Low-intensity focused ultrasound to the posterior insula reduces temporal summation of pain.

BACKGROUND: The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization. OBJECTIVE/HYPOTHESIS: Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). METHODS: N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. RESULTS: Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. CONCLUSIONS: LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options.

Altered activation of the dorsal anterior cingulate cortex during oddball performance in individuals at risk for Alzheimer's disease.

INTRODUCTION: The neural mechanisms underlying neurodegenerative disorders in the elderly remain elusive, despite extensive neuroimaging research in recent decades. Amnestic type mild cognitive impairment (aMCI) and late-life major depressive disorder (MDD) are two such conditions characterized by intersecting cognitive and affective symptomatology, and they are at a higher risk for Alzheimer's disease. MATERIALS AND METHODS: This study analyzed the neural underpinnings of cognitive and depressive symptoms in a cohort comprising 12 aMCI subjects, 24 late-life MDD patients, and 26 healthy controls (HCs). Participants underwent a detailed neuropsychological assessment and completed a visual attentional oddball task during functional magnetic resonance imaging (fMRI), with evaluations at baseline and at 2-year follow-up. RESULTS: Initial findings showed that aMCI subjects had reduced dACC activation during oddball (target) stimulus detection, a pattern that persisted in longitudinal analyses and correlated with cognitive functioning measures. For HCs, subsequent dACC activation was linked to depression scores. Furthermore, in the affective-cognitive altered groups, later dACC activation correlated with oddball and memory performance. CONCLUSIONS: These findings enhance our comprehension of the neurobiological basis of cognitive and depressive disturbances in aging, indicating that dACC activation in response to a visual attentional oddball task could serve as a neural marker for assessing cognitive impairment and depression in conditions predisposing to Alzheimer's disease.

Switching tinnitus on or off: An initial investigation into the role of the pregenual and rostral to dorsal anterior cingulate cortices.

Research indicates that hearing loss significantly contributes to tinnitus, but it alone does not fully explain its occurrence, as many people with hearing loss do not experience tinnitus. To identify a secondary factor for tinnitus generation, we examined a unique dataset of individuals with intermittent chronic tinnitus, who experience fluctuating periods of tinnitus. EEGs of healthy controls were compared to EEGs of participants who reported perceiving tinnitus on certain days, but no tinnitus on other days.. The EEG data revealed that tinnitus onset is associated with increased theta activity in the pregenual anterior cingulate cortex and decreased theta functional connectivity between the pregenual anterior cingulate cortex and the auditory cortex. Additionally, there is increased alpha effective connectivity from the dorsal anterior cingulate cortex to the pregenual anterior cingulate cortex. When tinnitus is not perceived, differences from healthy controls include increased alpha activity in the pregenual anterior cingulate cortex and heightened alpha connectivity between the pregenual anterior cingulate cortex and auditory cortex. This suggests that tinnitus is triggered by a switch involving increased theta activity in the pregenual anterior cingulate cortex and decreased theta connectivity between the pregenual anterior cingulate cortex and auditory cortex, leading to increased theta-gamma cross-frequency coupling, which correlates with tinnitus loudness. Increased alpha activity in the dorsal anterior cingulate cortex correlates with distress. Conversely, increased alpha activity in the pregenual anterior cingulate cortex can transiently suppress the phantom sound by enhancing theta connectivity to the auditory cortex. This mechanism parallels chronic neuropathic pain and suggests potential treatments for tinnitus by promoting alpha activity in the pregenual anterior cingulate cortex and reducing alpha activity in the dorsal anterior cingulate cortex through pharmacological or neuromodulatory approaches.

Alcohol sipping patterns, personality, and psychopathology in Children: Moderating effects of dorsal anterior cingulate cortex (dACC) activation.

