Striatal dopamine D2/D3 receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans.

Impulsive behavior is thought to reflect a traitlike characteristic that can have broad consequences for an individual's success and well-being, but its neurobiological basis remains elusive. Although striatal dopamine D2-like receptors have been linked with impulsive behavior and behavioral inhibition in rodents, a role for D2-like receptor function in frontostriatal circuits mediating inhibitory control in humans has not been shown. We investigated this role in a study of healthy research participants who underwent positron emission tomography with the D2/D3 dopamine receptor ligand [¹8F]fallypride and BOLD fMRI while they performed the Stop-signal Task, a test of response inhibition. Striatal dopamine D2/D3 receptor availability was negatively correlated with speed of response inhibition (stop-signal reaction time) and positively correlated with inhibition-related fMRI activation in frontostriatal neural circuitry. Correlations involving D2/D3 receptor availability were strongest in the dorsal regions (caudate and putamen) of the striatum, consistent with findings of animal studies relating dopamine receptors and response inhibition. The results suggest that striatal D2-like receptor function in humans plays a major role in the neural circuitry that mediates behavioral control, an ability that is essential for adaptive responding and is compromised in a variety of common neuropsychiatric disorders.

Negative affect and craving during abstinence from smoking are both linked to default mode network connectivity.

BACKGROUND: Negative affect and craving during abstinence from cigarettes predict resumption of smoking. Therefore, understanding their neural substrates may guide development of new interventions. Negative affect and craving have traditionally been linked to functions of the brain's threat and reward networks, respectively. However, given the role of default mode network (DMN), particularly the posterior cingulate cortex (PCC), in self-related thought, we examined whether DMN activity underlies both craving and negative affective states in adults who smoke. METHODS: 46 adults who smoke abstained from smoking overnight and underwent resting-state fMRI, after self-reporting their psychological symptoms (negative affect) and craving on the Shiffman-Jarvik Withdrawal Scale and state anxiety (negative affect) on the Spielberger State-Trait Anxiety Inventory. Within-DMN functional connectivity using 3 different anterior PCC seeds was tested for correlations with self-report measures. Additionally, independent component analysis with dual regression was performed to measure associations of self-report with whole-brain connectivity of the DMN component. RESULTS: Craving correlated positively with connectivity of all three anterior PCC seeds with posterior PCC clusters (pcorr<0.04). The measures of negative affective states correlated positively with connectivity of the DMN component to various brain regions, including posterior PCC (pcorr=0.02) and striatum (pcorr<0.008). Craving and state anxiety were correlated with connectivity of an overlapping region of PCC (pcorr=0.003). Unlike the state measures, nicotine dependence and trait anxiety were not associated with PCC connectivity within DMN. CONCLUSIONS: Although negative affect and craving are distinct subjective states, they appear to share a common neural pathway within the DMN, particularly involving the PCC.

Different forms of self-control share a neurocognitive substrate.

Psychological and neurocognitive studies have suggested that different kinds of self-control may share a common psychobiological component. If this is true, performance in affective and nonaffective inhibitory control tasks in the same individuals should be correlated and should rely upon integrity of this region. To test this hypothesis, we acquired high-resolution magnetic resonance images from 44 healthy and 43 methamphetamine-dependent subjects. Individuals with methamphetamine dependence were tested because of prior findings that they suffer inhibitory control deficits. Gray matter structure of the inferior frontal gyrus was assessed using voxel-based morphometry. Subjects participated in tests of motor and affective inhibitory control (stop-signal task and emotion reappraisal task, respectively); and methamphetamine-dependent subjects provided self-reports of their craving for methamphetamine. Performance levels on the two inhibitory control tasks were correlated with one another and with gray matter intensity in the right pars opercularis region of the inferior frontal gyrus in healthy subjects. Gray matter intensity of this region was also correlated with methamphetamine craving. Compared with healthy subjects, methamphetamine-dependent subjects exhibited lower gray matter intensity in this region, worse motor inhibitory control, and less success in affect regulation. These findings suggest that self-control in different psychological domains involves a common substrate in the right pars opercularis, and that successful self-control depends on integrity of this substrate.

An affective neuroscience model of boosting resilience in adults.

Although research has identified dozens of behavioral and psychosocial strategies for boosting resilience in adults, little is known about the common underlying pathways. A comprehensive review of these strategies using an affective neuroscience approach indicates three distinct general routes to resilience: 1) down-regulating the negative (e.g., exposure, cognitive reappraisal) by reducing distress-related responses of the amygdala, hypothalamic-pituitary-adrenal axis, and autonomic nervous system; 2) up-regulating the positive (e.g., optimism, social connectedness) by activating mesostriatal reward pathways, which in turn can buffer the effects of stress; and 3) transcending the self (e.g., mindfulness, religious engagement) by reducing activation in the default mode network, a network associated with self-reflection, mind-wandering, and rumination. Some strategies (e.g., social support) can boost resilience via more than one pathway. Under- or over-stimulation of a pathway can result in vulnerability, such as over-stimulation of the reward pathway through substance abuse. This tripartite model of resilience-building is testable, accounts for a large body of data on adult resilience, and makes new predictions with implications for practice.

