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. Using a randomized, double-blind, within-subject design, we analyzed resting-state fMRI data of 66 healthy young participants who were scanned once each after administration of bromocriptine (a dopamine agonist with preferential affinity for D2 receptor), tolcapone (an inhibitor of catechol-O-methyltransferase), and placebo, to determine whether dopaminergic stimulation modulated effective functional connectivity between hierarchically organized frontal regions in the left hemisphere. We found that dopaminergic drugs modulated connections from the caudal middle frontal gyrus and the inferior frontal sulcus to both rostral and caudal frontal areas. In dorsal frontal regions, effectivity connectivity strength was increased, whereas in ventral frontal regions, effective connectivity strength was decreased. These findings suggest that connections within frontal cortex are differentially modulated by dopamine, which may bias the influence that frontal regions exert over each other.

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. Here, we take a step toward addressing this issue by developing a neurally inspired cognitive model of a class of ill-structured decisions in which choice options must be self-generated. Specifically, using a model in which semantic memory retrieval is assumed to constrain the set of options available during valuation, we generate highly accurate out-of-sample predictions of choices across multiple categories of goods. Our model significantly and substantially outperforms models that only account for valuation or retrieval in isolation or those that make alternative mechanistic assumptions regarding their interaction. Furthermore, using neuroimaging, we confirm our core assumption regarding the engagement of, and interaction between, semantic memory retrieval and valuation processes. Together, these results provide a neurally grounded and mechanistic account of decisions with self-generated options, representing a step toward unraveling cognitive mechanisms underlying adaptive decision-making in the real world.

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. 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 (Badre and D'Esposito, 2007). 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 STATEMENTAbstract 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 because of 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.

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. If true, selective increases in cortical dopamine tone should preferentially enhance maintenance over gating mechanisms. To test this hypothesis, tolcapone, a catechol-O-methyltransferase inhibitor that preferentially increases cortical dopamine tone, was administered in a randomized, double-blind, placebo-controlled, within-subject fashion to 49 participants who completed a hierarchical working memory task that varied maintenance and gating demands. Tolcapone improved performance in a condition with higher maintenance requirements and reduced gating demands, reflected in a reduction in the slope of RTs across the distribution. Resting-state fMRI data demonstrated that the degree to which tolcapone improved performance in individual participants correlated with increased connectivity between a region important for stimulus response mappings (left dorsal premotor cortex) and cortical areas implicated in visual working memory, including the intraparietal sulcus and fusiform gyrus. Together, these results provide evidence that augmenting cortical dopamine tone preferentially improves working memory maintenance.

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. 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.

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. In this study, we demonstrate the benefits of creating an intermediate, cohort-specific template in conjunction with diffeomorphism-based methods to normalize structural MRI images in stroke patients. We show that including this cohort-specific template improves accuracy compared to standard methods for normalizing lesioned brains. Critically, this method reduces overall differences in normalization accuracy between stroke patients and healthy controls, and may improve the localization and connectivity of BOLD signal in functional neuroimaging data.

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-O-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. Given previous work demonstrating that drug effects on behavior are dependent on baseline DA tone, participants were stratified according to genetic polymorphisms associated with cortical (COMT Val158Met) and striatal (Taq1A) DA system function. Our results were partially consistent with an inverted-U-shaped relationship between tolcapone and robust rule maintenance (interaction with COMT genotype) and between bromocriptine and cued rule switching (interaction with Taq1A genotype). However, when task instructions were ambiguous, a third relationship emerged to explain drug effects on spontaneous task switching (interaction of COMT genotype and bromocriptine). Together, this pattern of results suggests that the effects of DA drugs vary not only as a function of the DA system component upon which they act but also on subtle differences in task demands and context.

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. Previous work has primarily examined these types of decisions in isolation. Here we independently varied salience in both the perceptual and categorical domains in a random dot-motion framework by manipulating dot-motion coherence and motion direction relative to a category boundary, respectively. Behavioral and modeling results suggest that categorical (more abstract) information, which is more relevant to subjects' decisions, is weighted more strongly than perceptual (more concrete) information, although they also have significant interactive effects on choice. Within the brain, BOLD activity within frontal regions strongly differentiated categorical salience and weakly differentiated perceptual salience; however, the interaction between these two factors activated similar frontoparietal brain networks. Notably, explicitly evaluating feature interactions revealed a frontal-parietal dissociation: parietal activity varied strongly with both features, but frontal activity varied with the combined strength of the information that defined the motor response. Together, these data demonstrate that frontal regions are driven by decision-relevant features and argue that perceptual decisions and rule-based categorization reflect similar cognitive processes and activate similar brain networks to the extent that they define decision-relevant stimulus-response mappings.NEW & NOTEWORTHY Here we study the behavioral and neural dynamics of perceptual categorization when decision information varies in multiple domains at different levels of abstraction. Behavioral and modeling results suggest that categorical (more abstract) information is weighted more strongly than perceptual (more concrete) information but that perceptual and categorical domains interact to influence decisions. Frontoparietal brain activity during categorization flexibly represents decision-relevant features and highlights significant dissociations in frontal and parietal activity during decision making.

