Selective attention is reflected neurally in changes in the power of posterior neural oscillations in the alpha (8–12 Hz) and gamma (40–100 Hz) bands. Although a neural mechanism that allows relevant information to be selectively processed has its advantages, it may lead to lucrative or dangerous information going unnoticed. Neural systems are also in place for processing rewarding and punishing information. Here, we examine the interaction between selective attention (left vs. right) and stimulus's learned value associations (neutral, punished, or rewarded) and how they compete for control of posterior neural oscillations. We found that both attention and stimulus–value associations influenced neural oscillations. Whereas selective attention had comparable effects on alpha and gamma oscillations, value associations had dissociable effects on these neural markers of attention. Salient targets (associated with positive and negative outcomes) hijacked changes in alpha power—increasing hemispheric alpha lateralization when salient targets were attended, decreasing it when they were being ignored. In contrast, hemispheric gamma-band lateralization was specifically abolished by negative distractors. Source analysis indicated occipital generators of both attentional and value effects. Thus, posterior cortical oscillations support both the ability to selectively attend while at the same time retaining the ability to remain sensitive to valuable features in the environment. Moreover, the versatility of our attentional system to respond separately to salient from merely positively valued stimuli appears to be carried out by separate neural processes reflected in different frequency bands.

A balance has to be struck between supporting distractor-resistant representations in working memory and allowing those representations to be updated. Catecholamine, particularly dopamine, transmission has been proposed to modulate the balance between the stability and flexibility of working memory representations. However, it is unclear whether drugs that increase catecholamine transmission, such as methylphenidate, optimize this balance in a task-dependent manner or bias the system toward stability at the expense of flexibility (or vice versa). Here we demonstrate, using pharmacological fMRI, that methylphenidate improves the ability to resist distraction (cognitive stability) but impairs the ability to flexibly update items currently held in working memory (cognitive flexibility). These behavioral effects were accompanied by task-general effects in the striatum and opposite and task-specific effects on neural signal in the pFC. This suggests that methylphenidate exerts its cognitive enhancing and impairing effects through acting on the pFC, an effect likely associated with methylphenidate's action on the striatum. These findings highlight that methylphenidate acts as a double-edged sword, improving one cognitive function at the expense of another, while also elucidating the neurocognitive mechanisms underlying these paradoxical effects.

Acute stress has frequently been shown to impair cognitive flexibility. Most studies have examined the effect of stress on cognitive flexibility by measuring how stress changes performance in paradigms that require participants to switch between different task demands. These processes typically implicate pFC function, a region known to be impaired by stress. However, cognitive flexibility is a multifaceted construct. Another dimension of flexibility, updating to incorporate relevant information, involves the dorsal striatum. Function in this region has been shown to be enhanced by stress. Using a within-subject design, we tested whether updating flexibility in a DMS task would be enhanced by an acute stress manipulation (cold pressor task). Participants' cortisol response to stress positively correlated with a relative increase in accuracy on updating flexibility (compared with trials with no working memory interference). In contrast, in line with earlier studies, cortisol responses correlated with worse performance when switching between trials with different task demands. These results demonstrate that stress-related increases in cortisol are associated with both increases and decreases in cognitive flexibility, depending on task demands.

Working memory and reward processing are often thought to be separate, unrelated processes. However, most daily activities involve integrating these two types of information, and the two processes rarely, if ever, occur in isolation. Here, we show that working memory and reward interact in a task-dependent manner and that this task-dependent interaction involves modulation of the pFC by the ventral striatum. Specifically, BOLD signal during gains relative to losses in the ventral striatum and pFC was associated not only with enhanced distractor resistance but also with impairment in the ability to update working memory representations. Furthermore, the effect of reward on working memory was accompanied by differential coupling between the ventral striatum and ignore-related regions in the pFC. Together, these data demonstrate that reward-related signals modulate the balance between cognitive stability and cognitive flexibility by altering functional coupling between the ventral striatum and the pFC.

Everyday life, as well as psychiatric illness, is replete with examples where appetitive and aversive stimuli hijack the will, leading to maladaptive behavior. Yet the mechanisms underlying this phenomenon are not well understood. Here we investigate how motivational cues influence action tendencies in healthy individuals with a novel paradigm. Behaviorally, we observed that an appetitive cue biased go behavior (making a response), whereas an aversive cue biased no-go behavior (withholding a response). We hypothesized that the origin of this behavioral go/no-go bias occurs at the motor system level. To test this, we used single-pulse TMS as a motor system probe (rather than a disruptive tool) to index motivational biasing. We found that the appetitive cue biased the participants to go more by relatively increasing motor system excitability, and that the aversive cue biased participants to no-go more by relatively decreasing motor system excitability. These results show, first, that maladaptive behaviors arise from motivational cues quickly spilling over into the motor system and biasing behavior even before action selection and, second, that this occurs in opposing directions for appetitive and aversive cues.

