The effect of rat anterior cingulate inactivation on cognitive flexibility.

The present experiment investigated the effects of muscimol injections into the rat dorsal anterior cingulate on the acquisition and reversal learning of a 4-choice odor discrimination. Long-Evans rats were trained to dig in cups that contained distinct odors. In the odor discrimination, one odor cup contained a cereal reinforcement in acquisition whereas a different odor cup contained a cereal reinforcement in reversal learning. The other 2 odor cups were never associated with reinforcement. Bilateral infusions of the gamma aminobutyric acid-A agonist muscimol did not impair acquisition of the odor discrimination but impaired reversal learning in a dose-dependent manner. During reversal learning, dorsal anterior cingulate inactivation did not lead to perseveration but selectively increased errors to the odor cups that were never reinforced. These findings suggest that the dorsal anterior cingulate supports learning when conditions require a shift in choice patterns and may enhance cognitive flexibility by decreasing interference of irrelevant stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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 for 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of scopolamine infusions into the anterior and posterior cingulate on passive avoidance and water maze navigation

We examined the role of anterior and posterior cingulate cortical muscarinic receptors in water maze spatial learning and passive avoidance. Pretraining and posttraining trial scopolamine (a mixed a muscarinic acetylcholine antagonist) infusions into the anterior cingulate cortex dose dependently (3 no effect; 10 and 30 micrograms impaired) impaired passive avoidance performance. Pretesting infusion into the anterior cingulate had no effect on passive avoidance. Scopolamine infusion into the anterior cingulate did not impair spatial navigation. On the contrary, scopolamine (3 micrograms no effect, 10 and 30 micrograms impaired) infusions into the posterior cingulate before daily training trials impaired water maze navigation to a hidden platform, but did not affect navigation to a visible escape platform or passive avoidance. Posttraining and pretesting infusion into the posterior cingulate did not impair WM spatial navigation. The present results indicate that muscarinic acetylcholine receptor antagonist may modulate passive avoidance performance via cholinergic receptors located in anterior cingulate cortex and the ability to develop a spatial navigation strategy via muscarinic receptors located in posterior cingulate.     

Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an impaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS + significantly less often than controls, failing to discriminate between the CS + and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial geniculate lesions block amygdalar and cingulothalamic learning-related neuronal activity

This study assessed the role of the thalamic medial geniculate (MG) nucleus in discriminative avoidance learning, wherein rabbits acquire a locomotory response to a tone [conditioned stimulus (CS)+] to avoid a foot shock, and they learn to ignore a different tone (CS-) not predictive of foot shock. Limbic (anterior and medial dorsal) thalamic, cingulate cortical, or amygdalar lesions severely impair acquisition, and neurons in these areas develop training-induced activity (TIA): more firing to the CS+ than to the CS-. MG neurons exhibit TIA during learning and project to the amygdala. The MG neurons may supply afferents essential for amygdalar and cingulothalamic TIA and for avoidance learning. To test this hypothesis, bilateral electrolytic or excitotoxic ibotenic acid MG nuclear lesions were induced, and multiunit recording electrodes were chronically implanted into the anterior and posterior cingulate cortex, the anterior-ventral and medial-dorsal thalamic nuclei, and the basolateral nucleus of the amygdala before training. Learning was severely impaired and TIA was abolished in all areas in rabbits with lesions. Thus learning and TIA require the integrity of the MG nucleus. Only damage in the medial MG division was significantly correlated with the learning deficit. The lesions abolished the sensory response of amygdalar neurons, and they attenuated (but did not eliminate) the sensory response of cingulothalamic neurons, suggesting the existence of extra geniculate sources of auditory transmission to the cingulothalamic areas.     

