Medial Frontal Cortex Lesions Research Articles

Unilateral medial frontal cortex lesions cause a cognitive decision-making deficit in rats.

The medial frontal cortex (MFC) is critical for cost–benefit decision-making. Generally, cognitive and reward-based behaviour in rodents is not thought to be lateralised within the brain. In this study, however, we demonstrate that rats with unilateral MFC lesions show a profound change in decision-making on an effort-based decision-making task. Furthermore, unilateral MFC lesions have a greater effect when the rat has to choose to put in more effort for a higher reward when it is on the contralateral side of space to the lesion. Importantly, this could not be explained by motor impairments as these animals did not show a turning bias in separate experiments. In contrast, rats with unilateral dopaminergic midbrain lesions did exhibit a motoric turning bias, but were unimpaired on the effort-based decision-making task. This rare example of a cognitive deficit caused by a unilateral cortical lesion in the rat brain indicates that the MFC may have a specialised and lateralised role in evaluating the costs and benefits of actions directed to specific spatial locations.

Bilateral lesions of the medial frontal cortex disrupt recognition of social hierarchy during antiphonal communication in naked mole-rats (Heterocephalus glaber)

Generation of the motor patterns of emotional sounds in mammals occurs in the periaqueductal gray matter of the midbrain and is not directly controlled by the cortex. The medial frontal cortex indirectly controls vocalizations, based on the recognition of social context. We examined whether the medial frontal cortex was responsible for antiphonal vocalization, or turn-taking, in naked mole-rats. In normal turn-taking, naked mole-rats vocalize more frequently to dominant individuals than to subordinate ones. Bilateral lesions of the medial frontal cortex disrupted differentiation of call rates to the stimulus animals, which had varied social relationships to the subject. However, medial frontal cortex lesions did not affect either the acoustic properties of the vocalizations or the timing of the vocal exchanges. This suggests that the medial frontal cortex may be involved in social cognition or decision making during turn-taking, while other regions of the brain regulate when animals vocalize and the vocalizations themselves.

Behavioral effect of medial frontal cortex lesions on social transmission of avoidance in rats

Behavioral effect of medial frontal cortex lesions on social transmission of avoidance in rats

Medial frontal cortex and response conflict: Evidence from human intracranial EEG and medial frontal cortex lesion

The medial frontal cortex (MFC) has been implicated in the monitoring and selection of actions in the face of competing alternatives, but much remains unknown about its functional properties, including electrophysiological oscillations, during response conflict tasks. Here, we recorded intracranial EEG during a modified Flanker task from the MFC of two patients undergoing pre-surgical evaluation for the treatment of epilepsy. Performance on the task was associated with a suppression of beta (15–30 Hz) frequency oscillation power prior to and just following the response and an enhancement of theta (4–8 Hz) frequency power following the response. Beta (theta) power was anatomically distributed towards more dorsal/caudal (rostral/ventral) electrode sites along the cortex, suggesting an anatomical/functional specialization along the medial frontal wall for pre-response versus post-response action monitoring. Inter-site phase coherence analyses demonstrated that the ventral/rostral MFC theta oscillations were coupled with theta oscillations observed at scalp electrodes Fz and Cz. One patient was tested before and after having epileptogenic tissue in the MFC surgically removed; task performance increased from chance levels to near-perfect, and an ERP conflict effect was observed only following surgery. These findings provide novel evidence for the role of MFC oscillations and their relation to surface EEG-recorded potentials during action monitoring.

Experience-dependent amelioration of motor impairments in adulthood following neonatal medial frontal cortex injury in rats is accompanied by motor map expansion

One of the most common, and disruptive, neurological symptoms following neonatal brain injury is a motor impairment. Neonatal medial frontal cortical lesions in rats produce enduring motor impairments, and it is thought that lesion-induced abnormal cortical morphology and connectivity may underlie the motor deficits. In order to investigate the functional consequences of the lesion-induced anatomical abnormalities in adulthood, we used intracortical microstimulation to determine the neurophysiologic organization of motor maps within the lesion hemisphere. In addition, groups of neonatal lesion rats were given reach training or complex housing rehabilitation in adulthood and then mapped with intracortical microstimulation. The results demonstrate that neonatal medial frontal cortex lesions produce motor deficits in adulthood that are associated with abnormal motor maps. Further, adult behavioral treatment promoted partial recovery that was supported by reorganization of the motor maps whereby there were increases in the size of the forelimb motor maps. The experience-induced expansion of the forelimb motor maps in adulthood provides a neural mechanism for the experience-dependent improvements in motor performance.

