The self in context: brain systems linking mental and physical health.

Increasing evidence suggests that mental health and physical health are linked by neural systems that jointly regulate somatic physiology and high-level cognition. Key systems include the ventromedial prefrontal cortex and the related default-mode network. These systems help to construct models of the 'self-in-context', compressing information across time and sensory modalities into conceptions of the underlying causes of experience. Self-in-context models endow events with personal meaning and allow predictive control over behaviour and peripheral physiology, including autonomic, neuroendocrine and immune function. They guide learning from experience and the formation of narratives about the self and one's world. Disorders of mental and physical health, especially those with high co-occurrence and convergent alterations in the functionality of the ventromedial prefrontal cortex and the default-mode network, could benefit from interventions focused on understanding and shaping mindsets and beliefs about the self, illness and treatment.

Listening to the Data: Computational Approaches to Addiction and Learning.

Computational approaches hold great promise for identifying novel treatment targets and creating translational therapeutics for substance use disorders. From circuitries underlying decision-making to computationally derived neural markers of drug-cue reactivity, this review is a summary of the approaches to data presented at our 2023 Society for Neuroscience Mini-Symposium. Here, we highlight data- and hypothesis-driven computational approaches that recently afforded advancements in addiction and learning neuroscience. First, we discuss the value of hypothesis-driven algorithmic modeling approaches, which integrate behavioral, neural, and cognitive outputs to refine hypothesis testing. Then, we review the advantages of data-driven dimensionality reduction and machine learning methods for uncovering novel predictor variables and elucidating relationships in high-dimensional data. Overall, this review highlights recent breakthroughs in cognitive mapping, model-based analysis of behavior/risky decision-making, patterns of drug taking, relapse, and neuromarker discovery, and showcases the benefits of novel modeling techniques, across both preclinical and clinical data.

Estradiol effects on an emotional interference task in adolescents with current and remitted depression.

Attentional biases to emotional stimuli are thought to reflect vulnerability for mood disorder onset and maintenance. This study examined the association between the endogenous sex hormone estradiol and emotional attentional biases in adolescent females with either current or remitted depression. Three groups of participants (mean age ± SD) completed the Emotional Interrupt Task: 1) 20 adolescent females (15.1 ± 1.83 years) currently diagnosed with Major Depressive Disorder (MDD), 2) 16 adolescent females (16.4 ± 1.31 years) who had experienced at least one episode of MDD in their lifetime but currently met criteria for MDD in remission, and 3) 30 adolescent female (15.4 ± 1.83 years) healthy controls. Attentional interference (AI) scores were calculated as differences in target response reaction time between trials with emotional facial expressions versus neutral facial expressions. Estradiol levels were assayed by Salimetrics LLC using saliva samples collected within 30 min of waking on assessment days. Robust multiple regression with product terms evaluated estradiol's main effect on AI scores, as well as hypothesized estradiol × diagnostic group interactions. Although neither mean estradiol levels nor mean AI scores in the current-MDD and remitted-MDD groups differed from controls, the relationship between estradiol and overall AI score differed between control adolescents and the remitted-MDD group. Specifically, the remitted-MDD adolescents performed worse (i.e., showed greater attentional interference) when they had higher estradiol; no significant relationship existed in the current-MDD group. Because this finding was driven by angry and not happy stimuli, it appears higher estradiol levels were associated with greater susceptibility to the attention-capturing effects of negatively-valenced emotional content in girls at risk for MDD from prior history.

Neuromarkers in addiction: definitions, development strategies, and recent advances.

Substance use disorders (SUDs) are the most costly and prevalent psychiatric conditions. Recent calls emphasize a need for biomarkers-measurable, stable indicators of normal and abnormal processes and response to treatment or environmental agents-and, in particular, brain-based neuromarkers that will advance understanding of the neurobiological basis of SUDs and clinical practice. To develop neuromarkers, researchers must be grounded in evidence that a putative marker (i) is sensitive and specific to the psychological phenomenon of interest, (ii) constitutes a predictive model, and (iii) generalizes to novel observations (e.g., through internal cross-validation and external application to novel data). These neuromarkers may be used to index risk of developing SUDs (susceptibility), classify individuals with SUDs (diagnostic), assess risk for progression to more severe pathology (prognostic) or index current severity of pathology (monitoring), detect response to treatment (response), and predict individualized treatment outcomes (predictive). Here, we outline guidelines for developing and assessing neuromarkers, we then review recent advances toward neuromarkers in addiction neuroscience centering our discussion around neuromarkers of craving-a core feature of SUDs. In doing so, we specifically focus on the Neurobiological Craving Signature (NCS), which show great promise for meeting the demand of neuromarkers.

