Activity In Anterior Cingulate Cortex Research Articles

From childhood trauma to hyperarousal in adults: The mediating effect of maladaptive shame coping and insomnia.

A new line of insomnia research focuses on the developmental trajectories from early live stress to insomnia in adulthood. Adverse childhood experiences (ACE's) might create a vulnerability for later maladaptive coping with distress, as seen in chronic hyperarousal or insomnia. In an functional magnetic resonance imaging (fMRI) study, failure to dissociate the neurobiological components of shame from autobiographical shameful memories in insomnia was reflected by continued activation of the dorsal anterior cingulate cortex (dACC), which may be a result of maladaptive coping in the wake of ACE's. Following up on that study, the current pilot study explores the relation between ACE's, shame coping-styles, adult insomnia, hyperarousal, and neurobiology of autobiographical memory. We used existing data (N = 57) from individuals with insomnia (N = 27) and controls (N = 30), and asked these participants to complete the childhood trauma questionnaire (CTQ). Two structural equation models were used to test the hypotheses that shame-coping styles and insomnia symptom severity mediate the association between ACE's and (1) self-rated hyperarousal symptoms and (2) dACC activation to recall of autobiographical memories. For the association between ACE's and hyperarousal, there was a significant mediation of shame-coping style (p < 0.05). This model also indicated worse shame coping with more ACE's (p < 0.05) and worse insomnia symptoms with more ACES's (p < 0.05), but no association between shame coping and insomnia symptoms (p = 0.154). In contrast, dACC activation to recall of autobiographical memories could only be explained by its direct association with ACE's (p < 0.05), albeit that in this model more ACE's were also associated with worse insomnia symptoms. These findings could have an implication for the approach of treatment for insomnia. It could be focused more on trauma and emotional processing instead of conventional sleep interventions. Future studies are recommended to investigate the relationship mechanism between childhood trauma and insomnia, with additional factors of attachment styles, personality, and temperament.

Neurocomputational mechanism of real-time distributed learning on social networks.

Social networks shape our decisions by constraining what information we learn and from whom. Yet, the mechanisms by which network structures affect individual learning and decision-making remain unclear. Here, by combining a real-time distributed learning task with functional magnetic resonance imaging, computational modeling and social network analysis, we studied how humans learn from observing others' decisions on seven-node networks with varying topological structures. We show that learning on social networks can be approximated by a well-established error-driven process for observational learning, supported by an action prediction error encoded in the lateral prefrontal cortex. Importantly, learning is flexibly weighted toward well-connected neighbors, according to activity in the dorsal anterior cingulate cortex, but only insofar as social observations contain secondhand, potentially intertwining, information. These data suggest a neurocomputational mechanism of network-based filtering on the sources of information, which may give rise to biased learning and the spread of misinformation in an interconnected society.

Prenatal exposure to air pollution and childhood internalizing problems: roles of shyness and anterior cingulate cortex activity.

Prenatal exposure to air pollution increases the risk for psychiatric disorders characterized by internalizing problems. In this study, we examined the roles of shyness and anterior cingulate cortex (ACC) activity in the association between prenatal exposure to polycyclic aromatic hydrocarbons (PAH) and children's internalizing problems at 7-9 years old. Participants include 53 children (31 girls, 22 boys). Personal air monitoring was conducted over 48 continuous hours during the third trimester of pregnancy to measure 8 PAHs. Mothers reported children's shyness (Emotionality Activity Sociability Temperament Survey) at age 5 and internalizing problems (Child Behavior Checklist) at ages 7-9. ACC activity was measured by fMRI during the Simon Spatial Incompatibility task at ages 7-9. Shyness mediated the association between prenatal PAH exposure and internalizing problems. Higher prenatal PAH exposure predicted increased shyness, which in turn predicted greater internalizing problems. Moreover, left ACC activity during the Simon task moderated the association between prenatal PAH exposure and internalizing problems. Prenatal PAH exposure predicted increased risk for internalizing problems only when children showed heightened left ACC activity during the resolution of cognitive conflict. Our study innovatively synthesizes the fields of developmental psychology and environmental health science to offer new insights into the risk factors for anxiety disorders. Facilitating the development of healthy reactive and regulatory processes may improve the developmental outcomes for children highly exposed to air pollution.