Functional Specialization within Medial Frontal Cortex of the Anterior Cingulate for Evaluating Effort-Related Decisions

The rat medial frontal cortex (MFC) has been implicated in allowing animals to work harder to receive larger rewards. However, it is unknown what role the individual MFC regions [anterior cingulate cortex (ACC) and prelimbic-infralimbic cortex (PL-IL)] play in such decision making. To investigate this, we trained rats on a T-maze cost-benefit task with two possible courses of action, shown previously to be affected by complete MFC lesions. One response involved climbing a 30 cm barrier to obtain a large quantity of reward (high cost-high reward), whereas the other had a lower energetic demand but also a smaller reward gain (low cost-low reward). Before surgery, all animals preferred to select the high cost-high reward option. However, after excitotoxic ACC lesions, there was a complete reversal of behavior, with the ACC group selecting the low cost-low reward response on nearly every trial. In contrast, both control animals and rats with PL-IL lesions continued to choose to climb the barrier for the larger reward. When the same rats were tested on a delayed match-to-sample paradigm however, it was the PL-IL group that was significantly impaired at learning the response rule, with the performance of ACC rats being comparable with controls. This double dissociation indicates that the ACC is the important region within the MFC when evaluating how much effort to expand for a specific reward.

Perceptual Attentional Set-Shifting Is Impaired in Rats with Neurotoxic Lesions of Posterior Parietal Cortex

The posterior parietal cortex (PPC) is believed to be involved in the representation of spatial information, including spatial attentional processing. Because the PPC is extensively interconnected with frontal cortical regions involved in attention and executive function, we sought to determine whether PPC was involved in nonspatial attentional processes such as those of the frontal areas to which it projects. Lesions of the medial frontal cortex (in rats) or lateral prefrontal cortex (in nonhuman primates) impair the ability to shift attention from one perceptual dimension of a stimulus to another (referred to as an extradimensional shift). Rats with neurotoxic lesions of the PPC tested in an attentional set-shifting paradigm demonstrated a pattern of impairment identical to that of rats with medial frontal cortex lesions: they were selectively impaired on the extradimensional shift phase of the task. Performance in other phases of the task was indistinguishable from that of control rats, including the ability to reverse a previously learned discrimination. These findings are consistent with models that assign the PPC a prominent role in cortical attentional processing networks, as well as a role for the PPC in processing information about expectancy and surprise. They also suggest, importantly, that the interaction between the PPC and the frontal cortex is not limited to spatial attentional processing.

The Role of Rat Medial Frontal Cortex in Effort-Based Decision Making

We conducted a series of experiments to elucidate the role of rat medial frontal cortex (MFC) (including prelimbic, infralimbic, and cingulate cortices) in effort-based decision making. Rats were trained on a cost-benefit T-maze task in which they could either choose to climb a barrier to obtain a high reward in one arm (HR arm) or could obtain a small reward in the other with no barrier present (LR arm). Before surgery, all animals were selecting the HR arm on almost every trial. However, after excitotoxic lesions to MFC, the rats shifted to selecting the LR arm on almost every trial. This was not caused by a spatial memory or motor deficit because the same rats returned to selecting the HR arm when the amount of effort needed to be expended to obtain reward in either arm was equalized by putting an identical barrier in the LR arm. Additional experiments demonstrated that the change in effort-based decisions observed in the rats was not caused by a complete insensitivity to reward and effort because they returned to choosing the HR arm if either the cost was reduced (by making the barrier smaller) or the benefit was increased (increasing the food ratio differential). Instead, the MFC lesion shifted the animals' decision criterion, making them more likely to choose the LR arm than the sham-lesioned animals. These results imply that medial frontal cortex is important for allowing the animal to put in more work to obtain greater rewards.

Lesions of the medial and lateral striatum in the rat produce differential deficits in attentional performance.

