BACKGROUND:Family-Based Treatment (FBT) is evidence based for patients younger than 18 with anorexia nervosa; however, continued refinement of FBT is needed to increase response and remission rates. AIMS:This study aimed to compare traditional FBT with an interoceptive exposure (IE) intervention that targets visceral sensitivity and autonomous eating in a family context. We hypothesized that IE would reduce food avoidance to a greater degree than FBT, as measured by laboratory feeding independent of weight gain. METHODS:Adolescents diagnosed with a low-weight eating disorder (LWED) were randomized to six sessions of FBT or IE. Before and after the intervention, patients completed interviews and self-report questionnaires, laboratory test meals (single and multi-item), and functional magnetic resonance imaging. Healthy controls provided a comparison group for these assessments. The study was registered as follows: clinicaltrials.gov NCT02795455 (https://clinicaltrials.gov/study/NCT02795455?term=NCT02795455&rank=1), GCO 15-0939 Reward Systems and Food Avoidance in Eating Disorders. RESULTS:Adolescents receiving IE (n = 30) consumed significantly more energy (kcal) during the post-treatment single item (Mdiff = 98.12 kcal, SDpooled = 119.84, d = 0.82) and multi-item meals (Mdiff = 137.11 kcal, SDpooled = 301.85, d = 0.45) than the FBT group (n = 30). No significant differences were found for age and sex adjusted % expected body weight between groups. Adolescents with LWED reported significantly more symptoms on all clinical measures than controls (n = 27). CONCLUSIONS:Six sessions of a novel form of IE yielded significant changes in eating behavior, namely an approximately two-fold increase in energy consumed in both multi-item and single-item meals among those randomized to IE. Additional research using a fully expanded version of these treatments is needed.

OBJECTIVE:Numerous publications utilize data from the Adolescent Brain and Cognitive Development (ABCD) Study. This review aimed to evaluate how data from the ABCD cohort contributes to understanding the pathophysiology of incipient eating disorders. METHOD:Searches were completed using PubMed and the ABCD Study research publications database. All available neuroimaging articles assessing prevalence and predictors of disordered eating/eating disorders were included. RESULTS:Thirty-eight articles met inclusion criteria, 10 of which presented neuroimaging results, all analyzing baseline brain data. The majority (n = 9) assessed brain structure and function in children with binge eating (BE)/binge eating disorder (BED). Results were inconsistent across imaging modalities. Structural MRI studies included widespread increases in gray matter density and reductions in cortical thickness associated with eating pathology. Task-based fMRI studies reported conflicting findings, with frontostriatal activation during reward processing in children with BE/BED reduced, increased, or not different compared to controls. Resting-state fMRI analyses consistently identified reduced functional connectivity in key frontal circuits, although patterns differed when samples were stratified by sex or BMI. Non-imaging studies showed positive associations between eating disorders/disordered eating and several sociodemographic, cognitive, behavioral, and biological correlates. DISCUSSION:Alterations in brain structure and function associated with binge eating are identified in neuroimaging analyses of baseline scans from the ABCD cohort, with inconsistent results. One potential pattern suggests alterations in reward system function, although the direction and exact location of such alterations are unclear. Consistency in methodological approaches is necessary to allow patterns in neural alterations to be more clearly identified. There is significant and ongoing potential for the ABCD Study dataset to quantify developmental aspects of binge eating. Recommendations for future analyses as the sample progresses through puberty and eating disorder prevalence increases are also presented.

Binge eating disorder (BED) is the most prevalent eating disorder. However, current diagnostic frameworks remain largely grounded in symptom-based criteria rather than underlying biological mechanisms, thereby limiting early detection and the development of biologically-informed interventions. Emerging studies have begun to investigate the neurobiological signatures of BED, yet their findings are often difficult to generalize due to the reliance on hypothesis-driven parametric models, single-modality analyses, and limited data diversity. Therefore, there is a critical need for advanced data-driven frameworks capable of modeling multimodal data to uncover generalizable and biologically meaningful signatures of BED. In this study, we propose the Interpretable Modality-Aware Mixture-of-Experts (IMA-MoE), a novel architecture designed to integrate heterogeneous neuroimaging, behavioral, hormonal, and demographic measures within a unified predictive framework. By encoding each measure as a distinct token, IMA-MoE enables flexible modeling of cross-modal dependencies while preserving modality-specific characteristics. We further introduce a token-importance mechanism to enhance interpretability by quantifying the contribution of each measure to model predictions. Evaluated on the large-scale Adolescent Brain Cognitive Development (ABCD) dataset, IMA-MoE demonstrates superior performance in differentiating BED from healthy controls compared with baseline methods, while revealing sex-specific predictive patterns, with hormonal measures contributing more prominently to prediction in females. Collectively, these findings highlight the promise of interpretable, data-driven multimodal modeling in advancing biologically-informed characterization of BED and facilitating more precise and personalized interventions in neuropsychiatric disorders.

