Distinguishing deception from its confounds by improving the validity of fMRI-based neural prediction.

Deception is a universal human behavior. Yet longstanding skepticism about the validity of measures used to characterize the biological mechanisms underlying deceptive behavior has relegated such studies to the scientific periphery. Here, we address these fundamental questions by applying machine learning methods and functional magnetic resonance imaging (fMRI) to signaling games capturing motivated deception in human participants.

A dopaminergic basis of behavioral control.

Both goal-directed and automatic processes shape human behavior, but these processes often conflict. is the decision about which process guides behavior. Despite the importance of behavioral control for adaptive decision-making, its neural mechanisms remain unclear.

Cerebral perfusion in post-stroke aphasia and its relationship to residual language abilities.

Stroke alters blood flow to the brain resulting in damaged tissue and cell death. Moreover, the disruption of cerebral blood flow (perfusion) can be observed in areas surrounding and distal to the lesion. These structurally preserved but suboptimally perfused regions may also affect recovery.

Dopamine Modulates Effective Connectivity in Frontal Cortex.

There is increasing evidence that the left lateral frontal cortex is hierarchically organized such that higher-order regions have an asymmetric top-down influence over lower order regions. However, questions remain about the underlying neuroarchitecture of this hierarchical control organization. Within the frontal cortex, dopamine plays an important role in cognitive control functions, and we hypothesized that dopamine may preferentially influence top-down connections within the lateral frontal hierarchy.

From scanner to court: A neuroscientifically informed "reasonable person" test of trademark infringement.

Many legal decisions center on the thoughts or perceptions of some idealized group of individuals, referred to variously as the "average person," "the typical consumer," or the "reasonable person." Substantial concerns exist, however, regarding the subjectivity and vulnerability to biases inherent in conventional means of assessing such responses, particularly the use of self-report evidence. Here, we addressed these concerns by complementing self-report evidence with neural data to inform the mental representations in question.

Connectivity-Defined Subdivisions of the Intraparietal Sulcus Respond Differentially to Abstraction during Decision-Making.

The intraparietal sulcus (IPS) has been implicated in numerous functions that range from representation of visual stimuli to action planning, but its role in abstract decision-making has been unclear, in part because low-level functions often act as confounds. Here, we address this problem using a task that dissociates abstract decision-making from sensory salience, attentional control, motor planning, and motor output. Functional MRI data were collected from healthy female and male human subjects while they performed a policy abstraction task requiring use of a more abstract (second-order) rule to select between two less abstract (first-order) rules that informed the motor response.

Enhancing dopamine tone modulates global and local cortical perfusion as a function of COMT val158met genotype.

The cognitive effects of pharmacologically enhancing cortical dopamine (DA) tone are variable across healthy human adults. It has been postulated that individual differences in drug responses are linked to baseline cortical DA activity according to an inverted-U-shaped function. To better understand the effect of divergent starting points along this curve on DA drug responses, researchers have leveraged a common polymorphism (rs4680) in the gene encoding the enzyme catechol-O-methyltransferase (COMT) that gives rise to greater (Met allele) or lesser (Val allele) extracellular levels of cortical DA.

Working memory, cortical dopamine tone, and frontoparietal brain recruitment in post-traumatic stress disorder: a randomized controlled trial.

Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance.

Improved normalization of lesioned brains via cohort-specific templates.

In MRI studies, spatial normalization is required to infer results at the group level. In the presence of a brain lesion, such as in stroke patients, the normalization process can be affected by tissue loss, spatial deformations, signal intensity changes, and other stroke sequelae that introduce confounds into the group analysis results. Previously, most neuroimaging studies with lesioned brains have used normalization methods optimized for intact brains, raising potential concerns about the accuracy of the resulting transformations and, in turn, their reported group level results.

Retrieval-constrained valuation: Toward prediction of open-ended decisions.

Real-world decisions are often open ended, with goals, choice options, or evaluation criteria conceived by decision-makers themselves. Critically, the quality of decisions may heavily rely on the generation of options, as failure to generate promising options limits, or even eliminates, the opportunity for choosing them. This core aspect of problem structuring, however, is largely absent from classical models of decision-making, thereby restricting their predictive scope.

