Frontal Cortex Lesions Research Articles

Serial Magnetic Resonance Imaging Findings of Rasmussen''s Encephalitis —Case Report—

A 12-year-old boy presented with Rasmussen's encephalitis. Serial magnetic resonance (MR) imaging one year after the onset of seizure showed no abnormality. T2-weighted imaging detected a high intensity lesion in the left frontal cortex when the frequency of seizures increased 11 months later. MR imaging showed the lesion rapidly spread into the white matter, then gradually regressed after biopsy and immunoglobulin therapy, and mild focal atrophy of the left frontal lobe in spite of recurrence of seizures 3 months after the therapy. Histological examination of the biopsy sample showed the characteristic findings of Rasmussen's encephalitis. Five months after the biopsy, another new high intensity lesion was detected next to the previous one, although his seizures were well controlled at that time. Although the extent of the high intensity lesion did not correlate with the frequency of seizures, such sequential changes in MR imaging appearance seemed to reflect the course of this disease.

Extended brain disinhibition following small photothrombotic lesions in rat frontal cortex.

The effect of an ischaemic focal cortical lesion on the excitability of surrounding and remote brain areas was investigated. Infarcts were produced photothrombotically in rat frontal cortex and brain excitability was assessed by a extracellular paired-pulse stimulation in coronal slices 7 days later. The cortical lesions caused a reduction of inhibition. The extent and grade of these electrophysiological effects depended on the depth of the lesion: in animals with a lesion affecting the deeper cortical layers a pronounced transcortical diaschisis was found, whereas animals with a shallow lesion showed only a slight ipsilateral affliction. The study shows that focal lesions in the motor cortex cause widespread disinhibition, probably resulting from deafferentation, and these may have a significant impact on recovery of function.

Dissociable effects of cingulate and medial frontal cortex lesions on stimulus-reward learning using a novel Pavlovian autoshaping procedure for the rat: implications for the neurobiology of emotion.

The effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on stimulus-reward learning were investigated with a novel Pavlovian autoshaping procedure in an apparatus allowing the automated presentation of computer-graphic stimuli to rats (T. J. Bussey, J. L. Muir, & T. W. Robbins, 1994). White vertical rectangles were presented on the left or the right of a computer screen. One of these conditioned stimuli (the CS+) was always followed by the presentation of a sucrose pellet; the other, the CS-, was never followed by reward. With training, rats came to approach the CS+ more often than the CS-. Anterior cingulate cortex-lesioned rats failed to demonstrate normal discriminated approach, making significantly more approaches to the CS- than did sham-operated controls. Medial frontal cortex-lesioned rats acquired the task normally but had longer overall approach latencies. Posterior cingulate cortex lesions did not affect acquisition.

Triple dissociation of anterior cingulate, posterior cingulate, and medial frontal cortices on visual discrimination tasks using a touchscreen testing procedure for the rat.

Four experiments examined effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on tests of visual discrimination learning, using a new "touchscreen" testing method for rats. Anterior cingulate cortex lesions impaired acquisition of an 8-pair concurrent discrimination task, whereas posterior cingulate cortex lesions facilitated learning but selectively impaired the late stages of acquisition of a visuospatial conditional discrimination. Medial frontal cortex lesions selectively impaired reversal learning when stimuli were difficult to discriminate; lesions of anterior and posterior cingulate cortex had no effect. These results suggest roles for the anterior cingulate, posterior cingulate, and medial frontal cortex in stimulus-reward learning, stimulus-response learning or response generation, and attention during learning, respectively.

Accelerated time experience after left frontal cortex lesion

Accelerated time experience after left frontal cortex lesion

Accelerated Time Experience after Left Frontal Cortex Lesion

Accelerated Time Experience after Left Frontal Cortex Lesion

Microglial reactions to retrograde degeneration of tracer-identified thalamic neurons after frontal sensorimotor cortex lesions in adult rats.

