Increased Anterior Cingulate Cortex Activity Research Articles

Intrinsic cerebral activity at resting state in adults with major depressive disorder: A meta-analysis

Numerous neuroimaging studies have been undertaken to detect cerebral intrinsic activity in major depressive disorder (MDD) with resting state fMRI (rs-fMRI). However, the inconsistent results have hindered our understanding of the exact neuropathology related to MDD. The current meta-analysis used state-of-the-art conjunction analysis techniques to systematically review and summarize all available neuroimaging studies using rs-fMRI with amplitude of low frequency fluctuation (ALFF) and/or fractional ALFF (fALFF) on MDD patients and further explored the effect of antidepressants on the intrinsic activity of the brain. The anisotropic effect size version of signed differential mapping (AES-SDM) was applied to investigate changes in ALFF/fALFF in depression. We performed a subgroup analysis and group comparison on medicated and drug naïve patients to detect drug effect on MDD patients and conjunction analysis to identify congruent results between the two methods. Meta-regression was used to explore the effects of demographics and clinical characteristics. Adult MDD patients showed a robust increase in intrinsic activity in the resting state in the anterior cingulate cortex (ACC) in both ALFF (P<0.001) and fALFF (P<0.01) studies. The subgroup analysis demonstrated that the increased activity in the ACC was prominent in medicated patients only and not seen in drug-naïve MDD patients, while medication-naïve patients showed a specific decreased activity in the cerebellum (P<0.01). Group comparison showed that the intrinsic ACC activity is elevated in medicated MDD patients compared with drug naïve MDD patients. Meta-regression analysis demonstrated that the increased ACC activation was positively correlated with illness duration (P<0.001). Our findings suggest that increased activity of the ACC is more likely to be associated with antidepressant treatment, while decreased intrinsic activity of the cerebellum might be a specific biomarker for current MDD.

Look who's judging—Feedback source modulates brain activation to performance feedback in social anxiety

It is as yet unknown if behavioral and neural correlates of performance monitoring in socially anxious individuals are affected by whether feedback is provided by a person or a computer. This fMRI study investigated modulation of feedback processing by feedback source (person vs. computer) in participants with high (HSA) (N=16) and low social anxiety (LSA) (N=16). Subjects performed a choice task in which they were informed that they would receive positive or negative feedback from a person or the computer. Subjective ratings indicated increased arousal and anxiety in HSA versus LSA, most pronounced for social and negative feedback. FMRI analyses yielded hyperactivation in ventral medial prefrontal cortex (vmPFC)/anterior cingulate cortex (ACC) and insula for social relative to computer feedback, and in mPFC/ventral ACC for positive relative to negative feedback in HSA as compared to LSA. These activation patterns are consistent with increased interoception and self-referential processing in social anxiety, especially during processing of positive feedback. Increased ACC activation in HSA to positive feedback may link to unexpectedness of (social) praise as posited in social anxiety disorder (SAD) psychopathology. Activation in rostral ACC showed a reversed pattern, with decreased activation to positive feedback in HSA, possibly indicating altered action values depending on feedback source and valence. The present findings corroborate a crucial role of mPFC for performance monitoring in social anxiety.

A pilot study investigating changes in neural processing after mindfulness training in elite athletes

The ability to pay close attention to the present moment can be a crucial factor for performing well in a competitive situation. Training mindfulness is one approach to potentially improve elite athletes’ ability to focus their attention on the present moment. However, virtually nothing is known about whether these types of interventions alter neural systems that are important for optimal performance. This pilot study examined whether an intervention aimed at improving mindfulness [Mindful Performance Enhancement, Awareness and Knowledge (mPEAK)] changes neural activation patterns during an interoceptive challenge. Participants completed a task involving anticipation and experience of loaded breathing during functional magnetic resonance imaging recording. There were five main results following mPEAK training: (1) elite athletes self-reported higher levels of interoceptive awareness and mindfulness and lower levels of alexithymia; (2) greater insula and anterior cingulate cortex (ACC) activation during anticipation and post-breathing load conditions; (3) increased ACC activation during the anticipation condition was associated with increased scores on the describing subscale of the Five Facet Mindfulness Questionnaire; (4) increased insula activation during the post-load condition was associated with decreases in the Toronto Alexithymia Scale identifying feelings subscale; (5) decreased resting state functional connectivity between the PCC and the right medial frontal cortex and the ACC. Taken together, this pilot study suggests that mPEAK training may lead to increased attention to bodily signals and greater neural processing during the anticipation and recovery from interoceptive perturbations. This association between attention to and processing of interoceptive afferents may result in greater adaptation during stressful situations in elite athletes.

