Sex differences in emotion- and reward-related neural responses predicting increases in substance use in adolescence.

Adolescent substance use is a significant public health problem and there is a need for effective substance use preventions. To develop effective preventions, it is important to identify neurobiological risk factors that predict increases in substance use in adolescence and to understand potential sex differences in risk mechanisms. The present study used functional magnetic resonance imaging and hierarchical linear modeling to examine negative emotion- and reward-related neural responses in early adolescence predicting growth in substance use to middle adolescence in 81 youth, by sex. Adolescent neural responses to negative emotional stimuli and monetary reward receipt were assessed at age 12-14. Adolescents reported on substance use at age 12-14 and at 6 month, and 1, 2, and 3 year follow-ups. Adolescent neural responses did not predict initiation of substance use (yes/no), but, among users, neural responses predicted growth in substance use frequency. For girls, heightened right amygdala responses to negative emotional stimuli in early adolescence predicted growth in substance use frequency through middle adolescence. For boys, blunted left nucleus accumbens and bilateral ventromedial prefrontal cortex responses to monetary reward predicted growth in substance use frequency. Findings suggest different emotion and reward-related predictors of the development of substance use for adolescent girls versus boys.

Behavioral inhibition and approach tendencies are associated with striatal activation to loss: Implications for adolescent substance use.

Behavioral inhibition/avoidance and approach systems (BIS/BAS), which facilitate avoidance of aversive stimuli and approach of enticing stimuli, are thought to underlie engagement in substance use (SU). However, little is known about the neural correlates of these systems, particularly in adolescence. The current study examined associations between BIS/BAS tendencies and neural response to reward and loss and then examined whether there was an indirect effect of BIS/BAS on later SU initiation through these neural responses. 79 12-14 year olds underwent fMRI at baseline during a card guessing task. Adolescents reported on their BIS/BAS at baseline and on their SU at baseline and through a 3-year follow-up period. Results showed that higher BIS was associated with lower striatal activation and higher BAS with higher striatal activation to monetary loss. BIS and BAS were not associated with neural activation to monetary reward. There was no support that BIS or BAS predicted SU initiation through striatal activation to monetary loss. Overall, these results may suggest that adolescents with the tendency to avoid aversive stimuli assign less salience and adolescents with the tendency to approach enticing stimuli assign more salience to monetary loss.

Task-based functional connectivity patterns: Links to adolescent emotion regulation and psychopathology.

Adolescence is a developmental period characterized by heightened emotional reactivity, neurobiological changes, and increased rates of anxiety and depression. Emotion regulation (ER) difficulties-or the inability to effectively regulate one's emotions-have been theoretically and empirically conceptualized as a transdiagnostic factor implicated in virtually all forms of psychopathology among youth. The current fMRI study investigates how young adolescents' ER abilities longitudinally mediate the relationship between their task-based (n=67) limbic-prefrontal functional connectivity values and subsequent levels of internalizing and externalizing symptoms. Findings revealed that adolescents with stronger limbic-prefrontal connectivity when viewing negative emotional images reported more ER difficulties one year later which, in turn, predicted higher levels of adolescent-reported internalizing and externalizing symptoms (with the exception of ADHD) two years later. This is the only study to date that provides compelling-albeit preliminary-evidence that ER problems longitudinally mediate the association between task-based functional connectivity patterns and future psychological symptoms among adolescents. Of note, participants were only scanned at baseline, limiting our ability to assess change in adolescents' task-based functional connectivity patterns as a function of developing ER abilities or burgeoning psychological symptomology. In sum, rather than conferring risk for any particular disorder, our results suggest that functional connectivity and subsequent ER abilities may serve a transdiagnostic risk factor for psychopathology. These findings may inform future emotion-focused prevention and intervention efforts aimed at youth susceptible to future internalizing and externalizing problems.

Neural activation to loss and reward among alcohol naive adolescents who later initiate alcohol use.

Adolescent alcohol use is associated with adverse psychosocial outcomes, including an increased risk of alcohol use disorder in adulthood. It is therefore important to identify risk factors of alcohol initiation in adolescence. Research to date has shown that altered neural activation to reward is associated with alcohol use in adolescence; however, few studies have focused on neural activation to loss and alcohol use. The current study examined neural activation to loss and reward among 64 alcohol naive 12-14 year olds that did (n = 20) and did not initiate alcohol use by a three year follow-up period. Results showed that compared to adolescents that did not initiate alcohol use, adolescents that did initiate alcohol use by the three year follow-up period had increased activation to loss in the left striatum (i.e., putamen), right precuneus, and the brainstem/pons when they were alcohol naive at baseline. By contrast, alcohol initiation was not associated with neural activation to winning a reward. These results suggest that increased activation in brain regions implicated in salience, error detection/self-referential processing, and sensorimotor function, especially to negative outcomes, may represent an initial vulnerability factor for alcohol use in adolescence.