Thalamic neuronal degeneration after neocortical lesions involve both anterograde and retrograde components. This study deals with the thalamic microglial response after neocortical aspiration lesions, using fluorogold fluorescent prelabeling, to identify retrogradely degenerating thalamocortical neurons, combined with histochemical or immunohistochemical staining of microglial cells. Adult male Wistar rats were injected with the retrograde fluorescent tracer fluorogold, in the right sensorimotor cortex (forepaw area) in order to retrogradely label thalamic neurons projecting to this area. After 1 week, the fluorogold injection site was removed by aspiration, axotomizing at the same time the thalamic projection neurons now retrogradely labeled with fluorogold. After 3, 7, 14, and 28 days the animals were killed and processed for nucleoside diphosphatase histochemistry or complement type 3 receptor immuno-histochemistry and class I and II major histocompatibility complex immunohistochemistry using OX42, OX18, and OX6 antibodies. The histological analysis showed a prominent and progressive nucleoside diphosphatase-, OX42-, and OX6-positive microglial cell response in the ventrolateral, posterior, and ventrobasal thalamic nuclei with ongoing retrograde and anterograde neuronal degeneration. Initially the reactive microglia had a bushy morphology and were succeeded by ameboid microglia and microglial cluster cells as the reaction progressed. However, in the reticular thalamic nucleus, which suffered exclusively anterograde neuronal degeneration, a different picture was seen with only bushy microglia. The neurons undergoing retrograde degeneration in the ventrolateral, posterior, and ventrobasal thalamic nuclei were retrogradely labeled by the fluorogold tracer. Individual nucleoside diphosphatase-, OX42-, or OX6-positive microglial cells extended long cytoplasmic processes surrounding fluorogold-labeled neurons and had in some cases apparently phagocytized these. Several microglial cells were thus double-labeled with nucleoside diphosphatase or OX42 and fluorogold. In addition, small nucleoside diphosphatase-positive, fluorogold-labeled perivascular cells were observed in the neocortex near the fluorogold-injected and ablated neocortical areas and in the ipsilateral thalamus. This study demonstrates: (1) that the microglial response to thalamic degeneration after neocortical lesion is graded with a limited reaction to the well-known massive anterograde axonal degeneration and a more extended reaction to the axotomy-induced retrograde cell death; and (2) that also perivascular cells and possibly macrophages may contribute to this reaction, as seen by uptake of fluorogold from axotomized neurons in the degenerating thalamic nuclei.

Accelerated time experience after left frontal cortex lesion

Abstract We report a patient, BW, with an accelerated time experience as a result of a glioblastoma in his left superior prefrontal cortex. He experienced external events as seeming to occur at a much faster rate than before the lesion, but he showed normal awareness of time, place, and identity. He displayed behavioral slowness, some aphasia, right hemispatial neglect, and other neuropsychological problems typical of left frontal damage. When asked to produce 60 s durations, BWs mean production was extremely long (286.0 s). This finding is consistent with the notion that subjective duration had decreased relative to objective duration. Several explanations for the findings are discussed, including the possibility that the rate of an internal pacemaker was greatly slowed.

Prefrontal cortex dysfunction in borna disease virus (BDV)-infected rats

Viruses have been proposed to play a role in the pathogenesis of schizophrenia; however, the mechanisms by which infection could cause the affective, cognitive, and movement disorders of schizophrenia are not understood. The neurotropic RNA virus, Borna disease (BD) virus, linked to schizophrenia by serologic studies, causes movement and behavior disorders in a wide variety of mammalian and bird hosts. BD rats have hyperactivity and stereotyped behaviors similar to those that follow neurotoxic or electrolytic lesions in frontal cortex or its catecholamine afferents in rats. BD rats have high levels of viral nucleic acid in the prefrontal cortex (PFC), abnormal mesocortical dopamine activity (elevated levels of DOPAC in PFC), yet no alteration in specific binding of D1 or D2 receptor radioligands in PFC. Since frontal lobe dysfunction is frequently reported in schizophrenia, the BD rat model may provide insights into pathogenesis and management of this debilitating psychiatric disease.

A comparison of the effects of frontal cortical and thalamic lesions on measures of spatial learning and memory in the rat

Two experiments were conducted to compare the effects of radiofrequency lesions of thalamus and frontal cortex on three measures of spatial learning and memory: delayed non-matching to sample (DNMTS), radial arm maze with imposed delays, and serial reversal learning. Thalamic lesions were aimed at the lateral internal medullary lamina (L-IML) and cortical lesions at the projection areas of the mediodorsal nucleus along the medial wall (MW) and dorsal to the rhinal sulcus (RS) in frontal cortex. In Experiment 1 rats were trained on DNMTS prior to surgery. After recovery, rats with MW lesions showed persistent deficits on DNMTS that were significantly greater than for RS lesions. The deficits observed in MW lesioned animals were comparable to the effects of L-IML lesions on this task that have been described in previous studies. In Experiment 2 animals were trained to perform the radial arm maze task prior to treatment. After recovery, animals with L-IML lesions were impaired on the radial arm maze and on subsequent acquisition of the serial reversal task. Rats with RS and MW lesions showed transient impairments on the radial arm maze task, but otherwise performed as well as controls on both these tasks.

The cerebral cortex of the rat and visual attentional function: dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task.