Aim:Although a risk factor for the later development of eating disorders, few studies examine the neural underpinnings of binge eating (BE) in children. Preliminary evidence suggests a role of the corticostriatal system; the purpose of this study was to evaluate the role of the inhibitory control brain network for risk of BE in children. Methods:Data from 65 children with BE (57% girls) and 84 matched controls (52% girls) from the 4.0 baseline release of the Adolescent Brain Cognitive Development (ABCD) Study were included. Stop Signal Task-based fMRI data were analyzed using graph theoretic techniques. Global and nodal network properties (e.g. efficiency, betweenness-centrality) were compared for between-group differences and sex-by-group interactions. Results:Despite comparable behavioral performance, children with BE showed significantly increased nodal efficiency of the right postcentral gyrus and left middle frontal gyrus (MFG), and increased connectedness of the right postcentral gyrus compared to control children. Children with BE showed distinct network hubs including the right MFG and left insula, while controls had distinct hubs in the right orbitofrontal and left fusiform gyri. Group-specific sex differences were found in the functioning of insular and frontal cortices. Conclusion:Increased efficiency and connectedness in frontal and parietal nodes of the inhibitory control network functioning in children with BE may represent a vulnerability for overeating. Distinct sex differences in functioning in children with BE compared to control children may reflect specific vulnerabilities to BE in the inhibitory control system in boys and girls that may contribute to sex differences in prevalence.

OBJECTIVE:This randomized controlled study tested the effect of interoceptive exposure on anterior insula function and connectivity for the extinction of palatable and rotten food-cue associations in adolescent girls with low weight eating disorders (LWED). METHOD:A food-related conditioning paradigm was performed by 39 adolescent girls with LWED and 19 matched controls during functional magnetic resonance imaging (fMRI). Adolescents with LWED were then randomized to 6 sessions of either interoceptive exposure (n = 18) or family-based (n = 21) treatment, followed by a second functional magnetic resonance imaging scan. Whole-brain activation and insula-driven connectivity for the extinction of palatable and rotten food-cue associations were compared between groups, and changes over treatment were compared between the 2 therapies. RESULTS:Adolescents with LWED exhibited diminished bilateral anterior insula activation for the extinction of palatable food-cue associations compared with controls (t1,55 = 3.9-4.1, p < .001; Hedges g = 0.47-0.55). Brief interoceptive exposure treatment increased left anterior insula activation for the extinction of palatable food-cue associations (t1,37 = 5.10, p < .001; Hedges g = 1.59) and nonsignificantly improved palatability ratings for these associations during extinction compared with family-based treatment (β = -1.492, p = .087). There were no effects of group or therapy on connectivity or activation for rotten food-cue associations. CONCLUSION:These results suggest that targeting food avoidance in adolescent girls with LWED using interoceptive exposure engages anterior insula regions that mediate the visceral sensation of disgust and may underlie the resistance to extinction. The findings present a window into possible pathophysiological mechanisms of anorexia nervosa and other LWED PLAIN LANGUAGE SUMMARY: This randomized controlled study tested the effect of interoceptive exposure, which aims to reduce conditioned disgust responses to food. This treatment was compared to family-based treatment and the focus was on changes in anterior insula function. 39 adolescent girls with low-weight eating disorders (LWED) and 19 matched controls underwent food-related conditioning during functional magnetic resonance imaging, followed by interoceptive exposure or family-based treatment and a post-intervention imaging session. Key results showed that brief interoceptive exposure treatment increased left anterior insula activation for the extinction of palatable food-cue associations. These results offer new insights into the role of disgust and possible triggers and pathways to anorexia nervosa and other LWED. CLINICAL TRIAL REGISTRATION INFORMATION:Reward Systems and Food Avoidance in Eating Disorders; https://clinicaltrials.gov/study/NCT02795455.