Neuroeconomic dissociation of semantic dementia and behavioural variant frontotemporal dementia.

Many neuropsychiatric disorders are marked by abnormal behaviour and decision-making, but prevailing diagnostic criteria for such behaviours are typically qualitative and often ambiguous. Behavioural variant frontotemporal dementia and semantic variant primary progressive aphasia (also called semantic dementia) are two clinical variants of frontotemporal dementia with overlapping but distinct anatomical substrates known to cause profound changes in decision-making. We investigated whether abnormal decision-making in these syndromes could be more precisely characterized in terms of dissociable abnormalities in patients' subjective evaluations of valence (positive versus negative outcome) and of time (present versus future outcome). We presented 28 patients with behavioural variant frontotemporal dementia, 14 patients with semantic variant primary progressive aphasia, 25 patients with Alzheimer's disease (as disease controls), and 61 healthy older control subjects with experimental tasks assaying loss aversion and delay discounting. In general linear models controlling for age, gender, education and Mini-Mental State Examination score, patients with behavioural variant frontotemporal dementia were less averse to losses than control subjects (P < 0.001), while patients with semantic variant primary progressive aphasia discounted delayed rewards more steeply than controls (P = 0.019). There was no relationship between loss aversion and delay discounting across the sample, nor in any of the subgroups. These findings suggest that abnormal behaviours in neurodegenerative disease may result from the disruption of either of two dissociable neural processes for evaluating the outcomes of action. More broadly, these findings suggest a role for computational methods to supplement traditional qualitative characterizations in the differential diagnosis of neuropsychiatric disorders.

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. 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.

A Neural Correlate of Strategic Exploration at the Onset of Adolescence.

The onset of adolescence is associated with an increase in the behavioral tendency to explore and seek novel experiences. However, this exploration has rarely been quantified, and its neural correlates during this period remain unclear. Previously, activity within specific regions of the rostrolateral PFC (rlPFC) in adults has been shown to correlate with the tendency for exploration. Here we investigate a recently developed task to assess individual differences in strategic exploration, defined as the degree to which the relative uncertainty of rewards directs responding toward less well-evaluated choices, in 62 girls aged 11-13 years from whom resting state fMRI data were obtained in a separate session. Behaviorally, this task divided our participants into groups of explorers (n = 41) and nonexplorers (n = 21). When seed ROIs within the rlPFC were used to interrogate resting state fMRI data, we identified a lateralized connection between the rlPFC and posterior putamen/insula whose strength differentiated explorers from nonexplorers. On the basis of Granger causality analyses, the preponderant direction of influence may proceed from posterior to anterior. Together, these data provide initial evidence concerning the neural basis of exploratory tendencies at the onset of adolescence.

Error-monitoring and post-error compensations: dissociation between perceptual failures and motor errors with and without awareness.

Whether humans adjust their behavior in response to unaware errors remains a controversial issue relevant to insight in neuropsychiatric conditions. Initial error awareness studies found that the error-related negativity (ERN), an event-related potential (ERP) originating in the medial prefrontal cortex after errors, activated equally for aware and unaware errors, suggesting a candidate preconscious mechanism. However, recent studies demonstrate that the ERN decreases after unaware errors. We hypothesized that the ERN is dependent upon awareness, and predicted that previous discrepancies might be due to unaware errors not being differentiated from perceptually uncertain, low-confidence responses that might increase the ERN amplitude. Here we addressed this hypothesis by distinguishing between aware errors, unaware errors, and uncertain responses, and using stimuli (faces) associated with well established sensory ERPs to evaluate the degree of stimulus processing for each trial type. We found that while aware and unaware errors were related to failures at the time of response, uncertain responses were due to failures at the time of stimulus processing indexed by lower amplitude sensory ERPs. Moreover, uncertain responses showed similar ERN activity as aware errors, in comparison with decreased activity for unaware errors. Finally, compared with aware errors, uncertain responses and unaware errors showed reduced neural compensations, such as alpha suppression. Together these findings suggest that the ERN is activated by aware motor errors as well as sensory failures, and that both awareness and certainty are necessary for neural adaptations after errors.