Neural correlates of mental time travel in individuals with high level of schizotypy

BackgroundMental time travel (MTT) is the ability to re-experience past events (autobiographic memory, AM) and pre-experience possible future events (episodic future thinking, EFT) through mental simulation. Empirical findings suggest that individuals with high level of schizotypy exhibit MTT impairment. However, the neural correlates of this impairment remain unclear. MethodThirty-eight individuals with high level of schizotypy and 35 low level of schizotypy were recruited to complete an MTT imaging paradigm. Participants were required to recall past events (AM condition), imagine possible future events (EFT condition) related to cue words, or generate exemplars related to category words (control condition) while undergoing functional Magnetic Resonance Imaging (fMRI). ResultsAM showed greater activation in precuneus, bilateral posterior cingulate cortex, thalamus, and middle frontal gyrus than EFT. Individuals with high level of schizotypy exhibited reduced activation in the left anterior cingulate cortex during AM (vs. Control) and in the medial frontal gyrus during EFT (vs. Control) compared to individuals with low level of schizotypy. Although psychophysiological interaction analyses did not show any significant group difference, individuals with high level of schizotypy exhibited functional connectivity between left anterior cingulate cortex (seed) and right thalamus, between medial frontal gyrus (seed) and left cerebellum during MTT, whereas individuals with low level of schizotypy did not exhibit these functional connectivities. ConclusionThese findings suggest that decreased brain activations may underlie MTT deficits in individuals with high level of schizotypy.

Activation of Internal Correctness Monitoring Circuitry in Youths With Psychosis Spectrum Symptoms

BackgroundSelf-directed performance monitoring is a critical contributor to cognitive performance and general functioning and is impacted by psychiatric symptoms and personality traits, but has been understudied in psychosis-risk states. We have shown that ventral striatum (VS) responds to correctness during cognitive tasks where no explicit feedback is required, and this intrinsic reinforcement response is reduced in schizophrenia. MethodsHere, we examined this phenomenon in youths (n = 796, age range 11–22 years) from the Philadelphia Neurodevelopmental Cohort (PNC) performing a working memory functional magnetic resonance imaging task. We hypothesized that VS would respond to internal correctness monitoring, while classic salience network regions, such as dorsal anterior cingulate cortex and anterior insular cortex, would reflect internal error monitoring and that these responses would increase with age. We expected that neurobehavioral measures of performance monitoring would be reduced in youths with subclinical psychosis spectrum features and would correlate with amotivation severity. ResultsSupporting these hypotheses, we found correct>incorrect activation in VS and incorrect>correct activation in anterior cingulate cortex and anterior insular cortex. Furthermore, VS activation was positively correlated with age, reduced in youths with psychosis spectrum features, and inversely correlated with amotivation. However, these patterns were not significant in anterior cingulate cortex and anterior insular cortex. ConclusionsThese findings advance our understanding of the neural underpinnings of performance monitoring and its impairment in adolescents with psychosis spectrum features. Such understanding can facilitate investigation of the developmental trajectory of normative and aberrant performance monitoring; contribute to early identification of youths at elevated risk for poor academic, occupational, or psychiatric outcomes; and provide potential targets for therapeutic development.

Temporal discounting for self and friends in adolescence: A fMRI study

Adolescence is characterized by impulsivity but also by increased importance of friendships. This study took the novel perspective of testing temporal discounting in a fMRI task where choices could affect outcomes for 96 adolescents (aged 10–20-years) themselves and their best friend. Decisions either benefitted themselves (i.e., the Self Immediate – Self Delay’ condition) or their friend (i.e., ‘Friend Immediate – Friend Delay’ condition); or juxtaposed rewards for themselves and their friends (i.e., the ‘Self Immediate – Friend Delay’ or ‘Friend Immediate – Self Delay’ conditions). We observed that younger adolescents were more impulsive; and all participants were more impulsive when this was associated with an immediate benefit for friends. Individual differences analyses revealed increased activity in the subgenual anterior cingulate cortex extending in the ventral striatum for immediate relative to delayed reward choices for self. Temporal choices were associated with activity in the prefrontal cortex, parietal cortex, insula, and ventral striatum, but only activity in the right inferior parietal lobe was associated with age. Finally, temporal delay choices for friends relative to self were associated with increased activity in the temporo-parietal junction and precuneus. Overall, this study shows a unique role of the social context in adolescents’ temporal decision making.