Effects of medial prefrontal or anterior cingulate cortex lesions on responding for cocaine under fixed-ratio and second-order schedules of reinforcement in rats

Four experiments examined the effects of excitotoxic, axon-sparing lesions of the medial prefrontal cortex or anterior cingulate cortex in rats on responding under different schedules of intravenous cocaine self-administration and on the locomotor stimulant effects of cocaine. Experiment 1 tested the acquisition and maintenance of cocaine self-administration under a fixed ratio schedule. Rats with medial prefrontal cortex lesions showed facilitated acquisition and enhanced responding for low doses of the drug when lesions were induced before self-administration behaviour was established. Lesions of the anterior cingulate cortex did not affect cocaine self-administration. In experiment 2, rats were trained to respond under a second-order schedule of cocaine reinforcement, where responding during the fixed interval was reinforced by presentation of a cocaine-associated visual stimulus under fixed-ratio contingencies. In control rats, these schedule conditions were found to maintain high rates of responding and a scalloped pattern of responding over time. Omission of conditioned stimulus presentation during the fixed interval significantly disrupted response patterns, confirming that the stimulus served to maintain responding during the fixed interval. By contrast, rats with medial prefrontal cortex lesions showed higher rates and disrupted patterns of responding that were unchanged by stimulus omission. Rats with lesions of the anterior cingulate cortex responded at high rates throughout the fixed interval under all test conditions, indicating that the cocaine-associated stimulus did not serve to maintain temporal patterns of responding in these rats. Experiment 3 demonstrated the lack of effect of either lesion on the acquisition of responding for a non-drug reinforcer, sucrose. In experiment 4, measures of spontaneous and cocaine-induced locomotor activity revealed that rats in both lesion groups were significantly more active than controls regardless of test conditions. These data indicate that facilitated acquisition of cocaine self-administration and disrupted response patterns under second-order schedule contingencies may result from deficits in behavioural inhibition induced by medial prefrontal cortical lesions that contrast with deficits following damage to other limbic cortical regions, such as the basolateral amygdala or anterior cingulate cortex.     

"Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory": Correction to Ragozzino et al. (1998).

Reports an error in "Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory" by Michael E. Ragozzino, Spencer Adams and Raymond P. Kesner (Behavioral Neuroscience, 1998[Apr], Vol 112[2], 293-303). Figure 1 (page 295) and Figure 4 (page 299) were printed incorrectly. The corrected figure pages and corresponding captions are provided in the erratum. (The following abstract of the original article appeared in record 1998-01023-003.) The present study examined the effects of quinolinic acid lesions of the dorsal anterior cingulate and prelimbic-infralimbic cortices on spatial working memory and spatial discrimination using go/no-go procedures. All testing occurred in a 12-arm radial maze. In a working memory task, rats were allowed to enter 12 arms for a cereal reward. Three or 4 arms were presented for a 2nd time in a session, which did not result in a reward. In a spatial discrimination task, rats had successive access to 2 different arms. One arm always contained a reward, and the other never contained a reward. Prelimbic-infralimbic lesions impaired spatial working memory but only produced a transient spatial discrimination deficit. Dorsal anterior cingulate lesions did not induce a deficit in either task. These findings suggest that the prelimbic-infralimbic cortices, but not the anterior cingulate cortex, are important in spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Painful stimuli evoke potentials recorded over the human anterior cingulate gyrus

Clinical studies of cingulotomy patients and imaging studies predict that the human cingulate gyrus might display pain-related activity. We now report potentials evoked by painful cutaneous stimulation with a CO2 laser (LEP) and recorded from subdural electrodes over the medial wall of the hemisphere. In response to facial laser stimulation on both sides, a negative (latency 211-242 ms) and then a positive wave (325-352 ms) were recorded from the cortex of right medial wall and from the falcine dura overlying the left medial wall. Medial wall LEPs were similar to scalp LEPs and were largest over the anterior cingulate and superior frontal gyri just anterior to motor cortex contralateral to the side of stimulation. These results demonstrate that there is significant direct nociceptive input to the human anterior cingulate gyrus (Brodmann's area 24).     

Neurotoxic lesions of retrosplenial cortex disrupt signaled and unsignaled contextual fear conditioning.

