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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. By identifying IPS subdivisions with preferential connectivity to prefrontal regions that are differentially responsive to task abstraction, we found that a caudal IPS (cIPS) subregion with strongest connectivity to the pre-premotor cortex was preferentially active for second-order cues, whereas a rostral IPS subregion (rIPS) with strongest connectivity to the dorsal premotor cortex was active during attentional control over first-order cues. These effects for abstraction were seen in addition to cIPS activity that was specific to sensory salience, and rIPS activity that was specific to motor output. Notably, topographic responses to the second-order cue were detected along the caudal-rostral axis of IPS, mirroring the broader organization seen in lateral prefrontal cortex. Together, these data demonstrate that subregions within IPS exhibit activity responsive to policy abstraction, and they suggest that IPS may be organized into frontoparietal subnetworks that support hierarchical cognitive control. SIGNIFICANCE STATEMENT Abstract decision-making allows us to flexibly adapt our behavior to new contexts. Although much previous work has focused on the role of lateral prefrontal cortex in such decisions, the contributions of parietal cortex have been relatively understudied. Here, we demonstrate that spatially segregated subregions of human IPS with strong functional connections to lateral prefrontal cortex demonstrate activity selective for abstract decisions. This activity can be distinguished from responses resulting from cognitive processes related to sensory salience, attentional control, motor planning, and movement. Together, these findings indicate that different task demands are reflected in the topography of IPS, and they explicitly reveal a role in abstract decision-making.

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. Here we examined the extent to which changes in resting cortical perfusion following the administration of two mechanistically-distinct dopaminergic drugs vary by COMT genotype, and thereby track predictions of the inverted-U model. Using arterial spin labeling (ASL) and a double-blind, within-subject design, perfusion was measured in 75 healthy, genotyped participants once each after administration of tolcapone (a COMT inhibitor), bromocriptine (a DA D2/3 agonist), and placebo. COMT genotype and drug interacted such that COMT Val homozygotes exhibited increased prefusion in response to both drugs, whereas Met homozygotes did not. Additionally, tolcapone-related perfusion changes in the right inferior frontal gyrus correlated with altered performance on a task of executive function. No comparable effects were found for a genetic polymorphism (rs1800497) affecting striatal DA system function. Together, these results indicate that both the directionality and magnitude of drug-induced perfusion change provide meaningful information about individual differences in response to enhanced cortical DA tone.

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. We therefore examined whether increasing frontal dopamine tone via a single dose of the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in human gamblers (n=14) in a randomized double-blind placebo-controlled crossover study. Data were analyzed using hierarchical Bayesian parameter estimation and a combined risky choice drift diffusion model. Model comparison revealed a non-linear mapping from value differences to trial-wise drift rates, confirming recent findings. An increase in risk-taking under tolcapone vs. placebo was about five times more likely, given the data, than a decrease (BF = 0.2). Examination of drug effects on diffusion model parameters revealed that an increase in the value-dependency of the drift rate under tolcapone was about thirteen times more likely than a decrease (BF = .073). In contrast, a reduction in the maximum drift rate under tolcapone was about seven times more likely than an increase (BF = 7.51). Results add to previous work on COMT inhibitors in behavioral addictions and to mounting evidence for the applicability of diffusion models in value-based decision-making. Future work should focus on individual genetic, clinical and cognitive factors that might account for heterogeneity in the effects of COMT inhibition. Significance statement Gambling disorder is associated with impairments in value-based decision-making and cognitive control, functions regulated by the neurotransmitter dopamine. Here we examined whether increasing frontal dopamine tone via the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in a group of gamblers. Computational modeling did not reveal consistent reductions in risky decision-making under tolcapone in gamblers. If anything, tolcapone increased risky choice. Future work should focus on individual genetic, clinical and cognitive factors that might account for heterogeneity in the effects of COMT inhibition.

© 2016 The Authors 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. In this task, participants could choose on each trial to play or pass based on explicit information about the risk level and stakes involved in their decision. We administered this task to 58 11-to-13-year-old girls while functional MRI images were obtained to examine reward-related brain processes associated with their risky choices. Results showed that higher testosterone levels were associated with increased risk taking, which was mediated by increased medial orbitofrontal cortex activation. Furthermore, higher estradiol levels were associated with increased nucleus accumbens activation, which in turn related to decreased risk taking. These findings offer potential neuroendocrine mechanisms that can explain why some adolescent girls might engage in more risk taking compared to others.

