Dissociation between conflict detection and error monitoring in the human anterior cingulate cortex

The relative importance of the anterior cingulate cortex (ACC) for the detection and resolution of response conflicts versus its role in error monitoring remains under debate. One disputed issue is whether conflict detection and error monitoring can be viewed as unitary functions performed by the same region of the ACC, or whether these processes can be dissociated functionally and anatomically. We used a combination of electrophysiological and neuropsychological methods to assess these competing hypotheses. A neurological patient with a rare focal lesion of rostral-to-middorsal ACC was tested in an event-related potential study designed to track the time course of neural activity during conflicts and erroneous responses. Compared with controls, the error-related negativity component after incorrect responses was attenuated in the patient, accompanied by lower error-correction rates. Conversely, the stimulus-locked component on correct conflict trials, the N450, was enhanced, and behavioral performance was impaired. We hypothesize that intact regions of lateral prefrontal cortex were able to detect response conflict, but damage to the dorsal ACC impaired response inhibition, which may be due to disconnection from cingulate and supplementary motor areas. The results implicate rostral-dorsal ACC in error monitoring and suggest this function can be dissociated from conflict-detection processes.     

Anticipation of conflict monitoring in the anterior cingulate cortex and the prefrontal cortex

The anterior cingulate cortex (ACC) has been suggested as a monitoring center that is responsible for online detection of response conflicts. In this view, the conflict signal detected by the ACC is transmitted to other brain regions, such as the dorsal part of the lateral prefrontal cortex (lPFC), to increase the level of cognitive control. In this functional MRI (fMRI) study, we examined the conflict resolution that goes beyond online detection of response conflicts. Participants learned pseudoarithmetic problem-solving tasks that involve stimulus-response mapping rules with high or low conflicts. On half of the trials, participants had a preview of the upcoming operator that allowed advance preparation for the mapping rules. The preview significantly reduced the conflict effects on latency. During the preview, both the ACC and lPFC were activated in anticipation of conflict, and this anticipatory activation was highly predictive of the subsequent latency. These results suggest that the ACC and lPFC are responsible for both anticipatory preparation and online adjustment in response to conflicts. The results also confirm the roles of the lPFC and ACC in managing conflict during problem solving and extend these roles to include responding to anticipation of conflicts that may arise between incompatible stimulus-response mappings maintained in working memory during preparation.     

Dorsal anterior cingulate cortex: A role in reward-based decision making

Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (P < 10(-4)) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew > or = FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control.     

Dissociable effects of surprise and model update in parietal and anterior cingulate cortex