Adaptive behavior involves interactions between systems regulating Pavlovian and instrumental control of actions. Here, we present the first investigation of the neural mechanisms underlying aversive Pavlovian–instrumental transfer using fMRI in humans. Recent evidence indicates that these Pavlovian influences on instrumental actions are action-specific: Instrumental approach is invigorated by appetitive Pavlovian cues but inhibited by aversive Pavlovian cues. Conversely, instrumental withdrawal is inhibited by appetitive Pavlovian cues but invigorated by aversive Pavlovian cues. We show that BOLD responses in the amygdala and the nucleus accumbens were associated with behavioral inhibition by aversive Pavlovian cues, irrespective of action context. Furthermore, BOLD responses in the ventromedial prefrontal cortex differed between approach and withdrawal actions. Aversive Pavlovian conditioned stimuli modulated connectivity between the ventromedial prefrontal cortex and the caudate nucleus. These results show that action-specific aversive control of instrumental behavior involves the modulation of fronto-striatal interactions by Pavlovian conditioned stimuli.

This study presents the first direct investigation of the hypothesis that dopamine depletion of the dorsal striatum in mild Parkinson disease leads to impaired stimulus–response habit formation, thereby rendering behavior slow and effortful. However, using an instrumental conflict task, we show that patients are able to rely on direct stimulus–response associations when a goal-directed strategy causes response conflict, suggesting that habit formation is not impaired. If anything our results suggest a disease severity–dependent deficit in goal-directed behavior. These results are discussed in the context of Parkinson disease and the neurobiology of habitual and goal-directed behavior.

We assessed electrophysiological activity over the medial frontal cortex (MFC) during outcome-based behavioral adjustment using a probabilistic reversal learning task. During recording, participants were presented two abstract visual patterns on each trial and had to select the stimulus rewarded on 80% of trials and to avoid the stimulus rewarded on 20% of trials. These contingencies were reversed frequently during the experiment. Previous EEG work has revealed feedback-locked electrophysiological responses over the MFC (feedback-related negativity; FRN), which correlate with the negative prediction error [Holroyd, C. B., & Coles, M. G. The neural basis of human error processing: Reinforcement learning, dopamine, and the error-related negativity. Psychological Review, 109, 679–709, 2002] and which predict outcome-based adjustment of decision values [Cohen, M. X., & Ranganath, C. Reinforcement learning signals predict future decisions. Journal of Neuroscience, 27, 371–378, 2007]. Unlike previous paradigms, our paradigm enabled us to disentangle, on the one hand, mechanisms related to the reward prediction error, derived from reinforcement learning (RL) modeling, and on the other hand, mechanisms related to explicit rule-based adjustment of actual behavior. Our results demonstrate greater FRN amplitudes with greater RL model-derived prediction errors. Conversely expected negative outcomes that preceded rule-based behavioral reversal were not accompanied by an FRN. This pattern contrasted remarkably with that of the P3 amplitude, which was significantly greater for expected negative outcomes that preceded rule-based behavioral reversal than for unexpected negative outcomes that did not precede behavioral reversal. These data suggest that the FRN reflects prediction error and associated RL-based adjustment of decision values, whereas the P3 reflects adjustment of behavior on the basis of explicit rules.

Cognitive dysfunction in Parkinson's disease (PD) has been hypothesized to reflect a failure of cortical control. In keeping with this hypothesis, some of the cognitive deficits in PD resemble those seen in patients with lesions in the lateral pFC, which has been associated with top–down attentional control. However, there is no direct evidence for a failure of top–down control mechanisms in PD. Here we fill this gap by demonstrating disproportionate control by bottom–up attention to dimensional salience during attentional set shifting. Patients needed significantly more trials to criterion than did controls when shifting to a low-salient dimension while, remarkably, needing significantly fewer trials to criterion than did controls when shifting to a high-salient dimension. Thus, attention was captured by bottom–up attention to salient information to a greater extent in patients than in controls. The results provide a striking reinterpretation of prior set-shifting data and provide the first direct evidence for a failure of top–down attentional control, resembling that seen after catecholamine depletion in the pFC.