The increased prevalence of binge eating during puberty is predominantly in girls, coinciding with a surge in pubertal hormones. This suggests that hormone-activated alterations in widespread brain networks, such as attention network, can contribute to the pathophysiology of the disorder in girls, while distinct mechanisms may exist in boys. This study proposed to examine the topological properties and their temporal dynamics of the sustained attention network in preadolescent children with binge eating symptoms (BE) and matched controls and to test the relation of these properties to circulating levels of pubertal hormones. Data from 77 children with BE and 104 group-matched controls were analyzed. In a static network comprising the entire task duration, the nodal topological properties, i.e., nodal efficiency, betweenness-centrality and degree, of the caudate nucleus, hippocampus and inferior parietal gyrus (IPG) significantly differentiated children with and without BE; and that of left caudate were significantly associated with pubertal hormone levels in girls with and without BE, but not in boys. During different substages of sustained attention processing, Variability of the topological properties in key network nodes, such as bilateral IPG, bilateral precentral gyrus and left hippocampus, demonstrated significant between-group differences and/or unique group-by-sex interactions. These results suggest that the association between pubertal hormones and network topological organization may contribute towards the specific rise of BE in girls, while neural mechanisms of BE in boys may alternatively link to suboptimal functional dynamics associated with precentral gyrus, during their interactions with other cortical and subcortical regions when sustained attention is performed.

BackgroundUnderstanding the emotional context of feeding behavior may help identify causal mechanisms of food avoidance among individuals with anorexia nervosa. Although predominant food avoidance models assume fear of fat drives feeding behavior, disgust may be more theoretically and proximally relevant to moment-to-moment experiences of feeding. This study, therefore, aimed to examine affect and food avoidance using automated affect analysis from facial response by measuring time-specific transitions in disgust during a laboratory eating paradigm. We hypothesized that phase transitions in disgust would distinguish temporally self-initiated eating from food avoidance.MethodsSixty-three adolescents with anorexia nervosa or another low-weight eating disorder (LWED) and 27 age- and sex-matched controls were recruited as part of a larger study; 45 patients and 22 controls provided data on autonomous eating and facial affect during a laboratory meal. Dynamic structural equation models quantified moment-to-moment relationships between disgust and feeding behavior.ResultsSelf-initiated eating was associated with greater increases in disgust, but not fear, intensity among those with LWED relative to control participants and greater disgust intensity predicted lower likelihood of self-initiated eating.DiscussionPhasic transitions in disgust provide moment-to-moment evidence of affective influence on self-initiated eating and lend credibility to the hypothesis that disgust contributes to food avoidance and initiation in individuals with LWED.

Objective: Few studies have considered the neural underpinnings of binge eating disorder (BED) in children, despite clinical and subclinical symptom presentation occurring in this age group. Symptom presentation at this age is of clinical relevance, as early onset of binge eating is linked to negative health outcomes. Studies in adults have highlighted dysfunction in the frontostriatal reward system as a potential candidate for binge eating pathophysiology, although the exact nature of such dysfunction is currently unclear. Method: Data from 83 children (mean age 9.9 years, SD = 0.60) with symptoms of BED (57% girls) and 123 control participants (mean age 10.0 years, SD = 0.60) (52% girls) were acquired from the 4.0 baseline release of the Adolescent Brain Cognitive Development Study. Task-based graph theoretic techniques were used to analyze data from anticipation trials of the monetary incentive delay task. Network and nodal properties were compared between groups. Results: The BED-S group showed alterations in topological properties associated with the frontostriatal subnetwork, such as reduced nodal efficiency in the superior frontal gyrus, nucleus accumbens, putamen, and in normal sex-difference patterns of these properties, such as diminished girls-greaterthan-boys pattern of betweenness-centrality in nucleus accumbens observed in controls. Conclusion: Distinct network properties and sex-difference patterns in preadolescent children with BED-S suggest dysregulation in the reward system compared to those of matched controls. For the first time, these results quantify this dysregulation in terms of systems-level properties during anticipation of monetary reward and significantly inform the early and sex-related brain markers of BED symptoms. Plain language summary: Binge eating disorder is the most common eating disorder. One factor that may contribute to binge eating is dysregulation of the reward system in the brain. This study analyzed brain activity during anticipation of monetary rewards in 83 youth with and 123 children without binge eating disorder symptoms from the Adolescent Brain Cognitive Development Study. The authors found specific alterations in the frontostriatal system, responsible for reward processing, in children with binge eating disorder symptoms, compared to the control group, suggesting dysregulation of the reward system.