The lasting effect of words on feelings: words may facilitate exposure effects to threatening images.

Previous studies have shown that mere words, particularly affective words, can dampen emotional responses. However, the effect of affective labels on emotional responding in the long term is unknown. The authors examined whether repeated exposure to aversive images would lead to more reduction in autonomic reactivity a week later if the images were exposed with single-word labels than without labels. In Experiment 1, healthy individuals were exposed to pictures of disturbing scenes with or without labels on Day 1. On Day 8, the same pictures from the previous week were exposed, this time without labels. In Experiment 2, participants were spider fearful and were exposed to pictures of spiders. In both experiments, although repeated exposure to aversive images (without labels) led to long-term attenuation of autonomic reactivity, exposure plus affective labels, but not nonaffective labels, led to more attenuation than exposure alone. Thus, affective labels may help dampen emotional reactivity in both the short and long terms. Implications for exposure therapy and translational studies are discussed.

Fairness and cooperation are rewarding: evidence from social cognitive neuroscience.

To motivate their consumers or employees, corporations often offer monetary incentives, such as cash-back deals or salary bonuses. However, human behavior is not solely driven by material outcome; fairness and equity matter as well. In a recent neuroimaging study, fair offers led to higher happiness ratings and increased activity in several reward regions of the brain compared with unfair offers of equal monetary value. Other neuroimaging studies have similarly shown activation in reward regions in response to cooperative partners or cooperative play. Here, we review these findings and discuss the implications for organizational settings.

Common prefrontal regions activate during self-control of craving, emotion, and motor impulses in smokers.

It has been posited that self-regulation of behaviors, emotions, and temptations may all rely on a common resource. Recent reviews suggest this common resource may include the inferior frontal cortex (IFC). However, to our knowledge no single functional neuroimaging study has tested this hypothesis. We obtained fMRI scans as 25 abstinent treatment-seeking cigarette smokers completed motor, affective, and craving self-control tasks before smoking cessation treatment. We identified two regions in left IFC and a region in pre-supplementary motor area (preSMA) that were commonly activated in all three tasks. Further, PPI analyses suggest that IFC may involve dissociable pathways in each self-control domain. Specifically, the IFC showed negative functional connectivity with large portions of the thalamus and precentral gyrus during motor stopping, with the insula and other portions of the thalamus during craving regulation, and potentially with a small limbic region during emotion regulation. We discuss implications for understanding self-control mechanisms.

Mindful attention reduces neural and self-reported cue-induced craving in smokers.

An emerging body of research suggests that mindfulness-based interventions may be beneficial for smoking cessation and the treatment of other addictive disorders. One way that mindfulness may facilitate smoking cessation is through the reduction of craving to smoking cues. The present work considers whether mindful attention can reduce self-reported and neural markers of cue-induced craving in treatment seeking smokers. Forty-seven (n = 47) meditation-naïve treatment-seeking smokers (12-h abstinent from smoking) viewed and made ratings of smoking and neutral images while undergoing functional magnetic resonance imaging (fMRI). Participants were trained and instructed to view these images passively or with mindful attention. Results indicated that mindful attention reduced self-reported craving to smoking images, and reduced neural activity in a craving-related region of subgenual anterior cingulate cortex (sgACC). Moreover, a psychophysiological interaction analysis revealed that mindful attention reduced functional connectivity between sgACC and other craving-related regions compared to passively viewing smoking images, suggesting that mindfulness may decouple craving neurocircuitry when viewing smoking cues. These results provide an initial indication that mindful attention may describe a 'bottom-up' attention to one's present moment experience in ways that can help reduce subjective and neural reactivity to smoking cues in smokers.

Subjective responses to emotional stimuli during labeling, reappraisal, and distraction.

Although multiple neuroimaging studies suggest that affect labeling (i.e., putting feelings into words) can dampen affect-related responses in the amygdala, the consequences of affect labeling have not been examined in other channels of emotional responding. We conducted four studies examining the effect of affect labeling on self-reported emotional experience. In study one, self-reported distress was lower during affect labeling, compared to passive watching, of negative emotional pictures. Studies two and three added reappraisal and distraction conditions, respectively. Affect labeling showed similar effects on self-reported distress as both of these intentional emotion regulation strategies. In each of the first three studies, however, participant predictions about the effects of affect labeling suggest that unlike reappraisal and distraction, people do not believe affect labeling to be an effective emotion regulation strategy. Even after having the experience of affect labels leading to lower distress, participants still predicted that affect labeling would increase distress in the future. Thus, affect labeling is best described as an incidental emotion regulation process. Finally, study four employed positive emotional pictures and here, affect labeling was associated with diminished self-reported pleasure, relative to passive watching. This suggests that affect labeling tends to dampen affective responses in general, rather than specifically alleviating negative affect.