FMRI Study of Social Anxiety during Social Ostracism with and without Emotional Support.

Social anxiety is characterized by an excessive fear of being embarrassed in social interactions or social performance situations. Emotional support can help to decrease or diminish social distress. Such support may play an important role at different points of social interaction. However, it is unclear how the beneficial effects of social support are represented in the brains of socially anxious individuals. To explore this, we used the same paradigm previously used to examine the effects of emotional support on social pain caused by exclusion. Undergraduates (n = 46) showing a wide range of social anxiety scores underwent functional magnetic resonance imaging (fMRI) while participating in a Cyberball game. Participants were initially included and later excluded from the game. In the latter half of the session in which participants were excluded, they were provided with supportive messages. In line with our previous work, we found that social exclusion led to increased anterior cingulate cortex (ACC) activity, whereas emotional support led to increased left dorsolateral prefrontal cortex (DLPFC) activity. Despite validation of the paradigm, social anxiety was not associated with increased ACC activity during social exclusion, or during perceived emotional support. Instead, fear of negative evaluation as assessed by the Brief Fear of Negative Evaluation (BFNE) scale showed positive associations with left DLPFC activation while receiving emotional support, compared to while being socially excluded. The more socially anxious an individual was, the greater was the left DLPFC activity increased during receipt of messages. This suggests that highly socially anxious people still have the ability to perceive social support, but that they are nevertheless susceptible to negative evaluation by others.

Reward salience and risk aversion underlie differential ACC activity in substance dependence.

The medial prefrontal cortex, especially the dorsal anterior cingulate cortex (ACC), has long been implicated in cognitive control and error processing. Although the association between ACC and behavior has been established, it is less clear how ACC contributes to dysfunctional behavior such as substance dependence. Evidence from neuroimaging studies investigating ACC function in substance users is mixed, with some studies showing disengagement of ACC in substance dependent individuals (SDs), while others show increased ACC activity related to substance use. In this study, we investigate ACC function in SDs and healthy individuals performing a change signal task for monetary rewards. Using a priori predictions derived from a recent computational model of ACC, we find that ACC activity differs between SDs and controls in factors related to reward salience and risk aversion between SDs and healthy individuals. Quantitative fits of a computational model to fMRI data reveal significant differences in best fit parameters for reward salience and risk preferences. Specifically, the ACC in SDs shows greater risk aversion, defined as concavity in the utility function, and greater attention to rewards relative to reward omission. Furthermore, across participants risk aversion and reward salience are positively correlated. The results clarify the role that ACC plays in both the reduced sensitivity to omitted rewards and greater reward valuation in SDs. Clinical implications of applying computational modeling in psychiatry are also discussed.

Neural activation during processing of aversive faces predicts treatment outcome in alcoholism

Neuropsychological studies reported decoding deficits of emotional facial expressions in alcohol-dependent patients, and imaging studies revealed reduced prefrontal and limbic activation during emotional face processing. However, it remains unclear whether this reduced neural activation is mediated by alcohol-associated volume reductions and whether it interacts with treatment outcome. We combined analyses of neural activation during an aversive face-cue-comparison task and local gray matter volumes (GM) using Biological Parametric Mapping in 33 detoxified alcohol-dependent patients and 33 matched healthy controls. Alcoholics displayed reduced activation toward aversive faces-neutral shapes in bilateral fusiform gyrus [FG; Brodmann areas (BA) 18/19], right middle frontal gyrus (BA46/47), right inferior parietal gyrus (BA7) and left cerebellum compared with controls, which were explained by GM differences (except for cerebellum). Enhanced functional activation in patients versus controls was found in left rostral anterior cingulate cortex (ACC) and medial frontal gyrus (BA10/11), even after GM reduction control. Increased ACC activation correlated significantly with less (previous) lifetime alcohol intake [Lifetime Drinking History (LDH)], longer abstinence and less subsequent binge drinking in patients. High LDH appear to impair treatment outcome via its neurotoxicity on ACC integrity. Thus, high activation of the rostral ACC elicited by affective faces appears to be a resilience factor predicting better treatment outcome. Although no group differences were found, increased FG activation correlated with patients' higher LDH. Because high LDH correlated with worse task performance for facial stimuli in patients, elevated activation in the fusiform 'face' area may reflect inefficient compensatory activation. Therapeutic interventions (e.g. emotion evaluation training) may enable patients to cope with social stress and to decrease relapses after detoxification.