Dissociable effects of bilateral excitotoxic lesions of different regions of the rat neocortex, including medial prefrontal and anterior cingulate cortices, were investigated in a five-choice serial reaction time task that provides several indices of the accuracy and speed of attentional function. Whereas medial prefrontal cortical lesions impaired performance of the task as revealed by a reduction in choice accuracy, an increase in the latency to respond correctly to the visual target and enhanced perseverative responding, lesions of the anterior cingulate cortex specifically increased premature responding. By contrast, lateral frontal cortical lesions did not significantly disrupt baseline performance of the task, but rather increased the latency to respond correctly to the visual target during various behavioral manipulations, for example, when the length of the intertrial interval was varied unpredictably and during interpolation of distracting bursts of white noise. Lesions of the parietal cortex failed to disrupt any aspect of task performance investigated. These behavioral effects in the five-choice task were compared with the effect of these same lesions on acquisition and retention of a one-trial passive avoidance task. The main finding from this paradigm was that lesions of the lateral frontal cortex produced a significant disruption to the retention of passive avoidance, which stands in marked contrast to the successful retention observed by animals of the other lesion groups. In addition, this pattern of results reveals that the 'disinhibitory' effect of cingulate cortex lesions are relatively specific to the five-choice attentional task. Finally, the results of the present study are compared with the findings of previous experiments using the five-choice task, which have examined the effect of selective manipulations of the ascending noradrenergic, cholinergic, dopaminergic, and serotonergic projections. In particular, the deficits in attentional function observed following cholinergic lesions of the nucleus basalis magnocellularis appear to be attributable to cholinergic denervation of the medial frontal cortex. These results are discussed in terms of the role of parallel distributed neural systems within the neocortex that mediate continuous attentional performance in the rat.

Medial frontal cortex lesions selectively attenuate the hot plate response: possible nocifensive apraxia in the rat

Lesions in the cingulate cortex have attenuated pain-related behavior in humans. We wished to evaluate an animal model of this effect by studying the effects of bilateral lesions within the medial frontal cortex, including rat cingulate cortex, on performance in 3 behavioral tests: the formalin, hot-plate, and tail-flick tests. Average hot-plate latencies, but not formalin test scores or tail-flick latencies, were significantly increased by an average of 82% in rats with medial frontal cortex lesions, as compared to sham-operated control rats. Motor function, as tested by righting and foot lifting responses and clinical observation, was not impaired. No effects were seen on hot-plate latencies, tail-flick latencies, and formalin pain scores in sham-operated rats. These results suggest that the medial frontal cortex of the rat mediates certain types of supraspinally organized responses to noxious heat pain. Lesions that include the medial frontal and anterior cingulate cortex appear to disrupt the integration of increasing heat nociceptive input with motor responses that are necessary to execute quickly the escape behavior in the hot-plate test.

Decreased dominance in a limited access test but normal maternal behavior in micrencephalic rats

Micrencephalic offspring produced by gestational treatment with the antimitotic compound methylazoxymethanol acetate (MAM) are remarkable for substantial preservation of function concurrent with severe neural stunting. Altered behaviors in these micrencephalics, including light shyness and response perseveration, are similar to those produced by frontal cortex lesions. Consistent with this, the frontal cortex is one of several regions severely stunted by gestational MAM treatment. Because the frontal cortex has been implicated in rodent social behavior, maternal behavior in females and dominance in both sexes were assessed. Dominance was measured via water competition in 24-h water-deprived dyads (1 control and 1 MAM) matched for sex and body weight. Micrencephalic rats exhibited shorter drinking time than controls (males: 101 vs. 219 s, p < 0.001; females: 114 vs. 176 s, p < 0.03), indicating that micrencephalics were more submissive. For maternal behavior tests, micrencephalic and control females were bred to control males and pup retrieval was measured on postnatal days 3–13. Micrencephalic dams were unimpaired in any aspect of pup retrieval. Of 8 standard behavior measures used here and previously, access time in water competition tests produced the clearest differentiation between control and micrencephalic rats. These studies indicate that at least one aspect of social dominance in both sexes is severely reduced by MAM treatment while maternal behavior remains intact.

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

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

My behavior made me do it: The uncaused cause of teleological behaviorism

AbstractToward a neurobiologically grounded approach to explaining self-control we discuss the case of a patient with a bilateral lesion in frontal ventromedial cortex. Patients with such lesions display a marked deficit in social decision making. Compared with an account that examines the causal antecedents of self-control, Rachlin's behaviorist approach seems lacking in explanatory strength.