The majority of research regarding contextual learning and memory has focused on the contributions of the hippocampus and related medial temporal lobe structures. However, little is known about other possible cortical contributions to these processes. Our laboratory recently demonstrated that electrolytic lesions of the retrosplenial cortex (RSP), a posterior region of cingulate cortex, impaired contextual but not cue-specific fear conditioning. The present experiments further examined the role of RSP in contextual fear memory using fiber-sparing neurotoxic lesions and both signaled and unsignaled fear conditioning paradigms. Despite comparable acquisition of the conditioned fear response, rats with neurotoxic lesions of RSP exhibited impaired contextual memory relative to control animals in both the signaled and unsignaled paradigms. These results further suggest an important role for RSP in contextual learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attentional effects of lesions to the anterior cingulate cortex: How prior reinforcement influences distractibility.

Morphological changes in the anterior cingulate cortex are found in subjects with schizophrenia, attention deficit hyperactivity disorder, and obsessive–compulsive disorder. These changes are hypothesized to underlie the impairments these individuals show on tasks that require cognitive control. The anterior cingulate cortex has previously been shown to be active in situations involving high conflict, presentation of salient, distracting stimuli, and error processing, that is, situations that occur when a shift in attention or responding is required. However, there is some uncertainty as to what specific role the anterior cingulate cortex plays in these situations. The current study used converging evidence from two behavioral paradigms to determine the effects of excitotoxic lesions in the anterior cingulate cortex on executive control. The first assay tests reversal learning, attentional set formation and shifting. The second assesses sustained attention with and without distractors. Animals with anterior cingulate cortex lesions were impaired during reinforcement reversals, discriminations that required subjects to disregard previously relevant stimulus attributes and showed a more rapid decline in attentional ability than Sham-Lesioned subjects when maintaining sustained attention for extended periods of time. These results are consistent with the hypothesis that the anterior cingulate cortex is involved in attending to stimulus attributes that currently predict reinforcement in the presence of previously relevant, salient distractors and maintaining sustained attention over prolonged time on task. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Hippocampal modulation of cingulo-thalamic neuronal activity and discriminative avoidance learning in rabbits

Two experiments assessed the effects of 1) combined subicular complex and posterior cingulate cortical lesions on training-induced neuronal activity (TIA) in the anterior ventral (AV) and medial dorsal (MD) thalamic nuclei; 2) hippocampal (Ammon's horn and dentate gyrus) lesions on TIA in cingulate cortex and in the AV and MD thalamic nuclei. The rabbits acquired a conditioned avoidance response (CR), stepping in an activity wheel upon hearing a 0.5-s tone (CS+), in order to prevent a foot-shock scheduled 5 s after tone onset. No response was required after a different, safety-predictive tone (CS-). In experiment 1 the combined subicular and cingulate cortical lesions enhanced thalamic TIA during acquisition and increased CR incidence in the first session of acquisition. These results confirmed the hypothesis that subicular and cingulate cortical efferents are not essential for thalamic TIA or for avoidance learning. Hippocampal lesions (experiment 2) also enhanced thalamic TIA. However, unlike subicular lesions, hippocampal lesions enhanced posterior cingulate cortical TIA as well, especially during extinction training. Hippocampal lesions did not affect CR performance. The results suggested that subicular excitatory efferents are responsible for incrementing cingulate cortical TIA, which is viewed as subserving associative attention. Activity from hippocampus downregulates the cue-elicited neuronal activity of the cingulo-thalamic circuits by suppressing the excitatory influence of the subiculum. The hippocampal influence reduces cingulo-thalamic cue-elicited activation in particular circumstances, such as the onset of CR extinction, when an expected reinforcer is omitted.     

Dissociation of the contributions of the prefrontal, motor, and parietal cortex of the control of movement in the rat: An experimental review.

Studied 48 male Long-Evans rats with or without lesions of the motor, medial frontal, or posterior parietal cortex or all the neocortex (decorticate) on a battery of tests. The tests assessed sensorimotor behavior, postural reflexes, feeding behavior, tongue extension, grooming, beam walking, response to the puzzle latch box, swimming, and food hoarding. Removal of the motor cortex produced abnormalities in postural reflexes and in behaviors requiring fine movements of the distal effectors. In contrast, removal of the medial frontal, orbital frontal, or posterior parietal cortex produced chronic impairments in specific behavioral patterns, depending on the precise region that was removed: Ss with medial frontal lesion were impaired at the use of the forepaws; Ss with orbital frontal lesions were impaired at making fine movements of the tongue and snout; and Ss with posterior parietal lesions were impaired at placement of the limbs in space. Complete removal of the neocortex produced abnormalities in every behavior. The possibility of deriving models of cortical function of primates from the rat is discussed. (French abstract) (66 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of muscarinic cholinergic receptor blockade in the rat anterior cingulate and Prelimbic/Infralimbic cortices on spatial working memory

