Cost-benefit Decision Research Articles

Do privacy concerns determine online information disclosure? The case of internet addiction

PurposeIt is a widely held belief that users make a rational cost-benefit decision when choosing whether to disclose information online. Yet, in the privacy context, the evidence is far from conclusive suggesting that strong and as-yet unmeasured influences on behaviour may exist. This paper aims to demonstrate one such link – the effect of internet addiction on information disclosure.Design/methodology/approachData from 216 Web users was collected regarding their perceptions on privacy and information disclosure intentions as well as avoidance behaviour, an element of internet addiction. Using a research model based on the Privacy Calculus theory, structural equation modelling was applied to quantify the determinants of online disclosure under various conditions.FindingsThe authors show that not all aspects of privacy (a multi-dimensional construct) influence information disclosure. While concerns about data collection influence self-disclosure behaviour, the level of awareness about privacy does not. They next examine the impact of internet addiction on these relationships, finding that internet addiction weakens the influence of privacy concerns to the point of non-significance.Originality/valueThe authors highlight some of the influences of self-disclosure behaviour, showing that some but not all aspects of privacy are influential. They also demonstrate that there are powerful influences on user behaviour that have not been accounted for in prior work; internet addiction is one of these factors. This provides some of the first evidence of the potentially deleterious effect of internet addiction on the privacy calculus.

Stimulation in the Rat Anterior Insula and Anterior Cingulate During an Effortful Weightlifting Task.

When performing tasks, animals must continually assess how much effort is being expended, and gage this against ever-changing physiological states. As effort costs mount, persisting in the task may be unwise. The anterior cingulate cortex (ACC) and the anterior insular cortex are implicated in this process of cost-benefit decision-making, yet their precise contributions toward driving effortful persistence are not well understood. Here we investigated whether electrical stimulation of the ACC or insular cortex would alter effortful persistence in a novel weightlifting task (WLT). In the WLT an animal is challenged to pull a rope 30 cm to trigger food reward dispensing. To make the action increasingly effortful, 45 g of weight is progressively added to the rope after every 10 successful pulls. The animal can quit the task at any point – with the rope weight at the time of quitting taken as the “break weight.” Ten male Sprague-Dawley rats were implanted with stimulating electrodes in either the ACC [cingulate cortex area 1 (Cg1) in rodent] or anterior insula and then assessed in the WLT during stimulation. Low-frequency (10 Hz), high-frequency (130 Hz), and sham stimulations were performed. We predicted that low-frequency stimulation (LFS) of Cg1 in particular would increase persistence in the WLT. Contrary to our predictions, LFS of Cg1 resulted in shorter session duration, lower break weights, and fewer attempts on the break weight. High-frequency stimulation of Cg1 led to an increase in time spent off-task. LFS of the anterior insula was associated with a marginal increase in attempts on the break weight. Taken together our data suggest that stimulation of the rodent Cg1 during an effortful task alters certain aspects of effortful behavior, while insula stimulation has little effect.

Analytical Framework for Homeowner-Focused Computational Cost-Benefit Mitigation Decision Making

As a result of increasing windstorm losses in the United States over the past 50 years, a variety of residential wind hazard mitigation strategies have been recommended. Wind hazard mitigation undoubtedly reduces windstorm losses; however, little customized information is available to support the economic decision-making process for individual stakeholders, especially at the consumer level. Therefore, there is a need for decision support tools to calculate, evaluate, and present the economic benefits of mitigation over variable decision-making time horizons for unique building characteristics in specific geographical locations. This paper presents a cost-benefit computational decision-making recommendation framework that evaluates and presents the cost effectiveness of mitigation, customized based on location, years of interest, and building characteristics. The decision-making framework consists of two cores. The user-independent core and user-dependent core which consists of eight steps, divided into four subprocesses: (1) data acquisition, (2) data evaluation, (3) cost-benefit calculation, and (4) results comparison and decision making. To demonstrate the framework, a wood-framed single-family home in light suburban terrain in Golden Meadow, Louisiana, is used as a case study, considering retrofit mitigation with a $15,000 budget and a decision-making time horizon of 30 years. The case study provides six mitigation options, with cost ranging between approximately $2,000 and $15,000 and net benefit/cost ratios ranging from 2.4 to 13. Once fully implemented in a decision making information tool, the developed mitigation recommendation framework will provide valuable information that can be used by home designers, builders, owners, and other stakeholders to better understand the economic facets of wind hazard mitigation, providing critical information as part of the overall decision-making process.