BACKGROUND:Borderline personality disorder (BPD) is the prototypical disorder of emotion dysregulation. We have previously shown that patients with BPD are impaired in their capacity to engage cognitive reappraisal, a frequently employed adaptive emotion regulation strategy. METHODS:Here, we report on the efficacy of longitudinal training in cognitive reappraisal to enhance emotion regulation in patients with BPD. Specifically, the training targeted psychological distancing, a reappraisal tactic whereby negative stimuli are viewed dispassionately as though experienced by an objective, impartial observer. At each of 5 sessions over 2 weeks, 22 participants with BPD (14 female) and 22 healthy control participants (13 female) received training in psychological distancing and then completed a widely used picture-based reappraisal task. Self-reported negative affect ratings and functional magnetic resonance imaging data were acquired at the first and fifth sessions. In addition to behavioral analyses, we performed whole-brain pattern expression analyses using independently defined patterns for negative affect and cognitive reappraisal implementation for each session. RESULTS:Patients with BPD showed a decrease in negative affect pattern expression following reappraisal training, reflecting a normalization in neural activity. However, they did not show significant change in behavioral self-reports. CONCLUSIONS:To our knowledge, this study represents the first longitudinal functional magnetic resonance imaging examination of task-based cognitive reappraisal training. Using a brief, proof-of-concept design, the results suggest a potential role for reappraisal training in the treatment of patients with BPD.

Background: Research examining the potential effects of stimulant exposure in childhood on subsequent development of substance use disorder (SUD) have focused on differences in the brain reward system as a function of risk. Methods: 18 drug naïve children ages 7 to 12 years (11 High Risk [ADHD + ODD/CD]; 7 Low Risk [ADHD only]), underwent fMRI scans before and after treatment with mixed amphetamine salts, extended release (MAS-XR). We examined correlations between clinical ratings and fMRI activation at baseline and following treatment as a function of risk status. Results: High Risk children had higher activation than Low Risk children at baseline during both the Reward and Surprising Non-Reward conditions. Treatment produced strong differential effects on brain activation pertinent to group and reward outcome. Conclusions: Findings support the hypothesized role of reward mechanisms in SUD risk, and suggest that stimulant treatment may have differential effects on reward processing in relation to SUD risk.

BACKGROUND:ADHD is often described as a disorder of altered reward sensitivity, yet few studies have examined the extent to which: (i) treatments for ADHD impact reward-related mechanisms; and (ii) changes in the reward system are associated with clinical improvement. This study addresses these issues - examining the extent to which clinical improvement following lisdexamfetamine (LDX) treatment is associated with changes in brain reward system activation. METHODS:Twenty adults (M = 11, 55%, F = 9, 45%), ages 19-52 (M = 33.9, SD = 10.0) with ADHD participated in a randomized cross-over study with lisdexamfetamine (LDX) and placebo (PB). Changes in brain activation were assessed during functional magnetic resonance (fMRI) scans: after receiving 3-5 weeks of treatment with LDX and 3-5 weeks of no drug/PB. fMRI contrasts were derived from the passive-avoidance (PA) learning task, which assessed reward-related learning using computational variables. We analyzed the following conditions: the Choice-Phase, modulated by the expected value (EV; i.e., object-choose and object-reject), and the Feedback-Phase, modulated by the prediction error (PE; i.e., reward and punish). Clinical symptom severity was assessed via interview with the ADHD-Rating Scale (ADHD-RS-IV). To address the primary objective, we performed group-level mass-univariate regression analyses between LDX and PB of percent change of the ADHD-RS total scores and the four contrast images under the Choice- and Feedback-conditions. Significance was set at a whole-brain voxel-wise threshold of p < 0.05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. RESULTS:Improvement in ADHD symptoms with LDX was accompanied by significantly increased activation in a series of brain regions previously implicated in reinforcement processing in the choice and feedback conditions (e.g., left caudate and putamen, right orbitofrontal cortex, left middle frontal, superior frontal, and precentral gyri). CONCLUSIONS:These findings, while preliminary, are the first to show that ADHD symptom improvement with stimulant treatment is associated with increased responsiveness of brain systems engaged in reward processing. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD. Trial RegistrationClinicaltrials.gov Identifier: NCT01924429.

