Medial prefrontal cortex lesions and spatial delayed alternation in the developing rat: Recovery of sparing?

In Exp 1, Long-Evans rat pups received medial prefrontal cortex (PFC) aspirations or sham surgery on Postnatal Day 10 (PND10) and were then trained on PND23 to perform 1 of 2 T-maze tasks: discrete-trials delayed alternation (DA) or simple position discrimination. Early PFC damage produced a selective failure to learn the DA task. In Exp 2, pups given the same lesion or sham surgery were trained on DA on PND19, PND27, or PND33. In relation to sham-operated controls, pups with PFC damage were impaired on PND19, somewhat impaired on PND27, and entirely unimpaired when tested on PND33. In Exp 3, pups given larger lesions of the frontal cortex on PND10 were impaired on DA when tested on PND23 but not when tested on PND33. These findings indicate that early PFC lesions result in a memory deficit around the time of weaning, which then recovers over the next 10–24 days of development. Moreover, the early deficit is selective for a late developing cognitive process (or processes) that is involved in acquisition of DA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal hemidecortication or frontal cortex ablation produces similar behavioral sparing but opposite effects on morphogenesis of remaining cortex.

Made behavioral comparisons between Long-Evans rats with complete removal of the neocortex of one hemisphere (hemidecorticate) or of the cortex anterior to bregma in both hemispheres (frontal cortex) in adulthood and rats with similar removals at 7 days of age. Neonatal ablation of the frontal cortex produced partial sparing of performance on the Morris water task and reduced the thickness of the remaining neocortex. Neonatal hemidecortication produced similar sparing of function on the water task but increased the thickness of the contralateral neocortex. Results are consistent with hemispherectomy studies done with children and imply that behavioral sparing following neonatal cortical lesions is independent of the gross morphogenesis of the remaining neocortex. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Medial prefrontal lesions in the rat and spatial navigation: Evidence for impaired planning.

Rats with medial prefrontal cortical lesions were tested in a modified water maze navigation task. In Stage 1, the rats were trained to locate a hidden platform from a single start location. They were then subjected to a series of trials during which a second start position was used (Stage 2). In Stage 3, the rats had to navigate to a new goal location from the 2 experienced start positions. Stage 4 required the rats to navigate to the same goal as in Stage 3, starting from 4 distinct positions. Finally, a single probe trial with no platform was conducted. Rats with prefrontal lesions were impaired only during Stage 4. This deficit was specific to the 2 start positions newly introduced during this stage, suggesting a dysfunction of planning processes. This impairment might result from a working memory deficit, precluding the animal from forming an adequate representation of the whole course of movements required to reach the platform. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional reorganization of the rat motor cortex following motor skill learning

Functional reorganization of the rat motor cortex following motor skill learning. J. Neurophysiol. 80: 3321-3325, 1998. Adult rats were allocated to either a skilled or unskilled reaching condition (SRC and URC, respectively). SRC animals were trained for 10 days on a skilled reaching task while URC animals were trained on a simple bar pressing task. After training, microelectrode stimulation was used to derive high resolution maps of the forelimb and hindlimb representations within the motor cortex. In comparison with URC animals, SRC animals exhibited a significant increase in mean area of the wrist and digit representations but a decrease in elbow/shoulder representation within the caudal forelimb area. No between-group differences in areal representation were found in either the hindlimb or rostral forelimb areas. These results demonstrate that motor skill learning is associated with a reorganization of movement representations within the rodent motor cortex.     

Selective sparing after lesions of visual cortex in newborn kittens.

Previous findings are discordant regarding the effects of perinatal lesions of Cortical Areas 17 and 18 on visual discrimination learning in cats. Three potential determinants of such sparing were investigated: age at lesion (4 or 181 days), age at testing (3 or 9 months), and stimulus complexity. Age at testing was not significant, but performance varied with stimulus complexity and cortical damage, and there was an interaction between stimulus complexity and age at lesion. Both operated groups were transiently impaired in discriminating objects and subsequently learned to discriminate simple 2-dimensional patterns as well as done by controls, but the lesion groups were permanently impaired in discriminating similiar patterns circumscribed by irrelevant lines. The age-at-lesion groups differed, however, in discriminating patterns masked by superimposed lines. The group lesioned at 181 days was severely impaired at both acquisition and subsequent intercurrent performance; the group lesioned at 4 days was impaired only at intercurrent performance. This study suggests that sparing after early postnatal damage of Areas 17 and 18 occurs only under limited circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preserved negative patterning and impaired spatial learning in pigeons (Columba livia) with lesions of the hippocampus.