BACKGROUND: Alcohol, the most consumed drug in the United States, is associated with various psychological disorders and abnormal personality traits. Despite extensive research on adolescent alcohol consumption, the impact of early alcohol sipping patterns on changes in personality and mental health over time remains unclear. There is also limited information on the latent trajectory of early alcohol sipping, beginning as young as 9-10 years old. The dorsal anterior cingulate cortex (dACC) is crucial for cognitive control and response inhibition. However, the role of the dACC remains unclear in the relationship between early alcohol sipping and mental health outcomes and personality traits over time. METHODS: Utilizing the large data from the Adolescent Brain Cognitive Development study (N = 11,686, 52% males, 52% white, mean [SD] age 119 [7.5] months, 9807 unique families, 22 sites), we aim to comprehensively examine the longitudinal impact of early alcohol sipping patterns on psychopathological measures and personality traits in adolescents, filling crucial gaps in the literature. RESULTS: We identified three latent alcohol sipping groups, each demonstrating distinct personality traits and depression score trajectories. Bilateral dACC activation during the stop-signal task moderated the effect of early alcohol sipping on personality and depression over time. Additionally, bidirectional effects were observed between alcohol sipping and personality traits. CONCLUSIONS: This study provides insights into the impact of early alcohol consumption on adolescent development. The key finding of our analysis is that poor response inhibition at baseline, along with increased alcohol sipping behaviors may accelerate the changes in personality traits and depression scores over time as individuals transition from childhood into adolescence.

White matter integrity of right frontostriatal circuit predicts internet addiction severity among internet gamers.

Excessive use of the internet, which is a typical scenario of self-control failure, could lead to potential consequences such as anxiety, depression, and diminished academic performance. However, the underlying neuropsychological mechanisms remain poorly understood. This study aims to investigate the structural basis of self-control and internet addiction. In a cohort of 96 internet gamers, we examined the relationships among grey matter volume and white matter integrity within the frontostriatal circuits and internet addiction severity, as well as self-control measures. The results showed a significant and negative correlation between dACC grey matter volume and internet addiction severity (p < 0.001), but not with self-control. Subsequent tractography from the dACC to the bilateral ventral striatum (VS) was conducted. The fractional anisotropy (FA) and radial diffusivity of dACC-right VS pathway was negatively (p = 0.011) and positively (p = 0.020) correlated with internet addiction severity, respectively, and the FA was also positively correlated with self-control (p = 0.036). These associations were not observed for the dACC-left VS pathway. Further mediation analysis demonstrated a significant complete mediation effect of self-control on the relationship between FA of the dACC-right VS pathway and internet addiction severity. Our findings suggest that the dACC-right VS pathway is a critical neural substrate for both internet addiction and self-control. Deficits in this pathway may lead to impaired self-regulation over internet usage, exacerbating the severity of internet addiction.

Aberrant function of the salience network related to maltreatment experiences during thought-action fusion.

Childhood maltreatment (CM) causes early deviations in cognitive and affective processes, leading to future adaptation failures and psychopathology. Specifically, CM has been linked to cognitive distortions, and recent studies have focused on the impact of CM on the higher level of metacognitive beliefs. However, only a few studies have revealed the neural mechanisms underlying the association between altered metacognition and CM. Therefore, this functional magnetic resonance imaging (fMRI) study investigated the neural correlates of thought-action fusion (TAF) tendency and CM experiences. Overall, 40 young and healthy adults (21 men) participated in this study and underwent fMRI during the TAF task as well as psychological evaluation for CM, TAF tendency, anxiety, and depressive symptoms. During the TAF task, they were asked to read negative (Neg) or neutral (Neu) statements about neutral or close people (CP). Notably, significant activations were found in regions such as the bilateral anterior insula, dorsal anterior cingulate cortex (dACC), caudate, thalamus, medial prefrontal cortex, precuneus, and right amygdala in the NegCp > NeuCP contrast. Furthermore, anterior insula and dACC activities were significantly correlated with total scores of CM experiences and TAF. Exaggerated TAF tendency in persons with CM experiences was associated with increased response of the anterior insula and dACC, which are two core hubs of the salience network. Our results therefore seem to suggest insights for a better understanding of the neural mechanisms underlying metacognitive beliefs related to CM experiences.

