Cortical volume alterations in the limbic network in adolescents with high reactive aggression.

Previous studies show aggression-related structural alterations in frontal and limbic brain regions. Most studies have focused on overall aggression, instead of its subtypes, and on specific regions instead of networks. This study aims to identify both brain networks and regions that are associated with reactive and proactive subtypes of aggression. Structural MRI data were collected from 340 adolescents (125 F/215 M) with a mean age of 16.29 (SD = 1.20). Aggression symptomology was indexed via the Reactive Proactive Aggression Questionnaire (RPQ). Freesurfer was used to estimate Cortical Volume (CV) from seven networks and regions within specific networks associated with aggression. Two multivariate analyses of covariance (MANCOVAs) were conducted on groups for low versus higher reactive and proactive RPQ scores. Our reactive aggression MANCOVA showed a main effect in CV [F(14,321) = 1.935, p = 0.022,ηp2 = 0.078] across all the 7-Networks. Unpacking this main effect revealed significant volumetric differences in the right Limbic Network (LN) (p = 0.029) and the Temporal Pole (p = 0.011), where adolescents in the higher reactive aggression group showed higher cortical volumes. Such findings are consistent with region/voxel-specific analyses that have associated atypical structure within the LN and reactive aggression. Moreover, the temporal pole is highly interconnected with regions important in the regulation and initiation of reactive aggression.

Dysfunction in differential reward-punishment responsiveness in conduct disorder relates to severity of callous-unemotional traits but not irritability.

BACKGROUND: Conduct disorder (CD) has been associated with dysfunction in reinforcement-based decision-making. Two forms of affective traits that reflect the components of CD severity are callous-unemotional (CU; reduced guilt/empathy) traits and irritability. The form of the reinforcement-based decision-making dysfunction with respect to CD and CU traits remains debated and has not been examined with respect to irritability in cases with CD. The goals of the current study were to determine the extent of dysfunction in differential (reward v. punishment) responsiveness in CD, and CU traits and irritability in participants with CD. METHODS: The study involved 178 adolescents [typically developing (TD; N = 77) and cases with CD (N = 101)]. Participants were scanned with fMRI during a passive avoidance task that required participants to learn to respond to (i.e. approach) stimuli that engender reward and refrain from responding to (i.e. passively avoid) stimuli that engender punishment. RESULTS: Adolescents with CD showed reduced differential reward-punishment responsiveness within the striatum relative to TD adolescents. CU traits, but not irritability, were associated with reduced differential reward-punishment responsiveness within the striatum, rostromedial, and lateral frontal cortices. CONCLUSIONS: The results suggest CD is associated with reduced differential reward-punishment responsiveness and the extent of this dysfunction in participants with CD is associated with the severity of CU traits but not irritability.

Latent profiles of substance use, early life stress, and attention/externalizing problems and their association with neural correlates of reinforcement learning in adolescents.

BACKGROUND: Adolescent substance use, externalizing and attention problems, and early life stress (ELS) commonly co-occur. These psychopathologies show overlapping neural dysfunction in the form of reduced recruitment of reward processing neuro-circuitries. However, it is unclear to what extent these psychopathologies show common v. different neural dysfunctions as a function of symptom profiles, as no studies have directly compared neural dysfunctions associated with each of these psychopathologies to each other. METHODS: In study 1, a latent profile analysis (LPA) was conducted in a sample of 266 adolescents (aged 13-18, 41.7% female, 58.3% male) from a residential youth care facility and the surrounding community to investigate substance use, externalizing and attention problems, and ELS psychopathologies and their co-presentation. In study 2, we examined a subsample of 174 participants who completed the Passive Avoidance learning task during functional magnetic resonance imaging to examine differential and/or common reward processing neuro-circuitry dysfunctions associated with symptom profiles based on these co-presentations. RESULTS: In study 1, LPA identified profiles of substance use plus rule-breaking behaviors, attention-deficit hyperactivity disorder, and ELS. In study 2, the substance use/rule-breaking profile was associated with reduced recruitment of reward processing and attentional neuro-circuitries during the Passive Avoidance task (p < 0.05, corrected for multiple comparisons). CONCLUSIONS: Findings indicate that there is reduced responsivity of striato-cortical regions when receiving outcomes on an instrumental learning task within a profile of adolescents with substance use and rule-breaking behaviors. Mitigating reward processing dysfunction specifically may represent a potential intervention target for substance-use psychopathologies accompanied by rule-breaking behaviors.

Evaluating instrumental learning and striatal-cortical functional connectivity in adolescent alcohol and cannabis use.