Increased error-related brain activity in youth with obsessive-compulsive disorder and other anxiety disorders

The error-related negativity (ERN) is a negative deflection in the event-related potential after an incorrect response that is thought to reflect activity in the anterior cingulate cortex (ACC) and is often increased in patients with anxiety disorders. This study measured the ERN and correct response negativity (CRN) during an Eriksen flanker task to assess performance monitoring in 26 youth with obsessive-compulsive disorder (OCD), 13 youth with a non-OCD anxiety disorder consisting of either generalized anxiety disorder or separation anxiety disorder, and 27 age-matched healthy controls ranging in age from 8 to 16 years. Compared to healthy controls, ERN amplitude was significantly increased in patients with either OCD or a non-OCD anxiety disorder. There were no significant group differences in CRN amplitude. Treatment with a serotonergic antidepressant or cognitive-behavior therapy had no effect on the ERN in patients. Scores from the Child Behavior Checklist DSM-oriented anxiety problems scale had a significant correlation with ERN amplitude in all subjects. The results provide further evidence that the pathophysiology of OCD and some non-OCD anxiety disorders involves increased ACC activity and that the ERN may serve as a quantitative phenotype in genetic and longitudinal studies of these complex traits.

Social reinforcement can regulate localized brain activity

Social learning is essential for adaptive behavior in humans. Neurofeedback based on functional magnetic resonance imaging (fMRI) trains control over localized brain activity. It can disentangle learning processes at the neural level and thus investigate the mechanisms of operant conditioning with explicit social reinforcers. In a pilot study, a computer-generated face provided a positive feedback (smiling) when activity in the anterior cingulate cortex (ACC) increased and gradually returned to a neutral expression when the activity dropped. One female volunteer without previous experience in fMRI underwent training based on a social reinforcer. Directly before and after the neurofeedback runs, neural responses to a cognitive interference task (Simon task) were recorded. We observed a significant increase in activity within ACC during the neurofeedback blocks, correspondent with the a-priori defined anatomical region of interest. In the course of the neurofeedback training, the subject learned to regulate ACC activity and could maintain the control even without direct feedback. Moreover, ACC was activated significantly stronger during Simon task after the neurofeedback training when compared to before. Localized brain activity can be controlled by social reward. The increased ACC activity transferred to a cognitive task with the potential to reduce cognitive interference. Systematic studies are required to explore long-term effects on social behavior and clinical applications.

Default-mode network dysfunction and cognitive impairment in progressive MS

This study explores default-mode network (DMN) abnormalities in patients with secondary progressive (SP) and primary progressive (PP) multiple sclerosis (MS) and whether such abnormalities correlate with cognitive impairment and damage to selected white matter (WM) fiber bundles, quantified using diffusion tensor (DT) MRI tractography. Resting state (RS) functional MRI and DT MRI data were acquired from 33 patients with SPMS, 24 patients with PPMS, and 24 controls. Independent component analysis (ICA) was used to identify the DMN. SPM5 was used to assess within- and between-group activations. Between-group differences in DMN activity were found in the left medial prefrontal cortex (mPFC), left precentral gyrus (PcG), and anterior cingulate cortex (ACC). Compared to controls, patients with SPMS had reduced activity in the mPFC (p = 0.01) and PcG (p = 0.02), while patients with PPMS had reduced activity in the PcG (p = 0.008) and the ACC (p = 0.002). Compared to patients with PPMS, patients with SPMS had increased ACC activity (p = 0.04). Reduction of RS activity in the ACC was more pronounced in cognitively impaired vs cognitively preserved patients with MS (p = 0.02). In patients with MS, DMN abnormalities correlated with the PASAT and word list test scores (r values ranging from 0.35 to 0.45) and DT MRI changes in the corpus callosum and the cingulum (r values ranging from 0.82 to 0.87). These results suggest that a dysfunction of the anterior components of the default-mode network may be among the factors responsible for the accumulation of cognitive deficits in patients with progressive multiple sclerosis.