Affective Neural Mechanisms of a Parenting-Focused Mindfulness Intervention.

OBJECTIVES: Behavioral evidence suggests that parenting-focused mindfulness interventions can improve parenting practices and enhance family wellbeing, potentially operating through altered emotional processing in parents. However, the mechanisms through which parent mindfulness interventions achieve their positive benefits have not yet been empirically tested, knowledge which is key to refine and maximize intervention effects. Thus, as part of a randomized controlled trial, the present study examined the affective mechanisms of an 8-week parenting-focused mindfulness intervention, the Parenting Mindfully (PM) intervention, versus a minimal-intervention parent education control. METHODS: Twenty highly stressed mothers of adolescents completed pre- and post-intervention behavioral and fMRI sessions, in which mothers completed a parent-adolescent conflict interaction, fMRI emotion task, and fMRI resting state scan. Mothers reported on their mindful parenting, and maternal emotional reactivity to the parent-adolescent conflict task was assessed via observed emotion expression, self-reported negative emotion, and salivary cortisol reactivity. RESULTS: Results indicated that the PM intervention increased brain responsivity in left posterior insula in response to negative affective stimuli, and altered resting state functional connectivity in regions involved in self-reference, behavioral regulation, and social-emotional processing. Changes in mothers' brain function and connectivity were associated with increased mindful parenting and decreased emotional reactivity to the parent-adolescent conflict task. CONCLUSIONS: Findings suggest that mindfulness-based changes in maternal emotional awareness at the neurobiological level are associated with decreased emotional reactivity in parenting interactions, illuminating potential neurobiological targets for future parent-focused intervention.

Temporal Dynamics of the Neural Representation of Social Relationships.

Humans can rapidly encode information from faces to support social judgments and facilitate interactions with others. We can also recall complex knowledge about those individuals, such as their social relationships with others, but the time course of this process has not been examined in detail. This study addressed the temporal dynamics of emerging visual and social relationship information using EEG and representational similarity analysis. Participants (female = 23, male = 10) became familiar with a 10-person social network, and were then shown faces of that network's members while EEG was recorded. To examine the temporal dynamics of the cognitive processes related to face perception, we compared the similarity structure of neural pattern responses to models of visual processing, face shape similarity, person identity, and social relationships. We found that all types of information are associated with neural patterns after a face is seen. Visual models became significant early after image onset, and identity across a change in facial expression was uniquely associated with neural patterns at several points throughout the time course. Additionally, a model reflecting perceived frequency of social interaction was present beginning at ∼110 ms, even in the absence of an explicit task to think about the relationships among the network members. This study highlights the speed and salience of social information relating to group dynamics that are present in the brain during person perception.SIGNIFICANCE STATEMENT We live our lives in social groups where complex relationships form among and around us. It is likely that some of the information about social relationships that we observe is integral during person perception, to better help us interact in differing situations with a variety of people. However, when exactly this information becomes relevant has been unclear. In this study, we present evidence that information reflecting observed relationships among a social network is spontaneously represented in whole-brain patterns shortly following presentation of a face. These results are consistent with neuroimaging studies showing spontaneous spatial representation of social network characteristics, and contribute novel insights into the timing of these neural processes.

Maternal Neurobiological Processing of Negative Adolescent Stimuli: Relations With Positive Parenting and Relationship Quality.

We examined associations between maternal affective neurobiology and positive parenting in a study of 20 mothers of adolescents. Mothers underwent functional magnetic resonance imaging during an emotion image task, rated parent-adolescent relationship quality, and completed an adolescent interaction task in which positive parenting behaviors were observed. Maternal structure was associated with lower responsivity in emotional processing regions in the general negative image contrast and was related to greater dorsolateral prefrontal cortex activation to negative adolescent images. Parent-adolescent relationship quality was associated with lower precuneus activation to negative adolescent images. Findings are among the first to connect functional brain processing with observed parenting behaviors for parents of adolescent children, and underscore the relative importance of affective processing in parenting older children.

