Longitudinal associations between neighborhood safety and adolescent adjustment: The moderating role of affective neural sensitivity.

Research on social determinants of health has highlighted the influence of neighborhood characteristics (e.g., neighborhood safety) on adolescents' health. However, it is less clear how changes in neighborhood environments play a role in adolescent development, and who are more sensitive to such changes. Utilizing the first three waves of data from the Adolescent Brain Cognitive Development (ABCD) project (N = 7932, M (SD) age = 9.93 (.63) years at T1; 51% boys), the present study found that increases in neighborhood safety were associated with decreased adolescent externalizing symptoms, internalizing symptoms, but not sleep disturbance over time, controlling for baseline neighborhood safety. Further, adolescents' insula and anterior cingulate cortex (ACC) reactivity to positive emotional stimuli moderated the association between changes in neighborhood safety and adolescent adjustment. Among youth who showed higher, but not lower, insula and ACC reactivity to positive emotion, increases in neighborhood safety were linked with better adjustment. The current study contributes to the differential susceptibility literature by identifying affective neural sensitivity as a marker of youth's susceptibility to changes in neighborhood environment. The findings highlight the importance of neighborhood safety for youth during the transition to adolescence, particularly for those with heightened affective neural sensitivity.

Neural substrates of the interaction between effort-expenditure reward decision-making and outcome anticipation.

OBJECTIVE: Reward anticipation is important for future decision-making, possibly due to re-evaluation of prior decisions. However, the exact relationship between reward anticipation and prior effort-expenditure decision-making, and its neural substrates are unknown. METHOD: Thirty-three healthy participants underwent fMRI scanning while performing the Effort-based Pleasure Experience Task (E-pet). Participants were required to make effort-expenditure decisions and anticipate the reward. RESULTS: We found that stronger anticipatory activation at the posterior cingulate cortex was correlated with slower reaction time while making decisions with a high-probability of reward. Moreover, the substantia nigra was significantly activated in the prior decision-making phase, and involved in reward-anticipation in view of its strengthened functional connectivity with the mammillary body and the putamen in trial conditions with a high probability of reward. CONCLUSIONS: These findings support the role of reward anticipation in re-evaluating decisions based on the brain-behaviour correlation. Moreover, the study revealed the neural interaction between reward anticipation and decision-making.

Economic value in the Brain: A meta-analysis of willingness-to-pay using the Becker-DeGroot-Marschak auction.

Forming and comparing subjective values (SVs) of choice options is a critical stage of decision-making. Previous studies have highlighted a complex network of brain regions involved in this process by utilising a diverse range of tasks and stimuli, varying in economic, hedonic and sensory qualities. However, the heterogeneity of tasks and sensory modalities may systematically confound the set of regions mediating the SVs of goods. To identify and delineate the core brain valuation system involved in processing SV, we utilised the Becker-DeGroot-Marschak (BDM) auction, an incentivised demand-revealing mechanism which quantifies SV through the economic metric of willingness-to-pay (WTP). A coordinate-based activation likelihood estimation meta-analysis analysed twenty-four fMRI studies employing a BDM task (731 participants; 190 foci). Using an additional contrast analysis, we also investigated whether this encoding of SV would be invariant to the concurrency of auction task and fMRI recordings. A fail-safe number analysis was conducted to explore potential publication bias. WTP positively correlated with fMRI-BOLD activations in the left ventromedial prefrontal cortex with a sub-cluster extending into anterior cingulate cortex, bilateral ventral striatum, right dorsolateral prefrontal cortex, right inferior frontal gyrus, and right anterior insula. Contrast analysis identified preferential engagement of the mentalizing-related structures in response to concurrent scanning. Together, our findings offer succinct empirical support for the core structures participating in the formation of SV, separate from the hedonic aspects of reward and evaluated in terms of WTP using BDM, and show the selective involvement of inhibition-related brain structures during active valuation.

Prelimbic neuron assemblies with delayed activation encode the economic decision-making process in a bandit game.

The medial prefrontal cortex (mPFC) is critical to an animal's value-based decision-making process. However, due to heterogeneity of local mPFC neurons, which neuron group and how it contributes to the alteration of the animal's decision is yet to be explored. And the effect of empty reward in this process is often neglected. Here, we adopted a two-port bandit game paradigm for mice and applied synchronized calcium imaging to the prelimbic area of the mPFC. The results showed that neurons recruited in the bandit game exhibit three distinct firing patterns. Specially, neurons with delayed activation (deA neurons1) carried exclusive information on reward type and changes of choice value. We demonstrated that these deA neurons were essential for the construction of choice-outcome correlation and the trial-to-trial modification of decision. Additionally, we found that in a long-term gambling game, members of the deA neuron assembly were dynamically shifting while maintaining the function, and the importance of empty reward feedbacks were gradually elevated to the same level as reward. Together, these results revealed a vital role for prelimbic deA neurons in the gambling tasks and a new perspective on the encoding of economic decision-making.

