In search of a human self-regulation system.

The capacity for self-regulation allows people to control their thoughts, behaviors, emotions, and desires. In spite of this impressive ability, failures of self-regulation are common and contribute to numerous societal problems, from obesity to drug addiction. Such failures frequently occur following exposure to highly tempting cues, during negative moods, or after self-regulatory resources have been depleted. Here we review the available neuroscientific evidence regarding self-regulation and its failures. At its core, self-regulation involves a critical balance between the strength of an impulse and an individual's ability to inhibit the desired behavior. Although neuroimaging and patient studies provide consistent evidence regarding the reward aspects of impulses and desires, the neural mechanisms that underlie the capacity for control have eluded consensus, with various executive control regions implicated in different studies. We outline the necessary properties for a self-regulation control system and suggest that the use of resting-state functional connectivity analyses may be useful for understanding how people regulate their behavior and why they sometimes fail in their attempts.

Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues.

Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body mass and adiposity, a dominant model was most predictive of NAcc size and responsivity to food cues. These findings suggest that children genetically at risk for obesity are predisposed to represent reward signals more strongly, which, in turn, may contribute to unhealthy eating behaviors later in life.

Reward-related regions form a preferentially coupled system at rest.

Neuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting-state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence in the absence of goal-directed tasks. Here we use seed-based and graph-theory RSFC approaches to characterize the systems-level organization of putative reward regions of at rest. Peaks of connectivity from seed-based RSFC patterns for the nucleus accumbens (NAcc) and orbitofrontal cortex (OFC) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph-theory was then used to determine system-level membership for all regions. Several regions previously implicated in reward-processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta-analyses of task-based reward studies. This reward system shares between-system connectivity with systems implicated in cognitive control and self-regulation, including the fronto-parietal, cingulo-opercular, and default systems. Differences may exist in the pathways through which control systems interact with reward system components. Whereas NAcc is functionally connected to cingulo-opercular and default systems, OFC regions show stronger connectivity with the fronto-parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in this work to explore potential relationships to appetitive behaviors, self-regulation failure, and addiction.

The Dorsal Medial Prefrontal Cortex Responds Preferentially to Social Interactions during Natural Viewing.

UNLABELLED: Humans display a strong tendency to make spontaneous inferences concerning the thoughts and intentions of others. Although this ability relies upon the concerted effort of multiple brain regions, the dorsal medial prefrontal cortex (DMPFC) is most closely associated with the ability to reason about other people's mental states and form impressions of their character. Here, we investigated this region's putative social category preference using fMRI as 34 participants engaged in uninstructed viewing of a complex naturalistic stimulus. Using a data-driven "reverse correlation" approach, we characterize the DMPFC's stimulus response profile from ongoing neural responses to a dynamic movie stimulus. Results of this analysis demonstrate that the DMPFC's response profile is dominated by the presence of scenes involving social interactions between characters. Subsequent content analysis of video clips created from this response profile confirmed this finding. In contrast, regions of the inferotemporal and parietal cortex were selectively tuned to faces and actions, both features that often covary with social interaction but may be difficult to disentangle using standard event-related approaches. Together, these findings suggest that the DMPFC is finely tuned for processing social interaction above other categories and that this preference is maintained during unrestricted viewing of complex natural stimuli such as movies. SIGNIFICANCE STATEMENT: Recently, studies have brought into question whether the dorsal medial prefrontal cortex (DMPFC), a region long associated with social cognition, is specialized for the processing of social information. We examine the response profile of this region during natural viewing of a reasonably naturalistic stimulus (i.e., a Hollywood movie) using a data-driven reverse correlation technique. Our findings demonstrate that, during natural viewing, the DMPFC is strongly tuned to the social features of the stimulus above other categories. Moreover, this response differs from other areas with previously well characterized response profiles such as the lateral and medial fusiform gyrus. These findings suggest that this region's dominant function in everyday situations is to support reasoning about the thoughts and intentions of conspecifics.

Generation and Evaluation of a Cortical Area Parcellation from Resting-State Correlations.