Sex-Differentiated Associations among Negative Parenting, Emotion-Related Brain Function, and Adolescent Substance Use and Psychopathology Symptoms.

Parenting is a critical factor in adolescent social-emotional development, with maladaptive parenting leading to risk for the development of psychopathology. However, the emotion-related brain mechanisms underlying the influence of parenting on psychopathology symptoms are unknown. The present study utilized functional magnetic resonance imaging and laboratory measures to examine sex-differentiated associations among parenting, adolescent emotion-related brain function, and substance use and psychopathology symptoms in 66 12-14 year olds. Maternal parenting behaviors (warmth, negative parenting) were observed in a laboratory task. Adolescent brain responses to negative emotional stimuli were assessed in emotion processing regions of interest (left [L] and right [R] amygdala, anterior insula, anterior cingulate cortex [ACC]). Adolescents reported on substance use and depressive, anxiety, and externalizing symptoms. Maternal negative parenting predicted adolescent brain activation differently by sex. For girls, negative parenting predicted heightened R ACC activation to negative emotional stimuli. For boys, negative parenting predicted blunted L and R anterior insula and L ACC activation. Furthermore, for girls, but not boys, heightened L anterior insula and heightened L and R ACC activation were associated with substance use and depressive symptoms, respectively. Findings suggest neural response to negative emotion as a possible sex-specific pathway from negative parenting to psychopathology.

Adolescent Brain Response to Reward Is Associated with a Bias toward Immediate Reward.

The current study examines associations between neural activation to the receipt of monetary reward in a rewarding game task and bias toward immediate reward measured in a behavioral delay discounting task among early adolescents (N = 58, 12-14 years). As expected, heightened brain activation in reward-related regions were correlated with higher bias toward immediate reward. This suggests that bias toward immediate reward in delay discounting tasks may be linked to heightened activation to reward in reward processing regions. This interplay between neural reward processing and bias toward immediate reward might explain the sharp increases in bias toward immediate reward that occur in early adolescence.

Maternal stress and adolescent brain structure and function.

INTRODUCTION: Adolescence is a time of heightened sensitivity in biological stress systems and the emergence of stress-related psychopathology. Thus, understanding environmental factors in adolescence that might be associated with adolescents'' stress systems is important. Maternal stress levels may be involved. However, the relationship between maternal stress and the adolescent brain is unknown. METHOD: The present study examined the association between mothers' self-reported stress levels and mothers' cortisol stress reactivity and their early adolescents' brain structure and functional activation to stressful negative emotional images. Participants included 66 mothers and their 12- to 14-year old adolescents. Mother's perceived stress and salivary cortisol reactivity to a stressful task were collected. Then, adolescents' brain structure and function were assessed in a magnetic resonance imaging session. RESULTS: Functional whole-brain analyses revealed that mothers' higher reported perceived stress, but not cortisol reactivity, predicted adolescents' higher responses in the medial prefrontal cortex (mPFC) to stressful negative emotional stimuli. There were no statistically significant associations for structural analyses. CONCLUSIONS: Given the finding of maternal stress reactivity related to adolescent mPFC function-an integral structure related to stress responses-parent stress may play a role in the development of neural stress systems in adolescence, with potential implications for development of psychopathology.

Temporal and spatial discounting are distinct in humans.

Previous research on temporal and spatial discounting has largely focused on temporal discounting in which responses to reward stimuli are altered by the time taken to reach the reward. However, there is currently minimal research on the behavioral effects of spatial discounting. In addition, contrary to the current findings, previous research on reward discounting has suggested a correlation between temporal and spatial discounting. Here we present results from three studies, all of which employed a spatial and temporal discounting task in which subjects were immersed in a virtual reality environment and were presented with a choice between two monetary rewards, each reward varying in distance and duration. In addition, in experiments 2 and 3, the speed at which a subject could move within the virtual environment was manipulated. Our findings indicate some of the first evidence that space and time may in fact be estimated independently when discounting rewards.

The Neural Representational Space of Social Memory.