Effect of modafinil on learning and task-related brain activity in methamphetamine-dependent and healthy individuals.

Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function. Therefore, medications that improve cognition in these subjects may improve the success of therapy for their addiction, especially when cognitive behavioral therapies are used. Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers. We therefore conducted a randomized, double-blind, placebo-controlled, cross-over study, using functional magnetic resonance imaging, to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent, MA-dependent, and healthy control participants. Modafinil (200 mg) and placebo were administered orally (one single dose each), in counterbalanced fashion, 2 h before each of two testing sessions. Under placebo conditions, MA-dependent participants showed worse learning performance than control participants. Modafinil boosted learning in MA-dependent participants, bringing them to the same performance level as control subjects; the control group did not show changes in performance with modafinil. After controlling for performance differences, MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants. The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control. These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence.

Impulsive choice and altruistic punishment are correlated and increase in tandem with serotonin depletion.

Human cooperation may partly depend on the presence of individuals willing to incur personal costs to punish noncooperators. The psychological factors that motivate such 'altruistic punishment' are not fully understood; some have argued that altruistic punishment is a deliberate act of norm enforcement that requires self-control, while others claim that it is an impulsive act driven primarily by emotion. In the current study, we addressed this question by examining the relationship between impulsive choice and altruistic punishment in the ultimatum game. As the neurotransmitter serotonin has been implicated in both impulsive choice and altruistic punishment, we investigated the effects of manipulating serotonin on both measures. Across individuals, impulsive choice and altruistic punishment were correlated and increased following serotonin depletion. These findings imply that altruistic punishment reflects the absence rather than the presence of self control, and suggest that impulsive choice and altruistic punishment share common neural mechanisms.

The sunny side of fairness: preference for fairness activates reward circuitry (and disregarding unfairness activates self-control circuitry).

Little is known about the positive emotional impact of fairness or the process of resolving conflict between fairness and financial interests. In past research, fairness has covaried with monetary payoff, such that the mental processes underlying preference for fairness and those underlying preference for greater monetary outcome could not be distinguished. We examined self-reported happiness and neural responses to fair and unfair offers while controlling for monetary payoff. Compared with unfair offers of equal monetary value, fair offers led to higher happiness ratings and activation in several reward regions of the brain. Furthermore, the tendency to accept unfair proposals was associated with increased activity in right ventrolateral prefrontal cortex, a region involved in emotion regulation, and with decreased activity in the anterior insula, which has been implicated in negative affect. This work provides evidence that fairness is hedonically valued and that tolerating unfair treatment for material gain involves a pattern of activation resembling suppression of negative affect.

Serotonin modulates behavioral reactions to unfairness.

Serotonin (5-HT) has long been implicated in social behavior and impulsivity, but the mechanisms through which it modulates self-control remain unclear. We observed the effects of manipulating 5-HT function on behavior in the ultimatum game, where players must decide whether to accept or reject fair or unfair monetary offers from another player. Participants with depleted 5-HT levels rejected a greater proportion of unfair offers, but not fair offers, without showing changes in mood, fairness judgment, basic reward processing, or response inhibition. Our results suggest that 5-HT plays a critical role in regulating emotion during social decision-making.

Alexithymia, interhemispheric transfer, and right hemispheric specialization: a critical review.

BACKGROUND: One neural model of alexithymia relates the condition to poor interhemispheric transfer, while another model associates it with a disturbance in right hemisphere activity. METHODS: The available empirical evidence directly relating alexithymia to a deficit in interhemispheric transfer and/or in right hemisphere activity is critically reviewed. RESULTS: The interhemispheric transfer studies have related alexithymia to a deficit in transfer, but the nature and directionality of the transfer deficit have yet to be determined. Many of the hemispheric specialization studies do not relate alexithymia to a right hemisphere dysfunction. Shortcomings of these studies are reviewed. CONCLUSIONS: The hypothesis that alexithymia is related to a deficit in the right-to-left transfer of emotional information and to a right hemisphere impairment in emotion processing remains to be tested directly and definitively. Suggestions for future research are made.

An fMRI study of causal judgments.

The capacity to evaluate causal relations is fundamental to human cognition, and yet little is known of its neurocognitive underpinnings. A functional magnetic resonance imaging study was performed to investigate an hypothesized dissociation between the use of semantic knowledge to evaluate specifically causal relations in contrast to general associative relations. Identical pairs of words were judged for causal or associative relations in different blocks of trials. Causal judgments, beyond associative judgments, generated distinct activation in left dorsolateral prefrontal cortex and right pre-cuneus. These findings indicate that the evaluation of causal relations in semantic memory involves additional neural mechanisms relative to those required to evaluate associative relations.