The salience network causally influences default mode network activity during moral reasoning.

Large-scale brain networks are integral to the coordination of human behaviour, and their anatomy provides insights into the clinical presentation and progression of neurodegenerative illnesses such as Alzheimer's disease, which targets the default mode network, and behavioural variant frontotemporal dementia, which targets a more anterior salience network. Although the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, patients with Alzheimer's disease give normal responses to these dilemmas whereas patients with behavioural variant frontotemporal dementia give abnormal responses to these dilemmas. We hypothesized that this apparent discrepancy between activation- and patient-based studies of moral reasoning might reflect a modulatory role for the salience network in regulating default mode network activation. Using functional magnetic resonance imaging to characterize network activity of patients with behavioural variant frontotemporal dementia and healthy control subjects, we present four converging lines of evidence supporting a causal influence from the salience network to the default mode network during moral reasoning. First, as previously reported, the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, but patients with behavioural variant frontotemporal dementia producing atrophy in the salience network give abnormally utilitarian responses to these dilemmas. Second, patients with behavioural variant frontotemporal dementia have reduced recruitment of the default mode network compared with healthy control subjects when deliberating about these dilemmas. Third, a Granger causality analysis of functional neuroimaging data from healthy control subjects demonstrates directed functional connectivity from nodes of the salience network to nodes of the default mode network during moral reasoning. Fourth, this Granger causal influence is diminished in patients with behavioural variant frontotemporal dementia. These findings are consistent with a broader model in which the salience network modulates the activity of other large-scale networks, and suggest a revision to a previously proposed 'dual-process' account of moral reasoning. These findings also characterize network interactions underlying abnormal moral reasoning in frontotemporal dementia, which may serve as a model for the aberrant judgement and interpersonal behaviour observed in this disease and in other disorders of social function. More broadly, these findings link recent work on the dynamic interrelationships between large-scale brain networks to observable impairments in dementia syndromes, which may shed light on how diseases that target one network also alter the function of interrelated networks.

Abstract rule learning: the differential effects of lesions in frontal cortex.

Learning progressively more abstract stimulus-response mappings requires progressively more anterior regions of the lateral frontal cortex. Using an individual differences approach, we studied subjects with frontal lesions performing a hierarchical reinforcement-learning task to investigate how frontal cortex contributes to abstract rule learning. We predicted that subjects with lesions of the left pre-premotor (pre-PMd) cortex, a region implicated in abstract rule learning, would demonstrate impaired acquisition of second-order, as opposed to first-order, rules. We found that 4 subjects with such lesions did indeed demonstrate a second-order rule-learning impairment, but that these subjects nonetheless performed better than subjects with other frontal lesions in a second-order rule condition. This finding resulted from both their restricted exploration of the feature space and the task structure of this condition, for which they identified partially representative first-order rules. Significantly, across all subjects, suboptimal but above-chance performance in this condition correlated with increasing disconnection of left pre-PMd from the putative functional hierarchy, defined by reduced functional connectivity between left pre-PMd and adjacent nodes. These findings support the theory that activity within lateral frontal cortex shapes the search for relevant stimulus-response mappings, while emphasizing that the behavioral correlate of impairments depends critically on task structure.

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. Thus, to better understand aphasia recovery, the relationship between cerebral perfusion and language needs to be systematically examined. In the current study, we aimed to evaluate (i) how stroke affects perfusion outside of lesioned areas in chronic aphasia and (ii) how perfusion in specific cortical areas and perilesional tissue relates to language outcomes in aphasia. We analysed perfusion data from a large sample of participants with chronic aphasia due to left hemisphere stroke (n = 43) and age-matched healthy controls (n = 25). We used anatomically defined regions of interest that covered the frontal, parietal, and temporal areas of the perisylvian cortex in both hemispheres, areas typically known to support language, along with several control regions not implicated in language processing. For the aphasia group, we also looked at three regions of interest in the perilesional tissue. We compared perfusion levels between the two groups and investigated the relationship between perfusion levels and language subtest scores while controlling for demographic and lesion variables. First, we observed that perfusion levels outside the lesioned areas were significantly reduced in frontal and parietal regions in the left hemisphere in people with aphasia compared to the control group, while no differences were observed for the right hemisphere regions. Second, we found that perfusion in the left temporal lobe (and most strongly in the posterior part of both superior and middle temporal gyri) and inferior parietal areas (supramarginal gyrus) was significantly related to residual expressive and receptive language abilities. In contrast, perfusion in the frontal regions did not show such a relationship; no relationship with language was also observed for perfusion levels in control areas and all right hemisphere regions. Third, perilesional perfusion was only marginally related to language production abilities. Cumulatively, the current findings demonstrate that blood flow is reduced beyond the lesion site in chronic aphasia and that hypoperfused neural tissue in critical temporoparietal language areas has a negative impact on behavioural outcomes. These results, using perfusion imaging, underscore the critical and general role that left hemisphere posterior temporal regions play in various expressive and receptive language abilities. Overall, the study highlights the importance of exploring perfusion measures in stroke.