Anterior cingulate cortex and ventral tegmental area activity during cost-benefit decision-making following maternal immune activation

Abstract Schizophrenia is associated with deficits in memory, behavioural flexibility, and motivation, which can result in difficulties in decision-making. The anterior cingulate cortex (ACC) and ventral tegmental area (VTA) are two brain regions that are involved in decision-making, and display dysfunction in schizophrenia. We investigated ACC and VTA activity in the maternal immune activation (MIA) model of a schizophrenia risk factor. Control and MIA rats completed a cost-benefit decision-making task in a continuous T-maze, choosing between a high cost and high reward (HCHR), and a low cost and low reward (LCLR), option. A choice reversal occurred halfway through each session. Single unit activity in the ACC and local field potentials (LFPs) in the VTA were monitored. Overall, MIA and control rats made a similar proportion of HCHR and LCLR choices across the whole recording session, suggesting similar levels of motivation. However, MIA rats made different decisions than controls during periods of increased uncertainty. This appeared to reflect memory deficits and behavioural inflexibility. MIA animals displayed an increase in ACC activity associated with cost, an increase in synchrony of ACC neurons to the VTA theta oscillation, and a decrease in coherence in the delta frequency between the ACC and VTA. These changes suggest that MIA animals may be biased towards focussing on the cost rather than the benefits of the task, a change also seen in schizophrenia. Here, however, the MIA animals may be able to increase motivation to maintain behaviour despite this change.

BDNF and p-GSK3β in the hippocampus mediate the impairment of delay-based decision making in morphine-dependent rats

It has been shown that morphine addiction impairs cognitive brain functions. However, there is no document to consider the effect of morphine dependency and its withdrawal on cost-benefit decision making and its molecular pathways. The present study aimed to evaluate the influences of morphine dependency and its withdrawal on delay-based decision making and the BDNF, p-GSK3β, and p-CREB levels during the decision making in the hippocampus. Different groups of rats were trained in a T-maze with the delay-based cost-benefit decision-making paradigm. After that, the animals were dependent on morphine, and the percentage of the high reward preference was evaluated. After behavioral tests, BDNF level, p-GSK3β/GSK3β ratio, and p-CREB/CREB ratio in the hippocampus measured by Western blot analysis. The gathered data showed that level of BDNF enhanced while p-GSK3β/GSK3β ratio and p-CREB/CREB ratio in the hippocampus did not change during delay-based decision making. In morphine-dependent rats, the p-GSK3β/GSK3β ratio increased, the BDNF level and p-CREB/CREB ratio did not change in the decision making procedure. After withdrawal from morphine, the BDNF level raised while p-GSK3β/GSK3β ratio and p-CREB/CREB ratio did not change compared to the addiction group. The data declared that BDNF in the hippocampus has a critical role in delay-based decision making. Change in p-CREB in the hippocampus is not related to decision making in normal and morphine-dependent rats. P-GSK3 in the hippocampus is not involved in the decision making in normal rats, but during decision making in morphine-dependent rats, its level increased.

Distinct neural correlates of social and object reward seeking motivation.

The "Choose-a-Movie-CAM" is an established task to quantify the motivation for seeking social rewards. It allows participants to directly assess both the stimulus value and the effort required to obtain it. In the present study, we aimed to identify the neural mechanisms of such cost-benefit decision-making. To this end, functional Magnetic Resonance Imaging data were collected from 24 typical adults while they completed the CAM task. We partly replicated the results from our previous behavioural studies showing that typical adults prefer social over object stimuli and low effort over higher effort stimuli but found no interaction between the two. Results from neuroimaging data suggest that there are distinct neural correlates for social and object preferences. The precuneus and medial orbitofrontal cortex, two key areas involved in social processing are engaged when participants make a social choice. Areas of the ventral and dorsal stream pathways associated with object recognition are engaged when making an object choice. These activations can be seen during the decision phase even before the rewards have been consumed, indicating a transfer the hedonic properties of social stimuli to its cues. We also found that the left insula and bilateral clusters in the inferior occipital gyrus and the inferior parietal lobule were recruited for increasing effort investment. We discuss limitations and implications of this study which reveals the distinct neural correlates for social and object rewards, using a robust behavioural measure of social motivation.