ObjectivesEmerging evidence of sensitization following stimulant administration in humans represents a challenge for understanding the relationship between stimulant treatment for ADHD and the subsequent development of substance use disorders (SUD). We have proposed a hybrid model that the majority of youth with ADHD greatly benefit from treatments with stimulants, which are in turn protective against the development of SUD; however, a much smaller number may have heightened vulnerability, based on altered responsiveness of the brain reward system either at baseline or in response to stimulant treatment. To investigate this model, we used functional neuroimaging paired with ratings of reward sensitivity and sensation seeking, to assess changes in activation of the brain reward system and behavioral indices thought to underlie SUD risk in drug-naïve youth at high risk (HR) and low risk (LR) for SUD before and after treatment with stimulant medication.MethodsWe conducted an open clinical trial of mixed amphetamine salts (mean: 17.69 mg; SD = 3.8) for 52 days (SD = 37) paired with pre- to post-fMRI in 16 children with ADHD aged 8 to 12 years (LR: N = 7, ADHD only; HR: N = 9, ADHD + severe ODD/OCD). Participants were assessed using the Kirby scale (delay discounting), and the Urgency, Premeditation, Perseverance, Sensation Seeking (UPPS) scale at baseline and posttreatment; fMRI scans were obtained while performing 2 reward tasks (anticipation, conflict, reward, and passive avoidance tasks).ResultsWe found significant group effects for delay discounting, suggesting that HR and LR participants are different at baseline (F1,13 = 6.160; p = .028; n2 = .322). In addition, there were trends for differential response to treatment, with worsening of delay discounting posttreatment in the HR group. Similarly, the groups showed different patterns of change with regard to sensation seeking on the UPPS scale, with interaction effects at the trend level (F1,13 = 3.066; p = .103 n2 = .191). Neuroimaging analyses are ongoing.ConclusionsBehavioral indices of sensation seeking and delay discounting yield conflicting results; identification of neurobiological profiles at baseline and posttreatment may offer a more specific view of possible sensitization effects. Potential implications for clinical practice will be discussed.ADHD, IMAGS, STIM ObjectivesEmerging evidence of sensitization following stimulant administration in humans represents a challenge for understanding the relationship between stimulant treatment for ADHD and the subsequent development of substance use disorders (SUD). We have proposed a hybrid model that the majority of youth with ADHD greatly benefit from treatments with stimulants, which are in turn protective against the development of SUD; however, a much smaller number may have heightened vulnerability, based on altered responsiveness of the brain reward system either at baseline or in response to stimulant treatment. To investigate this model, we used functional neuroimaging paired with ratings of reward sensitivity and sensation seeking, to assess changes in activation of the brain reward system and behavioral indices thought to underlie SUD risk in drug-naïve youth at high risk (HR) and low risk (LR) for SUD before and after treatment with stimulant medication. Emerging evidence of sensitization following stimulant administration in humans represents a challenge for understanding the relationship between stimulant treatment for ADHD and the subsequent