The cortical surface is organized into a large number of cortical areas; however, these areas have not been comprehensively mapped in the human. Abrupt transitions in resting-state functional connectivity (RSFC) patterns can noninvasively identify locations of putative borders between cortical areas (RSFC-boundary mapping; Cohen et al. 2008). Here we describe a technique for using RSFC-boundary maps to define parcels that represent putative cortical areas. These parcels had highly homogenous RSFC patterns, indicating that they contained one unique RSFC signal; furthermore, the parcels were much more homogenous than a null model matched for parcel size when tested in two separate datasets. Several alternative parcellation schemes were tested this way, and no other parcellation was as homogenous as or had as large a difference compared with its null model. The boundary map-derived parcellation contained parcels that overlapped with architectonic mapping of areas 17, 2, 3, and 4. These parcels had a network structure similar to the known network structure of the brain, and their connectivity patterns were reliable across individual subjects. These observations suggest that RSFC-boundary map-derived parcels provide information about the location and extent of human cortical areas. A parcellation generated using this method is available at http://www.nil.wustl.edu/labs/petersen/Resources.html.

Individual Differences in Reward and Somatosensory-Motor Brain Regions Correlate with Adiposity in Adolescents.

The prevalence of adolescent obesity has increased dramatically over the past three decades, and research has documented that the number of television shows viewed during childhood is associated with greater risk for obesity. In particular, considerable evidence suggests that exposure to food marketing promotes eating habits that contribute to obesity. The present study examines neural responses to dynamic food commercials in overweight and healthy-weight adolescents using functional magnetic resonance imaging (fMRI). Compared with non-food commercials, food commercials more strongly engaged regions involved in attention and saliency detection (occipital lobe, precuneus, superior temporal gyri, and right insula) and in processing rewards [left and right nucleus accumbens (NAcc) and left orbitofrontal cortex (OFC)]. Activity in the left OFC and right insula further correlated with subjects' percent body fat at the time of the scan. Interestingly, this reward-related activity to food commercials was accompanied by the additional recruitment of mouth-specific somatosensory-motor cortices-a finding that suggests the intriguing possibility that higher-adiposity adolescents mentally simulate eating behaviors and offers a potential neural mechanism for the formation and reinforcement of unhealthy eating habits that may hamper an individual's ability lose weight later in life.

Striatal Associative Learning Signals Are Tuned to In-groups.

An important feature of adaptive social behavior is the ability to flexibly modify future actions based on the successes or failures of past experiences. The ventral striatum (VS) occupies a central role in shaping behavior by using feedback to evaluate actions and guide learning. The current studies tested whether feedback indicating the need to update social knowledge would engage the VS, thereby facilitating subsequent learning. We also examined the sensitivity of these striatal signals to the value associated with social group membership. Across two fMRI studies, participants answered questions testing their knowledge about the preferences of personally relevant social groups who were high (in-group) or low (out-group) in social value. Participants received feedback indicating whether their responses were correct or incorrect on a trial-by-trial basis. After scanning, participants were given a surprise memory test examining memory for the different types of feedback. VS activity in response to social feedback correlated with subsequent memory, specifying a role for the VS in encoding and updating social knowledge. This effect was more robust in response to in-group than out-group feedback, indicating that the VS tracks variations in social value. These results provide novel evidence of a neurobiological mechanism adaptively tuned to the motivational relevance of the surrounding social environment that focuses learning efforts on the most valuable social outcomes and triggers adjustments in behavior when necessary.

Neural predictors of giving in to temptation in daily life.

The ability to control desires, whether for food, sex, or drugs, enables people to function successfully within society. Yet, in tempting situations, strong impulses often result in self-control failure. Although many triggers of self-control failure have been identified, the question remains as to why some individuals are more likely than others to give in to temptation. In this study, we combined functional neuroimaging and experience sampling to determine if there are brain markers that predict whether people act on their food desires in daily life. We examined food-cue-related activity in the nucleus accumbens (NAcc), as well as activity associated with response inhibition in the inferior frontal gyrus (IFG). Greater NAcc activity was associated with greater likelihood of self-control failures, whereas IFG activity supported successful resistance to temptations. These findings demonstrate an important role for the neural mechanisms underlying desire and self-control in people's real-world experiences of temptations.