Value and choice as separable and stable representations in orbitofrontal cortex

Value-based decision-making requires different variables—including offer value, choice, expected outcome, and recent history—at different times in the decision process. Orbitofrontal cortex (OFC) is implicated in value-based decision-making, but it is unclear how downstream circuits read out complex OFC responses into separate representations of the relevant variables to support distinct functions at specific times. We recorded from single OFC neurons while macaque monkeys made cost-benefit decisions. Using a novel analysis, we find separable neural dimensions that selectively represent the value, choice, and expected reward of the present and previous offers. The representations are generally stable during periods of behavioral relevance, then transition abruptly at key task events and between trials. Applying new statistical methods, we show that the sensitivity, specificity and stability of the representations are greater than expected from the population’s low-level features—dimensionality and temporal smoothness—alone. The separability and stability suggest a mechanism—linear summation over static synaptic weights—by which downstream circuits can select for specific variables at specific times.

Simple Aesthetic Sense and Addiction Emerge in Neural Relations of Cost-Benefit Decision in Foraging

A rudimentary aesthetic sense is found in the stimulus valuations and cost-benefit decisions made by primitive generalist foragers. These are based on factors governing personal economic decisions: incentive, appetite, and learning. We find that the addictive process is an extreme expression of aesthetic dynamics. An interactive, agent-based model, ASIMOV, reproduces a simple aesthetic sense from known neural relations of cost-benefit decision in foraging. In the presence of very high reward, an addiction-like process emerges. A drug-like prey provides extreme reward with no nutritive value, initiating high selectivity and prolonged cravings for drug through reward learning. Varying reward experience, caused by homeostatic changes in the neural circuitry of reward, further establishes the course of addiction, consisting of desensitization, withdrawal, resensitization, and associated changes in nutritional choice and pain sensitivity. These observations are consistent with the early evolution of addiction mechanisms in simple generalist foragers as an aesthetic sense for evaluating prey. ASIMOV is accessible to inspection, modification, and experiment, is adaptable as an educational tool, and provides insight on the possible coevolutionary origins of aesthetics and the addiction process.

S119. A DIMENSIONAL APPROACH TO UNDERSTANDING COST-BENEFIT DECISION-MAKING IN SCHIZOPHRENIA AND DEPRESSION

BackgroundReductions in motivation figure prominently in the clinical presentation of schizophrenia (SZ) and major depressive disorder (MDD). One critical nexus in the motivation system that drives real-world behaviour is effort-based decision-making (EBDM), which refers to the cost-benefit calculations involved in computing the amount of effort one is willing to expend in order to obtain a desired reward. Important individual differences are associated with these processes, and impairments in motivation can arise if any relevant cost-benefit information is not properly computed, appraised, or integrated. Thus, in order to better understand the computations guiding choice behaviour, the present study sought to utilize a more person-centric approach to characterize individual differences in the effort-cost computations that underlie cost-benefit decision-making in individuals with SZ and MDD.MethodsA sample of 51 individuals with SZ, 43 individuals with MDD, and 51 healthy control (HC) participants underwent a comprehensive clinical and cognitive characterization, and completed the Effort Expenditure for Rewards Task (EEfRT) as a measure of EBDM. Random effects modelling was conducted to estimate the subject-specific predictors of reward magnitude, probability, and perceived cost on choice behaviour. Cluster analysis was subsequently applied to these predictors in order to identify subtypes of impairments within the entire sample, irrespective of diagnostic status.ResultsData-driven cluster analysis identified unique subgroups of individuals with distinct patterns of utilizing cost-benefit information to guide effort-based decision-making. Analyses of variance revealed significant differences between clusters with respect to their utilization of reward (F (3, 133) = 51.58, p < .001), probability (F (3, 133) = 48.71, p < .001), and cost (F (3, 133) = 45.24, p < .001). The first cluster was characterized by an indifference to all cost-benefit information, the second cluster was more influenced by perceived cost, the third cluster demonstrated a preference for reward-based information, and the fourth cluster mainly utilized probability to guide their decision-making. While the clusters did not differ in their severity of clinical amotivation (p = .11), there was a significant effect for cognition, specifically with impairments in clusters 1 and 2. All diagnostic groups were represented in each cluster, but the distribution of SZ, MDD, and HC participants was significantly different (X2 (6, N = 137) = 16.18, p = .013).DiscussionThe emergence of four distinct subgroups in our sample suggests that there are individual differences amongst SZ, MDD, and HC participants in their utilization of cost-benefit information to guide choice behaviour. Moreover, with elevated levels of clinical amotivation present in all four clusters, it is possible that these unique cost-benefit decision-making patterns represent different underlying motivational impairments, the nature of which depending on how reward magnitude, probability, and perceived cost are weighed. Thus, by characterizing the specific mechanisms underlying EBDM in SZ and MDD, the results of this work may be able to help guide the identification of more precise targets for the effective treatment of motivation deficits.