Dorsal anterior cingulate cortex activity during cognitive challenge in social anxiety disorder

BackgroundSocial anxiety disorder (SAD) is associated with aberrant emotional information processing while little is known about non-emotional cognitive processing biases. The dorsal anterior cingulate cortex (dACC) has been implicated in SAD neuropathology and is activated both by emotional and non-affective cognitive challenges like the Multisource Interference Task (MSIT). MethodsHere, we used fMRI to compare dACC activity and test performance during MSIT in 69 SAD patients and 38 healthy controls. In addition to patient-control comparisons, we examined whether neural activity in the dACC correlated with social anxiety, trait anxiety or depression levels. ResultsThe MSIT activated the dACC as expected but with no differences in task performance or neural reactivity between SAD patients and controls. There were no significant correlations between dACC activity and social or trait anxiety symptom severity. In patients, there was a significant negative correlation between dACC activity and depressive symptoms. ConclusionsIn absence of affective challenge, we found no disorder-related cognitive profile in SAD patients since neither MSIT task performance nor dACC neural activity deviated in patients relative to controls.

A neural substrate of sex-dependent modulation of motivation.

While there is emerging evidence of sex differences in decision-making behavior, the neural substrates that underlie such differences remain largely unknown. Here we demonstrate that in mice performing a value-based decision-making task, while choices are similar between the sexes, motivation to engage in the task is modulated by action value more strongly in females than in males. Inhibition of activity in anterior cingulate cortex (ACC) neurons that project to the dorsomedial striatum (DMS) preferentially disrupts this relationship between value and motivation in females, without affecting choice in either sex. In line with these effects, in females compared to males, ACC-DMS neurons have stronger representations of negative outcomes and more neurons are active when the value of the chosen option is low. By contrast, the representation of each choice is similar between the sexes. Thus, we identify a neural substrate that contributes to sex-specific modulation of motivation by value.

Altered dorsal anterior cingulate cortex activation in late-life depression and mild cognitive impairment during oddball task: an fmri study

Altered dorsal anterior cingulate cortex activation in late-life depression and mild cognitive impairment during oddball task: an fmri study

Reward-related neural dysfunction in youth with a history of suicidal ideation: The importance of temporal predictability

Abnormal reward processing is an important yet understudied risk factor for suicide. Recent neuroimaging studies have found that suicidality is associated with abnormal reward-related neural reactivity and connectivity across a wide range of brain regions and circuits. The varying, and oftentimes discrepant, findings have hindered progress in elucidating the neurobiological link between reward processing dysfunction and suicide risk. Some of this variability is likely related to different reward-related paradigms that are utilized across studies. The primary aim of the current study was to address these issues by comparing neural reactivity between youth with and without a history of suicidal ideation during direct manipulation of reward parameters. A total of 108 unmedicated youth, ages 17–19, were classified into two groups: 1) history of suicidal ideation (n = 39) and 2) no history of suicidal ideation (n = 69). All participants completed a novel reward anticipation task probing anticipation of predictable (P-reward) and unpredictable (U-reward) monetary reward. Results revealed that compared with controls, youth with a history of suicidal ideation exhibited increased neural activation in the dorsal anterior cingulate cortex (dACC) and right anterior insula (aINS) during anticipation of U-reward. There were no group differences during anticipation of P-reward. These findings suggest that propensity for suicidal ideation may be related to specific abnormalities during anticipation of U-reward, but not P-reward.

Shared and distinct neural activity during anticipation and outcome of win and loss: A meta-analysis of the monetary incentive delay task