Interactions between transient and sustained neural signals support the generation and regulation of anxious emotion.

Anxious emotion can manifest on brief (threat response) and/or persistent (chronic apprehension and arousal) timescales, and prior work has suggested that these signals are supported by separable neural circuitries. This fMRI study utilized a mixed block-event-related emotional provocation paradigm in 55 healthy participants to simultaneously measure brief and persistent anxious emotional responses, testing the specificity of, and interactions between, these potentially distinct systems. Results indicated that components of emotional processing networks were uniquely sensitive to transient and sustained anxious emotion. Whereas the amygdala and midbrain showed only transient responses, the ventral basal forebrain and anterior insula showed sustained activity during extended emotional contexts that tracked positively with task-evoked anxiety. States of lesser anxiety were associated with greater sustained activity in the ventromedial prefrontal cortex. Furthermore, ventromedial prefrontal recruitment was lower in individuals with higher scores on intolerance of uncertainty measures, and this hyporecruitment predicted greater transient amygdala responding to potential threat cues. This work demonstrates how brain circuitries interact across temporal scales to support brief and persistent anxious emotion and suggests potentially divergent mechanisms of dysregulation in clinical syndromes marked by brief versus persistent symptoms of anxiety.

Individual differences in nucleus accumbens activity to food and sexual images predict weight gain and sexual behavior.

Failures of self-regulation are common, leading to many of the most vexing problems facing contemporary society, from overeating and obesity to impulsive sexual behavior and STDs. One reason that people may be prone to engaging in unwanted behaviors is heightened sensitivity to cues related to those behaviors; people may overeat because of hyperresponsiveness to food cues, addicts may relapse following exposure to their drug of choice, and some people might engage in impulsive sexual activity because they are easily aroused by erotic stimuli. An open question is the extent to which individual differences in neural cue reactivity relate to actual behavioral outcomes. Here we show that individual differences in human reward-related brain activity in the nucleus accumbens to food and sexual images predict subsequent weight gain and sexual activity 6 months later. These findings suggest that heightened reward responsivity in the brain to food and sexual cues is associated with indulgence in overeating and sexual activity, respectively, and provide evidence for a common neural mechanism associated with appetitive behaviors.

Neural responses to ambiguity involve domain-general and domain-specific emotion processing systems.

Extant research has examined the process of decision making under uncertainty, specifically in situations of ambiguity. However, much of this work has been conducted in the context of semantic and low-level visual processing. An open question is whether ambiguity in social signals (e.g., emotional facial expressions) is processed similarly or whether a unique set of processors come on-line to resolve ambiguity in a social context. Our work has examined ambiguity using surprised facial expressions, as they have predicted both positive and negative outcomes in the past. Specifically, whereas some people tended to interpret surprise as negatively valenced, others tended toward a more positive interpretation. Here, we examined neural responses to social ambiguity using faces (surprise) and nonface emotional scenes (International Affective Picture System). Moreover, we examined whether these effects are specific to ambiguity resolution (i.e., judgments about the ambiguity) or whether similar effects would be demonstrated for incidental judgments (e.g., nonvalence judgments about ambiguously valenced stimuli). We found that a distinct task control (i.e., cingulo-opercular) network was more active when resolving ambiguity. We also found that activity in the ventral amygdala was greater to faces and scenes that were rated explicitly along the dimension of valence, consistent with findings that the ventral amygdala tracks valence. Taken together, there is a complex neural architecture that supports decision making in the presence of ambiguity: (a) a core set of cortical structures engaged for explicit ambiguity processing across stimulus boundaries and (b) other dedicated circuits for biologically relevant learning situations involving faces.

Rejection sensitivity polarizes striatal-medial prefrontal activity when anticipating social feedback.

