested on "rotation" sessions on which the distal cues were displaced. The outcome of such "rotations" demonstrated that-regardless of the presence or absence of proximal cues-scopolamine-treated rats relied at least as much as normal animals on the distal cues. The acquisition phase of both Experiments 1 and 2 demonstrated an almost complete lack of scopolamine-associated impairment in acquisition and performance of the place learning task. In Experiment 3 (when scopolamine was no longer administered) the subjects of Experiment 2 were exposed to a series of pharmacological "challenges" of their place learning performance and eventually to surgical ablation of the anteromedial prefrontal cortex. The outcome of the pharmacological challenges and the postoperative test of task performance demonstrated that the place learning performance of animals which had acquired the task under scopolamine was mediated by a neural substrate dissimilar to the substrate of task performance in normal animals. Rats acquiring the task while deprived of the cholinergic system demonstrated above-normal contributions to task mediation from catecholaminergic-probably dopaminergic-mechanisms and tentative results pointed to a "shift" toward prefrontal task mediation.     

Monocular acquisition and interocular transfer in albino guinea pigs as mediated by ipsi- or contralateral fiber systems.

Monocular acquisition and interocular transfer of a horizontal-vertical discrimination were measured in 12 male albino guinea pigs with unilateral lesions of the striate cortex, and in 6 sham-operated controls. In accordance with electrophysiological and anatomical findings, the animals learned readily using the contralateral fibers, while the ipsilateral fibers were found to be incapable of mediating either acquisition, or retention, of the discrimination. The control animals learned readily, but showed incomplete transfer.     

Hemispheric differences in temporal resolution

A review of the relevant clinical and experimental literature gives the conclusion that the cerebral hemispheres differ in temporal resolution of input, with the language-dominant hemisphere showing finer acuity. This conclusion is supported by evidence from performance of patients with unilateral brain damage on tests of temporal resolution, performance of developmental dyslexics on similar tasks, and left-right sensory field differences in temporal acuity in normal human subjects. While it is unlikely that a hemispheric difference in temporal resolution is sufficient to give a complete account of lateralized functions, such attempts to show more primitive physiological differences between the hemispheres are more likely to be fruitful than attempts which differentiate the hemispheres in terms of higher-order psychological functions.     

Anterograde and retrograde amnesia of place discrimination in retrosplenial cortex and hippocampal lesioned rats

Retrograde and anterograde amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS) and hippocampus (HPC) were investigated. To test retrograde amnesia, rats were trained with two-arm place discrimination in a radial maze 4 wk and 1 d before surgery with a different arm pair, respectively. In the retention test 1 wk after surgery, both lesion groups showed temporally ungraded retrograde amnesia. To test anterograde amnesia, animals were trained after surgery to discriminate three arm pairs successively within a day, and then after interposition of 1- to 4-wk intervals, one of these pairs, respectively, was tested for retention. RS-lesioned rats could acquire these pairs of place discriminations rapidly but showed a retention interval-dependent impairment in the retention test. Conversely, HPC-lesioned rats took more sessions to acquire these pairs than did the control group, and their retention was approximately 70% of correct performance regardless of retention interval. Results suggest that RS and HPC have different roles in spatial memory and that RS is important for remote memory process.     

Functional recovery of skilled forelimb use in rats obliged to use the impaired limb after grafting of the frontal cortex lesion with homotopic fetal cortex

The long-term effect of transplanting embryonic frontal cortex into a unilateral frontal cortex lesion has been studied in adult rats. Before surgery, activity in an open field, muscular strength of both forelimbs, and performance in a paw-reaching-for-food task were scored in 26 rats. In 21 animals a unilateral cortex lesion was then made in the forelimb motor area of the hemisphere contralateral to the preferred paw in the paw-reaching-for-food task, while the other 5 animals were sham-operated. On retesting, the lesion animals changed the preferred paw. A solid homotopic transplant of embryonic tissue (embryonic day 17) was then placed in the lesion cavity in 11 of the lesion rats. Three months later neither lesion alone nor lesion plus transplantation affected open field behavior and muscular strength, but the lesion permanently affected performance in the paw-reaching-for-food task, as shown by a change of preferred paw and a functional deficit in the paw contralateral to the lesion. Transplantation ameliorated the deficits caused by the lesion, but this was only evident when animals were forced to reach with the paw contralateral to the lesion plus transplant. The behavioral results were independent of the size of the lesion and graft. Connections between graft and host tissue were studied by means of the fluorescent tracer 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI). A dense array of labeled fibers was found in the host cortex adjacent to the transplant. The results suggest that functional recovery depends on grafting but is only evident when the animal is obliged to use the affected limb.     

Cognitive and AI models of reasoning

Although relatively few in number, cognitive neuroscience studies of reasoning have two general implications for cognitive theories of deduction. First, an important distinction among these theories is whether they focus on the effect of personally relevant content on the processes and representations underlying deductive reasoning. Evidence is reviewed indicating that there is a neuroanatomical basis for both content-independent and content-dependent theories of deduction. Clinical and neuroimaging studies appear to show that content-independent reasoning is mediated by the left hemisphere, whereas content-dependent reasoning is mediated by regions in the right hemisphere and the bilateral ventromedial frontal cortex. In normal subjects, reasoning is likely to be based on contributions from both hemispheres. Second, clinical evidence indicates that the visuospatial processes used in deductive reasoning are mediated by the posterior areas of the left hemisphere, and that verbal and visuospatial reasoning representations overlap at the neuroanatomical level. This finding weighs against the claims of mental-model theory that deduction involves a significant nonverbal component. Further investigation, particularly with contemporary neuroimaging methods, is needed to test these preliminary conclusions.     

Hemispace and information control by the two cerebral hemispheres: which interaction?

Two experiments employing subjects with different experience in tactile discrimination (blind and seeing subjects) were carried out to investigate the effect of the space location of stimuli on the information processing activity of the two cerebral hemispheres. An angle discrimination task that yields a right hemisphere superiority was used. In Experiment 1, seeing subjects showed a general superiority of the left hand (right hemisphere) which was more pronounced in the left hemispace with respect to the central and the right hemispace performance. In Experiment 2, blind subjects showed a significant superiority of the left hand in the central and in the left hemispace and no difference between the two hands in the right hemispace. In both experiments hemispace differences were due only to the modification of the left hand (right hemisphere) performance. These results suggest that the hemispace control by the contralateral hemisphere interacts only with the activity of the hemisphere dominant in the information processing.     

Effects of unilateral hippocampus-amygdala-partial temporal lobe resection on auditory EEG/MEG responses: a case study

Auditory orienting and discrimination were studied with combined multi-channel EEG and MEG recordings in a patient with unilateral amygdala-hippocampus-partial temporal lobe resection of the right hemisphere. The results revealed abnormalities of habituation in alerting- and orienting-related responses, and discrimination-related responses, elicited by auditory stimulation contralateral to the resected cerebral hemisphere. These results give support to the notions about the role of the amygdala and hippocampus in alerting and orienting, respectively, and of the temporal cortex in auditory discrimination.