Action-rule-based cognitive control enables efficient execution of stimulus-response conflict tasks: a model validation of Simon task performance.

Introduction: The human brain can flexibly modify behavioral rules to optimize task performance (speed and accuracy) by minimizing cognitive load. To show this flexibility, we propose an action-rule-based cognitive control (ARC) model. The ARC model was based on a stochastic framework consistent with an active inference of the free energy principle, combined with schematic brain network systems regulated by the dorsal anterior cingulate cortex (dACC), to develop several hypotheses for demonstrating the validity of the ARC model. Methods: A step-motion Simon task was developed involving congruence or incongruence between important symbolic information (illustration of a foot labeled "L" or "R," where "L" requests left and "R" requests right foot movement) and irrelevant spatial information (whether the illustration is actually of a left or right foot). We made predictions for behavioral and brain responses to testify to the theoretical predictions. Results: Task responses combined with event-related deep-brain activity (ER-DBA) measures demonstrated a key contribution of the dACC in this process and provided evidence for the main prediction that the dACC could reduce the Shannon surprise term in the free energy formula by internally reversing the irrelevant rapid anticipatory postural adaptation. We also found sequential effects with modulated dip depths of ER-DBA waveforms that support the prediction that repeated stimuli with the same congruency can promote remodeling of the internal model through the information gain term while counterbalancing the surprise term. Discussion: Overall, our results were consistent with experimental predictions, which may support the validity of the ARC model. The sequential effect accompanied by dip modulation of ER-DBA waveforms suggests that cognitive cost is saved while maintaining cognitive performance in accordance with the framework of the ARC based on 1-bit congruency-dependent selective control.

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

Introduction: 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. Methods: 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. Results: 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. Discussion: 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.

Error-related brain activity associated with obsessive-compulsive symptoms in youth.

BACKGROUND: Subclinical obsessive-compulsive symptoms (OCS) are common in children, and increase risk for later onset of obsessive-compulsive disorder (OCD). In pediatric patients with OCD, neuroimaging research implicates altered neural mechanisms for error-processing, but whether abnormal brain response occurs with subclinical OCS remains poorly understood. METHODS: Using functional magnetic resonance imaging (fMRI), 113 youth (8-18 years; 45 female) from a community sample were scanned during an error-eliciting Go/No-Go task. OCS were assessed dimensionally using the obsessive-compulsive subscale of the Child Behavior Checklist. The association between OCS scores and error-related brain activity was examined at the whole-brain level. RESULTS: Lower OCS scores associated with stronger response to errors in dorsal anterior cingulate cortex (dACC), caudate, putamen, thalamus, and occipital cortex. Additionally, lower OCS related to higher capacity for inhibitory control, as indexed by greater accuracy on No-Go trials during fMRI scanning. The relationship between lower OCS and better accuracy on No-Go trials was mediated by greater error-related dACC activity. CONCLUSIONS: The inverse relationship between OCS and error-related activity in the dACC and extended cortical-striatal-thalamic circuitry may index an adaptive process by which subclinical OCS are minimized in youth. Further, these results identify an observable pattern of brain activity that tracks with subclinical OCS severity. Understanding the link between neural networks for error processing and the normal to abnormal range of OCS may pave the way for brain-based strategies to identify children who are more likely to develop OCD and enable the targeting of preventive strategies to reduce risk.