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.

Moral Conflict in Economic Decision Making: The Role of the Anterior Cingulate Cortex-Striatum Pathway.

The present study combined a novel hypothetical investment game with functional magnetic resonance imaging to examine how moral conflict biases our real decision preference when it is not obvious or explicitly presented. Investment projects were chosen based on their prior subjective morality ratings to fit into 2 categories: a high level of moral conflict (HMC) or a low level of moral conflict (LMC). Participants were instructed to invest high or low amounts of capital into different projects. Behavioral and neural responses during decision making were recorded and compared. Behaviorally, we observed a significant decision bias such that investments were lower for HMC projects than for LMC projects. At the neural level, we found that moral conflict-related activity in the anterior cingulate cortex (ACC) was higher in the HMC condition than in the LMC condition and that reward-related activity in bilateral striatum was lower. Dynamic causal modeling further suggested that the moral conflict detected in the ACC influenced final decisions by modulating the representation of subjective value through the ACC's connection to the reward system.

Neural adaptation of cingulate and insular activity during delayed fear extinction: A replicable pattern across assessment sites and repeated measurements.

Adapting threat-related memories towards changing environments is a fundamental ability of organisms. One central process of fear reduction is suggested to be extinction learning, experimentally modeled by extinction training that is repeated exposure to a previously conditioned stimulus (CS) without providing the expected negative consequence (unconditioned stimulus, US). Although extinction training is well investigated, evidence regarding process-related changes in neural activation over time is still missing. Using optimized delayed extinction training in a multicentric trial we tested whether: 1) extinction training elicited decreasing CS-specific neural activation and subjective ratings, 2) extinguished conditioned fear would return after presentation of the US (reinstatement), and 3) results are comparable across different assessment sites and repeated measures. We included 100 healthy subjects (measured twice, 13-week-interval) from six sites. 24 h after fear acquisition training, extinction training, including a reinstatement test, was applied during fMRI. Alongside, participants had to rate subjective US-expectancy, arousal and valence. In the course of the extinction training, we found decreasing neural activation in the insula and cingulate cortex as well as decreasing US-expectancy, arousal and negative valence towards CS+. Re-exposure to the US after extinction training was associated with a temporary increase in neural activation in the anterior cingulate cortex (exploratory analysis) and changes in US-expectancy and arousal ratings. While ICCs-values were low, findings from small groups suggest highly consistent effects across time-points and sites. Therefore, this delayed extinction fMRI-paradigm provides a solid basis for the investigation of differences in neural fear-related mechanisms as a function of anxiety-pathology and exposure-based treatment.

Anterior Cingulate Cortex Lesions Abolish Budget Effects on Effort-Based Decision-Making in Rat Consumers.

Demand theory can be applied to analyze how animal consumers change their selection of commodities in response to changes in commodity prices, given budget constraints. Previous work has shown that demand elasticities in rats differed between uncompensated budget conditions in which the budget available to be spent on the commodities (e.g., the finite number of discrete operants to "purchase" rewards in two-alternative fixed-ratio schedules) was kept constant, and compensated budget conditions in which the budget was adjusted so that consumers could potentially continue to obtain the original reward bundles. Here, we hypothesized that rat anterior cingulate cortex (ACC) was necessary to produce this budget effect on demand elasticities. We applied excitotoxic or sham lesions to ACC in rats performing an effort task in which the prices of liquid vanilla or chocolate rewards (the effort required to obtain rewards) and the budget (the total number of operants) was manipulated. When reward prices changed, and the budget was compensated, all rats adjusted their demand for chocolate and vanilla accordingly. In sham-lesioned rats, changes in demand were even more pronounced when the budget was not compensated for the price changes. By contrast, ACC-lesioned animals did not show this additional budget effect. An in-depth comparison of the rats' choice patterns showed that, unlike sham rats, ACC-lesioned animals failed to maximize session-bundle utility after price/budget changes, revealing deficits in higher-order choice-strategy adaptations. Our results suggest a novel role of ACC in considering purchasing power during complex cost-benefit value computations.SIGNIFICANCE STATEMENT Anterior cingulate cortex (ACC) is important for allocating effort in cost-benefit calculations in animals and humans. Economic theory prescribes that the value of the costs in cost-benefit analyses not only depends on the net nominal costs required to purchase a reward, but also on the available budget resources, i.e., on the budget's "purchasing value." We asked whether ACC, a region implicated in effort-based decision-making and reward comparisons, is required for computing the value of effort relative to a budget constraint. Applying demand theory to describe rat choices in a rodent effort allocation task with varying effort prices and budgets, we show that ACC integrity was necessary for computing purchasing power, a core variable in economic choice theory.