development of substance use disorders (SUD). We have proposed a hybrid model that the majority of youth with ADHD greatly benefit from treatments with stimulants, which are in turn protective against the development of SUD; however, a much smaller number may have heightened vulnerability, based on altered responsiveness of the brain reward system either at baseline or in response to stimulant treatment. To investigate this model, we used functional neuroimaging paired with ratings of reward sensitivity and sensation seeking, to assess changes in activation of the brain reward system and behavioral indices thought to underlie SUD risk in drug-naïve youth at high risk (HR) and low risk (LR) for SUD before and after treatment with stimulant medication. MethodsWe conducted an open clinical trial of mixed amphetamine salts (mean: 17.69 mg; SD = 3.8) for 52 days (SD = 37) paired with pre- to post-fMRI in 16 children with ADHD aged 8 to 12 years (LR: N = 7, ADHD only; HR: N = 9, ADHD + severe ODD/OCD). Participants were assessed using the Kirby scale (delay discounting), and the Urgency, Premeditation, Perseverance, Sensation Seeking (UPPS) scale at baseline and posttreatment; fMRI scans were obtained while performing 2 reward tasks (anticipation, conflict, reward, and passive avoidance tasks). We conducted an open clinical trial of mixed amphetamine salts (mean: 17.69 mg; SD = 3.8) for 52 days (SD = 37) paired with pre- to post-fMRI in 16 children with ADHD aged 8 to 12 years (LR: N = 7, ADHD only; HR: N = 9, ADHD + severe ODD/OCD). Participants were assessed using the Kirby scale (delay discounting), and the Urgency, Premeditation, Perseverance, Sensation Seeking (UPPS) scale at baseline and posttreatment; fMRI scans were obtained while performing 2 reward tasks (anticipation, conflict, reward, and passive avoidance tasks). ResultsWe found significant group effects for delay discounting, suggesting that HR and LR participants are different at baseline (F1,13 = 6.160; p = .028; n2 = .322). In addition, there were trends for differential response to treatment, with worsening of delay discounting posttreatment in the HR group. Similarly, the groups showed different patterns of change with regard to sensation seeking on the UPPS scale, with interaction effects at the trend level (F1,13 = 3.066; p = .103 n2 = .191). Neuroimaging analyses are ongoing. We found significant group effects for delay discounting, suggesting that HR and LR participants are different at baseline (F1,13 = 6.160; p = .028; n2 = .322). In addition, there were trends for differential response to treatment, with worsening of delay discounting posttreatment in the HR group. Similarly, the groups showed different patterns of change with regard to sensation seeking on the UPPS scale, with interaction effects at the trend level (F1,13 = 3.066; p = .103 n2 = .191). Neuroimaging analyses are ongoing. ConclusionsBehavioral indices of sensation seeking and delay discounting yield conflicting results; identification of neurobiological profiles at baseline and posttreatment may offer a more specific view of possible sensitization effects. Potential implications for clinical practice will be discussed.ADHD, IMAGS, STIM Behavioral indices of sensation seeking and delay discounting yield conflicting results; identification of neurobiological profiles at baseline and posttreatment may offer a more specific view of possible sensitization effects. Potential implications for clinical practice will be discussed.