A potential role for adiponectin receptor 2 (AdipoR2) in the regulation of alcohol intake

The anterior cingulate cortex (ACC) has been implicated in alcohol and drug addiction. We recently identified the small G protein K-ras as an alcohol-regulated gene in the ACC by gene expression analysis. We show here that the adiponectin receptor 2 (AdipoR2) was differentially regulated by alcohol in the ACC in a K-ras-dependent manner. Additionally, withdrawal-associated increased drinking was attenuated in AdipoR2 null mice. Intracellular recordings revealed that adiponectin increased the excitability of ACC neurons and that this effect was more pronounced during alcohol withdrawal, suggesting that AdipoR2 signaling may contribute to increased ACC activity. Altogether, the data implicate K-ras-regulated pathways involving AdipoR2 in the cellular and behavioral actions of alcohol that may contribute to overactivity of the ACC during withdrawal and excessive alcohol drinking.

The val158met Polymorphism of Human Catechol-O-Methyltransferase (COMT) Affects Anterior Cingulate Cortex Activation in Response to Painful Laser Stimulation

BackgroundPain is a complex experience with sensory, emotional and cognitive aspects. Genetic and environmental factors contribute to pain-related phenotypes such as chronic pain states. Genetic variations in the gene coding for catechol-O-methyltransferase (COMT) have been suggested to affect clinical and experimental pain-related phenotypes including regional μ-opioid system responses to painful stimulation as measured by ligand-PET (positron emission tomography). The functional val158met single nucleotide polymorphism has been most widely studied. However, apart from its impact on pain-induced opioid release the effect of this genetic variation on cerebral pain processing has not been studied with activation measures such as functional magnetic resonance imaging (fMRI), PET or electroencephalography. In the present fMRI study we therefore sought to investigate the impact of the COMT val158met polymorphism on the blood oxygen level-dependent (BOLD) response to painful laser stimulation.Results57 subjects were studied. We found that subjects homozygous for the met158 allele exhibit a higher BOLD response in the anterior cingulate cortex (ACC), foremost in the mid-cingulate cortex, than carriers of the val158 allele.ConclusionThis result is in line with previous studies that reported higher pain sensitivity in homozygous met carriers. It adds to the current literature in suggesting that this behavioral phenotype may be mediated by, or is at least associated with, increased ACC activity. More generally, apart from one report that focused on pain-induced opioid release, this is the first functional neuroimaging study showing an effect of the COMT val158met polymorphism on cerebral pain processing.

In-group and out-group membership mediates anterior cingulate activation to social exclusion

Functional magnetic resonance imaging was employed to examine sensitivity to social exclusion in three conditions: same-race, other-race, and self-resembling faces. The anterior cingulate cortex (ACC), specifically the dorsal ACC, has been targeted as a key substrate in the physical and social pain matrix and was hypothesized to regulate activation response to various facial conditions. We show that participants demonstrated greatest ACC activation when being excluded by self-resembling and same-race faces, relative to other-race faces. Additionally, participants expressed greater distress and showed increased ACC activation as a result of exclusion in the same-race condition relative to the other-race condition. A positive correlation between implicit racial bias and activation in the amygdala was also evident. Implicit attitude about other-race faces partly explains levels of concern about exclusion by out-group individuals. These findings suggest that individuals are more distressed and their brain (i.e. neural alarm system) responds with greater activation when being excluded by individuals whom they are more likely to share group membership with.

Performance Monitoring in the Anterior Cingulate is Not All Error Related: Expectancy Deviation and the Representation of Action-Outcome Associations

Several converging lines of evidence suggest that the anterior cingulate cortex (ACC) is selectively involved in error detection or evaluation of poor performance. Here we challenge this notion by presenting event-related potential (ERP) evidence that the feedback-elicited error-related negativity, an ERP component attributed to the ACC, can be elicited by positive feedback when a person is expecting negative feedback and vice versa. These results suggest that performance monitoring in the ACC is not limited to error processing. We propose that the ACC acts as part of a more general performance-monitoring system that is activated by violations in expectancy. Further, we propose that the common observation of increased ACC activity elicited by negative events could be explained by an overoptimistic bias in generating expectations of performance. These results could shed light into neurobehavioral disorders, such as depression and mania, associated with alterations in performance monitoring and also in judgments of self-related events.