Brains use predictive models to facilitate the processing of expected stimuli or planned actions. Under a predictive model, surprising (low probability) stimuli or actions necessitate the immediate reallocation of processing resources, but they can also signal the need to update the underlying predictive model to reflect changes in the environment. Surprise and updating are often correlated in experimental paradigms but are, in fact, distinct constructs that can be formally defined as the Shannon information (I_S) and Kullback–Leibler divergence (D_KL) associated with an observation. In a saccadic planning task, we observed that distinct behaviors and brain regions are associated with surprise/I_S and updating/D_KL. Although surprise/I_S was associated with behavioral reprogramming as indexed by slower reaction times, as well as with activity in the posterior parietal cortex [human lateral intraparietal area (LIP)], the anterior cingulate cortex (ACC) was specifically activated during updating of the predictive model (D_KL). A second saccade-sensitive region in the inferior posterior parietal cortex (human 7a), which has connections to both LIP and ACC, was activated by surprise and modulated by updating. Pupillometry revealed a further dissociation between surprise and updating with an early positive effect of surprise and late negative effect of updating on pupil area. These results give a computational account of the roles of the ACC and two parietal saccade regions, LIP and 7a, by which their involvement in diverse tasks can be understood mechanistically. The dissociation of functional roles between regions within the reorienting/reprogramming network may also inform models of neurological phenomena, such as extinction and Balint syndrome, and neglect.In a nonrandom environment, brains can and should make use of past experience to facilitate the processing of incoming sensory information and the selection of actions, through prediction (1, 2). An important aspect of brain function is therefore the construction and tuning of internal models to represent statistics of the environment that are relevant for future behavior.The use of predictive internal models implies that not only are some events well predicted (high probability under the model) but, conversely, some events (which have a low probability under the model) are surprising (3). Surprising events may be associated with behavioral costs; for example, although valid attentional cues speed reaction times (RTs), invalid cues lengthen them (3, 4). However, surprising events can have a further significance for the observer in that they sometimes provide evidence for a change in the environment, which would imply a need to update the brain’s internal models to predict future events accurately.Here, we explore the possibility that the brain carries out at least two distinct operations when a surprising event occurs: (i) within trial reorienting processes evoked by surprise, including reallocation of resources to a previously deprioritized region of space and/or replanning a motor response to an unexpected stimulus, and (ii) between-trial processes, particularly the possible need to update the internal model to predict future observations accurately in a changeable environment.The within- and between-trial processes could be broadly characterized in terms of surprise (or rather the reprogramming/reorienting response caused by the surprising stimulus) and updating (of the entire model), respectively. Consider, for example, the classic Posner orienting task (3), in which the locations of visual events are predicted either explicitly by symbolic cues or implicitly by the fact that targets appear more frequently in certain locations. Invalidly cued (surprising) targets evoke behavioral reorienting (redirecting of attention or gaze to the surprising target location), but they may also cause the participant to update his/her beliefs about the probable locations of future targets.Information theory gives distinct definitions of surprise and updating that formalize the distinction between the surprise (and consequent behavioral reorienting) evoked by a particular stimulus and updating of the overall model of the environment.In information theory, the surprise associated with a particular stimulus value, α, is characterized by its Shannon information [I_S(α)]:where p(α|prior) is the prior probability that the observation α would be made, given the brain’s internal model just before the data point was observed. Therefore, the I_S captures how unexpected or unlikely a particular observation is, given the internal model.In contrast, updating of the internal model is captured by the Kullback–Leibler divergence (D_KL) between the posterior and the prior:where p(α|prior) is the probability that the observation α would be made, given the model just before α was observed, and p(α|post) is the same quantity, given the updated model just after α was observed.As evident in Eq. 2, the D_KL is the probability-weighted average change in the I_S across all possible stimuli as a consequence of updating the model. Hence, although the I_S describes the degree of surprise evoked by observing a particular data point α, the D_KL describes how the model, as a whole, is updated as a consequence of observing α.Although surprise and updating have distinct computational definitions, they are usually strongly correlated in experimental paradigms. As already noted, invalid targets in a Posner paradigm could evoke just surprise or both surprise and updating, depending on the task design. More theoretically, in temporal difference learning (5), the updating of action or stimulus values is driven by prediction error (surprise). Furthermore, the terminology used is confusing because the D_KL (updating of the model) has been described as “Bayesian” surprise (6). Note, however, that the constructs are behaviorally dissociable: Surprise need not necessarily lead to updating, and updating can be triggered without surprise. The relationship between surprise and updating depends, among other things, on the learning rate (7), the degree of expected stochasticity in the environment (8, 9), and the expected frequency or rate of change in the underlying environment (10). Furthermore, there exist scenarios in which we might hypothesize that updating should be triggered in the absence of surprising observations; for example, if the observer moves into a new context in which he knows a priori that his old internal models are unlikely to be valid (11).In the present study, we wished to investigate the neural mechanisms by which expectations (internal models) are updated, as distinct from the mechanisms by which the immediate behavioral response is reprogrammed to a surprising stimulus. We used saccadic planning as a context in which to investigate this problem.The choice of a saccadic planning task was motivated as follows. First, spatial attention and saccadic planning are clear examples of predictive models, in which the violation of predictions (as in invalid trials on a Posner task) evokes a process of behavioral reorienting that is measurable in terms of RT costs (3).Second, the neural nature of predictive models over saccadic target locations (the representations to be updated) is relatively well understood. Networks of spatially tuned cells in macaque parietal cortex represent maps over space of variables relevant to saccadic planning, such as the probability of targets appearing or the reward value associated with making a saccade to different points in space (12–15).Finally, the contrast between saccadic reprogramming (as evoked by surprise) and updating of internal models has intriguing parallels in the neurological literature. Although it is generally recognized that the posterior parietal cortex plays a key role in control of eye movements and spatial attention, it has long been noted that there is a fundamental difference between the neurological syndromes that follow damage to the intraparietal sulcus (IPS), including the lateral intraparietal area (LIP), and to the inferior parietal lobule (IPL) (16, 17). On the one hand, impairments in the ability to reorient or redirect the eyes (18) in Balint syndrome or the covert focus of attention (4) in the extinction syndrome, for example, are associated with damage to the IPS that includes the LIP. By contrast, the quite distinct syndrome of neglect is associated with damage to the IPL (16, 19). In the neglect syndrome, patients’ problems cannot be described as simply the inability to reorient to the neglected visual field when two stimuli are present as is the case in extinction. Instead, patients with the neglect syndrome are unable to acquire, despite experience and instruction, an expectation of any event of significance in the neglected field.We developed a paradigm in which participants made speeded saccades to visual targets, the locations of which could be predicted by estimating their underlying spatial distribution. To dissociate the neural processes associated with surprise and updating in the experimental paradigm, we used a simple manipulation of the relevance of surprising targets in terms of the extent to which they predicted the locations of future targets, so that both surprise (probability of observations under the internal model) and updating (change in the internal model) varied independently across trials. Using functional MRI (fMRI) and behavioral measures, including pupillometry, we observed both neural and behavioral dissociations between surprise and the updating of an internal model.     