Reward and punishment motivate decision making and behavioral changes. Numerous studies have examined regional activities during anticipation and outcome of win and loss in the monetary incentive delay task (MIDT). However, the great majority of studies reported findings of anticipation or outcome and of win or loss alone. It remains unclear how the neural correlates share and differentiate amongst these processes. We conducted an Activation Likelihood Estimation meta-analysis of 81 studies of the MIDT (5,864 subjects), including 24 published since the most recent meta-analysis, to identify and, with conjunction and subtraction, contrast regional responses to win anticipation, loss anticipation, win outcome, and loss outcome. Win and loss anticipation engaged a shared network of bilateral anterior insula (AI), striatum, thalamus, supplementary motor area (SMA), and precentral gyrus. Win and loss outcomes did not share regional activities. Win and loss outcome each engaged higher activity in medial orbitofrontal cortex (mOFC) and dorsal anterior cingulate cortex. Bilateral striatum and right occipital cortex responded to both anticipation and outcome of win, and right AI to both phases of loss. Win anticipation vs. outcome engaged higher activity in bilateral AI, striatum, SMA and precentral gyrus and right thalamus, and lower activity in bilateral mOFC and posterior cingulate cortex as well as right inferior frontal and angular gyri. Loss anticipation relative to outcome involved higher activity in bilateral striatum and left AI. These findings collectively suggest shared and distinct regional responses during monetary wins and losses. Delineating the neural correlates of these component processes may facilitate empirical research of motivated behaviors and dysfunctional approach and avoidance in psychopathology.

The left-lateralisation of citrate synthase activity in the anterior cingulate cortex of male violent suicide victims

The anterior cingulate cortex (AC) as a part of prefrontal cortex plays a crucial role in behavioural regulation, which is profoundly disturbed in suicide. Citrate synthase (CS) is a key enzyme of tricarboxylic acid cycle fundamental for brain energetics and neurotransmitter synthesis, which are deteriorated in suicidal behaviour. However, CS activity has not been yet studied in brain structures of suicide victims. CS activity assay was performed bilaterally on frozen samples of the rostral part of the AC of 24 violent suicide completers (21 males and 3 females) with unknown psychiatric diagnosis and 24 non-suicidal controls (20 males and 4 females). Compared to controls, suicide victims revealed decreased CS activity in the right AC, however, insignificant. Further statistical analysis of laterality index revealed the left-lateralisation of CS activity in the AC in male suicides compared to male controls (U-test P = 0.0003, corrected for multiple comparisons). The results were not confounded by postmortem interval, blood alcohol concentration, age, and brain weight. Our findings suggest that disturbed CS activity in the AC plays a role in suicide pathogenesis and correspond with our previous morphological and molecular studies of prefrontal regions in suicide.

An accessory prefrontal cortex-thalamus circuit sculpts maternal behavior in virgin female mice.

The ability to care for the young is innate and readily displayed by postpartum females after delivery to ensure offspring survival. Upon pup exposure, rodent virgin (nulliparous) females also develop parental behavior that over time becomes displayed at levels equivalent to parenting mothers. Although maternal behavior in postpartum females and the associated neurocircuits are well characterized, the neural mechanisms underlying the acquisition of maternal behavior without prior experience remain poorly understood. Here, we show that the development of maternal care behavior in response to first-time pup exposure in virgin females is initiated by the activation of the anterior cingulate cortex (ACC). ACC activity is dependent on feedback excitation by Vglut2+ /Galanin+ neurons of the centrolateral nucleus of the thalamus (CL), with their activity sufficient to display parenting behaviors. Accordingly, acute bidirectional chemogenetic manipulation of neuronal activity in the ACC facilitates or impairs the attainment of maternal behavior, exclusively in virgin females. These results reveal an ACC-CL neurocircuit as an accessory loop in virgin females for the initiation of maternal care upon first-time exposure to pups.

Cortical networks underlying successful control of nociceptive processing using real-time fMRI.

Real-time fMRI (rt-fMRI) enables self-regulation of neural activity in localized brain regions through neurofeedback. Previous studies showed successful up- and down-regulation of neural activity in the anterior cingulate cortex (ACC) and the insula (Ins) during nociceptive stimulation. Such self-regulation capacity is, however, variable across subjects, possibly related to the ability of cognitive top-down control of pain. Moreover, how specific brain areas interact to enable successful regulation of nociceptive processing and neurofeedback-based brain modulation is not well understood. A connectivity analysis framework in the frequency domain was used to examine the up- or down-regulation in the ACC and Ins and pain intensity and unpleasantness ratings were assessed. We found that successful up- and down-regulation was mediated by the ACC and by its functional connectivity with the Ins and secondary somatosensory cortex. There was no significant relationship between successful up- or downregulation and pain ratings. These findings demonstrate functional interactions between brain areas involved in nociceptive processing during regulation of ACC and Ins activity, and the relevance of the frequency domain connectivity analysis for real-time fMRI. Moreover, despite successful neural regulation, there was no change in pain ratings, suggesting that pain is a complex perception, which may be more difficult to modify than other sensory or emotional processes.