Social interpretation inflexibility moderates emotional reactions to social situations in children and adolescents.

Interpretation biases and inflexibility (i.e., difficulties revising interpretations) have been linked to increased internalizing symptoms. Although adolescence is a developmental period characterized by novel social situations and increased vulnerability to internalizing disorders, no studies have examined interpretation inflexibility in adolescents. Additionally, no studies (on adolescents or adults) have examined interpretation flexibility as a protective factor against adverse outcomes of interpersonal events. Using a novel task and a 28-day diary we examined relations among interpretation bias and inflexibility, internalizing symptoms, and negative interpersonal events in a sample of children and adolescents (N = 159, ages 9-18). At baseline, negative interpretation bias was positively correlated with social anxiety symptoms, and positive interpretation bias negatively correlated with social anxiety and depressive symptoms. Inflexible positive interpretations were correlated with higher social anxiety and depressive symptoms, while inflexible negative interpretations were correlated with higher social anxiety. Finally, interpretation inflexibility moderated daily associations between negative interpersonal events and depressive symptoms in daily life, such that higher inflexibility was associated with stronger associations between interpersonal events and subsequent depressive symptoms, potentially increasing depressive symptom instability. These results suggest that interpretation biases and inflexibility may act as both risk and protective factors for adolescent anxiety and depression.

Emotion regulation and disordered eating behaviour in youths: Two daily-diary studies.

OBJECTIVE: Disordered eating cognitions and behaviours in childhood and adolescence have been identified as precursors for the development of eating disorders. Another important contributor to eating disorder risk is maladaptive emotion regulation. However, while the regulation of negative affect has been the focus of much research, the literature on the role of positive emotion regulation in eating pathology is extremely limited. The present study extends previous research by examining the regulation of both positive and negative affect in disordered eating using two waves of a daily diary design. METHOD: Every evening for 21 days, 139 youths (8-15 years) reported their use of rumination, dampening, and disordered eating cognitions and behaviours. 1 year later, during the onset of the COVID-19 pandemic, 115 of these youths were followed-up. RESULTS: As predicted, higher levels of rumination and dampening were found to be associated with a higher frequency of weight concerns and restrictive eating on person-level (both Waves) and day-level (Wave 2). Further, a higher frequency of rumination at Wave 1 predicted increases in the frequency of restrictive eating 1 year later. CONCLUSIONS: Our findings underline the importance of examining regulation of both positive and negative emotion in order to understand eating disorder risk.

Efficacy of single-session transcranial direct current stimulation on addiction-related inhibitory control and craving: a randomized trial in males with Internet gaming disorder.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (dlPFC) may reduce substance use and other addictive behaviours. However, the cognitive mechanisms that underpin such effects remain unclear. Impaired inhibitory control linked to hypoactivation of the prefrontal cortex may allow craving-related motivations to lead to compulsive addictive behaviours. However, very few studies have examined whether increasing the activation of the dlPFC via anodal tDCS could enhance inhibitory control over addiction-related distractors. The current study aimed to enrich empirical evidence related to this issue. METHODS: Thirty-three males with Internet gaming disorder underwent active (1.5 mA for 20 minutes) and sham tDCS 1 week apart, in randomized order. We assessed inhibitory control over gaming-related distractors and craving pre- and post-stimulation. RESULTS: Relative to sham treatment, active tDCS reduced interference from gaming-related (versus non-gaming) distractors and attenuated background craving, but did not affect cue-induced craving. LIMITATIONS: This study was limited by its relatively small sample size and the fact that it lacked assessments of tDCS effects on addictive behaviour. Future tDCS studies with multiple sessions in larger samples are warranted to examine the effects on addictive behaviours of alterations in addiction-related inhibitory control. CONCLUSION: These findings demonstrate that stimulation of the dlPFC influences inhibitory control over addiction-related cues and addiction-related motivation. This is the first empirical study to suggest that enhanced inhibitory control may be a cognitive mechanism underlying the effects of tDCS on addictions like Internet gaming disorder. Our finding of attenuated background craving replicated previous tDCS studies. Intriguingly, our finding of distinct tDCS effects on 2 forms of craving suggests that they may have disparate underlying mechanisms or differential sensitivity to tDCS. CLINICAL TRIALS #: NCT03352973.

