Effects Of Prefrontal Cortex Lesions Research Articles

A Novel Translational Assay of Response Inhibition and Impulsivity: Effects of Prefrontal Cortex Lesions, Drugs Used in ADHD, and Serotonin 2C Receptor Antagonism

Animal models are making an increasing contribution to our understanding of the psychology and brain mechanisms underlying behavioral inhibition and impulsivity. The aim here was to develop, for the first time, a mouse analog of the stop-signal reaction time task with high translational validity in order to be able to exploit this species in genetic and molecular investigations of impulsive behaviors. Cohorts of mice were trained to nose-poke to presentations of visual stimuli. Control of responding was manipulated by altering the onset of an auditory 'stop-signal' during the go response. The anticipated systematic changes in action cancellation were observed as stopping was made more difficult by placing the stop-signal closer to the execution of the action. Excitotoxic lesions of medial prefrontal cortex resulted in impaired stopping, while the clinically effective drugs methylphenidate and atomoxetine enhanced stopping abilities. The specific 5-HT2C receptor antagonist SB242084 also led to enhanced response control in this task. We conclude that stop-signal reaction time task performance can be successfully modeled in mice and is sensitive to prefrontal cortex dysfunction and drug treatments in a qualitatively similar manner to humans and previous rat models. Additionally, using this model we show novel and highly discrete effects of 5-HT2C receptor antagonism that suggest manipulation of 5-HT2C receptor function may be of use in correcting maladaptive impulsive behaviors and provide further evidence for dissociable contributions of serotonergic transmission to response control.

Visual attention task performance in Wistar and Lister Hooded rats: response inhibition deficits after medial prefrontal cortex lesions

The prefrontal cortex has traditionally been implicated in a variety of cognitive processes, including memory, attention and decision making. The detection of effects of prefrontal cortex lesions on attention has been shown to depend on the procedure used to assess the attentional process. We therefore investigated the effects of lesions of the prefrontal cortex in two different visual attention tasks, i.e. a three-choice serial reaction time task involving sustained and divided attention processes and a visual timing task involving sustained attention and response inhibition processes. In two rat strains that are frequently used in behavioural analysis, i.e. albino Wistar rats and pigmented Lister Hooded rats, lesions of the medial prefrontal cortex caused a deterioration of performance in both tasks, although the effect lasted much longer in the visual timing task. This latter task proved to be especially sensitive to detect the consequences of medial prefrontal cortex lesions, consisting of a loss of both attention control and response inhibition. In both attention tasks, Wistar rats performed less accurate and made more anticipatory responses than Listers. Strain differences could not entirely be attributed to possible visual deficits in albinos, which was also evident when locomotor activity in an open field and food-motivated behaviour in a hoarding paradigm were assessed. Due to slower habituation rates, Lister rats were more active and displayed little food hoarding behaviour. In Wistar rats, hoarding was disrupted by medial prefrontal cortex lesions, showing the effectiveness of the lesion. The results indicate that, although different rat strains provide different baseline levels of behaviour for testing lesion- or drug-induced behavioural changes, lesions of the medial prefrontal cortex do not only disrupt sustained attention processes, but also induce a strong impairment in response inhibition in both Wistar and Lister rats.

Procedural learning is impaired in patients with prefrontal lesions.

To 1) determine the effect of prefrontal cortex lesions on procedural learning (PL), measured by a serial reaction-time task (SRTT); 2) confirm whether visuomotor PL is lateralized to one hemisphere; and 3) clarify the relation between visuomotor sequence learning and verbal sequence learning, working memory, and executive functions. Previous cognitive neuroscience research has implicated the prefrontal cortex in visuomotor PL but there is a lack of studies examining patients with prefrontal cortex lesions. We studied 22 patients with strictly unilateral prefrontal cortex lesions (traumatic, ischemic, hemorrhagic, or tumors) and 52 cognitively intact controls matched for age, sex, and educational level. We administered to subjects long (10-item sequence) and short (4-item sequence) versions of the SRTT. With the long version, each hand was evaluated separately. Learning was indicated by the shortening of response times (RT) and decrease in errors across the sequential blocks and, most importantly, the rebound increase in RTs and errors when comparing the last sequence block with the next random block. Frontal lobe functions and verbal sequence learning were also assessed. Patients with unilateral prefrontal cortex lesions show PL impairment that involves both hands, although more errors were observed when the hand contralateral to the lesion was performing. Only those patients whose lesions were >2 cm in diameter were impaired. Neuropsychologic evaluation indicated impaired verbal sequence learning and executive function deficits. Patients with poorer working memory and verbal sequence learning were also more impaired in visuomotor sequence learning. The prefrontal cortex has a role in PL and is part of the neural circuit that mediates this type of learning.

P3-186 - Effects of prefrontal cortex lesions on short-term memory and attentional function assessed with a 3-lever operant apparatus in rats

P3-186 - Effects of prefrontal cortex lesions on short-term memory and attentional function assessed with a 3-lever operant apparatus in rats

An examination of prefrontal lesion size and the effects of cortical grafts on performance of the Morris water task by rats

We studied the effects of prefrontal cortex lesions and prefrontal cortical grafts on the performance of rats in the Morris water task. Adult male rats received cortical tissue grafts (E21) 2 weeks after aspiration of the medial prefrontal cortex. They were later studied in the Morris water maze, and their behavior was subsequently correlated with lesion size, graft presence, and graft size. The results showed that lesion size had a major effect on behavior: animals with lesions including the prelimbic cortex were unable to learn the location of the hidden platform, whereas those with lesions sparing this cortex eventually learned the task, although they were impaired relative to control animals. The presence of cortical grafts had no chronic effect upon behavior, and the size of the graft also did not predict behavior. True Blue injections into the host or graft in different animals showed that although the grafts invaded the hosts, the hosts did not invade the grafts themselves. These results are consistent with the growing body of evidence that suggests that cortical grafts do not allow the re-establishment of neural networks that replace the lost tissue, although there may be a general trophic effect of cortical grafts.