Background This pilot study outlines the development and psychometric evaluation of a therapist adherence coding measure for a novel treatment, Family-Based Treatment Interoceptive Exposure (FBT-IE). Methods The IE Adherence Coding Framework (IE-ACF) was developed from the FBT-IE Manual using an iterative process. Items on the IE-ACF were coded by two independent coders as either present or absent with therapists considered adherent if both independent coders coded the item as “present.” Videotaped sessions of FBT-IE of 30 adolescents with low-weight eating disorders (DSM-5 typical/atypical anorexia nervosa) and their families were coded. Participants received the FBT-IE intervention as part of a randomized controlled trial. Results Seventy FBT-IE videos were coded. The IE-ACF identified a mean (SD) rating of 80% (±5%) therapist adherence to the protocol across the six-session treatment, with a per item adherence ranging from 36–100%. Two independent coders demonstrated moderate to almost perfect inter-rater reliability (κ range 0.78–0.96) across the sessions. Conclusion IE-ACF measured therapist adherence to our novel FBT-IE treatment for adolescents with low-weight eating disorders. Through this study, we demonstrated that 1) our therapists were adherent to the FBT-IE manual in the context of an ongoing clinical trial and 2) that independent coders reliably coded sessions using our novel IE-ACF.

Objective This study examined the distinctiveness of Attention Deficit Hyperactivity Disorder—Inattentive (ADHD-I) and ADHD in context of Sluggish Cognitive Tempo (ADHD + SCT) utilizing the Attention Network Test (ANT) and Continuous Performance Test (CPT) as external validators. Due to the SCT characteristics of being sluggish, spacey, and slow to arouse, we hypothesized that SCT behavioral descriptors would be uniquely related to alerting/arousal mechanisms that the ANT is uniquely designed to capture, and that ADHD symptoms would be more highly associated with cognitive control on the CPT. Method We examined associations between baseline ANT and CPT scores for N = 137 well-characterized, culturally and racially diverse youth with ADHD ( n = 107) either medication naïve or washed out prior to testing and typically developing controls ( n = 30) ages 6–17 years. Results Presence and severity of SCT were associated with ANT Alerting ( r 2 = −.291, p = .005), but not with ANT Orienting, ANT Executive Control, or any CPT measures. There was a distinct association between the presence and severity of ADHD inattention symptoms with CPT T -scores for Commission Errors ( r 2 = .282, p = .002), Omission Errors ( r 2 = .254, p = .005), Variability ( r 2 = .328, p < .001), and Hit Rate SE ( r 2 = .272, p = .002), but not with other CPT or any ANT domain measures. All associations remained significant after Bonferroni correction. Conclusions The small but enduring double dissociation, with ADHD-I symptom severity related to measures of cognitive and behavioral control measures on the CPT, and SCT symptom severity related to attentional processes underlying tonic arousal in preparation for cue detection on the ANT—provides the first objective evidence suggestive of partial neurocognitive independence of SCT from ADHD. Moreover, it points to possibly distinguishable neurobiological neurocognitive underpinnings of the two conditions.

Background: The objective of this study was to examine changes in the activation of the brain reward system following treatment with lisdexamfetamine (LDX) vs. placebo (PL) as a function of clinical improvement in attention deficit/hyperactivity disorder (ADHD) symptoms. Methods: Twenty adults with ADHD were included in a randomized cross-over study. Participants underwent two functional magnetic resonance imaging (fMRI) scans, after receiving 3 to 5 weeks of treatment with both LDX and PL. During scanning, participants performed the passive-avoidance learning task to assess reward-related learning using computational variables (e.g., estimated value and prediction error). Pre-treatment to post-treatment symptom change was assessed via the ADHD Rating Scale (ADHD-RS). The imaging contrasts were Object Choose or Object Refuse during the object choice component of the task, modulated by expected value (reward vs. nonreward cue), and Reward vs. Punishment during feedback, modulated by prediction error (expected vs. actual outcome). To address the primary objective, we performed group-level mass univariate analyses between pre-treatment to post-treatment percent change of the ADHD-RS total scores and the four contrast images under the choice and feedback conditions, with significance set at a whole-brain voxel-wise threshold of p < .05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. Results: Improvement in ADHD symptoms was accompanied by significant increases of brain activation during the Object Refuse, Reward and Punishment contrasts in a widespread network including left caudate and putamen, and right orbitofrontal cortex (i.e., reward-related signaling) and left middle frontal, superior frontal, and precentral gyri (i.e., executive control). Conclusions: These findings are the first to show that the increase in responsiveness of systems engaged in reward processing with LDX treatment is positively related to symptom improvement. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD.

The functional organization of the human brain adapts dynamically in response to a rapidly changing environment. However, the relation of these rapid changes in functional organization to cognitive functioning is not well understood. This study used a graph-based time-frame modularity analysis approach to identify temporally recurrent functional configuration patterns in neural responses to an n-back working memory task during fMRI. Working memory load was manipulated to investigate the functional relevance of the identified brain states. Four distinct brain states were defined by the predominant patterns of activation in the task-positive, default-mode, sensorimotor, and visual networks. Associated with escalating working memory load, the occurrence of the task-positive state and the probability of transitioning into this state increased. In contrast, the occurrence of the default-mode and sensorimotor states and the probability of these 2 states transitioning away from the task-positive state decreased. The task-positive state occurrence rate and the probability of transitioning from the default-mode state back to the task-positive state explained a significant and unique portion of the variance in task performance. The results demonstrate that dynamic brain activities support successful cognitive functioning and may have heuristic value for understanding abnormal cognitive functioning associated with multiple neuropsychiatric disorders.

Borderline personality disorder (BPD) is a psychiatric disorder characterized by unstable relationships, affective instability, and a broad inability to appropriately trust others. Social exchange games have given us a laboratory tool to understand the social components of various pathologies and have demonstrated impaired cooperation in BPD participants.