Pigeons (Columba livia) with bilateral electrolytic lesions of the hippocampus and area parahippocampalis were compared with control pigeons on 2 tasks: negative patterning and delayed spatial alternation. Negative patterning demands configural stimulus representations for its successful solution. The only effect of hippocampal lesions on this task was an increased response rift to the rewarded stimuli. On the delayed spatial alternation task, hippocampal birds showed deficits relative to controls. Differences in the results of prior studies on negative patterning appear to be due to different response requirements to the nonreinforced stimuli. These results are consistent with prior work with rats and suggest that the avian hippocampus is essential for spatial memory and response inhibition but is not involved in configural learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of parietal cortex lesions on spatial problem solving in the rat

The Maier 3-table task was used to examine spatial representations in rats with lesions of the parietal cortex. Some animals had anteriorly placed lesions, some posteriorly placed in cortical areas, sometimes regarded as 'parietal' in earlier studies. After 5 days of familiarization, animals were given 18 days of testing on the standard Maier task. Both parietal groups were initially impaired, but reached the same level of performance as controls by the end of the test period. Learning occurred both within and between sessions for the anterior group, but only between sessions for the posterior group. There was no major functional differentiation apparent on this task between the two 'parietal' areas. Rate of exploration increased in both parietal groups across test sessions as task performance improved. It is argued that the change in exploratory activity across sessions in parietal groups may reflect the adoption of a compensatory strategy which improved performance, but that improvement could also have been due to neural changes, as structures, such as the frontal cortex or hippocampus, assume some functions normally mediated by the parietal area.     

Changes in the neonatal gonadal hormonal environment prevent behavioral sparing and alter cortical morphogenesis after early frontal cortex lesions in male and female rats.

The effects of perinatal exposure to testicular hormones were studied in male and female rats given medial prefrontal cortical (PFC) lesions on Postnatal Day 7. Hormonally intact rats with PFC lesions showed recovery of performance of the Morris water task but no recovery on a forelimb reaching task. Recovery was abolished in both males gonadectomized at birth and in females given testosterone at birth. Male rats with PFC lesions showed an increase in pyramidal cell spine density. This was blocked in gonadectomized animals. In contrast, female rats with PFC lesions showed an increase in dendritic arbor. This was reduced by perinatal testosterone. Interference with the gonadal hormonal environment reduced the brain's ability to compensate for the effects of early cortical lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of NMDA lesions centered on the postrhinal cortex on spatial memory tasks in the rat.

Rats with bilateral N-methyl-D-aspartate lesions centered on the postrhinal cortex (POR) and sham lesions were tested in a series of spatial memory tasks. The POR-lesioned rats were significantly impaired compared with sham rats in the reference memory version of both the water maze and radial arm maze tasks and in the standard radial arm maze working memory task. The POR-lesioned rats displayed a delay-independent impairment in the working memory versions of the water maze and in a delayed nonmatching-to-place (DNMP) version of the radial arm maze task. The POR-lesioned rats were also impaired in a DNMP procedure conducted in the T-maze. These findings indicate that the POR has a delay-independent role in the processing of spatial information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of cytotoxic perirhinal cortex lesions on spatial learning by rats: A comparison of the dark Agouti and Sprague-Dawley strains.

The effects of perirhinal cortex lesions in rats on spatial memory might depend on the choice of strain. The present study, therefore, compared perirhinal lesions in Sprague-Dawley rats (associated with deficits) with Dark Agouti rats (associated with null effects). Tests of reference memory and working memory in the water maze failed to provide evidence that perirhinal lesions disrupt overall levels of performance (irrespective of strain) or that these lesions have differential effects on the rates of spatial learning in these 2 strains. Strain differences were, however, found, as the Dark Agouti strain was often superior. Furthermore, the perirhinal lesions did have differential effects in the 2 strains, but these did not appear to relate directly to changes in spatial learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contribution of ingestive behaviors to taste-aversion learning in the rat.

