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. (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)     

Dissociable effects of selective lesions to hippocampal subsystems on exploratory behavior, contextual learning, and spatial learning.

Rats received excitotoxic lesions of different subsystems within the hippocampal system--either the hippocampus proper (cornu ammonis and dentate gyrus; hippocampal lesions) or the entorhinal cortex-subicular region (entorhinal lesions). Subsequently, their activity in an operant chamber was monitored both before and after footshock had been delivered (Experiment 1). Rats with hippocampal lesions showed enhanced activity before the delivery of footshock and reduced freezing after the delivery of shock. Rats with entorhinal lesions showed control levels of activity before the delivery of footshock and control levels of freezing after the delivery of footshock. Both types of lesion impaired spatial learning in a water maze (Experiment 2). These results suggest that the deficits arising from damage to the hippocampal system in contextual and spatial learning have different origins. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Afferent connections of the medial frontal cortex of the rat. II. Cortical and subcortical afferents

In order to compare the frontal cortex of rat and macaque monkey, cortical and subcortical afferents to subdivisions of the medial frontal cortex (MFC) in the rat were analyzed with fluorescent retrograde tracers. In addition to afferent inputs common to the whole MFC, each subdivision of the MFC has a specific pattern of afferent connections. The dorsally situated precentral medial area (PrCm) was the only area to receive inputs from the somatosensory cortex. The specific pattern of afferents common to the ventrally situated prelimbic (PL) and infralimbic (IL) areas included projections from the agranular insular cortex, the entorhinal and piriform cortices, the CA1-CA2 fields of the hippocampus, the subiculum, the endopiriform nucleus, the amygdalopiriform transition, the amygdalohippocampal area, the lateral tegmentum, and the parabrachial nucleus. In all these structures, the number of retrogradely labeled cells was larger when the injection site was located in area IL. The dorsal part of the anterior cingulate area (ACd) seemed to be connectionally intermediate between the adjacent areas PrCm and PL; it receives neither the somatosensory inputs characteristic of area PrCm nor the afferents characteristic of areas PL and IL, with the exception of the afferents from the caudal part of the retrosplenial cortex. A comparison of the pattern of afferent and efferent connections of the rat MFC with the pattern of macaque prefrontal cortex suggests that PrCm and ACd areas share some properties with the macaque premotor cortex, whereas PL and IL areas may have characteristics in common with the cingulate or with medial areas 24, 25, and 32 and with orbital areas 12, 13, and 14 of macaques.     

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)     

Some tests of response habituation in rats with discrete lesions to the orbital or medial frontal cortex.

Studied the inter- and intrasession habituation rates of 33 male albino rats with aspiration lesions to the medial frontal or orbital frontal cortex or with no lesions in 2 situations (open field and investigatory head poke). Medial frontal lesions produced impaired intrasession habituation in both test situations, while orbital frontal lesions failed to alter significantly intrasession habituation in either situation, and neither lesion significantly altered intersession habituation rates. Data confirm earlier reports of functional dissociation within the prefrontal cortex of the rat and suggest that only the medial frontal cortex is involved in the habituation process. (French summary) (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of amphetamine and food deprivation on self-stimulation of the lateral hypothalamus and medial frontal cortex.

Intracranial self-stimulation of the lateral hypothalamus in 5 male Sprague-Dawley rats was markedly increased by subcutaneous dextroamphetamine administration and by food deprivation. In contrast, similar self-stimulation response rates obtained in the same Ss from the medial frontal cortex were unaffected by food deprivation and only slightly increased by dextroamphetamine administration. Furthermore, a large difference between dextro- vs levoamphetamine on response rate was obtained for lateral hypothalamic but not for medial frontal cortex self-stimulation. Results are consistent with a noradrenergic self-stimulation system for the lateral hypothalamus. Medial frontal cortex self-stimulation, however, appears to be mediated by a neuroanatomical and neurochemical system different from that of the lateral hypothalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison between the effects of medial septal lesions and entorhinal cortex lesions on performance of nonspatial working memory tasks and reversal learning

Two studies explored the relationship between cognitions and long-term symptoms in adult child sexual abuse (CSA) survivors. In Study 1, an American sample of 43 survivors completed questionnaires assessing attributional style and dysfunctional beliefs in cognitive themes affected by victimization, as well as measures of posttraumatic symptoms. Survivors' attributions of negative events were more internal, stable, and global than those of 29 comparison subjects without a history of CSA. However, only the globality scale was significantly related with severity of long-term symptoms. High correlations between dysfunctional beliefs concerning safety, trust, esteem, or intimacy, and posttrauma symptoms were found. The latter finding was replicated in Study 2 with a German sample of 35 CSA survivors, even when controlling for frequency of abuse.     