A Counting Stroop Functional Magnetic Resonance Imaging Study on the Effects of ORADUR-Methylphenidate in Drug-Naive Children with Attention-Deficit/Hyperactivity Disorder.

Objective: Methylphenidate is effective in reducing the clinical symptoms of patients with attention-deficit/hyperactivity disorder (ADHD). ORADUR®-methylphenidate is a new extended-release preparation of methylphenidate. This study aimed at identifying brain regions with activation changes and their correlations with neuropsychological functions after treatment with ORADUR-methylphenidate in children with ADHD. Methods: We recruited drug-naive children with ADHD and age- and sex-matched typically developing (TD) children. They were all scanned with the functional magnetic resonance imaging (fMRI) during the counting Stroop task at baseline, and those with ADHD had the second fMRI assessment after 8-week treatment with ORADUR-methylphenidate. The Rapid Visual Information Processing (RVP) and Conners' Continuous Performance Test (CCPT) were used to assess the attention performance of the ADHD (before and after treatment) and TD groups. Results: ORADUR-methylphenidate significantly decreased inattention (Cohen d = 2.17) and hyperactivity-impulsivity (Cohen d = 0.98) symptoms. We found less activation in the right inferior frontal gyrus (rIFG) in the pre-treatment ADHD children than TD children and greater treatment-induced activation in the dorsal anterior cingulate cortex (dACC) and the right dorsolateral prefrontal cortex (rDLPFC). There was no significant difference between the post-treatment ADHD and TD groups. However, the treatment-related activations in the dACC, rDLPFC, and rIFG were significantly correlated with CCPT and RVP measures. Conclusions: Our findings indicated that ORADUR-methylphenidate increased brain activations in the dACC, rDLPFC, and rIFG in children with ADHD, associated with improved focused attention, reduced impulsivity, and enhanced inhibition control. Activities of these brain regions might be biomarkers for the treatment effectiveness of methylphenidate for ADHD. Clinical Trials Registration: ClinicalTrials.gov number, NCT02450890.

Comparison of behavioral and brain indices of fear renewal during a standard vs. novel immersive reality Pavlovian fear extinction paradigm in healthy adults

Pavlovian conditioning paradigms model the learned fear associations inherent in posttraumatic stress disorder, including the renewal of inappropriate fear responses following extinction learning. However, very few studies in humans investigate the underlying neural mechanisms involved in fear renewal despite its clinical importance. To address this issue, our lab designed a novel, immersive-reality Pavlovian fear acquisition, extinction, recall, and renewal paradigm. We utilized an ecological threat - a snake striking towards the participant - as the unconditioned stimulus (US). Context and background were dynamic and included both visual and auditory cues that are relevant to everyday life. Using functional magnetic resonance imaging and behavioral measures (US expectancy ratings), we examined the validity of this Novel paradigm in healthy adults (n = 49) and compared it to a Standard, well-validated 2D paradigm (n = 28). The Novel paradigm, compared to the Standard, was associated with greater hippocampal activation throughout the task. Participants who underwent the Standard paradigm, compared to the Novel, also displayed insula activation; however, this was not specific to stimulus or time. During fear renewal, the Novel paradigm was associated with dorsal anterior cingulate cortex activation to CS+ (> CS-). Overall, we found that our Novel, immersive-reality paradigm, which features an ecologically relevant US, elicited greater corticolimbic activation. These results suggest that immersive Pavlovian fear conditioning paradigms paired with innately fearful stimuli may improve translatability of preclinical paradigms to clinical interventions for fear-based disorders.

