Activation of adenosine receptors in the posterior cingulate cortex impairs memory retrieval in the rat

Adenosine A1 and A2A receptor agonists and antagonists have been reported to alter learning and memory. The aim of our study was to investigate the involvement of adenosinergic system in memory retrieval into posterior cingulate cortex (PCC) of Wistar rats. To clarify this question, we tested specifics agonist and antagonists of adenosine A1 and A2A receptors in rats submitted to a one-trial inhibitory avoidance task. The stimulation of adenosine A1 and A2A receptors by CPA and CGS21680, respectively, impaired memory retrieval for inhibitory avoidance task, into PCC. These findings provide behavioral evidence for the role of adenosinergic system in the memory retrieval into PCC.     

Cognitive and emotional influences in anterior cingulate cortex

Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.     

Involvement of the rat anterior cingulate cortex in control of instrumental responses guided by reward expectancy

The anterior cingulate cortex (ACC) plays a critical role in stimulus-reinforcement learning and reward-guided selection of actions. Here we conducted a series of experiments to further elucidate the role of the ACC in instrumental behavior involving effort-based decision-making and instrumental learning guided by reward-predictive stimuli. In Experiment 1, 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 (four pellets) in one arm or a low reward (two pellets) in the other with no barrier present. In line with previous studies, our data reveal that rats with quinolinic acid lesions of the ACC selected the response involving less work and smaller reward. Experiment 2 demonstrates that breaking points of instrumental performance under a progressive ratio schedule were similar in sham-lesioned and ACC-lesioned rats. Thus, lesions of the ACC did not interfere with the effort a rat is willing to expend to obtain a specific reward in this test. In a subsequent task, we examined effort-based decision-making in a lever-press task where rats had the choice between pressing a lever to receive preferred food pellets under a progressive ratio schedule, or free feeding on a less preferred food, i.e. lab chow. Results show that sham- and ACC-lesioned animals had similar breaking points and ingested comparable amounts of less-preferred food. Together, the results of Experiment 1 and 2 suggest that the ACC plays a role in evaluating how much effort to expend for reward; however, the ACC is not necessary in all situations requiring an assessment of costs and benefits. In Experiment 3 we investigated learning and reversal learning of instrumental responses guided by reward predictive stimuli. A reaction time (RT) task demanding conditioned lever release was used in which the upcoming reward magnitude (five vs. one food pellet) was signalled in advance by discriminative visual stimuli. Results revealed that rats with ACC lesions were able to discriminate reward magnitude-predictive stimuli and to adapt instrumental behavior to reversed stimulus-reward magnitude contingencies. Thus, in a simple discrimination task as used here, the ACC appears not to be required to discriminate reward magnitude-predictive stimuli and to use the learned significance of the stimuli to guide instrumental behavior.     

Anterior cingulate cortex in schema assimilation and expression

In humans and in animals, mental schemas can store information within an associative framework that enables rapid and efficient assimilation of new information. Using a hippocampal-dependent paired-associate task, we now report that the anterior cingulate cortex is part of a neocortical network of schema storage with NMDA receptor-mediated transmission critical for information updating, and AMPA receptor-mediated transmission required for the expression and updating of stored information.     

Emotional processing in anterior cingulate and medial prefrontal cortex

Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal-caudal cognitive and ventral-rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal-caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral-rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions.     

Expectations,gains, and losses in the anterior cingulate cortex

The anterior cingulate cortex (ACC) participates in evaluating actions and outcomes. Little is known on how action-reward values are processed in ACC and if the context in which actions are performed influences this processing. In the present article, we report ACC unit activity of monkeys performing two tasks. The first task tested whether the encoding of reward values is context dependent—that is, dependent on the size of the other rewards that are available in the current block of trials. The second task tested whether unexpected events signaling a change in reward are represented. We show that the context created by a block design (i.e., the context of possible alternative rewards) influences the encoding of reward values, even if no decision or choice is required. ACC activity encodes the relative and not absolute expected reward values. Moreover, cingulate activity signals and evaluates when reward expectations are violated by unexpected stimuli, indicating reward gains or losses.     

The subgenual anterior cingulate cortex in mood disorders

The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.     

Risk prediction and aversion by anterior cingulate cortex

The recently proposed error-likelihood hypothesis suggests that anterior cingulate cortex (ACC) and surrounding areas will become active in proportion to the perceived likelihood of an error. The hypothesis was originally derived from a computational model prediction. The same computational model now makes a further prediction that ACC will be sensitive not only to predicted error likelihood, but also to the predicted magnitude of the consequences, should an error occur. The product of error likelihood and predicted error consequence magnitude collectively defines the general “expected risk” of a given behavior in a manner analogous but orthogonal to subjective expected utility theory. New fMRI results from an incentive change signal task now replicate the errorlikelihood effect, validate the further predictions of the computational model, and suggest why some segments of the population may fail to show an error-likelihood effect. In particular, error-likelihood effects and expected risk effects in general indicate greater sensitivity to earlier predictors of errors and are seen in risk-averse but not risktolerant individuals. Taken together, the results are consistent with an expected risk model of ACC and suggest that ACC may generally contribute to cognitive control by recruiting brain activity to avoid risk.     