A Hierarchical Bayesian Implementation of the Experience-Weighted Attraction Model.

Social and decision-making deficits are often the first symptoms of neuropsychiatric disorders. In recent years, economic games, together with computational models of strategic learning, have been increasingly applied to the characterization of individual differences in social behavior, as well as their changes across time due to disease progression, treatment, or other factors. At the same time, the high dimensionality of these data poses an important challenge to statistical estimation of these models, potentially limiting the adoption of such approaches in patients and special populations.

Augmenting Frontal Dopamine Tone Enhances Maintenance over Gating Processes in Working Memory.

The contents of working memory must be maintained in the face of distraction, but updated when appropriate. To manage these competing demands of stability and flexibility, maintained representations in working memory are complemented by distinct gating mechanisms that selectively transmit information into and out of memory stores. The operations of such dopamine-dependent gating systems in the midbrain and striatum and their complementary dopamine-dependent memory maintenance operations in the cortex may therefore be dissociable.

The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder.

Rationale: Individuals suffering from alcohol use disorder (AUD) demonstrate difficulty with decision-making and impulsivity that may be associated with impaired frontal cortical function. Therapeutics that enhance frontal dopamine tone could decrease impulsivity and in turn reduce alcohol consumption in individuals with AUD.

Objectives: To determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory-based decision-making tasks.

Dopamine and Risky Decision-Making in Gambling Disorder.

Gambling disorder is a behavioral addiction associated with impairments in value-based decision-making and cognitive control. These functions are thought to be regulated by dopamine within fronto-striatal circuits, but the role of altered dopamine neurotransmission in the etiology of gambling disorder remains controversial. Preliminary evidence suggests that increasing frontal dopamine tone might improve cognitive functioning in gambling disorder.

Effects of Dopaminergic Drugs on Cognitive Control Processes Vary by Genotype.

Dopamine (DA) has been implicated in modulating multiple cognitive control processes, including the robust maintenance of task sets and memoranda in the face of distractors (cognitive stability) and, conversely, the ability to switch task sets or update the contents of working memory when it is advantageous to do so (cognitive flexibility). In humans, the limited specificity of available pharmacological probes has posed a challenge for understanding the mechanisms by which DA, acting on multiple receptor families across the PFC and striatum, differentially influences these cognitive processes. Using a within-subject, placebo-controlled design, we contrasted the impact of two mechanistically distinct DA drugs, tolcapone (an inhibitor of catechol--methyltransferase [COMT], a catecholamine inactivator) and bromocriptine (a DA agonist with preferential affinity for the D2 receptor), on the maintenance and switching of task rules.

Amount and delay insensitivity during intertemporal choice in three neurodegenerative diseases reflects dorsomedial prefrontal atrophy.

Patients with Alzheimer's disease and other dementias often make poor financial decisions, but it remains unclear whether this reflects specific failures in decision-making or more general deficits in episodic and working memory. We investigated how patients with Alzheimer's disease, behavioral variant frontotemporal dementia (bvFTD), and semantic variant primary progressive aphasia (svPPA) apply information in an intertemporal choice task between smaller intermediate and larger delayed rewards, with minimal memory demands. Multilevel modeling estimated subject-level sensitivities to three attributes of choice (the relative difference in reward magnitude, delay length, and absolute reward magnitudes) as well as baseline impulsivity.

Dopamine and Gambling Disorder: Prospects for Personalized Treatment.

Purpose Of Review: To address variation in the severity of gambling disorder, this review evaluates the contribution of mesocorticolimbic dopamine neurons to potential behavioral endophenotypes, the influence of individual differences in the dopamine system on gambling and related behaviors, and the possible role for dopaminergic medications in the treatment of gambling disorder.

Recent Findings: Newer work has suggested that dopaminergic dysfunction can lead to increased reward anticipation and a greater sensitivity to uncertainty, which in turn may drive addictive gambling behaviors. In addition, increased impulsivity, a well-recognized risk factor for gambling disorder, has been linked to dopaminergic dysfunction.