Double dissociation of effects on learning of medial versus lateral hyperstriatal lesions in pigeons.

Three experiments examined the effects of medial and lateral hyperstriatal lesions in two groups of pigeons. In Experiment 1, both hyperstriatal groups were impaired, relative to unoperated and operated control groups, in postoperative performance of preoperatively acquired serial reversal of both spatial and visual discriminations. The deficits of the two hyperstriatal groups appeared both quantitatively and qualitatively similar. Experiment 2 found that performance of spatial reversals was disrupted in the medial, but not in the lateral, hyperstriatal group by a long intertrial interval. Experiment 3 found that acquisition of simultaneous matching-to-sample was disrupted by lateral, but not by medial, hyperstriatal lesions; the lateral group also showed a lower rate of response to the sample stimulus than any of the other groups. Implications of these findings for current theories of hyperstriatal function are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the effects of frontal cortical and thalamic lesions on measures of olfactory learning and memory in the rat

Rats were trained on an olfactory continuous delayed nonmatching-to-sample (DNMTS) task and then given 1 of 4 treatments: sham surgery or radio-frequency lesion of the lateral internal medullary lamina of the thalamus or of the frontal cortex along the medial wall or dorsal to the rhinal sulcus. Thalamic lesions produced persistent deficits on the continuous DNMTS task, and both the cortical lesions resulted in transient impairments that disappeared with continued training. Manipulations of stimulus set size and the delay between trials affected continuous DNMTS performance but did not exacerbate group differences. All 3 lesion groups performed normally when next trained on a discrimination task with odorants and go-no-go procedures comparable to continuous DNMTS. These results indicate that lesions did not affect ability to perform go-no-go procedures, to discriminate among odorants, or to use reference memory to respond on the basis of a fixed stimulus-response rule.     

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)     

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.     

Dissociation of attention in learning and action: Effects of lesions of the amygdala central nucleus, medial prefrontal cortex, and posterior parietal cortex.

Many associative learning theories assert that the predictive accuracy of events affects the allocation of attention to them. More reliable predictors of future events are usually more likely to control action based on past learning, but less reliable predictors are often more likely to capture attention when new information is acquired. Previous studies showed that a circuit including the amygdala central nucleus (CEA) and the cholinergic substantia innominata/nucleus basalis magnocellularis (SI/nBM) is important for both sustained attention guiding action in a five-choice serial reaction time (5CSRT) task and for enhanced new learning about less predictive cues in a serial conditioning task. In this study, the authors found that lesions of the cholinergic afferents of the medial prefrontal cortex interfered with 5CSRT performance but not with surprise-induced enhancement of learning, whereas lesions of cholinergic afferents of posterior parietal cortex impaired the latter effects but did not affect 5CSRT performance. CEA lesions impaired performance in both tasks. These results are consistent with the view that CEA affects these distinct aspects of attention by influencing the activity of separate, specialized cortical regions via modulation of SI/nBM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Retrograde degeneration of thalamic neurons in the mediodorsal nucleus after neonatal and adult aspiration lesions of the medial prefrontal cortex in the rat. Implications for mechanisms of functional recovery

The behavioural consequences of neonatal lesions of the frontal cortex are limited as compared with similar lesions performed in adulthood. The present study has investigated, using unbiased quantitative methods with randomized systematic sampling, the total neuronal cell numbers in the mediodorsal nucleus of the thalamus after aspiration lesions of the medial prefrontal cortex performed in neonatal and in adult rats. It was found that the reduction in total cell numbers after neonatal prefrontal cortex lesions was similar to that found after adult cortex lesions. In neonatally lesioned animals the neuronal cell density was significantly increased by 13%, whereas in adult lesioned animals it was unchanged. On the other hand, the volume of the mediodorsal nucleus was reduced by 27% in neonatally, and 20% in adult lesioned animals. Total neuronal cell number of the mediodorsal nucleus was significantly decreased in neonatally as well as in adult lesioned rats, by 14% and 21%, respectively. These findings are discussed in the light of the previously proposed role of the thalamus as a neural substrate of functional sparing after neonatal cortical lesions.     

Comparisons of behavioral effects of hippocampal and prefrontal cortex lesions in the rat.

5 groups of 5 male Wistar rats each, with aspiration lesions of dorsomedial frontal cortex, ventrolateral frontal cortex, hippocampus, or posterior cortex, or with sham operations, were tested in 5 behavioral situations: emotionality assessment, serial spatial reversals, 70:30 spatial probability, differential reinforcement of low rates (DRL), and barpress extinction. Ss with posterocortical lesions did not differ from operated controls on any task. The effects of lesions in the 2 anatomically defined frontal subfields were clearly dissociated on spatial reversals, spatial probability, and DRL. Lesions in either subfield produced a significant increase in emotionality relative to controls, and neither lesion affected barpress extinction. Results suggest that both frontal subfields may be functionally related to the hippocampus but in different ways. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation of egocentric and allocentric space following medial prefrontal and parietal cortex lesions in the rat.