Adolescence is a vulnerable time for the acquisition of substance use disorders, potentially relating to ongoing development of neural circuits supporting instrumental learning. Striatal-cortical circuits undergo dynamic changes during instrumental learning and are implicated in contemporary addiction theory. Human studies have not yet investigated these dynamic changes in relation to adolescent substance use. Here, functional magnetic resonance imaging was used while 135 adolescents without (AUD-CUDLow ) and with significant alcohol (AUDHigh ) or cannabis use disorder symptoms (CUDHigh ) performed an instrumental learning task. We assessed how cumulative experience with instrumental cues altered cue selection preferences and functional connectivity strength between reward-sensitive striatal and cortical regions. Adolescents in AUDHigh and CUDHigh groups were slower in learning to select optimal instrumental cues relative to AUD-CUDLow adolescents. The relatively fast learning observed for AUD-CUDLow adolescents coincided with stronger functional connectivity between striatal and frontoparietal regions during early relative to later periods of task experience, whereas the slower learning for the CUDHigh group coincided with the opposite pattern. The AUDHigh group not only exhibited slower learning but also produced more instrumental choice errors relative to AUD-CUDLow adolescents. For the AUDHigh group, Bayesian analyses evidenced moderate support for no experience-related changes in striatal-frontoparietal connectivity strength during the task. Findings suggest that adolescent cannabis use is related to slowed instrumental learning and delays in peak functional connectivity strength between the striatal-frontoparietal regions that support this learning, whereas adolescent alcohol use may be more closely linked to broader impairments in instrumental learning and a general depression of the neural circuits supporting it.

Reduced cortical volume of the default mode network in adolescents with generalized anxiety disorder.

BACKGROUND: Widespread structural alterations have been shown to be implicated in individuals with generalized anxiety disorder (GAD). However, there have been inconsistent findings in cortical volume (CV) differences. Most structural neuroimaging studies looking at GAD used region-based approach with relatively small sample sizes, let alone be specific to adolescents with GAD. We believe this is the first study to look at CV measures using a network-based approach in a larger sample of adolescents with GAD. The goal of the current study was to focus on three different brain networks (i.e., Limbic, Frontoparietal, and Default Mode Network [DMN]) in adolescents with GAD. METHOD: The study involved 81 adolescents with GAD and 112 typically developing (TD) comparison individuals matched on age (15.98 and 15.63 respective means), sex (42F/39M and 45F/67M), and IQ (101.90 and 103.94 respective means). Participants underwent structural MRI. Freesurfer was used to estimate CV (both network-specific and region-specific within networks) and region-specific sub-cortical volume measures. Multivariate analysis of covariance (MANCOVA; with sex, age, IQ, and intracranial volume [ICV] as potential covariates) was used to estimate group differences. RESULTS: We found significantly lower CV for the DMN in adolescents with GAD, compared with TD individuals. Adolescents with GAD also showed significantly lower hemispheric mean CV of the default-mode regions (particularly the prefrontal and temporal regions) and the hippocampus, compared with TD individuals. CONCLUSION: The current findings suggest structural alterations in adolescents with GAD. These structural alterations will need to be addressed when implementing and developing treatments for patients with GAD.

Association between emotional intelligence and effective brain connectome: A large-scale spectral DCM study.

INTRODUCTION: Emotional Intelligence (EI) is a well-documented aspect of social and interpersonal functioning, but the underlying neural mechanisms for this capacity remain poorly understood. Here we used advanced brain connectivity techniques to explore the associations between EI and effective connectivity (EC) within four functional brain networks. METHODS: The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) was used to collect EI data from 55 healthy individuals (mean age = 30.56±8.3 years, 26 males). The MSCEIT comprises two area cores - experiential EI (T1) and strategic EI (T2). The T1 core included two sub-scales - perception of emotions (S1) and using emotions to facilitate thinking (S2), and the T2 core included two sub-scales - understanding of emotions (S3) and management of emotions (S4). All participants underwent structural and resting-state functional magnetic resonance imaging (rsfMRI) scans. The spectral dynamic causal modeling approach was implemented to estimate EC within four networks of interest - the default-mode network (DMN), dorsal attention network (DAN), control-execution network (CEN) and salience network (SN). The strength of EC within each network was correlated with the measures of EI, with correlations at pFDR < 0.05 considered as significant. RESULTS: There was no significant association between any of the measures of EI and EC strength within the DMN and DAN. For CEN, however, we found that there were significant negative associations between EC strength from the right anterior prefrontal cortex (RAPFC) to the left anterior prefrontal cortex (LAPFC) and both S2 and T1, and significant positive associations between EC strength from LAPFC to RAPFC and S2. EC strength from the right superior parietal cortex (SPC) to RAPFC also showed significant negative association with S4 and T2. For the SN, S3 showed significant negative association with EC strength from the right insula to RAPFC and significant positive association with EC strength from the left insula to dorsal anterior cingulate cortex (DACC). CONCLUSIONS: We provide evidence that the negative ECs within the right hemisphere, and from the right to left hemisphere, and positive ECs within the left hemisphere and from the left to right hemisphere of CEN (involving bilateral frontal and right parietal region) and SN (involving right frontal, anterior cingulate and bilateral insula) play a significant role in regulating and processing emotions. These findings also suggest that measures of EC can be utilized as important biomarkers to better understand the underlying neural mechanisms of EI.