Psychological distress modulates dorsal anterior cingulate cortex responses to salient stimuli in obsessive-compulsive disorder.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) experience an exacerbation of symptoms under psychological distress. The neurobiological underpinnings of this effect of stress remain elusive. Here, we induced psychological distress to explore its effect on neural reactivity of the salience network during a symptom provocation task. METHODS: Twenty-three patients with OCD and twenty-three healthy volunteers underwent functional magnetic resonance imaging scanning after stress induction and a control condition in a cross-over design. Psychological distress was induced using the socially evaluated cold pressor test (SECPT) and neural responses were measured during a symptom provocation task. RESULTS: OCD participants showed a blunted cortisol response to the stressor. We found a group by stress interaction effect in the dorsal anterior cingulate cortex (dACC), such that psychological distress reduced dACC reactivity to emotionally salient pictures in OCD participants, whereas it increased dACC reactivity in healthy controls. LIMITATIONS: A considerable proportion of OCD participants was on medication, and the neuroimaging session was conducted more than 1 h after the initial stressor. CONCLUSIONS: Considering this timeline, we speculate that the blunted dACC reactivity towards emotionally salient pictures in OCD participants may reflect impaired emotion regulation in the aftermath of stress.

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.

The relationship between self-esteem and self-concept clarity is modulated by spontaneous activities of the dACC.

Although it has been found that self-esteem and self-concept clarity are positively correlated, self-determination theory shows that the positive relationship might be lowered for individuals whose basic psychological needs are chronically thwarted. The exact neural mechanisms underlying the relationship between self-esteem and self-concept clarity are still not fully understood. The dorsal anterior cingulate cortex (dACC) plays an important role in monitoring basic psychological needs, considering that it is more active when some basic psychological needs are actually or potentially thwarted. To better understand the neural mechanisms underlying the relationship between self-esteem and self-concept clarity, we investigated the differences in the relationship between self-esteem and self-concept clarity among healthy adults with different levels of spontaneous activities of the dACC using rs-fMRI combined with amplitude of low-frequency fluctuation (ALFF). As expected, the results showed that the positive relationship between self-esteem and self-concept clarity was modulated by the ALFF value of the right dACC, which indicated that the positive relationship was significant when the ALLF value of the right dACC was lower, but the positive relationship was not significant when the ALFF value of the right dACC was higher. The modulating roles of right dACC might also reflect that the individuals with higher ALFF value of dACC might experience chronically thwarted relatedness of basic psychological needs, which means the more disturbed by thwarting relatedness information in individuals, the lower positive relationship emerged.

Altered resting-state functional connectivity of the dorsal anterior cingulate cortex with intrinsic brain networks in male problematic smartphone users.

The excessive use of smartphones is associated with various medical complications and mental health problems. However, existing research findings on neurobiological mechanisms behind problematic smartphone use are limited. In this study, we investigated functional connectivity in problematic smartphone users, focusing on the default mode network (DMN) and attentional networks. We hypothesized that problematic smartphone users would have alterations in functional connectivity between the DMN and attentional networks and that such alterations would correlate with the severity of problematic smartphone use. This study included 30 problematic smartphone users and 35 non-problematic smartphone users. We carried out group independent component analysis (group ICA) to decompose resting-state functional magnetic resonance imaging (fMRI) data into distinct networks. We examined functional connectivity using seed-to-seed analysis and identified the nodes of networks in group ICA, which we used as region of interest. We identified greater functional connectivity of the dorsal anterior cingulate cortex (dACC) with the ventral attention network (VAN) and with the DMN in problematic smartphone users. In seed-to-seed analysis, problematic smartphone users showed atypical dACC-VAN functional connectivity which correlated with the smartphone addiction proneness scale total scores. Our resting-state fMRI study found greater functional connectivity between the dACC and attentional networks in problematic smartphone users. Our findings suggest that increased bottom-up and interoceptive attentional processing might play an important role in problematic smartphone use.

Self-control impacts symptoms defining Internet gaming disorder through dorsal anterior cingulate-ventral striatal pathway.