Theta-activity in anterior cingulate cortex predicts task rules and their adjustments following errors

Accomplishing even simple tasks depend on neuronal circuits to configure how incoming sensory stimuli map onto responses. Controlling these stimulus-response (SR) mapping rules relies on a cognitive control network comprising the anterior cingulate cortex (ACC). Single neurons within the ACC convey information about currently relevant SR mapping rules and signal unexpected action outcomes, which can be used to optimize behavioral choices. However, its functional significance and the mechanistic means of interaction with other nodes of the cognitive control network remain elusive and poorly understood. Here, we report that core aspects of cognitive control are encoded by rhythmic theta-band activity within neuronal circuits in the ACC. Throughout task performance, theta-activity predicted which of two SR mapping rules will be established before processing visual target information. Task-selective theta-activity emerged particularly early during those trials, which required the adjustment of SR rules following an erroneous rule representation in the preceding trial. These findings demonstrate a functional correlation of cognitive control processes and oscillatory theta-band activity in macaque ACC. Moreover, we report that spike output of a subset of cells in ACC is synchronized to predictive theta-activity, suggesting that the theta-cycle could serve as a temporal reference for coordinating local task selective computations across a larger network of frontal areas and the hippocampus to optimize and adjust the processing routes of sensory and motor circuits to achieve efficient sensory-motor control.     

Trace but not delay fear conditioning requires attention and the anterior cingulate cortex

Higher cognitive functions such as attention have been difficult to model in genetically tractable organisms. In humans, attention-distracting stimuli interfere with trace but not delay conditioning, two forms of associative learning. Attention has also been correlated with activation of anterior cingulate cortex (ACC), but its functional significance is unclear. Here we show that a visual distractor interferes selectively with trace but not delay auditory fear conditioning in mice. Trace conditioning is associated with increased neuronal activity in ACC, as assayed by relative levels of c-fos expression, and is selectively impaired by lesions of this structure. The effects of the ACC lesions are unlikely to be caused by indirect impairment of the hippocampus, which is required for mnemonic aspects of trace conditioning. These data suggest that trace conditioning may be useful for studying neural substrates of attention in mice, and implicate the ACC as one such substrate.     

Successful choice behavior is associated with distinct and coherent network states in anterior cingulate cortex

Successful decision making requires an ability to monitor contexts, actions, and outcomes. The anterior cingulate cortex (ACC) is thought to be critical for these functions, monitoring and guiding decisions especially in challenging situations involving conflict and errors. A number of different single-unit correlates have been observed in the ACC that reflect the diverse cognitive components involved. Yet how ACC neurons function as an integrated network is poorly understood. Here we show, using advanced population analysis of multiple single-unit recordings from the rat ACC during performance of an ecologically valid decision-making task, that ensembles of neurons move through different coherent and dissociable states as the cognitive requirements of the task change. This organization into distinct network patterns with respect to both firing-rate changes and correlations among units broke down during trials with numerous behavioral errors, especially at choice points of the task. These results point to an underlying functional organization into cell assemblies in the ACC that may monitor choices, outcomes, and task contexts, thus tracking the animal's progression through “task space.”     