Impairment of cost-benefit decision making in morphine-dependent rats is partly mediated via the alteration of BDNF and p-CREB levels in the nucleus accumbens

The ability to choose goals based on decision usefulness or the time required to reach the goals chosen are important aspects of decision making. There is considerable evidence in the literature indicating the fact that drug abuse affects different aspects of cognition. In the current study, we assessed the effects of morphine dependence and its withdrawal on cost-benefit decision making and furthermore the involvement of BDNF and p-CREB in the nucleus accumbens, a key brain area involved in decision making was measured. Different groups of male Wistar rats were trained in an effort-based and/or delay-based form of cost-benefit T-maze decision-making task. Thereafter, the animals were morphine dependent and the percentage of the high reward preference was evaluated. After behavioral tests, the BDNF level, and p-CREB/CREB ratio were measured by Western blot analysis. The results showed that during effort-based but not delay-based decision making, BDNF and p-CREB levels increased. During effort-based decision making in morphine dependent rats, BDNF decreased but there was no significant change in p-CREB. Besides, during delay-based decision making in the morphine dependent group, both BDNF and p-CREB did not show any significant change. These findings revealed that BDNF and p-CREB/CREB ratio in the NAc are essential factors for effort-based but not delay-based decision making. In addition, impairment of effort-based decision making in morphine dependent rats is related to the decrease of BDNF level but not p-CREB/CREB ratio in the NAc. However, delay-based decision making defects in morphine dependent rats did not associate with the change in BDNF and p-CREB levels in the NAc.

Dissociating the effects of dopamine D2 receptors on effort-based versus value-based decision making using a novel behavioral approach.

Cost-benefit decision making is essential for organisms to adapt to their ever-changing environment. Most studies of cost-benefit decision making involve choice conditions in which effort and value are varied simultaneously. This prevents identification of the aspects of cost-benefit decision making that are affected by experimental manipulations. We developed operant assays to isolate the individual impacts of effort and value manipulations on cost-benefit decision making. In the concurrent effort choice (CEC) task, mice choose between exerting two distinct types of effort: the number of responses and the duration of a response, to earn the same reward. By parametrically varying response cost, psychometric functions are obtained that reflect how the two types of effort scale against one another. Direct manipulations of effort shift the functions. Because reward value is held constant in this task, differences in scaling of the two response types must be related to the effort manipulations. In the concurrent value choice (CVC) task, mice make the same type of response to earn rewards of different value (e.g., pellets vs. sucrose solutions). Here the effort required to earn one reward type is parametrically varied to obtain the psychometric function that scales the value of the two rewards into the number of responses subjects will pay to earn one reward over the other. Direct value manipulations shift these functions. We tested the effect of the dopamine D2 receptor antagonist, haloperidol, on performance in the CEC and CVC assays and found that D2R signaling is important for effort-based, but not value-based decision making. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Responsible use of psychostimulants