Evidence for a close relationship between conscious effort and anterior cingulate cortex activity

The function of the anterior cingulate cortex (ACC) has been discussed in the last years in the context of conflict monitoring and error detection. In addition, ACC activity has been described in the context of “conscious effort”. Recent neurophysiological and neuroimaging studies have described a negative correlation between ACC activity and reaction times in simple or choice reaction time experiments. One suggested explanation for this finding has been that there is a relationship between effort and ACC activity. The present ERP-LORETA study of healthy volunteers ( n=35) was intended to directly investigate this relationship. In this experiment, three conditions were investigated: condition I was a choice reaction task with the instruction to stay relaxed during the task (relaxed condition), condition II was the same choice reaction task with the instruction to press the respective button as fast and correct as possible (effort condition). Condition III was just listening to the tones without button press (control condition). Subjects had to score directly after each experimental run on a visual analogue scale the amount of effort they have actually spent. The subjects showed significantly shorter reaction times during the high effort condition in comparison to the relaxed condition, as well as increased N1 amplitudes and increased ACC activity. In a subgroup analysis, this effect was present only in subjects who were (according to their self-ratings) following the instructions closely. These results provide direct evidence for a close relationship between conscious effort and ACC activity and suggest the usefulness of the applied effort-self-rating.

Regional brain activation in response to rectal distension in patients with irritable bowel syndrome and the effect of a history of abuse.

Previous studies have demonstrated alterations in brain response to rectal distension in patients with irritable bowel syndrome (IBS) compared to controls. Our aim was to compare regional brain activity in response to rectal balloon distension in patients with IBS and healthy controls. We studied six patients with IBS and six healthy controls. Positron emission tomography scans were obtained during rectal balloon distensions. Statistical parametric mapping and region of interest analysis were performed to identify and compare differences in regional cerebral blood flow (CBF) for each distension pressure within and between the groups of interest. In post-hoc analyses, patients with a history of sexual or physical abuse were compared to patients without abuse. In response to rectal distension, controls exhibit a greater increase in anterior cingulate cortex (ACC) activity compared to the IBS group (Z = 3.2, P = 0.001). Thalamic activity was higher in the IBS patients relative to the control group (Z = 3.3, P < 0.001). Increased ACC activity was observed in IBS patients with no history of abuse (Z = 5.2, P < 0.001) similar to controls, whereas no such increased activity was noticed in the abused group. In conclusion, this study replicates previous findings showing alterations in brain response to rectal distension in patients with IBS. The observations on the effect of abuse suggest a possible modulating role of abuse history on this brain response.

The relationship between reaction time, error rate and anterior cingulate cortex activity

Current concepts of cognitive control suggest that the anterior cingulate cortex (ACC) is involved in performance monitoring. This idea is supported by the finding that increased ACC activity is found in situations in which errors are likely to occur, even if none are actually made. In addition, recent results suggest that increased ACC activity is negatively correlated with reaction time. We have now compared the error rates and the ACC activity of healthy subjects with short ( n=19) vs. long reaction times ( n=17) in an auditory choice reaction paradigm and analysed the current density differences in the ACC in the time range of the N1 component with low resolution electromagnetic tomography. Subjects with short reaction times showed significantly more ACC activation (Brodmann Area 24) and an increased error rate. This finding suggests that increased ACC activity is associated with a gain in reaction speed at the expense of correctness and is discussed in the context of current concepts about the role of the ACC in cognitive functions.

A positron emission tomography study of silent and oral single word reading in stuttering and nonstuttering adults.

Over the last decade positron emission tomography (PET) has been used extensively for the study of language and other cognitive and sensorimotor processes in healthy and diseased individuals. In the present study, [15O]H2O PET scanning was used to investigate the lateralization and functional distribution of cortical and subcortical activity involved in single word reading in stuttering and nonstuttering individuals. Ten right-handed male stuttering adults and matched nonstuttering individuals were instructed to read individually presented single words either silently or out loud. Subtraction of functional brain images obtained during each of the two reading tasks, and during a non-linguistic baseline task, was used to calculate within-group and between-group differences in regional cerebral blood flow by means of statistical parametric mapping. Increased activation in the left anterior cingulate cortex (ACC) was observed during silent reading in the stuttering speakers but not in the nonstuttering group. Because of the hypothesized role of the ACC in selective attention and covert articulatory practice, it is suggested that the observed increased ACC activation in the stuttering individuals reflects the presence of cognitive anticipatory reactions related to stuttering. During the oral reading task, within-group comparisons showed bilateral cortical and subcortical activation in both the stuttering and the nonstuttering speakers. Between-group comparisons showed a proportionally greater left hemisphere activation in the nonstuttering speakers, and a proportionally greater right hemisphere activation in the stuttering individuals. The results of the present study provide qualified support for the hypothesis that stuttering adults show atypical lateralization of language processes.