Self-control is important for long-term success and could be a protective factor against maladaptive behaviours such as excessive gaming activity or Internet gaming disorder (IGD). However, the neurobiological basis of self-control and its relationship to IGD remain elusive. Using resting-state fMRI data from 89 participants aged from 18 to 26, we found that self-control and the number of IGD symptoms (IGD-S) were positively and negatively correlated with functional connectivity between right ventral striatum (rVS) and dorsal anterior cingulate cortex (dACC), respectively. A mediation analysis indicated that self-control influenced IGD-S partially through the rVS-dACC connectivity. In addition, step-wise regression analyses revealed that the rVS connectivity in a reward-anticipation limbic pathway contributed to IGD-S but not self-control, independent of the dACC pathway. These results suggest that the cingulate-ventral striatal functional connectivity may serve as an important neurobiological underpinning of self-control to regulate maladaptive behaviours such as these manifesting IGD through striatal circuitry balance.

Trait dialectical thinking is associated with the strength of functional coupling between the dACC and the default mode network.

Dialectical thinking is an overarching and sophisticated thinking style that involves accepting and resolving contradictions. The current study examined whether the dispositional tendency of dialectical thinking is mediated by organizational patterns of intrinsic brain networks. Based on previous theoretical and empirical works, we hypothesized that the dorsal anterior cingulate cortex (dACC), the hub for conflict processing, shows increased couplings with nodes in the default mode network (DMN). A sample of 380 young and healthy participants completed a self-reported measure of dialectical thinking and underwent resting-state functional magnetic resonance imaging scanning. Results of seed-based correlational ROI and whole-brain analyses supported our hypothesis that trait dialectical thinking was positively correlated with the strength of the dACC-DMN couplings. These findings demonstrate the possibility of identifying network-level neural representations of sociocultural orientations.

High-definition transcranial direct current stimulation of the dorsal anterior cingulate cortex modulates decision-making and executive control.

Previous neuroimaging evidence highlights the translational implications of targeting the dorsal anterior cingulate cortex (dACC), i.e. a key node of the networks underlying conflict monitoring and decision-making, in brain stimulation treatments with clinical or rehabilitative purposes. While the optimized modelling of "high-definition" current flows between multiple anode-cathode pairs might, in principle, allow to stimulate an otherwise challenging target, sensitive benchmark metrics of dACC neuromodulation are required to assess the effectiveness of this approach. On this basis, we aimed to assess the modulatory effect of anodal and cathodal high-definition tDCS (HD-tDCS) of the dACC on different facets of executive control and decision-making in healthy young individuals. A combined modelling/targeting procedure provided the optimal montage for the maximum intensity of dACC stimulation with six small "high-definition" electrodes delivering anodal, cathodal or sham HD-tDCS for 20 min in a within-subject design with three separate sessions. Following stimulation, participants performed Flanker and gambling tasks unveiling individual differences in executive control and both loss- and risk-aversion in decision-making, respectively. Compared to both anodal and sham conditions, cathodal dACC stimulation significantly affected task performance by increasing control over the Flanker conflict effect, and both loss and risk-aversion in decision-making. By confirming the feasibility and effectiveness of dACC stimulation with HD-tDCS, these findings highlight the implications of modelling and targeting procedures for neuromodulation in clinical research, whereby innovative protocols might serve as treatment addressing dysfunctional dACC activity, or combined with cognitive training, to enhance higher-order executive functioning in different neuropsychiatric conditions.

Neural substrates of expectancy violation associated with social feedback in individuals with subthreshold depression.