As a social species, humans are acutely aware of cues that signal inclusionary status. This study characterizes behavioral and neural responses when individuals anticipate social feedback. Across two fMRI studies, participants (n = 42) made social judgments about supposed peers and then received feedback from those individuals. Of particular interest was the neural activity occurring when participants were awaiting social feedback. During this anticipatory period, increased neural activity was observed in the ventral striatum, a central component of the brain's reward circuitry, and dorsomedial pFC, a brain region implicated in mentalizing about others. Individuals high in rejection sensitivity exhibited greater responses in both the ventral striatum and dorsomedial pFC when anticipating positive feedback. These findings provide initial insight into the neural mechanisms involved in anticipating social evaluations as well as the cognitive processes that underlie rejection sensitivity.

Self-regulatory depletion enhances neural responses to rewards and impairs top-down control.

To be successful at self-regulation, individuals must be able to resist impulses and desires. The strength model of self-regulation suggests that when self-regulatory capacity is depleted, self-control deficits result from a failure to engage top-down control mechanisms. Using functional neuroimaging, we examined changes in brain activity in response to viewing desirable foods among 31 chronic dieters, half of whom completed a task known to result in self-regulatory depletion. Compared with nondepleted dieters, depleted dieters exhibited greater food-cue-related activity in the orbitofrontal cortex, a brain area associated with coding the reward value and liking aspects of desirable foods; they also showed decreased functional connectivity between this area and the inferior frontal gyrus, a region commonly implicated in self-control. These findings suggest that self-regulatory depletion provokes self-control failure by reducing connectivity between brain regions that are involved in cognitive control and those that represent rewards, thereby decreasing the capacity to resist temptations.

Spontaneous action representation in smokers when watching movie characters smoke.

Do smokers simulate smoking when they see someone else smoke? For regular smokers, smoking is such a highly practiced motor skill that it often occurs automatically, without conscious awareness. Research on the brain basis of action observation has delineated a frontoparietal network that is commonly recruited when people observe, plan, or imitate actions. Here, we investigated whether this action observation network would be preferentially recruited in smokers when viewing complex smoking cues, such as those occurring in motion pictures. Seventeen right-handed smokers and 17 nonsmokers watched a popular movie while undergoing functional magnetic resonance imaging. Using a natural stimulus, such as a movie, allowed us to keep both smoking and nonsmoking participants naive to the goals of the experiment. Brain activity evoked by movie scenes of smoking was contrasted with nonsmoking control scenes that were matched for frequency and duration. Compared with nonsmokers, smokers showed greater activity in left anterior intraparietal sulcus and inferior frontal gyrus, regions involved in the simulation of contralateral hand-based gestures, when viewing smoking versus control scenes. These results demonstrate that smokers spontaneously represent the action of smoking when viewing others smoke, the consequence of which may make it more difficult to abstain from smoking.

Inducing negative affect increases the reward value of appetizing foods in dieters.

Experiencing negative affect frequently precedes lapses in self-control for dieters, smokers, and drug addicts. Laboratory research has similarly shown that inducing negative emotional distress increases the consumption of food or drugs. One hypothesis for this finding is that emotional distress sensitizes the brain's reward system to appetitive stimuli. Using functional neuroimaging, we demonstrate that inducing negative affect in chronic dieters increases activity in brain regions representing the reward value of appetitive stimuli when viewing appetizing food cues. Thirty female chronic dieters were randomly assigned to receive either a negative (n = 15) or neutral mood induction (n = 15) immediately followed by exposure to images of appetizing foods and natural scenes during fMRI. Compared with chronic dieters in a neutral mood, those receiving a negative mood induction showed increased activity in the OFC to appetizing food images. In addition, activity to food images in the OFC and ventral striatum was correlated with individual differences in the degree to which the negative mood induction decreased participants' self-esteem. These findings suggest that distress sensitizes the brain's reward system to appetitive cues, thereby offering a mechanism for the oft-observed relationship between negative affect and disinhibited eating.

Individual differences in the spontaneous recruitment of brain regions supporting mental state understanding when viewing natural social scenes.