Dopamine, corticostriatal connectivity, and intertemporal choice.

Value-based decisions optimize behavioral outcomes. Because delayed rewards are discounted, an increased tendency to choose smaller, immediate rewards can lead to suboptimal choice. Steep discounting of delayed rewards (impulsivity) characterizes subjects with frontal lobe damage and behavioral disorders including substance abuse. Correspondingly, animal studies and indirect evidence in humans suggest that lower dopamine in the frontal cortex contributes to steeper discounting by impairing corticostriatal function. To test this hypothesis directly, we performed a randomized, double-blind, counterbalanced, placebo-controlled study in which we administered the brain penetrant catechol-O-methyltransferase inhibitor tolcapone or placebo to healthy subjects performing a delay discounting task. Tolcapone significantly increased choice of delayed monetary rewards, and this tolcapone-induced increase covaried with increased BOLD activity in the left ventral putamen and anterior insula. Tolcapone also changed corticostriatal connectivity: specifically, by inducing a decrease in the coherence between ventral putamen and pregenual cingulate cortex. These results indicate that raising cortical dopamine levels attenuates impulsive choice by changing corticostriatal function.

The neural representation of sensorimotor transformations in a human perceptual decision making network.

Humans can quickly engage a neural network to transform complex visual stimuli into a motor response. Activity from a key region within this network, the intraparietal sulcus (IPS), has been associated with evidence accumulation and motor planning, thus implicating it in sensorimotor transformations. If such transformations occur within a brain region, a key and untested prediction is that neural activity reflecting both the parametric amount of evidence available and the timing of motor planning can be independently manipulated. To investigate these ideas, we constructed a dot motion discrimination task in which information about response modality (what to use) and response mapping (how to use it) was provided independently either before or after presentation of a dot motion coherence stimulus whose strength varied across trials. Consistent with our hypothesis, activity within IPS covaried with dot motion coherence during the stimulus phase, and as information necessary for the response was delayed, the peak of IPS activity shifted to the response phase. In contrast, areas such as the motion-sensitive region MT+ and the supplementary motor area demonstrated activity limited to the stimulus and response phases of the task, respectively. These results show that activity in IPS correlates with temporally dissociable representations consistent with both evidence accumulation and motor planning, and suggest that IPS is a core component for sensorimotor transformations within the perceptual decision-making network.

Double dissociation of two cognitive control networks in patients with focal brain lesions.

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.

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. Using an example from intellectual property law, we demonstrate that it is possible to construct a parsimonious neural index of visual similarity that can inform the reasonable person test of trademark infringement. Moreover, when aggregated across multiple participants, this index was able to detect experimenter-induced biases in self-report surveys in a sensitive and replicable fashion. Together, these findings potentially broaden the possibilities for neuroscientific data to inform legal decision-making across a range of settings.

Neural representations of relevant and irrelevant features in perceptual decision making.

Although perceptual decision making activates a network of brain areas involved in sensory, integrative, and motor functions, circuit activity can clearly be modulated by factors beyond the stimulus. Of particular interest is to understand how the network is modulated by top-down factors such as attention. Here, we demonstrate in a motion coherence task that selective attention produces marked changes in the blood oxygen level-dependent (BOLD) response in a subset of regions within a human perceptual decision-making circuit. Specifically, when motion is attended, the BOLD response decreases with increasing motion coherence in many regions, including the motion-sensitive area MT+, the intraparietal sulcus, and the inferior frontal sulcus. However, when motion is ignored, the negative parametric response in a subset of this circuit becomes positive. Through both modeling and connectivity analyses, we demonstrate that this inversion both reflects a top-down influence and segregates attentional from accumulation regions, thereby permitting us to further delineate the contributions of different regions to the perceptual decision.