Dexmedetomidine alleviates anxiety-like behavior in mice following peripheral nerve injury by reducing the hyperactivity of glutamatergic neurons in the anterior cingulate cortex

BackgroundTreatment of chronic pain is challenged by concurrent anxiety symptoms. Dexmedetomidine is known to produce sedation, analgesia, and anxiolysis. However, the neural mechanism of dexmedetomidine-elicited anxiolysis remains elusive. Here, we aimed to test the hypothesis that the anterior cingulate cortex might be involved in dexmedetomidine-induced anxiolysis in pain. MethodsA common peroneal nerve ligation mouse model was used to test the dexmedetomidine-induced analgesia and anxiolysis by assessing mechanical allodynia, open-field, light–dark transition, and acoustic startle reflex tests. In vivo calcium signal fiber photometry and ex vivo whole-cell patch-clamp recordings were used to measure the excitability of glutamatergic neurons in anterior cingulate cortex. Modulation of glutamatergic neurons was performed by chemogenetic inhibition or activation via viral injection. ResultsCompared with vehicle, dexmedetomidine (4 µg/kg) alleviated mechanical allodynia (P < 0.001) and anxiety-like behaviors (P < 0.001). The glutamatergic neurons’ excitability after dexmedetomidine administration was lower than that of the vehicle group (P = 0.001). Anxiety-like behaviors were rescued by inhibiting glutamatergic neurons in the model mice. Nociception-related anxiety-like behavior was induced by activation of glutamatergic neurons, which was rescued by dexmedetomidine. ConclusionsThe reduction in glutamatergic neuronal activity in anterior cingulate cortex may be involved in dexmedetomidine-elicited anxiolysis in chronic pain.

The neural correlates and the underlying processes of weak brand choices

Despite the advantages of strong brands over weak brands, consumers often choose weak brands. The authors test two competing explanations that can explain weak brand choices, by exploring the underlying strong/weak brand choice processes. We test these explanations in a simultaneous evaluation and choice-based scenario, using brands from several product categories. Through an fMRI study (and related behavioural studies), we found significant activation in Rostral Anterior Cingulate Cortex (ACC), Dorsal ACC and Right Dorsolateral Prefrontal Cortex (DLPFC) for weak brand choices. Our results suggest that weak brand choice involves an assessment of value/worth, including cognitive control over feelings of conflict, error-commission, and regret. Brain-behaviour correlation analyses, response times in a lexical-decision task, and choice responses in behavioural studies support these inferences. We contribute to the understanding of consumer-based brand equity, brand-affect associations, and joint/separate product evaluations, and also suggest actionable insights for firms/managers to leverage weak brands’ position.

Learning whom to cooperate with: neurocomputational mechanisms for choosing cooperative partners.

Cooperation is fundamental for survival and a functioning society. With substantial individual variability in cooperativeness, we must learn whom to cooperate with, and often make these decisions on behalf of others. Understanding how people learn about the cooperativeness of others, and the neurocomputational mechanisms supporting this learning, is therefore essential. During functional magnetic resonance imaging scanning, participants completed a novel cooperation-partner-choice task where they learned to choose between cooperative and uncooperative partners through trial-and-error both for themselves and vicariously for another person. Interestingly, when choosing for themselves, participants made faster and more exploitative choices than when choosing for another person. Activity in the ventral striatum preferentially responded to prediction errors (PEs) during self-learning, whereas activity in the perigenual anterior cingulate cortex (ACC) signaled both personal and vicarious PEs. Multivariate pattern analyses showed distinct coding of personal and vicarious choice-making and outcome processing in the temporoparietal junction (TPJ), dorsal ACC, and striatum. Moreover, in right TPJ the activity pattern that differentiated self and other outcomes was associated with individual differences in exploitation tendency. We reveal neurocomputational mechanisms supporting cooperative learning and show that this learning is reflected in trial-by-trial univariate signals and multivariate patterns that can distinguish personal and vicarious choices.

Maternal History of Childhood Maltreatment and Brain Responses to Infant Cues Across the Postpartum Period.

Adults with histories of childhood maltreatment (CM) are more likely to display problematic parenting behaviors. The goal of this study was to examine changes in maternal brain activation to negative infant cues over the early postpartum period among new mothers with and without histories of CM, as this is a period of immense neuroplasticity in the maternal brain. CM was measured using the Adverse Childhood Experiences Scale. Functional magnetic resonance imaging (fMRI) conducted at approximately 5 and 13 weeks postpartum measured brain responses to own and unfamiliar infant cues in primiparous women. Women with histories of CM displayed increasing activation in the anterior cingulate cortex, and greater increases in anterior cingulate cortex activation was associated with maternal reports of less regulatory capacity in their infants. Preliminary results suggest that new mothers with CM histories display greater brain responses to negative infant cues compared to new mothers without CM histories. Women with CM histories may benefit from additional supports during the transition to parenthood.