Mindfulness-based interventions for eating disorders: The potential to mobilize multiple associative-learning change mechanisms.

Mindfulness is a two-component skill that includes mindful awareness (attentional monitoring of present moment experience) and mindful acceptance (adopting an attitude of acceptance toward this experience). Although mindfulness-based interventions (MBIs) are efficacious for many conditions, there is a lack of research on MBIs for eating disorders (EDs). We propose that MBIs may be promising for EDs given their potential to mobilize not one, but multiple associative-learning change mechanisms in EDs-defined as adaptive processes of change involving one of two forms of associative-learning: Pavlovian and operant learning. We hypothesize how MBIs-via increasing either mindful awareness or mindful acceptance-may mobilize up to eight associative-learning change mechanisms, two involving Pavlovian learning, and six involving operant learning. We also elaborate on similarities and differences between MBIs and CBT approaches for EDs, as well as opportunities for synergy. Finally, we present recommendations for future research related to the development and evaluation of novel MBI interventions for EDs and the testing of mechanisms and patient-treatment matching hypotheses.

Training in cognitive strategies reduces eating and improves food choice.

Obesity rates continue to rise alarmingly, with dire health implications. One contributing factor is that individuals frequently forgo healthy foods in favor of inexpensive, high-calorie, unhealthy foods. One important mechanism underlying these choices is food craving: Craving increases with exposure to unhealthy foods (and food cues, such as advertisements) and prospectively predicts eating and weight. Prior work has shown that cognitive regulation strategies that emphasize the negative consequences of unhealthy foods reduce craving. In Studies 1 and 2, we show that cognitive strategies also increase craving for healthy foods by emphasizing their positive benefits, and change food valuation (willingness to pay) for both healthy and unhealthy foods. In Studies 3 and 4, we demonstrate that brief training in cognitive strategies ("Regulation of Craving Training"; ROC-T) increases subsequent healthy (vs. unhealthy) food choices. This was striking because this change in food choices generalized to nontrained items. Importantly, in Study 5, we show that brief training in cognitive strategies also reduces food consumption by 93-121 calories. Consumed calories correlated with changes in food choice. Finally, in Study 6, we show that the training component of ROC-T is necessary, above and beyond any effect of framing. Across all studies (NTOTAL = 1,528), we find that cognitive strategies substantially change craving and food valuation, and that training in cognitive strategies improves food choices by 5.4-11.2% and reduces unhealthy eating, including in obese individuals. Thus, these findings have important theoretical, public health, and clinical implications for obesity prevention and treatment.

Predicting Negative and Positive Affect During COVID-19: A Daily Diary Study in Youths.

The COVID-19 pandemic has the potential to profoundly affect youths' mental health. Understanding predictors of affective responding to the pandemic is critical for prevention and intervention efforts. This study examines emotion regulation as an important predictor of youth's changes in positive and negative affect. The present study of 115 participants (62 girls, Mage  = 11.77) explores the relation between pre-existing emotion regulation strategies, as measured by multi-week daily diaries pre-COVID, and youths' mean positive and negative affect levels and variability during a 28-day period amidst the pandemic, while including COVID-related worries and isolation as important moderators. The findings provide important insight into interactions between pre-existing vulnerabilities and COVID-related stressors in predicting affective adjustment in youth.

Neural stress reactivity relates to smoking outcomes and differentiates between mindfulness and cognitive-behavioral treatments.