Entorhinal-retrosplenial circuits for allocentric-egocentric transformation of boundary coding.

Spatial navigation requires landmark coding from two perspectives, relying on viewpoint-invariant and self-referenced representations. The brain encodes information within each reference frame but their interactions and functional dependency remains unclear. Here we investigate the relationship between neurons in the rat's retrosplenial cortex (RSC) and entorhinal cortex (MEC) that increase firing near boundaries of space. Border cells in RSC specifically encode walls, but not objects, and are sensitive to the animal's direction to nearby borders. These egocentric representations are generated independent of visual or whisker sensation but are affected by inputs from MEC that contains allocentric spatial cells. Pharmaco- and optogenetic inhibition of MEC led to a disruption of border coding in RSC, but not vice versa, indicating allocentric-to-egocentric transformation. Finally, RSC border cells fire prospective to the animal's next motion, unlike those in MEC, revealing the MEC-RSC pathway as an extended border coding circuit that implements coordinate transformation to guide navigation behavior.

Economic threat heightens conflict detection: sLORETA evidence.

Economic threat has far-reaching emotional and social consequences, yet the impact of economic threat on neurocognitive processes has received little empirical scrutiny. Here, we examined the causal relationship between economic threat and conflict detection, a critical process in cognitive control associated with the anterior cingulate cortex (ACC). Participants (N = 103) were first randomly assigned to read about a gloomy economic forecast (Economic Threat condition) or a stable economic forecast (No-Threat Control condition). Notably, these forecasts were based on real, publicly available economic predictions. Participants then completed a passive auditory oddball task composed of frequent standard tones and infrequent, aversive white-noise bursts, a task that elicits the N2, an event-related potential component linked to conflict detection. Results revealed that participants in the Economic Threat condition evidenced increased activation source localized to the ACC during the N2 to white-noise stimuli. Further, ACC activation to conflict mediated an effect of Economic Threat on increased justification for personal wealth. Economic threat thus has implications for basic neurocognitive function. Discussion centers on how effects on conflict detection could shed light on the broader emotional and social consequences of economic threat.

Spontaneous microstates related to effects of low socioeconomic status on neuroticism.

Individuals with high neuroticism had the decreased control functions of anterior cingulate cortex (ACC) over amygdala (emotion regions) and low socioeconomic status (SES) had negative effects on the functions of ACC. Based on these, we hypothesized that the decreased functions of ACC might make individuals with low SES had high level of neuroticism. According to the score of objective SES (OSES) and subjective SES (SSES) scales, subjects were divided into four groups (low SSES, high SSES, low OSES and high OSES) to investigate the roles of dynamic characteristics related to the ACC in the relationships between SES and neuroticism using resting-state EEG (RS-EEG) microstates analysis. It had been found that RS-EEG microstates can be divided into four types (MS1, MS2, MS3 and MS4) and the MS3 was related cingulo-opercular brain networks (including ACC and anterior insular). As our prediction, SSES had direct effects on neuroticism relative to OSES. Moreover, the neuroticism for low SSES was positively related to the occurrence and contribution of MS3, as well as the possibilities of transitions between MS3 and MS1. Based on these, we thought that low-SSES individuals might be more difficult to inhibit the negative emotions, especially inhibit the spontaneous thoughts related to these emotions.

Communication between the Anterior Cingulate Cortex and Ventral Tegmental Area during a Cost-Benefit Reversal Task.

The anterior cingulate cortex (ACC) is implicated in value-based decision making, anticipation, and adaptation; however, how ACC activity modulates these behaviors is unclear. One possibility is via the ACC's connections with the ventral tegmental area (VTA), a dopaminergic region implicated in motivation and feedback processing. We tested this by monitoring ACC and VTA local field potentials in rats performing a cost-benefit reversal task that elicited both value-based and anticipatory choices. Partial directed coherence analyses revealed that elevated 4-Hz ACC-to-VTA signaling accompanied decisions that appeared to be anticipatory. ACC-to-VTA signaling also occurred post-reversal, consistent with it being involved in the initiation of non-default behavior. An analysis of 4-Hz signals in the other direction (VTA-to-ACC) revealed that it was elevated when the rats committed errors and that this signal was followed by behavioral adaptation. Together, these findings suggest that bidirectional communication between the ACC and VTA supports behavioral flexibility.