Conducted 3 experiments with male Sprague-Dawley rats (N = 132). Ss tasting but not ingesting a flavored solution prior to toxicosis acquired weaker aversions to the flavor than Ss that actively consumed the CS during conditioning. Taste was isolated from ingestion either by curarizing the Ss or by infusing a flavored solution very rapidly into the oral cavity of non-water-deprived Ss. Control groups showed that the facilitatory effect of ingestion on taste-aversion learning did not depend on the consumption of very much of the CS solution. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evolution of cerebral cortex involvement in the acquisition of associative learning.

The presence of the c-Fos protein has been evidenced in the piriform cortex, subiculum, entorhinal and perirhinal cortices, and parietal and occipital cortices at different stages (Sessions 2, 4, and 6) in the acquisition of a trace conditioning in behaving rabbits. c-Fos immunostaining was also measured after a reminder (7th) session. c-Fos immunoreactivity increased significantly across conditioning on the contralateral side of the piriform, entorhinal, perirhinal, and parietal cortices as compared with the ipsilateral side of conditioned animals and the contralateral side of pseudo-conditioned ones. No difference in c-Fos immunostaining was observed between contra- and ipsilateral sides in the subiculum of conditioned animals. c-Fos production decreased significantly across conditioning but presented a noticeable bilateral increase after the reminder session in the piriform, entorhinal, perirhinal, and parietal cortices, but not in the subiculum. Peak production of c-Fos was observed after the 2nd and 7th (reminder) conditioning sessions for the piriform, entorhinal, perirhinal, and parietal cortices, and after the 4th session for the subiculum. It is proposed that different cortical areas process associative learning with different strengths and side dominances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anatomy of motor learning. I. Frontal cortex and attention to action

We used positron emission tomography to study new learning and automatic performance in normal volunteers. Subjects learned sequences of eight finger movements by trial and error. In a previous experiment we showed that the prefrontal cortex was activated during new learning but not during during automatic performance. The aim of the present experiment was to see what areas could be reactivated if the subjects performed the prelearned sequence but were required to pay attention to what they were doing. Scans were carried out under four conditions. In the first the subjects performed a prelearned sequence of eight key presses; this sequence was learned before scanning and was practiced until it had become overlearned, so that the subjects were able to perform it automatically. In the second condition the subjects learned a new sequence during scanning. In a third condition the subjects performed the prelearned sequence, but they were required to attend to what they were doing; they were instructed to think about the next movement. The fourth condition was a baseline condition. As in the earlier study, the dorsal prefrontal cortex and anterior cingulate area 32 were activated during new learning, but not during automatic performance. The left dorsal prefrontal cortex and the right anterior cingulate cortex were reactivated when subjects paid attention to the performance of the prelearned sequence compared with automatic performance of the same task. It is suggested that the critical feature was that the subjects were required to attend to the preparation of their responses. However, the dorsal prefrontal cortex and the anterior cingulate cortex were activated more when the subjects learned a new sequence than they were when subjects simply paid attention to a prelearned sequence. New learning differs from the attention condition in that the subjects generated moves, monitored the outcomes, and remembered the responses that had been successful. All these are nonroutine operations to which the subjects must attend. Further analysis is needed to specify which are the nonroutine operations that require the involvement of the dorsal prefrontal and anterior cingulate cortex.     

Neonatal ablations of the gustatory neocortex in the rat: Taste aversion learning and taste reactivity.