Functional imaging.

Functional imaging methodology has revolutionized our ability to understand brain-behavior relationships. In contrast with the static images obtained with standard imaging methods, functional images permit us to track brain activity as humans view stimuli, hear sounds, consider choices, and make decisions. The insights now possible because of this technology have not only provided new potential markers for disease but have also permitted questions of neural mechanism to be addressed in living humans.

Dopamine, time perception, and future time perspective.

Rationale: Impairment in time perception, a critical component of decision-making, represents a risk factor for psychiatric conditions including substance abuse. A therapeutic that ameliorates this impairment could be advantageous in the treatment of impulsivity and decision-making disorders.

Objectives: Here we hypothesize that the catechol-O-methyltransferase (COMT) inhibitor tolcapone, which increases dopamine tone in frontal cortex (Ceravolo et al Synapse 43:201-207, 2002), improves time perception, with predictive behavioral, genetic, and neurobiological components.

Effects of tolcapone and bromocriptine on cognitive stability and flexibility.

Rationale: The prefrontal cortex (PFC) and basal ganglia (BG) have been associated with cognitive stability and cognitive flexibility, respectively. We hypothesized that increasing PFC dopamine tone by administering tolcapone (a catechol-O-methyltransferase (COMT) inhibitor) to human subjects should promote stability; conversely, increasing BG dopamine tone by administering bromocriptine (a D2 receptor agonist) should promote flexibility.

Objective: We assessed these hypotheses by administering tolcapone, bromocriptine, and a placebo to healthy subjects who performed a saccadic eye movement task requiring stability and flexibility.

Perceptual and categorical decision making: goal-relevant representation of two domains at different levels of abstraction.

To date it has been unclear whether perceptual decision making and rule-based categorization reflect activation of similar cognitive processes and brain regions. On one hand, both map potentially ambiguous stimuli to a smaller set of motor responses. On the other hand, decisions about perceptual salience typically concern concrete sensory representations derived from a noisy stimulus, while categorization is typically conceptualized as an abstract decision about membership in a potentially arbitrary set.

Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers.

Failures of self-regulation in problem and pathological gambling (PPG) are thought to emerge from failures of top-down control, reflected neurophysiologically in a reduced capacity of prefrontal cortex to influence activity within subcortical structures. In patients with addictions, these impairments have been argued to alter evaluation of reward within dopaminergic neuromodulatory systems. Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT), reduced delay discounting, a measure of impulsivity, in healthy subjects.

The effect of social rank feedback on risk taking and associated reward processes in adolescent girls.

The onset of adolescence is associated with an increased tendency to engage in risky behaviors and a developmental shift toward peers that contributes to increased prioritization for learning about and achieving social status. There is relatively little understanding about the specific links between these adolescent-typical phenomena, particularly regarding their neural underpinnings. Based on existing models that suggest the role of puberty in promoting adolescent status-seeking and risk-taking tendencies, we investigated the relation of pubertal hormones with behavioral and neural responses to status-relevant social information in the context of risk taking.

Risky decision-making in adolescent girls: The role of pubertal hormones and reward circuitry.

Adolescence is a developmental period characterized by a greater tendency to take risks. While the adult literature has shown that sex steroids influence reward-related brain functioning and risk taking, research on the role of these hormones during puberty is limited. In this study, we examined the relation between pubertal hormones and adolescent risk taking using a probabilistic decision-making task.

Frontal Monitoring and Parietal Evidence: Mechanisms of Error Correction.

When we respond to a stimulus, our decisions are based not only on external stimuli but also on our ongoing performance. If the response deviates from our goals, monitoring and decision-making brain areas interact so that future behavior may change. By taking advantage of natural variation in error salience, as measured by the RT taken to correct an error (RTEC), here we argue that an evidence accumulation framework provides a potential underlying mechanism for this variable process of error identification and correction, as evidenced by covariation of frontal monitoring and parietal decision-making processes.