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. We study two early EEG signals linked to monitoring within medial PFC—the error-related negativity (ERN) and frontocentral theta activity—and a third EEG signal, the error positivity (Pe), that is thought to share the same parietal substrates as a signal (the P3b) proposed to reflect evidence accumulation. As predicted, our data show that on slow RTEC trials, frontal monitoring resources are less strongly employed, and the latency of the Pe is longer. Critically, the speed of the RTEC also covaries with the magnitude of subsequent neural (intertrial alpha power) and behavioral (post-error slowing) adjustments following the correction. These results are synthesized to describe a timing diagram for adaptive decision-making after errors and support a potential evidence accumulation mechanism in which error signaling is followed by rapid behavioral adjustments.

In perceptual decision making, the selection of an appropriate action depends critically on an organism’s ability to use sensory inputs to accumulate evidence for a decision. However, differentiating decision-related processes from effects of “time on task” can be difficult. Here we combine the response signal paradigm, in which the experimenter rather than the subject dictates the time of the response, and independent components analysis (ICA) to search for signatures consistent with time on task and decision making, respectively, throughout the brain. Using this novel approach, we identify two such independent components from BOLD activity related to a random dot motion task: one sensitive to the main effect of stimulus duration, and one to both the main effect of motion coherence and its interaction with duration. Furthermore, we demonstrate that these two components are expressed differently throughout the brain, with activity in occipital regions most reflective of the former, activity within intraparietal sulcus modulated by both factors, and more anterior regions including the anterior insula, pre-SMA, and inferior frontal sulcus driven almost exclusively by the latter. Consistent with these ICA findings, cluster analysis identifies a posterior-to-anterior gradient that differentiates regions sensitive to time on task from regions whose activity is strongly tied to motion coherence. Together, these findings demonstrate that progressively more anterior regions are likely to participate in progressively more proximate decision-related processes.

Although we often encounter circumstances with which we have no prior experience, we rapidly learn how to behave in these novel situations. Such adaptive behavior relies on abstract behavioral rules that are generalizable, rather than concrete rules mapping specific cues to specific responses. Though the frontal cortex is known to support concrete rule learning, less well understood are the neural mechanisms supporting the acquisition of abstract rules. Here we use a novel reinforcement learning paradigm to demonstrate that more anterior regions along the rostro-caudal axis of frontal cortex support rule learning at higher levels of abstraction. Moreover, these results indicate that when humans confront new rule learning problems, this rostro-caudal division of labor supports the search for relationships between context and action at multiple levels of abstraction simultaneously.

Neuroimaging studies of cognitive control have identified two distinct networks with dissociable resting state connectivity patterns. This study, in patients with heterogeneous damage to these networks, demonstrates network independence through a double dissociation of lesion location on two different measures of network integrity: functional correlations among network nodes and within-node graph theory network properties. The degree of network damage correlates with a decrease in functional connectivity within that network while sparing the nonlesioned network. Graph theory properties of intact nodes within the damaged network show evidence of dysfunction compared with the undamaged network. The effect of anatomical damage thus extends beyond the lesioned area, but remains within the bounds of the existing network connections. Together this evidence suggests that networks defined by their role in cognitive control processes exhibit independence in resting data.

Our ability to make rapid decisions based on sensory information belies the complexity of the underlying computations. Recently, “accumulator” models of decision making have been shown to explain the activity of parietal neurons as macaques make judgments concerning visual motion. Unraveling the operation of a decision-making circuit, however, involves understanding both the responses of individual components in the neural circuitry and the relationships between them. In this functional magnetic resonance imaging study of the decision process in humans, we demonstrate that an accumulator model predicts responses to visual motion in the intraparietal sulcus (IPS). Significantly, the metrics used to define responses within the IPS also reveal distinct but interacting nodes in a circuit, including early sensory detectors in visual cortex, the visuomotor integration system of the IPS, and centers of cognitive control in the prefrontal cortex, all of which collectively define a perceptual decision-making network.