Transcriptomic Landscape of von Economo Neurons in Human Anterior Cingulate Cortex Revealed by Microdissected-Cell RNA Sequencing.

The von Economo neurons (VENs) are specialized large bipolar projection neurons with restricted distribution in the human brain, and they are far more abundant in humans than in non-human primates. However, VEN functions remain elusive due to the difficulty of isolating VENs and dissecting their connections in the brain. Here, we combined laser-capture-microdissection with RNA sequencing to describe the transcriptomic profile of VENs from human anterior cingulate cortex (ACC). Using pyramidal neurons as reference cells, we identified 344 genes with VEN-associated expression differences, including 215 higher and 129 lower expression genes. Functional enrichment and protein-protein interaction network analyses showed that these genes with VEN-associated expression differences are involved in VEN morphogenesis and functions, such as dendrite branching and axon myelination, and many of them are associated with human social-emotional disorders. With the use of in situ hybridization and immunohistochemistry assays, we validated four novel VEN markers (VAT1L, CHST8, LYPD1, and SULF2). Collectively, we generated a full-spectrum expression profile of VENs from human ACC, greatly enlarging the pool of genes with VEN-associated expression differences that can help researchers to understand the role of VENs in normal and disordered human brains.

Gain control explains the effect of distraction in human perceptual, cognitive, and economic decision making.

When making decisions, humans are often distracted by irrelevant information. Distraction has a different impact on perceptual, cognitive, and value-guided choices, giving rise to well-described behavioral phenomena such as the tilt illusion, conflict adaptation, or economic decoy effects. However, a single, unified model that can account for all these phenomena has yet to emerge. Here, we offer one such account, based on adaptive gain control, and additionally show that it successfully predicts a range of counterintuitive new behavioral phenomena on variants of a classic cognitive paradigm, the Eriksen flanker task. We also report that blood oxygen level-dependent signals in a dorsal network prominently including the anterior cingulate cortex index a gain-modulated decision variable predicted by the model. This work unifies the study of distraction across perceptual, cognitive, and economic domains.

Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents.

Reinforcement-guided decision making is the ability to choose between competing courses of action based on the relative value of the benefits and their consequences. This process is integral to the normal human behavior and has been shown to be disrupted by neurological and psychiatric disorders such as addiction, schizophrenia, and depression. Rodents have long been used to uncover the neurobiology of human cognition. To this end, several behavioral tasks have been developed; however, most are non-automated and are labor-intensive. The recent development of the open-source microcontroller has enabled researchers to automate operant-based tasks for assessing a variety of cognitive tasks, standardizing the stimulus presentation, improving the data recording and consequently, improving the research output. Here, we describe an automated delay-based reinforcement-guided decision-making task, using an operant T-maze controlled by custom-written software programs. Using these decision-making tasks, we show the changes in the local field potential activities in the anterior cingulate cortex of a rat whilst it performs a delay-based cost-and-benefit decision-making task.

Motivation Modulates Brain Networks in Response to Faces Varying in Race and Status: A Multivariate Approach.

Previous behavioral and neuroimaging work indicates that individuals who are externally motivated to respond without racial prejudice tend not to spontaneously regulate their prejudice and prefer to focus on nonracial attributes when evaluating others. This fMRI multivariate analysis used partial least squares analysis to examine the distributed neural processing of race and a relevant but ostensibly nonracial attribute (i.e., socioeconomic status) as a function of the perceiver's external motivation. Sixty-one white male participants (Homo sapiens) privately formed impressions of black and white male faces ascribed with high or low status. Across all conditions, greater external motivation was associated with reduced coactivation of brain regions believed to support emotion regulation (rostral anterior cingulate cortex), introspection (middle cingulate), and social cognition (temporal pole, medial prefrontal cortex). The reduced involvement of this network irrespective of target race and status suggests that external motivation is related to the participant's overall approach to impression formation in an interracial context. The findings highlight the importance of examining network coactivation in understanding the role of external motivation in impression formation, among other interracial social processes.

Correlates of economic decisions in the dorsal and subgenual anterior cingulate cortices.