Structural atrophy of the right superior frontal gyrus in adolescents with severe irritability.

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability.

Reduced neural differentiation of rewards and punishment during passive avoidance learning in adolescents with generalized anxiety disorder.

BACKGROUND: It has been proposed that individuals with generalized anxiety disorder (GAD) show dysfunctional computations related to approach-avoidance decision-making. However, few studies have examined the neural basis of this impairment, particularly in adolescents with GAD. The goal of the current study was to address this gap in the literature. METHOD: The study involved 51 adolescents with GAD and 51 typically developing (TD) comparison individuals matched on age (16.10 and 15.75 respective means), gender (30 F/21 M and 24 F/27 M), and IQ (103.20 and 103.18 respective means). Participants underwent functional magnetic resonance imaging during a passive avoidance task. RESULTS: We found a significant Group-by-Reinforcement interaction within reward-related brain regions including the caudate, putamen, mid cingulate/paracentral lobule, and superior and middle frontal gyrus. TD adolescents showed a greater differential response to reward versus punishment feedback within these regions relative to adolescents with GAD. In particular, this reflected reduced responses to rewards in the adolescents with GAD. There were no group differences in neural responses when making approach/avoidance responses. CONCLUSION: The results of this study suggest reduced differential responsiveness to reinforcement as a component of the pathophysiology seen in adolescents with GAD. This dysfunction likely underpins decision-making impairments that may exacerbate the participants' worry.

A randomized, double-blind, placebo-controlled trial of blue wavelength light exposure on sleep and recovery of brain structure, function, and cognition following mild traumatic brain injury.

Sleep and circadian rhythms are among the most powerful but least understood contributors to cognitive performance and brain health. Here we capitalize on the circadian resetting effect of blue-wavelength light to phase shift the sleep patterns of adult patients (aged 18-48 years) recovering from mild traumatic brain injury (mTBI), with the aim of facilitating recovery of brain structure, connectivity, and cognitive performance. During a randomized, double-blind, placebo-controlled trial of 32 adults with a recent mTBI, we compared 6-weeks of daily 30-min pulses of blue light (peak λ = 469 nm) each morning versus amber placebo light (peak λ = 578 nm) on neurocognitive and neuroimaging outcomes, including gray matter volume (GMV), resting-state functional connectivity, directed connectivity using Granger causality, and white matter integrity using diffusion tensor imaging (DTI). Relative to placebo, morning blue light led to phase-advanced sleep timing, reduced daytime sleepiness, and improved executive functioning, and was associated with increased volume of the posterior thalamus (i.e., pulvinar), greater thalamo-cortical functional connectivity, and increased axonal integrity of these pathways. These findings provide insight into the contributions of the circadian and sleep systems in brain repair and lay the groundwork for interventions targeting the retinohypothalamic system to facilitate injury recovery.

Sex differences in limbic network and risk-taking propensity in healthy individuals.

Little is known about the structural neural substrates that may contribute to sex differences in risk-taking propensity (RTP). A close association between risk-seeking behavior and the emotional-regulation network led us to hypothesize that the sex differences in RTP would be associated with sex differences in brain morphometry of the limbic network (LN). We collected RTP scores using the bubble sheet version of the evaluation of risk (EVAR) scale and neuroanatomical data from 57 healthy individuals (29 males). The EVAR scale included sub-scales measuring recklessness/impulsivity, self-confidence, and need for control (NFC). We observed significant sex differences in NFC showing greater desire for control and dominance in males than females (multivariate analysis of covariance, MANCOVAN: p = .01). Morphometry analysis showed that it was only the right LN, which showed significant sex differences in normalized surface area, normalized cortical volume, and adjusted mean curvature index (females > males) at p < .01 (MANCOVAN, corrected for multiple comparisons). Correlation analysis showed that greater curvature of the right LN was significantly associated with lower desire for control in high-risk events (r = -.31, p = .02 at 95% CI of [-0.53, -0.05]). Our findings suggest that the normalized cortical measures could indicate specific sex differences in brain morphometry, particularly within the LN. The curvature index was the only differentiating factor for greater/lower propensity for risk-taking behavior in overall sample. Therefore, the LN and the curvature measures could be key biomarkers, which play an important role in predicting risk-taking behavior.