Animals with medial prefrontal cortex or parietal cortex lesions and sham-operated and non-operated controls were tested for the acquisition of an adjacent arm task that accentuated the importance of egocentric spatial lateralization and a cheese board task that accentuated the importance of allocentric spatial localization. Results indicated that relative to controls, animals with medial prefrontal cortex lesions are impaired on the adjacent arm task but displayed facilitation on the cheese board task. In contrast, relative to controls, rats with parietal cortex lesions are impaired on the cheese board task but show no impairment on the adjacent arm task. The data suggest a double dissociation of function between medial prefrontal cortex and parietal cortex in terms of coding of egocentric versus allocentric spatial information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of perirhinal cortex ablation and crossed unilateral lesions of the medial forebrain bundle from the inferior temporal cortex in the rhesus monkey: Effects on learning and retrieval.

Seven monkeys learned new object-reward associations and scene problems and were overtrained on 100 problems of each type. Four monkeys received crossed lesions of the medial forebrain bundle (MFB) and inferior temporal cortex, with the later addition of a fornix section ipsilateral to the MFB lesion. The remaining 3 monkeys received bilateral perirhinal cortex ablation. Disconnection of the MFB from the inferior temporal cortex impaired postoperative new learning, but the retrieval of problems overtrained preoperatively was relatively preserved. Subjects with perirhinal cortex ablation were severely impaired in new learning and at the retrieval of scene problems, but retention of object-reward associations was relatively well preserved. The results support the hypothesis that isolation of the inferior temporal cortex from basal forebrain and midbrain afferents results in dense anterograde amnesia, whereas the role of the perirhinal cortex in learning is dependent on the perceptual difficulty of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suppression of VMH-lesion-induced reactivity and aggressiveness in the rat by stimulation of lateral septum, but not medial septum or cingulate cortex.

32 male hooded rats made vicious with bilateral ventromedial hypothalamic lesions had bipolar electrodes implanted unilaterally in the lateral septum, medial septum, or cingulate cortex. Four days later, the Ss' reactivity and aggressiveness were evaluated 5 min before, during, and 5 min after stimulation at 20 muA (60 Hz, sine wave). Lateral septal stimulation suppressed reactivity and aggressiveness by almost 80% compared with pre- and poststimulation levels. Stimulation of neither the cingulate cortex nor the medial septum produced a change reliably different from that seen in unstimulated control Ss. Further tests with stimulation of the lateral septum at the 20 muA level showed that neither rewarding self-stimulation nor disruption of ongoing water drinking was produced. These results are congruent with evidence from lesion studies that the lateral septum normally acts to suppress reactivity and aggressiveness in the rat; they do not support previous suggestions that the medial septum is involved in the modulation of these behaviors. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Implications of emotion regulation for the shift from normative fear-relevant learning to anxiety-related psychopathology.

Replies to the article by Mineka and Zinbarg (see record 2006-00920-002), which illustrated how a contemporary learning theory informs the etiology and maintenance of anxiety disorders. In our view, the challenge facing contemporary learning theory is to explain how and why potentiated fear conditioning is problematic and capable of yielding an anxiety disorder. Neither potentiated fear and fear learning itself, nor individual differences that potentiate both, explain how an anxiety disorder develops. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive resources and dual-task interference effects at retrieval in normal people: The role of the frontal lobes and medial temporal cortex.

Conducted 3 experiments to examine the hypothesis that concurrent secondary tasks at retrieval will interfere more with long-term, episodic memory functions involving the frontal lobes than those involving the medial temporal lobes hippocampus (MTL/H). The rationale is that strategic retrieval processes mediated by the frontal lobes place greater demands on cognitive resources than do relatively automatic associative retrieval processes (ecphory) mediated by the temporal lobes. In Exps 1 and 2, sequential finger tapping was performed at encoding, at retrieval, at both, or at neither. Recall of a categorized list of 16 words from the California Verbal Learning Test in Exp 1, and release from proactive inhibition (PI) in Exp 2, both being tests that involve the frontal lobes, were impaired if normal Ss tapped at both encoding and retrieval. Concurrent tapping had little effect on rate of learning in Exp 1 and on total words recalled during the buildup of PI in Exp 2, both of which are indices that are affected more by MTL/H than by frontal lesions. In Exp 3, tapping by normal Ss affected letter fluency, a test more sensitive to frontal lobe than temporal lobe damage, but not category fluency, for which the reverse is true. (PsycINFO Database Record (c) 2010 APA, all rights reserved)