Neuroscience Psychostimulants have a place in the therapy of attentional disorders. However, they are also widely used off-label to enhance cognitive performance, and their mechanisms of action remain elusive. Westbrook et al. studied the effects of these drugs and concurrently measured striatal dopamine synthesis capacity in young, healthy participants (see the Perspective by Janes). They administered a placebo, methylphenidate (a dopamine and noradrenaline reuptake blocker), and sulpiride (a selective D2 receptor antagonist) while participants made explicit cost-benefit decisions about whether to engage in cognitive effort. Higher dopamine synthesis capacity in the caudate nucleus was associated with greater willingness to allocate cognitive effort. In addition, methylphenidate and sulpiride increased subjective values and motivation to work specifically for people with low dopamine synthesis capacity. Cognition-enhancing drugs may thus act at the motivational level rather than directly boosting cognition per se. Science , this issue p. [1362][1]; see also p. [1300][2] [1]: /lookup/doi/10.1126/science.aaz5891 [2]: /lookup/doi/10.1126/science.abb0265

Naloxone-precipitated withdrawal ameliorates impairment of cost-benefit decision making in morphine-treated rats: Involvement of BDNF, p-GSK3-β, and p-CREB in the amygdala

Several studies indicated that morphine administration impairs cognitive brain functions. Therefore, in the current study, we investigated the effect of subchronic exposure to morphine and its withdrawal on effort- and/or delay-based forms of cost-benefit decision making and alterations in p-CREB/CREB ratio, p-GSK3β/GSK3β ratio, and BDNF level during decision making in the amygdala. Our data displayed an impairment of both forms of cost-benefit decision making following subchronic exposure to morphine. However, preference of high reward/high effort and/or high delay reward increased after naloxone injection. In molecular section, levels of BDNF and p-CREB/CREB ratio increased during cost-benefit decision making while p-GSK3β/GSK3β ratio decreased in both forms of decision making. In morphine-treated rats, level of BDNF and p-CREB/CREB ratio reduced during both forms of decision making while p-GSK3β/GSK3β ratio increased during delay-based and did not have a significant difference with the control group during effort-based decision making. On the withdrawal day, BDNF level raised while p-GSK3β/GSK3β ratio attenuated compared to morphine-treated group in both form of decision making. In addition, p-CREB/CREB ratio increased only during delay-based decision making on the withdrawal day. In conclusion, our data revealed that subchronic exposure to morphine interferes with the cost-benefit decision making may be via changes in level of BDNF, p-CREB/CREB and p-GSK3β/GSK3β ratio in the amygdala.

Cumulative Burden of Illness in Veterans With Tardive Dyskinesia and Serious Mental Disorders.

To inform cost-benefit decisions for veterans, the risk of tardive dyskinesia (TD) and its impact on comorbidities and outcomes were assessed. In a retrospective study, veterans with schizophrenia/schizoaffective, and bipolar and major depressive disorders receiving antipsychotics during the period October 1, 2014, to September 30, 2015, were identified. Tardive dyskinesia was determined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Correlates of TD were examined using χ or t tests. Odds ratios (ORs) and β parameters with 95% confidence intervals (CIs) for categorical and continuous variables associated with TD were derived from a multivariate logistic and linear regression, respectively. Among 7985 veterans, 332 (4.2%) were diagnosed as having possible TD. The odds of having TD were higher for older veterans (OR, 1.04; 95% CI, 1.03-1.05; P < 0.0001) and veterans with schizophrenia/schizoaffective disorder (OR, 1.54; 95% CI, 1.23-1.91; P < 0.0001) or diabetes (OR, 1.64; 95% CI, 1.30-2.06; P < 0.0001). Veterans with TD received more antipsychotic prescriptions (mean ± SD, 18.4 ± 30.3 vs 13.3 ± 26.4; P = 0.003) and days of supply (233.9 ± 95.4 vs 211.4 ± 102.0; P < 0.0001). They were more likely to have received 2 or more antipsychotics (27.1% vs 19.7%, P = 0.0009) and benztropine (OR, 2.25: 95% CI 1.73-2.91; P < 0.0001). Veterans with TD had a higher Charlson Comorbidity Index score (β = 0.32; SE, 0.09; 95% CI, 0.14-0.49; P = 0.0003) and higher odds of any medical hospitalization (OR, 1.45; 95% CI, 1.07-1.95; P = 0.001). The diagnosis of possible TD was associated with older age, schizophrenia/schizoaffective disorder, medical comorbidity, and hospitalization. Tardive dyskinesia may be a marker for patients at risk of adverse health care outcomes and diminished quality of life.