Impairments on nonspatial self-ordered and externally ordered working memory tasks after lesions of the mid-dorsal part of the lateral frontal cortex in the monkey

Monkeys with lesions of the mid-dorsal part of the lateral frontal cortex, which extends above the sulcus principalis as far as the midline (MDL lesions), were shown to exhibit severe and long-lasting impairments on certain nonspatial working memory tasks: the self-ordered and externally ordered tasks (experiments 1, 2, 3, 5, 6, and 8). These tasks, which were modeled on similar ones previously used with patients, measure the capacity to monitor, within working memory, self-generated choices and the occurrence of externally ordered stimuli. Monkeys with lesions of the adjacent posterior dorsolateral frontal cortex, which surrounds the arcuate sulcus (PA lesions), performed as well as the normal control animals on these tasks. Experiments 4 and 5 showed that the critical variable accounting for the impairment on the self-ordered and externally ordered working memory tasks by monkeys with MDL lesions is the size of the set of stimuli that must be monitored. Furthermore, the MDL lesions did not affect basic recognition memory (experiment 6), or primacy and recency mnemonic effects [i.e., the capacity to discriminate between the initial (or final) items and other items in a list of stimuli (experiments 4 and 7), or the capacity to select from a set of stimuli on the basis of a learned fixed sequence (experiment 9)]. Thus, lesions of the mid-dorsal part of the lateral frontal cortex give rise to an impairment in working memory that depends on the size of the set of the stimuli that have to be monitored.

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 lesions (PFC) 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.

Localization of gliosis in the corpus striatum of mice following cortical lesions

Localized lesions of the medial and lateral frontal cortex were used to study gliosis, neurofilament content and changes in synaptic density in the mouse striatum. Relationships between the sites of cortical lesions and the localization of changes in different regions of the striatum were examined after 3 and 12 weeks. Independent of the location of frontal cortex lesions, glial fibrillary acidic protein (GFAP) immunoreactivity was increased throughout the entire striatum after 3 weeks. Twelve weeks after lesioning, increases in GFAP were confined to the dorsomedial (DM) striatum following medial cortical lesions, and to the dorsolateral (DL) striatum following lateral cortical lesions, suggesting persistent gliosis only in areas of striatal deafferentation. It appears, therefore, that the mechanisms which induce gliosis after short and long time periods are different.

Radial maze performance in inbred mice: Evidence for strain-dependent neural nets subserving spatial learning abilities

C57BL/6 (C57) and DBA/2 (DBA) inbred mice perform differently on spatial tasks, with C57 mice doing better than DBA ones. Previous results have shown that hippocampal lesions impair performance in a radial eight-arm maze in both strains, while amygdaloid and frontal-cortex lesions have a deleterious effect only in the “high-learner” C57 strain. The high spatial-learning abilities of C57 mice seem, therefore, to be based upon a neural net recruiting distinct brain areas. The aim of the present study was to examine whether the genotype-dependent involvement of brain structures remains the same in radial-maze tasks with procedures that reduce or abolish interstrain performance differences. C57 and DBA mice with hippocampal, amygdaloid, or sham lesions were tested in a spatial (Experiment 1) or a visually cued (Experiment 2) version of the 4-baited-arm task using a radial 8-arm maze. No interstrain difference in baseline performance was observed in the two tasks. In the spatial discrimination task, hippocampal lesions impaired performance in both strains, while amygdaloid lesions had a selective deleterious effect on reentry into baited arms in the C57 strain only. Hippocampal but not amygdaloid lesions impaired performance on the visual discrimination task in both strains. Spatial, but not visual, discriminative learning seems, therefore, to involve a different circuitry according to the strain considered. The question of whether the areas recruited for each circuit cooperate by processing distinct but complementary memory attributes or whether they are simply vicariant may have strong implications for studies concerning functional recovery.

Scopolamine induces recovery of shuttle box avoidance behavior after frontal cortex ablation

The learning and reversal of shuttle box active avoidance behavior in animals with a bilateral frontal cortex ablation was investigated during and after scopolamine or pilocarpine treatment. Scopolamine facilitated the performance of the avoidance task in normal animals and in those with frontal cortex lesions and also increased the number of intertrial responses, while pilocarpine increased the deleterious effects of the lesions. Furthermore, in the absence of scopolamine, the animals previously treated with the drug showed that its beneficial effects persisted while the number of intertrial responses were no longer increased. The results indicate that the beneficial effects of scopolamine treatment on active avoidance behavior are independent from the effects observed on intertrial activity since only the former are observed after drug withdrawal. Therefore, scopolamine treatment seems to induce a long lasting recovery process in frontal cortex ablated animals.