The anterior cingulate cortex can be divided into distinct ventral (subgenual, sgACC) and dorsal (dACC), portions. The role of dACC in value-based decision-making is hotly debated, while the role of sgACC is poorly understood. We recorded neuronal activity in both regions in rhesus macaques performing a token-gambling task. We find that both encode many of the same variables; including integrated offered values of gambles, primary as well as secondary reward outcomes, number of current tokens and anticipated rewards. Both regions exhibit memory traces for offer values and putative value comparison signals. Both regions use a consistent scheme to encode the value of the attended option. This result suggests that neurones do not appear to be specialized for specific offers (that is, neurones use an attentional as opposed to labelled line coding scheme). We also observed some differences between the two regions: (i) coding strengths in dACC were consistently greater than those in sgACC, (ii) neurones in sgACC responded especially to losses and in anticipation of primary rewards, while those in dACC showed more balanced responding and (iii) responses to the first offer were slightly faster in sgACC. These results indicate that sgACC and dACC have some functional overlap in economic choice, and are consistent with the idea, inspired by neuroanatomy, which sgACC may serve as input to dACC.

Increased rostral anterior cingulate activity following positive mental imagery training in healthy older adults.

The ability to form positive mental images may be an important aspect of mental health and well-being. We have previously demonstrated that the vividness of positive prospective imagery is increased in healthy older adults following positive imagery cognitive training. The rostral anterior cingulate cortex (rACC) is involved in the simulation of future affective episodes. Here, we investigate the effect of positive imagery training on rACC activity during the imagination of novel, ambiguous scenarios vs closely matched control training. Seventy-five participants received 4 weeks of positive imagery or control training. Participants underwent a functional magnetic resonance imaging scan, during which they completed an Ambiguous Sentences Task, which required them to form mental images in response to cues describing ambiguous social events. rACC activity was positively correlated with the pleasantness ratings of images formed. Positive imagery training increased rACC and bilateral hippocampal activity compared with the control training. Here, we demonstrate that rACC activity during positive imagery can be changed by the cognitive training. This is consistent with other evidence that this training enhances the vividness of positive imagery, and suggests the training may be acting to increase the intensity and affective quality of imagery simulating the future.

Human pursuance of equality hinges on mental processes of projecting oneself into the perspectives of others and into future situations.

In the pursuance of equality, behavioural scientists disagree about distinct motivators, that is, consideration of others and prospective calculation for oneself. However, accumulating data suggest that these motivators may share a common process in the brain whereby perspectives and events that did not arise in the immediate environment are conceived. To examine this, we devised a game imitating a real decision-making situation regarding redistribution among income classes in a welfare state. The neural correlates of redistributive decisions were examined under contrasting conditions, with and without uncertainty, which affects support for equality in society. The dorsal anterior cingulate cortex (dACC) and the caudate nucleus were activated by equality decisions with uncertainty but by selfless decisions without uncertainty. Activation was also correlated with subjective values. Activation in both the dACC and the caudate nucleus was associated with the attitude to prefer accordance with others, whereas activation in the caudate nucleus reflected that the expected reward involved the prospective calculation of relative income. The neural correlates suggest that consideration of others and prospective calculation for oneself may underlie the support for equality. Projecting oneself into the perspective of others and into prospective future situations may underpin the pursuance of equality.

The Neuroeconomics of Tobacco Demand: An Initial Investigation of the Neural Correlates of Cigarette Cost-Benefit Decision Making in Male Smokers.

How the brain processes cigarette cost-benefit decision making remains largely unknown. Using functional magnetic resonance imaging (fMRI), this study investigated the neural correlates of decisions for cigarettes (0-10 cigarettes) at varying levels of price during a Cigarette Purchase Task (CPT) in male regular smokers (N = 35). Differential neural activity was examined between choices classified as inelastic, elastic, and suppressed demand, operationalized as consumption unaffected by cost, partially suppressed by cost, and entirely suppressed by cost, respectively. Decisions reflecting elastic demand, putatively the most effortful decisions, elicited greater activation in regions associated with inhibition and planning (e.g., middle frontal gyrus and inferior frontal gyrus), craving and interoceptive processing (anterior insula), and conflict monitoring (e.g., anterior cingulate cortex). Exploratory examination in a harmonized dataset of both cigarette and alcohol demand (N = 59) suggested common neural activation patterns across commodities, particularly in the anterior insula, caudate, anterior cingulate, medial frontal gyrus, and dorsolateral prefrontal cortex. Collectively, these findings provide initial validation of a CPT fMRI paradigm; reveal the interplay of brain regions associated with executive functioning, incentive salience, and interoceptive processing in cigarette decision making; and add to the literature implicating the insula as a key brain region in addiction.