Stress and negative affect are known contributors to drug use and relapse, and several known treatments for addictions include strategies for managing them. In the current study, we administered a well-established stress provocation during functional magnetic resonance imaging (fMRI) to 23 participants who completed either mindfulness training (MT; N=11) or the American Lung Association's Freedom From Smoking (FFS; N=12), which is a cognitive-behavioral treatment (CBT) for smoking cessation. Across the entire sample, we found that stress reactivity in several brain regions including the amygdala and anterior/mid insula was related to reductions in smoking after treatment, as well as at 3-month post-treatment follow-up. Moreover, conjunction analysis revealed that these same regions also differentiated between treatment groups such that the MT group showed lower stress-reactivity compared to the FFS/CBT group. This suggests that reduction in stress reactivity may be one of the mechanisms that underlie the efficacy of MT in reducing smoking over time. The findings have important implications for our understanding of stress, the neural and psychological mechanisms that underlie mindfulness-based treatments, and for smoking cessation treatments more broadly.

Disrupted cortico-limbic connectivity during reward processing in remitted bipolar I disorder.

OBJECTIVES: Bipolar disorder (BD) is associated with elevated reward sensitivity and persistent positive affect, yet the neural mechanisms underlying these patterns are not well understood. In the present study, we examined putative disruptions in communication within a well-known cortico-limbic reward circuit during reward processing as a potential contributing mechanism to these symptoms. METHODS: The present investigation employed a within- and between-subjects design utilizing a monetary and social incentive delay task among adults with bipolar disorder type I (BD; N = 24) and a healthy non-psychiatric control group (HC; N = 25) during functional magnetic resonance imaging (fMRI). Participants in the BD group were remitted at the time of testing. RESULTS: Functional connectivity analyses revealed increased connectivity between the ventral striatum (VS) seed region and orbitofrontal cortex (OFC) as well as the amygdala during processing of reward receipt in the BD group. After omission of expected rewards, the BD group showed decreased functional connectivity between the VS and a medial frontopolar cortex (mFPC) region associated with consideration of behavioral alternatives. Follow-up analyses within the BD group showed that increased VS-OFC connectivity after reward receipt, and decreased VS-mFPC connected after reward omission, were associated with higher levels of subthreshold mania symptoms. CONCLUSIONS: Results point toward potential mechanisms implicated in elevated reward sensitivity in BD. Enhanced VS-OFC connectivity after reward receipt may be involved in elevated valuation of rewards whereas blunted VS-mFPC connectivity after reward omission may reflect a failure to consider behavioral alternatives to reward pursuit.

Gender-related Differences in Food Craving and Obesity.

Food craving is often defined as a strong desire to eat. Much work has shown that it consistently and prospectively predicts eating and weight-related outcomes, contributing to the growing obesity epidemic. Although there are clear gender differences in the prevalence and health consequences of obesity, relatively little recent work has investigated gender differences in craving, or any sex-hormone-based differences as they relate to phases of the menstrual cycle. Here, we propose that gender-related differences in food craving contribute to gender-related differences in obesity. Drawing on findings in the addiction literature, we highlight ways to incorporate gender-based differences in food craving into treatment approaches, potentially improving the efficacy of obesity and weight loss treatment. Overall, this review aims to emphasize the importance of investigating gender differences in food craving, with a view towards informing the development of more effective treatments for obesity and weight loss.

Cognitive regulation of craving in alcohol-dependent and social drinkers.

BACKGROUND: Helping alcohol-dependent individuals to cope with, or regulate, cue-induced craving using cognitive strategies is a therapeutic goal of cognitive behavioral therapy (CBT) for alcohol dependence. An assumption that underlies this approach is that alcohol dependence is associated with deficits in such cognitive regulation abilities. To date, however, the ability to utilize such strategies for regulation of craving has never been tested in a laboratory setting. METHODS: Here we compared 19 non-treatment-seeking, alcohol-dependent drinkers (AD) to 21 social drinkers (SD), using a laboratory task that measured the ability to reduce cue-induced alcohol craving by thinking about long-term negative consequences of drinking, which is a specific cognitive regulation strategy that is taught in CBT. The task also assessed the ability to reduce food craving elicited by high-calorie food cues using a similar strategy. RESULTS: The reduction in craving when using this cognitive regulation strategy was approximately double in SD, compared to AD, for both alcohol and food cues. Furthermore, in SD but not AD, the ability to regulate cue-induced alcohol craving was correlated with the ability to regulate food craving. There were no significant correlations found between the ability to regulate cue-induced alcohol craving and a number of self-report measures related to severity of alcohol dependence, baseline craving, impulsivity, and general self-regulation ability, for either AD or SD. CONCLUSIONS: The results suggest that alcohol dependence is associated with deficits in cognitive regulation of cue-induced craving and that these deficits are not specific to the regulation of alcohol craving, but generalize to the regulation of other appetitive states, such as food craving. Future studies may use similar procedures to address the neural and cognitive processes that underlie such regulation deficits, as well as the effects of treatments such as CBT on these processes.

Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies.

In recent years, an explosion of neuroimaging studies has examined cognitive reappraisal, an emotion regulation strategy that involves changing the way one thinks about a stimulus in order to change its affective impact. Existing models broadly agree that reappraisal recruits frontal and parietal control regions to modulate emotional responding in the amygdala, but they offer competing visions of how this is accomplished. One view holds that control regions engage ventromedial prefrontal cortex (vmPFC), an area associated with fear extinction, that in turn modulates amygdala responses. An alternative view is that control regions modulate semantic representations in lateral temporal cortex that indirectly influence emotion-related responses in the amygdala. Furthermore, while previous work has emphasized the amygdala, whether reappraisal influences other regions implicated in emotional responding remains unknown. To resolve these questions, we performed a meta-analysis of 48 neuroimaging studies of reappraisal, most involving downregulation of negative affect. Reappraisal consistently 1) activated cognitive control regions and lateral temporal cortex, but not vmPFC, and 2) modulated the bilateral amygdala, but no other brain regions. This suggests that reappraisal involves the use of cognitive control to modulate semantic representations of an emotional stimulus, and these altered representations in turn attenuate activity in the amygdala.

A pilot study linking reduced fronto-Striatal recruitment during reward processing to persistent bingeing following treatment for binge-eating disorder.

OBJECTIVE: The primary purpose of this study was to examine neurobiological underpinnings of reward processing that may relate to treatment outcome for binge-eating disorder (BED). METHOD: Prior to starting treatment, 19 obese persons seeking treatment for BED performed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Analyses examined how the neural correlates of reward processing related to binge-eating status after 4-months of treatment. RESULTS: Ten individuals continued to report binge-eating (BEpost-tx ) following treatment and 9 individuals did not (NBEpost-tx ). The groups did not differ in body mass index. The BEpost-tx group relative to the NBEpost-tx group showed diminished recruitment of the ventral striatum and the inferior frontal gyrus during the anticipatory phase of reward processing and reduced activity in the medial prefrontal cortex during the outcome phase of reward processing. DISCUSSION: These results link brain reward circuitry to treatment outcome in BED and suggest that specific brain regions underlying reward processing may represent important therapeutic targets in BED.

Meditation experience is associated with differences in default mode network activity and connectivity.

Many philosophical and contemplative traditions teach that "living in the moment" increases happiness. However, the default mode of humans appears to be that of mind-wandering, which correlates with unhappiness, and with activation in a network of brain areas associated with self-referential processing. We investigated brain activity in experienced meditators and matched meditation-naive controls as they performed several different meditations (Concentration, Loving-Kindness, Choiceless Awareness). We found that the main nodes of the default-mode network (medial prefrontal and posterior cingulate cortices) were relatively deactivated in experienced meditators across all meditation types. Furthermore, functional connectivity analysis revealed stronger coupling in experienced meditators between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices (regions previously implicated in self-monitoring and cognitive control), both at baseline and during meditation. Our findings demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. As such, these provide a unique understanding of possible neural mechanisms of meditation.

Back to Normal? Harnessing Long Short-term Memory Network to Examine the Associations Between Adolescent Social Interactions and Depressive Symptoms During Different Stages of COVID-19.