Previous findings indicate that cholinergic input to the medial prefrontal cortex may modulate mnemonic processes. The present experiment determined whether blockade of muscarinic cholinergic receptors in the rodent anterior cingulate and prelimbic/infralimbic cortices impairs spatial working memory. In a 12-arm radial maze, a working memory for spatial locations task was employed using a continuous recognition go/no-go procedure. Rats were allowed to enter 12 arms for a reinforcement. Of the 12 arm presentations, 3 or 4 arms were presented for a second time in a session that did not contain a reinforcement. The number of trials between the first and second presentations of an arm ranged from 0 to 6 (lags). Infusions of scopolamine (1, 5, and 10 microgram), a muscarinic cholinergic antagonist, into the prelimbic/infralimbic cortices, but not the anterior cingulate cortex, significantly impaired spatial working memory in a lag- and dose-dependent manner. The deficit induced by scopolamine (10 microgram) was attenuated by concomitant intraprelimbic/infralimbic injections of oxotremorine (2 microgram) a muscarinic cholinergic agonist. A separate group of rats was tested on a successive spatial discrimination task. Injections of scopolamine (1, 5, and 10 microgram) into the prelimbic/infralimbic cortices did not impair performance on the spatial discrimination task. These findings suggest that muscarinic transmission in the prelimbic/infralimbic cortices, but not the anterior cingulate cortex, is important for spatial working memory.     

Ventrolateral prefrontal cortex lesions in rats impair the acquisition and retention of a tactile-olfactory configural task.

Rats with aspirative lesions of the ventrolateral frontal cortex were tested on acquisition and postsurgical retention of an associative learning task that required that they learn a tactile–olfactory configural discrimination. The task required that they pull up a string to obtain attached food and that they identify the correct string using a compound of string size and odor. The rats were not impaired in initial learning or reversal of the olfactory elements of the discrimination. They were impaired in acquisition and retention of the compound, and their deficit was proportional to lesion size. The results confirm that the ventrolateral frontal cortex is involved in processing of olfactory information and imply that the prefrontal cortex is involved in at least certain types of cross-modal configural associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Promoter/repressor system of Lactobacillus plantarum phage og1e: characterization of the promoters pR49-pR-pL and overproduction of the cro-like protein cng in Escherichia coli

Previous studies have shown that extensive damage to the medial prefrontal cortex (mPFC) of rats causes reversal learning deficits. The mPFC of rats, however, consists of several subareas that are different from each other in both cytoarchitecture and neural connectivity, suggesting a functional dissociation among the mPFC subareas. In the present study, selective lesions of the mPFC of rats were made with a specially designed microknife whose intracranial placement could be controlled stereotaxically. Restricted lesions were made to each of the 3 parts of the mPFC: the anterior cingulate area (AC) (including the medial precentral area, PrCm), the prelimbic area (PL), and the infralimbic area (IL). One week after surgery, rats were trained in an aversively motivated visual discrimination task in a novel rotating T-maze. After reaching the acquisition criterion, rats were trained in a reversal task in the same maze. No difference was found in acquisition between control and mPFC lesioned rats. However, lesions of either the PL or the IL produced a marked deficit in the reversal task. This behavioral deficit was not found in rats with lesions of the AC. The results indicate that the mPFC of rats is not essential for discrimination learning, but that each of the 2 ventral subareas of the mPFC, PL, and IL, plays a critical role in reversal learning.     

Disconnection of the anterior cingulate cortex and nucleus accumbens core impairs Pavlovian approach behavior: Further evidence for limbic cortical–ventral striatopallidal systems.