People are able to rapidly infer complex personality traits and mental states even from the most minimal person information. Research has shown that when observers view a natural scene containing people, they spend a disproportionate amount of their time looking at the social features (e.g., faces, bodies). Does this preference for social features merely reflect the biological salience of these features or are observers spontaneously attempting to make sense of complex social dynamics? Using functional neuroimaging, we investigated neural responses to social and nonsocial visual scenes in a large sample of participants (n = 48) who varied on an individual difference measure assessing empathy and mentalizing (i.e., empathizing). Compared with other scene categories, viewing natural social scenes activated regions associated with social cognition (e.g., dorsomedial prefrontal cortex and temporal poles). Moreover, activity in these regions during social scene viewing was strongly correlated with individual differences in empathizing. These findings offer neural evidence that observers spontaneously engage in social cognition when viewing complex social material but that the degree to which people do so is mediated by individual differences in trait empathizing.

Dietary restraint violations influence reward responses in nucleus accumbens and amygdala.

Numerous studies have demonstrated that consuming high-calorie food leads to subsequent overeating by chronic dieters. The present study investigates the neural correlates of such self-regulatory failures using fMRI. Chronic dieters (n = 50) and non-dieters (n = 50) consumed either a 15-oz glass of cold water or a 15-oz milkshake and were subsequently imaged while viewing pictures of animals, environmental scenes, people, and appetizing food items. Results revealed a functional dissociation in nucleus accumbens and amygdala activity that paralleled well-established behavioral patterns of eating observed in dieters and non-dieters. Whereas non-dieters showed the greatest nucleus accumbens activity in response to food items after water consumption, dieters showed the greatest activity after consuming the milkshake. Activity in the left amygdala demonstrated the reverse interaction. Considered together with previously reported behavioral findings, the present results offer a suggested neural substrate for diet failure.

Musical imagery: sound of silence activates auditory cortex.

Auditory imagery occurs when one mentally rehearses telephone numbers or has a song 'on the brain'--it is the subjective experience of hearing in the absence of auditory stimulation, and is useful for investigating aspects of human cognition. Here we use functional magnetic resonance imaging to identify and characterize the neural substrates that support unprompted auditory imagery and find that auditory and visual imagery seem to obey similar basic neural principles.

Self-esteem modulates medial prefrontal cortical responses to evaluative social feedback.

Self-esteem is a facet of personality that influences perception of social standing and modulates the salience of social acceptance and rejection. As such, self-esteem may bias neural responses to positive and negative social feedback across individuals. During functional magnetic resonance imaging scanning, participants (n = 42) engaged in a social evaluation task whereby they ostensibly received feedback from peers indicating they were liked or disliked. Results demonstrated that individuals with low self-esteem believed that they received less positive feedback from others and showed enhanced activity to positive versus negative social feedback in the ventral anterior cingulate cortex/medial prefrontal cortex (vACC/mPFC). By contrast, vACC/mPFC activity was insensitive to positive versus negative feedback in individuals with high self-esteem, and these individuals consistently overestimated the amount of positive feedback received from peers. Voxelwise analyses supported these findings; lower self-esteem predicted a linear increase in vACC/mPFC response to positive versus negative social feedback. Taken together, the present findings propose a functional role for the vACC/mPFC in representing the salience of social feedback and shaping perceptions of relative social standing.

Medial temporal lobe BOLD activity at rest predicts individual differences in memory ability in healthy young adults.

Human beings differ in their ability to form and retrieve lasting long-term memories. To explore the source of these individual differences, we used functional magnetic resonance imaging to measure blood-oxygen-level-dependent (BOLD) activity in healthy young adults (n = 50) during periods of resting fixation that were interleaved with periods of simple cognitive tasks. We report that medial temporal lobe BOLD activity during periods of rest predicts individual differences in memory ability. Specifically, individuals who exhibited greater magnitudes of task-induced deactivations in medial temporal lobe BOLD signal (as compared to periods of rest) demonstrated superior memory during offline testing. This relationship was independent of differences in general cognitive function and persisted across different control tasks (i.e., number judgment versus checkerboard detection) and experimental designs (i.e., blocked versus event-related). These results offer a neurophysiological basis for the variability in mnemonic ability that is present amongst healthy young adults and may help to guide strategies aimed at early detection and intervention of neurological and mnemonic impairment.