P.150 Effect of cannabinoid activation in nucleus accumbens on cost-benefit decision making mediates via the change in BDNF and p-CREB levels

Action observation (AO) and motor imagery (MI) are simulation states that have been demonstrated to independently enhance motor skill performance. Historically, AO and MI were examined in isolation from one another; however recent neurophysiological and behavioural evidence indicates that using MI during AO (AO+MI) may be more potent at enhancing performance than either simulation state alone. The AO component of AO+MI is typically delivered via a self-modelled or peer-skilled model paradigm, via an observation video. The purpose of the proposed study is to further examine the implementation of AO+MI states by directly comparing the effectiveness of self-modelled AO+MI with peer-skilled modelled AO+MI to augment performance on a golf putting task with a sample of 56 skilled golfers. Our primary hypothesis predicts that skilled participants who engage with a self-modelled intervention will improve their performance more than those engaging with a peer-skilled model intervention. This hypothesis is predicated on the idea that self-modelling will be used in the context of performers’ existing mental representation and will facilitate improved performance, whereas the peer modelling may destabilize skilled performers’ existing mental representation.

Aberrant Cost–Benefit Integration During Effort-Based Decision Making Relates to Severity of Substance Use Disorders

Aberrant cost–benefit decision making is a key factor related to individual differences in the expression of substance use disorders (SUDs). Previous research highlights how delay-cost sensitivity affects variability in SUDs; however, other forms of cost–benefit decision making—effort-based choice—have received less attention. We administered the Effort Expenditure for Rewards Task (EEfRT) in an SUD-enriched community sample ( N = 80). Individuals with more severe SUDs were less likely to use information about expected value when deciding between high-effort, high-reward and low-effort, low-reward options. Furthermore, individuals whose severity of use was primarily related to avoiding aversive affective states and individuals with heightened sensitivity to delay costs during intertemporal decision making were the least sensitive to expected value signals when making decisions to engage in effortful behavior. Together, these findings suggest that individuals with more severe SUDs have difficulty integrating multiple decision variables to guide behavior during effort-based decision making.

Interoperability – Technical or economic challenge?

Abstract Interoperability in healthcare is a long-standing and addressed phenomenon. In the literature, it is discussed as both the cause of an insufficiently perceived digitalization and in context with an inadequate IT-based integration in healthcare. In particular, technical and organizational aspects are highlighted from the perspective of the different involved actors to achieve sufficient interoperability. Depending on the individual case, various established international industry standards in healthcare (e. g. DICOM, HL7 or FHIR) promise simple adaptation and various application advantages. In addition to the technical view, this article assumes economic challenges as the main causes for the lack of interoperability not discussed in the forefront. The economic challenges were mentioned and sparingly discussed in few cases in the literature. This article aims to fill this gap by offering a first characterization of identified and discussed economic challenges in the literature with respect to the lack of interoperability in healthcare. Based on a systematic literature search, 14 of the original 330 articles can be identified as relevant, allowing a more economic perspective on interoperability. In this context, different economic effects will be described; this includes cost-benefit decisions by individual stakeholders under different kinds of uncertainty or balancing of known individual costs for interoperability against uncertain and skewed distributed benefits within an ecosystem. Furthermore, more sophisticated cost-benefit approaches regarding interoperability challenges can be identified, including cost-benefit ratios that shift over time, or lock-in effects resulting from CRM-motivated measures that turn (non)interoperability decisions into cost considerations for single actors. Also, self-reinforcing effects through path dependencies, including direct and indirect network effects, have an impact on single and linked interoperability decisions.

Microstimulation of primate neocortex targeting striosomes induces negative decision-making.