Sprague-Dawley rats sustaining ablations of gustatory neocortex (GN) at 2, 10, 20, or 60 days of age were compared with control-lesion and anesthetized controls (N?=?151) in the acquisition and extinction of a learned taste aversion. Ss were also tested for taste preference across 5 concentrations of NaCl solution (.04, .08, .15, .3, and .6 M). Results indicate that GN ablation disrupted aversion acquisition and extinction regardless of age at surgery. Taste-response functions for solutions shown by all GN Ss mirrored those of controls: preference (relative to water baseline) for middle concentrations and rejection of the strongest concentration. It is suggested that the 20- and 60-day-old GN Ss were hyperresponsive to the suprathreshold concentrations of NaCl (excepting the .6-M concentration). The increased response to NaCl in 20- and 60-day-old GN Ss may have been related to the significant decreases in water consumption relative to that of controls. Water consumption of controls and GN Ss in 2- and 10-day-olds was essentially equal. It is concluded that infant ablation of the GN does not spare normal taste aversion learning and that rats with GN ablations, regardless of age at surgery, respond in a normal manner to the hedonic aspects of NaCl solutions. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perirhinal cortex and place–object conditional learning in the rat.

The present study examined whether excitotoxic lesions of the perirhinal cortex can affect acquisition of a place–object conditional task in which object and spatial information must be integrated. Testing was carried-out in a double Y-maze apparatus, in which rats learned a conditional rule of the type, "In Place X, choose Object A, not Object B (A+ vs B–); in Place Y, choose Object B, not Object A (A– vs B+)." Perirhinal cortex lesions significantly impaired acquisition of this task while sparing performance of an allocentric spatial memory task performed in a radial arm maze. Perirhinal cortex lesions also had no apparent effect on a 1-pair object discrimination task performed in the double Y-maze or on retention and acquisition of 4-pair concurrent discrimination problems performed in a computer-automated touch screen testing apparatus. The results suggest that, although the perirhinal cortex and hippocampus can be functionally dissociated, their normal mode of operation includes the integration of object and spatial information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extensive cytotoxic lesions of the rat retrosplenial cortex reveal consistent deficits on tasks that tax allocentric spatial memory.

Despite the connections of the retrosplenial cortex strongly suggesting a role in spatial memory, the lesion data to date have been equivocal. Whether subjects are impaired after retrosplenial lesions seems to depend on whether the lesions were aspirative or excitotoxic, with the latter failing to produce an impairment. A shortcoming of previous excitotoxic lesion studies is that they spared the most caudal part of the retrosplenial cortex. The present study thus used rats with extensive neurotoxic lesions of the retrosplenial cortex that encompassed the entire rostrocaudal extent of this region. These rats were consistently impaired on several tests that tax allocentric memory. In contrast, they were unimpaired on an egocentric discrimination task. Although the lesions did not appear to affect object recognition, clear deficits were found for an object-in-place discrimination. The present study not only demonstrates a role for the retrosplenial cortex in allocentric spatial memory, but also explains why previous excitotoxic lesions have failed to detect any deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some behavioral effects of entorhinal cortex lesions in the albino rat.

Performed 7 experiments on groups of adult male albino Sprague-Dawley rats (N = 74). Ss with lesions in the entorhinal cortex (a) were hyperactive in a novel open field and in activity wheels, (b) were less responsive to punishment than controls, and (c) showed complex changes in several avoidance behaviors. Mild hyperphagia was observed only when the lesions extended into the subiculum. Results support the idea that the entorhinal cortex may relay information from the cingulate cortex and olfactory areas to the hippocampus. It is suggested that entorhinal-midbrain connections demonstrated in other species may serve important functions in the rat. (36 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal frontal lesions in hamsters impair species-typical behaviors and reduce brain weight and neocortical thickness.

23 Syrian golden hamsters in which the medial or ventral subfields of the frontal cortex were removed at 2 days of age were compared behaviorally and neuroanatomically with 34 Ss experiencing similar lesions at 100 days of age. An additional 18 Ss served as controls. Ss with neonatal lesions showed little sparing of species-typical behaviors such as hoarding and nest building. Although as juveniles the operated Ss did not differ from their littermate controls, as they developed they failed to improve their performance as their littermates did. Nonetheless, under certain environmental conditions, the lesioned Ss were capable of performing the behaviors nearly as proficiently as controls. Compared with Ss operated on in adulthood, the brains of neonatal operates weighed less and the remaining neocortex was thinner. Findings are discussed in terms of functional subregions of the brain, environmental constraint on sparing, and the measurement of behavioral deficits. (48 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex.

Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)