Excitotoxic lesions of the medial frontal cortex and anterior cingulate cortex in rats have been shown to produce dissociable impairments on a reaction time visual attention (5-choice) task. Because these cortical areas project to the medial striatal region, the authors predicted similar deficits after lesions of this striatal area compared with the lateral area. Compared with sham-operated controls, rats with quinolinic acid-induced medial striatal lesions showed all the behavioral changes associated with medial frontal cortex and anterior cingulate cortex lesions. In contrast, lateral striatal lesions produced profound disturbances in the performance of the task. Control tests showed little evidence of gross deficits in either group of rats in terms of motivation, locomotor function, or Pavlovian appetitive conditioning. These data suggest that the medial and lateral striatum have contrasting roles in the control of instrumental responding related to the primary sources of their cortical innervation.

Lesions of the medial and lateral striatum in the rat produce differential deficits in attentional performance.

Excitotoxic lesions of the medial frontal cortex and anterior cingulate cortex in rats have been shown to produce dissociable impairments on a reaction time visual attention (5-choice) task. Because these cortical areas project to the medial striatal region, the authors predicted similar deficits after lesions of this striatal area compared with the lateral area. Compared with sham-operated controls, rats with quinolinic acid-induced medial striatal lesions showed all the behavioral changes associated with medial frontal cortex and anterior cingulate cortex lesions. In contrast, lateral striatal lesions produced profound disturbances in the performance of the task. Control tests showed little evidence of gross deficits in either group of rats in terms of motivation, locomotor function, or Pavlovian appetitive conditioning. These data suggest that the medial and lateral striatum have contrasting roles in the control of instrumental responding related to the primary sources of their cortical innervation.

Nicotine improves Morris water task performance in rats given medial frontal cortex lesions

The object of this study was to investigate whether nicotine would improve cognitive impairments produced by medial frontal cortex lesions in rats behaviorally tested on the Morris water task (MWT). Rats were assigned to either a lesion or sham group. In the lesion group, animals were given vehicle (peanut oil) treatment or treatment with nicotine for 11 consecutive days before, after, or before and after a medial frontal cortex lesion. Additionally, a sham group was included that was given vehicle both before and after the lesion. Results showed that lesioned rats receiving pre- or post-operative nicotine treatment demonstrated improved Morris task acquisition performance relative to the lesioned group given the vehicle, although a deficit was shown relative to shams. On the probe trial, rats that received a pre- and post-treatment of nicotine demonstrated performance equivalent to shams and had significantly better performance than rats that received nicotine treatment before the lesion and lesioned animals treated with the vehicle. These results demonstrate that nicotine has therapeutic effects in rats that have received cortical injury.

The medial frontal cortex and temporal memory: tests using spontaneous exploratory behaviour in the rat

Evidence from several sources indicates that the frontal cortex is involved in memory involving time, or temporal memory, and in behavioral sequencing. Rats were presented with two familiar objects and the amount of exploration directed at each was recorded. Subjects directed more exploration at the object encountered further ago in the past, even though the two objects differed by only 1 h. After bilateral medial frontal cortex lesion, animals did not differentiate between old and recent objects. Performance on an object recognition test (novel versus familiar objects) that also used exploration time did not change as a result of the medial frontal cortex lesions.

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.

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.

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.

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.

The effect of medial frontal cortex lesions on cardiovascular conditioned emotional responses in the rat