Here, we combined MRI-guided electrical microstimulation and viral tracing to examine the function of a corticostriatal circuit implicated by previous cortical microstimulation as modulating affective judgment and decision-making. Local microstimulation of a small part of the pregenual anterior cingulate cortex (pACC) was found to increase avoidance decisions in a cost-benefit decision-making task (Ap-Av task) in which differing amounts of "good" and "bad" options were given simultaneously. No effect of such stimulation was found when the monkeys performed a task in which both offers were rewarding, but given in different amounts. We asked whether we could identify the targets of such corticostriatal circuits when the cortical microstimulation sites were explicitly identified as affecting approach or avoidance in the Ap-Av task. We explored the pACC and caudal orbitofrontal cortex (cOFC) to look for such sites. For each cortical region, we found sites at which microstimulation induced increased avoidance behavior. After identifying these sites, we injected viral tracers carrying constructs allowing subsequent track-tracing post-mortem. For each site identified behaviorally as increasing avoidance choices, we found strong fiber projections to the anterior striatum with large parts of these targeting striosomes subsequently identified by serial section immunohistochemistry. With fMRI, we demonstrated that microstimulation in an anesthetized monkey at sites pre-identified as affecting Ap-Av choices induced blood oxygen level dependent activation of the anterior striatum, confirming that the microstimulation method that we applied was effective in activating the striatum. These findings outline circuits leading from pACC/cOFC to striosomes and causally modulating decision-making under emotional conflict.

Dopaminergic D1 Receptor Stimulation Affects Effort and Risk Preferences

BackgroundActivation of D1 receptors has been related to successful goal-directed behavior, but it remains unclear whether D1 receptor activation causally tips the balance of weighing costs and benefits in humans. Here, we tested the impact of pharmacologically stimulated D1 receptors on sensitivity to risk, delay, and effort costs in economic choice and investigated whether D1 receptor stimulation would bias preferences toward options with increased costs in a cost-specific manner. MethodsIn a randomized, double-blind, placebo-controlled, parallel-group phase 1 study, 120 healthy young volunteers received either placebo or 1 of 3 doses (6 mg, 15 mg, or 30 mg) of a novel, selective D1 agonist (PF-06412562). After drug administration, participants performed decision tasks measuring their preferences for risky, delayed, and effortful outcomes. ResultsHigher doses of the D1 agonist increased the willingness to exert physical effort for reward as well as reduced the preference for risky outcomes. We observed no effects on preferences for delayed rewards. ConclusionsThe current results provide evidence that D1 receptor stimulation causally affects core aspects of cost-benefit decision making in humans.

Approach-Avoidance Conflict in Major Depressive Disorder: Congruent Neural Findings in Humans and Nonhuman Primates

BackgroundMaladaptive approach-avoidance behavior has been implicated in the pathophysiology of major depressive disorder (MDD), but the neural basis of these abnormalities in decision making remains unclear. Capitalizing on recent preclinical findings, we adapted an approach-avoidance conflict task from nonhuman primate research for use in human functional magnetic resonance imaging (fMRI). MethodsForty-two female participants, including 18 unmedicated individuals with current MDD (mean age 25.2 ± 5.1 years) and 24 psychiatrically healthy control subjects (mean age 26.3 ± 7.6 years) completed the adapted approach-avoidance task during fMRI. To probe potential mechanistic factors underlying the observed behavioral and fMRI findings and to inform interpretation of putative group differences, we examined electrophysiological data from 2 female Macaca mulatta monkeys performing the approach-avoidance conflict task mimicked in the fMRI study. ResultsFindings demonstrated congruent neural correlates of approach-avoidance conflict and aversive responsiveness in the anterior cingulate cortex, including the pregenual cortex, of human subjects and macaques (humans: p < .05 whole-brain corrected; macaques: p < .05). The MDD group exhibited aberrant task-related activations in the anterior cingulate cortex, prefrontal cortex, and striatum (all ps < .05). Neural effects in the MDD group were cross-sectionally associated with stress and depressive symptoms. Importantly, they also prospectively predicted stress at 6-month follow-up (all ps < .05). ConclusionsFindings indicate that there is conservation of anterior cingulate activation across species and that frontal and striatal regions, in unmedicated humans with MDD, are abnormally responsive during cost-benefit decision making. We suggest that these disruptions could be valuable candidates for translational biomarkers.