BACKGROUND: Abnormal processing of social feedback is an important contributor to social dysfunction in depression, however the exact mechanisms remain unclear. One important factor may be the extent to which social processing depends on expectations, in particular whether social feedback confirms or violates expectations. METHODS: To answer this question, we studied behavioral and brain responses during the evaluative processing of social feedback in 25 individuals with subthreshold depression (SD) and 25 healthy controls (HCs). Participants completed a Social Judgment Task in which they first indicated expectation about whether a peer would like them or not, and then received peer's feedback indicating acceptance or rejection. RESULTS: Individuals with SD who reported greater depressive symptoms gave fewer positive expectations. Compared to HCs, individuals with SD showed reduced activation in the medial prefrontal cortex when expecting positive feedback. They also exhibited increased dorsal anterior cingulate cortex after receipt of unexpected social rejection, and reduced ventral striatum activity after receipt of unexpected social acceptance. CONCLUSIONS: The observed alternations are specific to unexpected social feedback processing and highlight an important role of expectancy violation in the brain dysfunction of social feedback perception and evaluation in individuals at risk for depression.

Fingolimod increases parvalbumin-positive neurons in adult mice.

In recent years, it has been shown that central nervous system agents, such as antidepressants and antiepileptic drugs, reopen a critical period in mature animals. Fingolimod, which is used for the treatment of multiple sclerosis, also restores neuroplasticity. In this study, we investigated the effects of parvalbumin (PV)-positive neurons and perineuronal nets (PNN) on fingolimod administration with respect to neuroplasticity. Fingolimod was chronically administered intraperitoneally to mature mice. PV-positive neurons and PNN in the hippocampus, prefrontal cortex, and somatosensory cortex were analyzed. An increase in PV-positive neurons was observed in the hippocampus, prefrontal cortex, and somatosensory cortex of the fingolimod-treated mice. An increase in Wisteria floribunda agglutinin-positive PNN was confirmed in mice treated with fingolimod in the somatosensory cortex only. Fingolimod increased the density of PV-positive neurons in the brains of mature mice. The results indicate that fingolimod may change the critical period in mature animals.

Neuronal activity in dorsal anterior cingulate cortex during economic choices under variable action costs.

The role of the dorsal anterior cingulate cortex (ACCd) in decision making has often been discussed but remains somewhat unclear. On the one hand, numerous studies implicated this area in decisions driven by effort or action cost. On the other hand, work on economic choices between goods (under fixed action costs) found that neurons in ACCd encoded only post-decision variables. To advance our understanding of the role played by this area in decision making, we trained monkeys to choose between different goods (juice types) offered in variable amounts and with different action costs. Importantly, the task design dissociated computation of the action cost from planning of any particular action. Neurons in ACCd encoded the chosen value and the binary choice outcome in several reference frames (chosen juice, chosen cost, chosen action). Thus, this area provided a rich representation of post-decision variables. In contrast to the OFC, neurons in ACCd did not represent pre-decision variables such as individual offer values in any reference frame. Hence, ongoing decisions are unlikely guided by ACCd. Conversely, neuronal activity in this area might inform subsequent actions.

Interaction between decision-making and interoceptive representations of bodily arousal in frontal cortex.

Decision-making and representations of arousal are intimately linked. Behavioral investigations have classically shown that either too little or too much bodily arousal is detrimental to decision-making, indicating that there is an inverted "U" relationship between bodily arousal and performance. How these processes interact at the level of single neurons as well as the neural circuits involved are unclear. Here we recorded neural activity from orbitofrontal cortex (OFC) and dorsal anterior cingulate cortex (dACC) of macaque monkeys while they made reward-guided decisions. Heart rate (HR) was also recorded and used as a proxy for bodily arousal. Recordings were made both before and after subjects received excitotoxic lesions of the bilateral amygdala. In intact monkeys, higher HR facilitated reaction times (RTs). Concurrently, a set of neurons in OFC and dACC selectively encoded trial-by-trial variations in HR independent of reward value. After amygdala lesions, HR increased, and the relationship between HR and RTs was altered. Concurrent with this change, there was an increase in the proportion of dACC neurons encoding HR. Applying a population-coding analysis, we show that after bilateral amygdala lesions, the balance of encoding in dACC is skewed away from signaling either reward value or choice direction toward HR coding around the time that choices are made. Taken together, the present results provide insight into how bodily arousal and decision-making are signaled in frontal cortex.