Social functioning involves learning about the social networks in which we live and interact; knowing not just our friends, but also who is friends with our friends. This study utilized an incidental learning paradigm and representational similarity analysis (RSA), a functional MRI multivariate pattern analysis technique, to examine the relationship between learning social networks and the brain's response to the faces within the networks. We found that accuracy of learning face pair relationships through observation is correlated with neural similarity patterns to those pairs in the left temporoparietal junction (TPJ), the left fusiform gyrus, and the subcallosal ventromedial prefrontal cortex (vmPFC), all areas previously implicated in social cognition. This model was also significant in portions of the cerebellum and thalamus. These results show that the similarity of neural patterns represent how accurately we understand the closeness of any two faces within a network. Our findings indicate that these areas of the brain not only process knowledge and understanding of others, but also support learning relations between individuals in groups.

Adolescents' Reward-related Neural Activation: Links to Thoughts of Nonsuicidal Self-Injury.

Adolescence is a critical developmental period marked by an increase in risk behaviors, including nonsuicidal self-injury (NSSI). Heightened reward-related brain activation and relatively limited recruitment of prefrontal regions contribute to the initiation of risky behaviors in adolescence. However, neural reward processing has not been examined among adolescents who are at risk for future engagement for NSSI specifically, but who have yet to actually engage in this behavior. In the current fMRI study (N = 71), we hypothesized that altered reward processing would be associated with adolescents' thoughts of NSSI. Results showed that NSSI youth exhibited heightened activation in the bilateral putamen in response to a monetary reward. This pattern of findings suggests that heightened neural sensitivity to reward is associated with thoughts of NSSI in early adolescence. Implications for prevention are discussed.

Associations Between Parent Emotional Arousal and Regulation and Adolescents' Affective Brain Response.

Parents' emotional functioning represents a central mechanism in the caregiving environment's influence on adolescent affective brain function. However, a paucity of research has examined links between parental emotional arousal and regulation and adolescents' affective brain function. Thus, the present study examined associations between parents' self-rated negative emotion, parent emotion regulation difficulties, and adolescent brain responsivity to negative and positive emotional stimuli. Participants included 64 12-14 year-old adolescents (31 females) and their female primary caregivers. Adolescents viewed negative, positive, and neutral emotional stimuli during an fMRI scanning session. Region of interest analyses showed that higher parent negative emotion was related to adolescents' greater ACC and vmPFC response to both negatively- and positively-valenced emotional stimuli; whereas, parent negative emotion was related to adolescents' greater amygdala response to negative emotional stimuli only. Furthermore, parent emotion regulation moderated the association between parent negative emotion and adolescents' brain response to negative emotional stimuli, such that parents with high negative emotion and high emotion regulation difficulties had adolescents with the greatest affective brain response. Findings highlight the importance of considering both parent emotional arousal and regulation in understanding the family affective environment and its relation to adolescent emotion-related brain development.

The impact of neural responses to food cues following stress on trajectories of negative and positive affect and binge eating in daily life.

Stress and affect have been implicated in the maintenance of binge eating for women with symptoms of bulimia nervosa (BN). Neuroimaging and ecological momentary assessment (EMA) have separately examined how these variables may contribute to eating disorder behavior. Though both methodologies have their own strengths, it's unclear how either methodology might inform the other. This study examined the impact of individual differences in neural reactivity to food cues following acute stress on the trajectories of positive affect (PA) and negative affect (NA) surrounding binge eating. Women (n = 16) with BN symptoms viewed palatable food cues before and after a stress induction in the scanner. For two weeks, participants responded to prompts assessing affect and binge episodes several times a day. EMA data revealed NA increased and PA decreased before binge episodes in the natural environment. Additionally, NA decreased while PA increased following binge episodes. Changes in activation in the ACC, amygdala, and the vmPFC significantly moderated the relationship of affect to binge eating. However, lateral differences of each brain region uniquely moderator the trajectory of PA, NA, or both to binge eating. Specifically, those with less change in BOLD response reported significantly increasing NA and decreasing PA prior to binges, while women with greater decreases reported no change in affect. Following binge eating, individuals with decreased change in BOLD response reported decreasing NA and increasing PA. This may suggest individual differences in neural response to food cues under stress appear to underlie affect driven theory on the antecedents to binge eating.

Associations between cortical thickness, structural connectivity and severity of dimensional bulimia nervosa symptomatology.