Lateral inferior prefrontal cortex and anterior cingulate cortex are engaged at different stages in the solution of insight problems

Two studies used puzzles that required participants to find a word that satisfied a set of constraints. The first study used a remote-association task, where participants had to find a word that would form compound words with 3 other words. The second study required participants to complete a word fragment with an associate of another word. Both studies produced distinct patterns of activity in the lateral inferior prefrontal cortex (LIPFC) and the anterior cingulate cortex (ACC). Activation in the LIPFC rose only as long as the participants were trying to retrieve the solution and dropped off as soon as the solution was obtained. However, activation in the ACC increased upon the retrieval of a solution, reflecting the need to process that solution. The data of the second experiment are fit by an information-processing model that interprets the activity in the LIPFC as reflecting retrieval operations and the activity in the ACC as reflecting subgoal setting.     

Parsing executive processes: strategic vs. evaluative functions of the anterior cingulate cortex

Event-related functional MRI and a version of the Stroop color naming task were used to test two conflicting theories of anterior cingulate cortex (ACC) function during executive processes of cognition. A response-related increase in ACC activity was present when strategic processes were less engaged, and conflict high, but not when strategic processes were engaged and conflict reduced. This is inconsistent with the widely held view that the ACC implements strategic processes to reduce cognitive conflicts, such as response competition. Instead, it suggests that the ACC serves an evaluative function, detecting cognitive states such as response competition, which may lead to poor performance, and representing the knowledge that strategic processes need to be engaged.     

辣椒素在大鼠前扣带回的痛觉调制作用

目的拟阐明辣椒素对吗啡在大鼠大脑前扣带皮层(ACC)中对伤害感受的可能影响。方法利用热板痛觉测试和压力痛觉测试方法、脑内微量注射和统计学技术,测定辣椒素及相关生理活性物质进入ACC后动物对热和压力刺激的痛阈改变,分析辣椒素在ACC镇痛或痛敏作用的影响及机制。结果大鼠端脑前扣带回内微量注射不同剂量的辣椒素对热痛和压痛的感受具有剂量和时间效应。结论大鼠端脑前扣带回内微量注射不同剂量的辣椒素,可产生镇痛或痛敏的不同效应,对热痛的影响甚于压痛。     

The anterior cingulate cortex mediates processing selection in the Stroop attentional conflict paradigm.

Regional cerebral blood flow, an index of local neuronal activity, was measured using positron emission tomography (PET) during the performance of the classic Stroop color/word task in eight healthy right-handed subjects. In the first condition of this paradigm, subjects name the color of the words presented on a video monitor. All the words are the color names congruent to the color presented (e.g., the noun "red" displayed in red color). In the second condition, subjects also name the color of the words presented on the monitor. However, during these trials all words are color names incongruent to the color presented (e.g., the noun "red" displayed in green color). The difference in brain activity between these two conditions (i.e., incongruent minus congruent) could reveal brain systems involved in the attentionally mediated resolution of the conflict between the habitual response of reading words vs. the task demands of naming the color of the words--i.e., the Stroop interference effect. The most robust responses occurred in the anterior cingulate cortex. Other responses noted were in the left premotor cortex, left postcentral cortex, left putamen, supplementary motor area, right superior temporal gyrus, and bilateral peristriate cortices. These data provide support for the role of the anterior cingulate cortex in attentional processing through the selection and recruitment of processing centers appropriate for task execution. Furthermore, the extensive distributed network of activated regions suggests that the Stroop interference effect cannot be explained simply in terms of stimulus encoding or response interference.     

Observation on the resting-state fMRI functional connectivity of the anterior cingulate cortex in unipolar and bipolar depression

<正>Objective To investigate the functional connection(FC) between the anterior cingulate cortex(ACC) and other brain regions in unipolar depression(UD) and bipolar depression(BD),and the correlation to the severity of depressive symptoms.Methods 30 patients who met the diagnosis criteria of unipolar depression in DSM-Ⅳ     

Distinct roles of the anterior cingulate and prefrontal cortex in the acquisition and performance of a cognitive skill

