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.

Real-life choices often require that we draw inferences about the value of options based on structured, schematic knowledge about their utility for our current goals. Other times, value information may be retrieved directly from a specific prior experience with an option. In an fMRI experiment, we investigated the neural systems involved in retrieving and assessing information from different memory sources to support value-based choice. Participants completed a task in which items could be conferred positive or negative value based on schematic associations (i.e., schema value) or learned directly from experience via deterministic feedback (i.e., experienced value). We found that ventromedial pFC (vmPFC) activity correlated with the influence of both experience- and schema-based values on participants' decisions. Connectivity between the vmPFC and middle temporal cortex also tracked the inferred value of items based on schematic associations on the first presentation of ingredients, before any feedback. In contrast, the striatum responded to participants' willingness to bet on ingredients as a function of the unsigned strength of their memory for those options' values. These results argue that the striatum and vmPFC play distinct roles in memory-based value judgment and decision-making. Specifically, the vmPFC assesses the value of options based on information inferred from schematic knowledge and retrieved from prior direct experience, whereas the striatum controls a decision to act on options based on memory strength.

The prefrontal cortex (PFC) is central to flexible, goal-directed cognition, and understanding its representational code is an important problem in cognitive neuroscience. In humans, multivariate pattern analysis (MVPA) of fMRI blood oxygenation level-dependent (BOLD) measurements has emerged as an important approach for studying neural representations. Many previous studies have implicitly assumed that MVPA of fMRI BOLD is just as effective in decoding information encoded in PFC neural activity as it is in visual cortex. However, MVPA studies of PFC have had mixed success. Here we estimate the base rate of decoding information from PFC BOLD activity patterns from a meta-analysis of published MVPA studies. We show that PFC has a significantly lower base rate (55.4%) than visual areas in occipital (66.6%) and temporal (71.0%) cortices and one that is close to chance levels. Our results have implications for the design and interpretation of MVPA studies of PFC and raise important questions about its functional organization.

Patient lesion and neuroimaging studies have identified a rostral-to-caudal functional gradient in the lateral frontal cortex (LFC) corresponding to higher-order (complex or abstract) to lower-order (simple or concrete) cognitive control. At the same time, monkey anatomical and human functional connectivity studies show that frontal regions are reciprocally connected with parietal and temporal regions, forming parallel and distributed association networks. Here, we investigated the link between the functional gradient of LFC regions observed during control tasks and the parallel, distributed organization of association networks. Whole-brain fMRI task activity corresponding to four orders of hierarchical control [Badre, D., & D'Esposito, M. Functional magnetic resonance imaging evidence for a hierarchical organization of the prefrontal cortex. Journal of Cognitive Neuroscience , 19 , 2082–2099, 2007] was compared with a resting-state functional connectivity MRI estimate of cortical networks [Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology , 106 , 1125–1165, 2011]. Critically, at each order of control, activity in the LFC and parietal cortex overlapped onto a common association network that differed between orders. These results are consistent with a functional organization based on separable association networks that are recruited during hierarchical control. Furthermore, corticostriatal functional connectivity MRI showed that, consistent with their participation in functional networks, rostral-to-caudal LFC and caudal-to-rostral parietal regions had similar, order-specific corticostriatal connectivity that agreed with a striatal gating model of hierarchical rule use. Our results indicate that hierarchical cognitive control is subserved by parallel and distributed association networks, together forming multiple localized functional gradients in different parts of association cortex. As such, association networks, while connectionally organized in parallel, may be functionally organized in a hierarchy via dynamic interaction with the striatum.

Adaptive memory retrieval requires mechanisms of cognitive control that facilitate the recovery of goal-relevant information. Frontoparietal systems are known to support control of memory retrieval. However, the mechanisms by which the brain acquires, evaluates, and adapts retrieval strategies remain unknown. Here, we provide evidence that ventral striatal activation tracks the success of a retrieval strategy and correlates with subsequent reliance on that strategy. Human participants were scanned with fMRI while performing a lexical decision task. A rule was provided that indicated the likely semantic category of a target word given the category of a preceding prime. Reliance on the rule improved decision-making, as estimated within a drift diffusion framework. Ventral striatal activation tracked the benefit that relying on the rule had on decision-making. Moreover, activation in ventral striatum correlated with a participant's subsequent reliance on the rule. Taken together, these results support a role for ventral striatum in learning and evaluating declarative retrieval strategies.

Free recall is a fundamental paradigm for studying memory retrieval in the context of minimal cue support. Accordingly, free recall has been extensively studied using behavioral methods. However, the neural mechanisms that support free recall have not been fully investigated due to technical challenges associated with probing individual recall events with neuroimaging methods. Of particular concern is the extent to which the uncontrolled latencies associated with recall events can confer sufficient design efficiency to permit neural activation for individual conditions to be distinguished. The present study sought to rigorously assess the feasibility of testing individual free recall events with fMRI. We used both theoretically and empirically derived free recall latency distributions to generate simulated fMRI data sets and assessed design efficiency across a range of parameters that describe free recall performance and fMRI designs. In addition, two fMRI experiments empirically assessed whether differential neural activation in visual cortex at onsets determined by true free recall performance across different conditions can be resolved. Collectively, these results specify the design and performance parameters that can provide comparable efficiency between free recall designs and more traditional jittered event-related designs. These findings suggest that assessing BOLD response during free recall using fMRI is feasible, under certain conditions, and can serve as a powerful tool in understanding the neural bases of memory search and overt retrieval.

The prefrontal cortex (PFC) is central to flexible and organized action. Recent theoretical and empirical results suggest that the rostro-caudal axis of the frontal lobes may reflect a hierarchical organization of control. Here, we test whether the rostro-caudal axis of the PFC is organized hierarchically, based on the level of abstraction at which multiple representations compete to guide selection of action. Four functional magnetic resonance imaging (fMRI) experiments parametrically manipulated the set of task-relevant (a) responses, (b) features, (c) dimensions, and (d) overlapping cue-to-dimension mappings. A systematic posterior to anterior gradient was evident within the PFC depending on the manipulated level of representation. Furthermore, across four fMRI experiments, activation in PFC subregions was consistent with the sub- and superordinate relationships that define an abstract representational hierarchy. In addition to providing further support for a representational hierarchy account of the rostro-caudal gradient in the PFC, these data provide important empirical constraints on current theorizing about control hierarchies and the PFC.