The effect of ventral medial frontal cortex (MFC) lesions on heart rate and blood pressure during conditioned emotional responses (CER) was investigated. Male Sprague-Dawley rats were divided into two groups: MFC-lesioned rats ( n = 11) sustained bilateral lesions of the infralimbic and ventral prelimbic regions of the MFC via microinjection of the neurotoxin N-methyl-D-aspartate; Controls ( n = 13) received sterile saline. Following a 2-week recovery period, all animals were trained; one of two tones served as the conditioned stimulus (CS) and a 2 mA footshock served as the unconditioned stimulus (US). The CS + tone was consistently paired with the US, while the CS − tone was randomly paired with the US. Heart rate and blood pressure were recorded during CS + and CS − presentations before and after administration of the following pharmacological agents: atropine, atenolol, and atropine + atenolol. All animals responded to the CS + with increased BP compared to baseline; the increase was not significantly different between groups. Controls responded to the CS + with increased HR, while MFC-lesioned animals displayed a bimodal HR response which was not significantly different from baseline, but was significantly different from Controls. Pharmacological blockade of the HR response revealed coactivation of the sympathetic and parasympathetic nervous systems during the CS +, with a significant decrease (52%) in the sympathetic tachycardia component of the CS + HR response in MFC-lesioned rats as compared to Controls; the parasympathetic bradycardia component was not altered by MFC lesions. In all cases, CS − responses were smaller than the CS + responses. Pharmacological analysis revealed that the CS − HR response was mediated by the sympathetic component only, which was also significantly reduced in MFC-lesioned animals as compared to Controls. This significant reduction in the sympathetically mediated HR component of both the reinforced CER (CS +) and the unreinforced CER (CS −) following ventral MFC lesions implies that the MFC is necessary for complete sympathetic activation of cardiovascular responses to both severely and mildly stressful stimuli. The role of the MFC in emotion is also discussed.

Medial Frontal Cortex Lesions: Deficits and Treatment with Nimodipine

Rats with bilateral lesions of the medial frontal cortex were tested in a T-maze for the ability to learn a position habit and to make four reversals of it. Rats with medial frontal cortical lesions showed deficits in reversal learning. In addition, they were found to be hyperactive in an open field. Treatment with the dihydropyridine calcium channel antagonist, nimodipine, did not reduce these behavioral deficits.

Medial frontal cortex lesions impair the aiming component of rat reaching

This study examined the contribution of medial frontal cortex (the medial portion of supplementary motor cortex, or Fr1) to the performance of rats on trained, or 'skilled', reaching tasks. Unilateral medial frontal cortex lesions moderately impaired reaching success on a task that demanded accuracy but they did not impair performance on a less demanding reaching task nor did they affect limb preference. Kinematic analyses indicated that the aiming component, in which the forearm of the limb is aligned along the midline of the body by adduction of the elbow, was chronically impaired. Rather than adducting the elbow to aim, the rats used a number of limb and whole body postural adjustments to compensate for incomplete or absent aiming. That medial frontal cortex is involved in the execution of at least one component of skilled reaching implies that a larger area of frontal cortex is involved in skilled limb movement than has been suggested by previous studies. The results also suggest that the different regions of frontal cortex may each have a relatively selective involvement in the execution of only a subset of the movements comprising a reach.

Do forebrain structures compete for behavioral expression? Evidence from amphetamine-induced behavior, microdialysis, and caudate-accumbens lesions in medial frontal cortex damaged rats

The neurochemical basis of behavioral changes following medial frontal cortex damage were investigated. Experiment 1 examined locomotion in response to d-amphetamine (1.5 and 5 mg/kg) in rats that had received bilateral aspirative lesions of the medial frontal cortex alone or in combination with 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens or caudate-putamen. Relative to controls, medial frontal cortex rats were initially hypoactive (day 1 postoperative) but rapidly became hyperactive (days 5–15 postoperative). Locomotor-time profiles and stereotypy ratings showed that amphetamine produced a selective enhancement of locomotion at the expense of stereotyped behavior. Nucleus accumbens lesions blocked the locomotion but enhanced stereotyped behavior in the medial frontal cortex damaged rats, suggesting that amphetamine-enhanced locomotion is dependent upon the integrity of the nucleus accumbens. In Experiment 2, intracerebral microdialysis was used to examine whether alterations in dopamine (DA) or monoamine metabolites in the nucleus accumbens or caudate-putamen accompanied the lesion-induced changes in locomotion. There were no differences in extracellular DA or monoamine levels between control rats and medial frontal cortex rats when tested on day 1 or day 15 postsurgery, either when they were at rest, while they walked on a motor-driven belt, or after amphetamine treatment. Therefore, it seems unlikely that changes in amphetamine-induced locomotion following medial frontal cortex lesions are related to underlying modifications in dopaminergic activity in the nucleus accumbens. It is suggested that neural structures compete for behavioral expression and that postlesion behavioral alterations reveal the competitive advantage of remaining intact neural systems.