The purpose of the present work is to study the functional roles of two predefined regions of interest: one in the left anterior cingulate cortex (ACC) that seems to reflect goal-relevant control demand, and one in the left prefrontal cortex (PFC) that reflects memory retrieval demand. Two slow event-related brain imaging experiments were conducted, adapting a cognitive skill acquisition paradigm. Experiment 1 found that both left ACC and left PFC activity increased parametrically with task difficulty. Using a slight modification of the same basic paradigm, Experiment 2 attempted to decouple retrieval and control demands over the course of learning. Participants were imaged early in training and again several days later, after substantial additional training in the task. There was a clear dissociation between activity in the left PFC and the left ACC. Although the PFC region showed a substantial decrease in activity over the course of learning, reflecting greater ease of retrieval, the ACC showed the opposite pattern of results with significantly greater activity after training, reflecting increased control demand. Moreover, the increased response in the ACC occurred when errors and latencies were smallest.     

Differential involvement of the hippocampus, anterior cingulate cortex, and basolateral amygdala in memory for context and footshock

Extensive evidence from contextual fear conditioning experiments suggests that the hippocampus is involved in processing memory for contextual information. Evidence also suggests that the rostral anterior cingulate cortex (rACC) may be selectively involved in memory for nociceptive stimulation. In contrast, many findings indicate that the basolateral amygdala (BLA) is more broadly involved in modulating the consolidation of different kinds of information. To investigate further the differential involvement of these brain regions in memory consolidation, the present experiments used a modified inhibitory avoidance training procedure that took place on 2 sequential days to separate context training from footshock training. Male Sprague-Dawley rats were implanted with unilateral cannulae aimed at the (i) hippocampus, (ii) rACC, or (iii) BLA, and given infusions of the muscarinic cholinergic agonist oxotremorine (OXO) immediately after either context training (day 1) or footshock training in that context (day 2). OXO enhanced retention when infused into the hippocampus after context, but not footshock, training. Conversely, OXO infusions enhanced memory when administered into the rACC immediately after footshock, but not context, training. Lastly, intra-BLA OXO infusions enhanced retention when administered after either context or footshock training. These findings are consistent with evidence that the hippocampus and rACC play selective roles in memory for specific components of training experiences. Additionally, they provide further evidence that the BLA is more liberally involved in modulating memory consolidation for various aspects of emotionally arousing experiences.     

Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome

BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. METHODS: Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. RESULTS: Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. CONCLUSIONS: The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.     

Metabolic changes of anterior cingulate cortex in patients with hepatic cirrhosis: A magnetic resonance spectroscopy study

Aim: The anterior cingulate cortex (ACC) plays an important role in cognitive functions. The purpose of this study is to compare metabolite concentrations in the ACC of cirrhotic patients with normal controls, and to correlate metabolite changes with Child–Pugh class and with severity of hepatic encephalopathy (HE). Methods: Fifty‐two cirrhotic patients and 30 healthy volunteers were included in this study. All subjects performed the number connection test type A (NCT‐A) and digital symbol test (DST) before multiple resonance (MR) examinations. Single‐voxel proton MR spectroscopy (MRS) data in the ACC were acquired on a 1.5‐T scanner. The ratios of all metabolites to creatine and phosphocreatine (Cr) were obtained. Statistical analysis was performed to evaluate the difference between control and cirrhotic patients, with respect to metabolite ratios. The correlation between metabolite ratios and Child–Pugh scale, severity of HE, venous ammonia and neuropsychiatric test results was analyzed. Results: The ratios of choline (Cho)/Cr and myo‐inositol (mIns)/Cr were significantly lower, and the ratio of glutamine– glutamate (Glx)/Cr was significantly higher in cirrhotic patients than those in controls (P < 0.001). mIns/Cr correlated negatively with Child–Pugh scale (r = −0.496, P < 0.001) and HE degree (r = −0.313, P < 0.05). Venous ammonia had a significant correlation with Cho/Cr (r = −0.329, P < 0.05) and mIns/Cr (r = −0.347, P < 0.05). No statistical correlation between metabolite ratios and neuropsychological tests was found for cirrhotic patients, but mIns/Cr did have a statistical correlation with NCT‐A (r = −0.270, P < 0.05) and DST (r = 0.463, P < 0.001) when all subjects were included in the analysis. Conclusion: Significant metabolite changes were seen in the ACC in cirrhotic patients. Of the metabolites examined, the mIns/Cr level in the ACC was most closely associated with the severity of HE and hepatic functional reserve reflected by Child–Pugh scale.