Cognitive deficits, schizophrenia, and the anterior cingulate cortex

Cognitive deficits are thought to be responsible for some of the symptoms and dysfunction in schizophrenia. Recent research on the anterior cingulate cortex supports this assumption. More detailed and definitive evidence for this association will require identification of specific neural networks whose abnormal structure, connections or activity create the cognitive deficits in question.     

Personality predicts working-memory-related activation in the caudal anterior cingulate cortex

Behavioral studies suggest that two affective dimensions of personality are associated with working memory (WM) function. WM load is known to modulate neural activity in the caudal anterior cingulate cortex (ACC), a brain region critical for the cognitive control of behavior. On this basis, we hypothesized that neural activity in the caudal ACC during a WM task should be associated with personality: correlated negatively with behavioral approach sensitivity (BAS) and positively with behavioral inhibition sensitivity (BIS). Using functional magnetic resonance imaging, we measured brain activity in 14 participants performing a three-back WM task. Higher self-reported BAS predicted better WM performance (r = .27) and lower WM-related activation in the caudal ACC (r = -.84), suggesting personality differences in cognitive control. The data bolster approach-withdrawal (action control) theories of personality and suggest refinements to the dominant views of ACC and personality.     

Probing human and monkey anterior cingulate cortex in variable environments

Previous research has identified the anterior cingulate cortex (ACC) as an important node in the neural network underlying decision making in primates. Decision making can, however, be studied under a large variety of circumstances, ranging from the standard well-controlled lab situation to more natural, stochastic settings, in which multiple agents interact. Here, we illustrate how these different varieties of decision making studied can influence theories of ACC function in monkeys. Converging evidence from unit recordings and lesion studies now suggest that the ACC is important for interpreting outcome information according to the current task context to guide future action selection. We then apply this framework to the study of human ACC function and discuss its potential implications.     

Motivation of extended behaviors by anterior cingulate cortex

Intense research interest over the past decade has yielded diverse and often discrepant theories about the function of anterior cingulate cortex (ACC). In particular, a dichotomy has emerged between neuropsychological theories suggesting a primary role for ACC in motivating or 'energizing' behavior, and neuroimaging-inspired theories emphasizing its contribution to cognitive control and reinforcement learning. To reconcile these views, we propose that ACC supports the selection and maintenance of 'options' - extended, context-specific sequences of behavior directed toward particular goals - that are learned through a process of hierarchical reinforcement learning. This theory accounts for ACC activity in relation to learning and control while simultaneously explaining the effects of ACC damage as disrupting the motivational context supporting the production of goal-directed action sequences.     

Conflict monitoring and anterior cingulate cortex: an update

One hypothesis concerning the human dorsal anterior cingulate cortex (ACC) is that it functions, in part, to signal the occurrence of conflicts in information processing, thereby triggering compensatory adjustments in cognitive control. Since this idea was first proposed, a great deal of relevant empirical evidence has accrued. This evidence has largely corroborated the conflict-monitoring hypothesis, and some very recent work has provided striking new support for the theory. At the same time, other findings have posed specific challenges, especially concerning the way the theory addresses the processing of errors. Recent research has also begun to shed light on the larger function of the ACC, suggesting some new possibilities concerning how conflict monitoring might fit into the cingulate's overall role in cognition and action.     

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

Animals 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 animals' reactivity and aggressiveness were evaluated 5 min before, during, and 5 min after stimulation at 20 micronA (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 animals. Further tests with stimulation of the lateral septum at the 20-micronA 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.     

Contrasting roles for cingulate and orbitofrontal cortex in decisions and social behaviour

There is general acknowledgement that both the anterior cingulate and orbitofrontal cortex are implicated in reinforcement-guided decision making, and emotion and social behaviour. Despite the interest that these areas generate in both the cognitive neuroscience laboratory and the psychiatric clinic, ideas about the distinctive contributions made by each have only recently begun to emerge. This reflects an increasing understanding of the component processes that underlie reinforcement-guided decision making, such as the representation of reinforcement expectations, the exploration, updating and representation of action values, and the appreciation that choices are guided not just by the prospect of reward but also by the costs that action entails. Evidence is emerging to suggest that the anterior cingulate and orbitofrontal cortex make distinct contributions to each of these aspects of decision making.