The nucleus accumbens (NAcc) has been implicated in a variety of forms of reward-related learning, reflecting its anatomical connections with limbic cortical structures. After confirming that excitotoxic lesions of the anterior cingulate cortex (Ant Cing) impaired the acquisition of appetitive Pavlovian conditioning in an autoshaping procedure, the effects of excitotoxic lesions to the NAcc core or shell on autoshaping were also assessed. Only selective core lesions impaired Pavlovian approach. A subsequent experiment studied the effects of a disconnection of the Ant Cing and NAcc core, using an asymmetric lesion procedure, to determine whether these structures interact sequentially as part of a limbic corticostriatal system. Such lesioned rats were also significantly impaired relative to controls at autoshaping. These results demonstrate that the NAcc core and Ant Cing are "nodes" of a corticostriatal circuit involved in stimulus-reward learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial

The ability of rats to learn the location of a hidden platform in a swim maze was compared in animals with excitotoxic lesions of the anterior or posterior (retrosplenial) cingulate cortex or radiofrequency lesions of the cingulum bundle or fimbria-fornix. Performance of this allocentric spatial task was unaffected by the posterior cingulate cortex lesions, while anterior cingulate cortex damage produced only a mild acquisition deficit. Transection of the fornix and lesions of the cingulum bundle produced similar patterns of impairment on initial acquisition, but the cingulum bundle lesions had less effect on reversal of the task. The results from the water maze, and from a subsequent T-maze alternation task, indicate that cingulum bundle lesions can produce a spatial deficit that is similar, but milder, to that observed after fornix transection. The results of the excitotoxic lesions suggest that previous studies examining conventional cingulate lesions may have been influenced by damage to adjacent fibre tracts, such as the cingulum bundle.     

Differential involvement of the dorsal anterior cingulate and prelimbic–infralimbic areas of the rodent prefrontal cortex in spatial working memory.

[Correction Notice: An erratum for this article was reported in Vol 112(4) of Behavioral Neuroscience (see record 2008-09590-001). Figure 1 (page 295) and Figure 4 (page 299) were printed incorrectly. The corrected figure pages and corresponding captions are provided in the erratum.] The present study examined the effects of quinolinic acid lesions of the dorsal anterior cingulate and prelimbic–infralimbic cortices on spatial working memory and spatial discrimination using go/no-go procedures. All testing occurred in a 12-arm radial maze. In a working memory task, rats were allowed to enter 12 arms for a cereal reward. Three or 4 arms were presented for a 2nd time in a session, which did not result in a reward. In a spatial discrimination task, rats had successive access to 2 different arms. One arm always contained a reward, and the other never contained a reward. Prelimbic–infralimbic lesions impaired spatial working memory but only produced a transient spatial discrimination deficit. Dorsal anterior cingulate lesions did not induce a deficit in either task. These findings suggest that the prelimbic–infralimbic cortices, but not the anterior cingulate cortex, are important in spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditional stimulus probability and activity of hippocampal, cingulate cortical, and limbic thalamic neurons during avoidance conditioning in rabbits.

Multi-unit and field potential responses in the anterior (AC) and posterior cingulate cortices (PC), dentate gyrus (DG), and anterior ventral (AV) and medial dorsal (MD) thalamic nuclei of rabbits were recorded during acquisition and performance of a locomotor conditioned response (CR). The CR, stepping in an activity wheel in response to a tone (conditioned stimulus [CS+]), prevented the occurrence of a shock unconditioned stimulus (UCS) scheduled 5 sec after CS+ onset. Ss also learned to ignore a different tone (CS–), not predictive of the UCS. Training was given daily until behavioral discrimination reached criterion. After criterion, asymmetric probability (AP) sessions were given that were the same as the conditioning session except for probability manipulation. A significant discriminative response developed in all regions during behavioral acquisition. The unit response in the AP session was enhanced in all areas by rare presentation of the CS–, compared with the equal and frequent CS– conditions. Rare presentation of the CS+ enhanced the unit response in the AC, PC, and DG, but it suppressed the firing of AV and MD neurons. Rare CS+ presentations did not alter AV and PC neuronal activity in Ss with subicular lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)