Adolescence is a developmental period in which social interactions are critical for mental health. While the onset of COVID-19 significantly disrupted adolescents' social environments and mental health, it remains unclear how adolescents have adapted to later stages of the pandemic. We harnessed a machine learning architecture of Long Short-Term Memory recurrent networks (LSTM) with gradient-based feature importance, to model the association among daily social interactions and depressive symptoms during three stages of the pandemic. A year before COVID-19, 148 adolescents reported social interactions and depressive symptoms, every day for 21 days. One hundred sixteen of these youths completed a 28-day diary after schools closed due to COVID-19. Seventy-nine of these youths and additional 116 new participants completed a 28-day diary approximately a year into the pandemic. Our results show that LSTM successfully predicted depressive symptoms from at least a week of social interactions for all three waves (r2 > .70). Our study shows the utility of using an analytic approach that can identify temporal and nonlinear pathways through which social interactions may confer risk for depression. Our unique analysis of the importance of input features enabled us to interpret the association between social interactions and depressive symptoms. Collectively, we observed a return to pre-pandemic patterns a year into the pandemic, with reduced gender and age differences during the pandemic closures. This pattern suggests that the system of social influences in adolescence was affected by COVID-19, and that this effect was attenuated in more chronic stages of the pandemic.

It's a balancing act: The ratio of maladaptive (vs. All) emotion regulation strategies is associated with depression.

Research on emotion regulation (ER) has increasingly recognized that people use multiple strategies simultaneously, often referred to as ER repertoire. Prior research found that ER repertoire is associated with psychopathology, but results have been mixed. Indeed, research from recent years suggests that it is the quality of ERs, more than their quantity, that needs to be considered. Based on the combination of the literatures on ER repertoire, polyregulation, and ER flexibility, we propose a novel metric: the ratio of using putatively maladaptive (vs. all) ER strategies. Using this metric, we examine (1) maladaptive ER ratio changes during the transition to adolescence, a developmental period in which the prevalence of depression sharply increases, and (2) whether changes in maladaptive ER ratio are associated with depressive symptoms. One-hundred and thirty-nine youths (baseline age: 8-15) reported ER strategies and depression daily for 21 days. One year later, 115 completed another 28-day daily-diary (Nassessments = 5631). Our results show that almost all youth use at least some maladaptive ERs. Importantly, maladaptive ER ratio decreases over a year of adolescence for most youths. Conversely, an increased maladaptive ER ratio predicted depression increases on the daily and on the yearly level. These results shed light on typical and atypical development of ER flexibility and emphasize the need to consider the balance between ERs in relation to psychopathology.

Development and initial testing of mindful journey: a digital mindfulness-based intervention for promoting recovery from Substance use disorder.

BACKGROUND/OBJECTIVES: There is a great unmet need for accessible adjunctive interventions to promote long-term recovery from substance use disorder (SUD). This study aimed to iteratively develop and test the initial feasibility and acceptability of Mindful Journey, a novel digital mindfulness-based intervention for promoting recovery among individuals with SUD. PATIENTS/MATERIALS: Ten adults receiving outpatient treatment for SUD. METHODS: Phase 1 (n = 5) involved developing and testing a single introductory digital lesson. Phase 2 included a separate sample (n = 5) and involved testing all 15 digital lessons (each 30- to 45-minutes) over a 6-week period, while also receiving weekly brief phone coaching for motivational/technical support. RESULTS: Across both phases, quantitative ratings (rated on a 5-point scale) were all at or above a 4 (corresponding with 'agree') for key acceptability dimensions, such as usability, understandability, appeal of visual content, how engaging the content was, and helpfulness for recovery. Additionally, in both phases, qualitative feedback indicated that participants particularly appreciated the BOAT (Breath, Observe, Accept, Take a Moment) tool for breaking down mindfulness into steps. Qualitative feedback was used to iteratively refine the intervention. For example, based on feedback, we added a second core mindfulness tool, the SOAK (Stop, Observe, Appreciate, Keep Curious), and we added more example clients and group therapy videos. In Phase 2, 4 out of 5 participants completed all 15 lessons, providing initial evidence of feasibility. Participants reported that the phone coaching motivated them to use the app. The final version of Mindful Journey was a smartphone app with additional features, including brief on-the-go audio exercises and a library of mindfulness practices. Although, participants used these additional features infrequently. CONCLUSIONS: Based on promising initial findings, future acceptability and feasibility testing in a larger sample is warranted. Future versions might include push notifications to facilitate engagement in the additional app features.