Bulimia nervosa (BN) is a psychiatric illness defined by preoccupation with body image (cognitive 'symptoms'), binge eating and compensatory behaviors. Although diagnosed BN has been related to grey matter alterations, characterization of brain structure in women with a range of BN symptoms has not been made. This study examined whether cortical thickness (CT) values scaled with severity of BN cognitions in 33 women with variable BN pathology. We then assessed global structural connectivity (SC) of CT to determine if individual differences in global SC relate to BN symptom severity. We used the Eating Disorder Examination Questionnaire (EDE-Q) as a continuous measure of BN symptom severity. EDE-Q score was negatively related to global CT and local CT in the left middle frontal gyrus, right superior frontal gyrus and bilateral orbitofrontal cortex (OFC) and temporoparietal regions. Moreover, cortical thinning was most pronounced in regions with high global connectivity. Finally, individual contributions to global SC at the group level related to EDE-Q score, where increased EDE-Q score correlated with reduced connectivity of the left OFC and middle temporal cortex and increased connectivity of the right superior parietal lobule. Findings represent the first evidence of cortical thinning that relates to cognitive BN symptoms.

The relation between craving and binge eating: Integrating neuroimaging and ecological momentary assessment.

The role of craving in binge eating characteristic of bulimia nervosa (BN) is inconclusive. A network of regions associated with cue reactivity to food and substances has been identified, comprised of the amygdala, orbitofrontal cortex, insula, and striatum. The goal of this study was to examine individual differences in BOLD response in this appetitive network as moderators of the relationship between craving and binging in the natural environment in women with BN. Women with BN (N = 16) completed a baseline measure of craving and a fMRI scan, where they viewed neutral cues and food cues. After each run, craving for food was assessed. Participants then completed an ecological momentary assessment six times a day via smart phone and recorded binge eating and craving. Participants exhibited significantly increased BOLD response in the left amygdala in response to food cues compared to neutral cues. However, individual differences in BOLD response were not correlated with self-report craving throughout the scan. The relationship between craving and binging in everyday life was moderated by individual differences in activation in the caudate, insula, and amygdala. Women with greater activation in these regions demonstrated significant increases in craving prior to binge eating. Those who did not exhibit increases in activation did not exhibit increases in craving prior to binge eating in the natural environment. Craving may not underlie binge eating for all individuals with BN. However, these results indicate that neural response to food cues may affect individual differences in the daily experience of craving and binge eating.

Reprint of "Biological motion perception links diverse facets of theory of mind during middle childhood".

Two cornerstones of social development-social perception and theory of mind-undergo brain and behavioral changes during middle childhood, but the link between these developing domains is unclear. One theoretical perspective argues that these skills represent domain-specific areas of social development, whereas other perspectives suggest that both skills may reflect a more integrated social system. Given recent evidence from adults that these superficially different domains may be related, the current study examined the developmental relation between these social processes in 52 children aged 7 to 12years. Controlling for age and IQ, social perception (perception of biological motion in noise) was significantly correlated with two measures of theory of mind: one in which children made mental state inferences based on photographs of the eye region of the face and another in which children made mental state inferences based on stories. Social perception, however, was not correlated with children's ability to make physical inferences from stories about people. Furthermore, the mental state inference tasks were not correlated with each other, suggesting a role for social perception in linking various facets of theory of mind.

Functional correlates of likelihood and prior representations in a virtual distance task.

Spatial navigation is an imperative cognitive function, in which individuals must interact with their environment in order to accurately reach a destination. Previous research has demonstrated that, when traveling a predetermined distance, humans must balance between noise in the measurement process and the prior history of traveled distances. This tradeoff has recently been formally described using Bayesian estimation; however, the neural correlates of Bayesian estimation during distance reproduction have yet to be investigated. Here, human subjects performed a virtual reality distance reproduction task during functional Magnetic Resonance Imaging (fMRI), in which they were required to reproduce various traveled distances in the absence of overt navigational cues. As previously demonstrated, subjects exhibited a central tendency effect, wherein reproduced distances gravitated to the mean of the stimulus set. fMRI activity during this task revealed distance-sensitive activity in a network of regions, including prefrontal and hippocampal regions. Using a computational index of central tendency, we found that activity in the retrosplenial cortex, a region highly implicated in spatial navigation, negatively covaried between subjects with the degree of central tendency observed; conversely, we found that activity in the anterior hippocampus/amygdala complex was positively correlated with the central tendency effect of gravitating to the average reproduced distance. These findings suggest dissociable roles for the retrosplenial cortex and hippocampal complex during distance reproduction, with both regions coordinating with the prefrontal cortex the influence of prior history of the environment with present experience. Hum Brain Mapp 37:3172-3187, 2016. © 2016 Wiley Periodicals, Inc.