Vulnerability to mood degradation during sleep deprivation is influenced by white-matter compactness of the triple-network model.

Sleep deprivation (SD) is often associated with significant shifts in mood state relative to baseline functioning. Prior work suggests that there are consistent trait-like differences among individuals in the degree to which their mood and performances are affected by sleep loss. The goal of this study was to determine the extent to which trait-like individual differences in vulnerability/resistance to mood degradation during a night of SD are dependent upon region-specific white and grey matter (WM/GM) characteristics of a triple-network model, including the default-mode network (DMN), control-execution network (CEN) and salience network (SN). Diffusion-weighted and anatomical brain data were collected from 45 healthy individuals several days prior to a 28-h overnight SD protocol. During SD, a visual analog mood scale was administered every hour from 19:15 (time point1; TP1) to 11:15 (TP17) the following morning to measure two positive and six negative mood states. Four core regions within the DMN, five within the CEN, and seven within the SN were used as regions of interest (ROIs). An index of mood resistance (IMR) was defined as the averaged differences between positive and negative mood states over 12 TPs (TP5 to TP16) relative to baseline (TP1 to TP4). For each ROI, characteristics of WM - quantitative anisotropy (QA) and mean curvature index (WM-MCI), and GM - cortical volume (CV) and GM-MCI were estimated, and used to predict IMR. WM characteristics, particularly QA, of all of regions within the DMN, and most of the regions within the CEN and SN predicted IMR during SD. In contrast, most ROIs did not show significant association between IMR and any of the GM characteristics (CV and MCI) or WM MCI. Our findings suggest that greater resilience to mood degradation induced by total SD appears to be associated with more compact axonal pathways within the DMN, CEN and SN.

Time-dependent differences in cortical measures and their associations with behavioral measures following mild traumatic brain injury.

There is currently a critical need to establish an improved understanding of time-dependent differences in brain structure following mild traumatic brain injury (mTBI). We compared differences in brain structure, specifically cortical thickness (CT), cortical volume (CV), and cortical surface area (CSA) in 54 individuals who sustained a recent mTBI and 33 healthy controls (HCs). Individuals with mTBI were split into three groups, depending on their time since injury. By comparing structural measures between mTBI and HC groups, differences in CT reflected cortical thickening within several areas following 0-3 (time-point, TP1) and 3-6 months (TP2) post-mTBI. Compared with the HC group, the mTBI group at TP2 showed lower CSA within several areas. Compared with the mTBI group at TP2, the mTBI group during the most chronic stage (TP3: 6-18 months post-mTBI) showed significantly higher CSA in several areas. All the above reported differences in CT and CSA were significant at a cluster-forming p < .01 (corrected for multiple comparisons). We also found that in the mTBI group at TP2, CT within two clusters (i.e., the left rostral middle frontal gyrus (L. RMFG) and the right postcentral gyrus (R. PostCG)) was negatively correlated with basic attention abilities (L. RMFG: r = -.41, p = .05 and R. PostCG: r = -.44, p = .03). Our findings suggest that alterations in CT and associated neuropsychological assessments may be more prominent during the early stages of mTBI. However, alterations in CSA may reflect compensatory structural recovery during the chronic stages of mTBI.

Chronic sleep restriction differentially affects implicit biases toward food among men and women: preliminary evidence.

Chronic sleep restriction and obesity are two major public health concerns. This study investigated how chronic sleep restriction changes implicit attitudes towards low- and high-calorie foods. In a randomized, counterbalanced cross-over design, 17 participants (eight females, nine males) underwent two laboratory testing sessions where they were either sleep-restricted for 3 weeks (i.e. underwent three weekly cycles of 5 nights of 4 h of sleep followed by 2 nights of 8 h of sleep opportunity) or received 3 weeks of control sleep (i.e. 8 h of sleep opportunity per night for 3 weeks). There was evidence for a significant sleep condition x sex interaction (F(1, 20)  = 4.60, P = 0.04). After chronic sleep restriction, men showed a trend towards a significant decrease in their implicit attitudes favouring low-calorie foods (P = 0.08), whereas women did not show a significant change (P = 0.16). Men may be at increased risk of weight gain when sleep-deprived due to a reduced bias towards low-calorie foods.

Greater cortical thickness within the limbic visceromotor network predicts higher levels of trait emotional awareness.

Previous studies of trait emotional awareness (EA) have not yet examined whether differences in cortical structure might account for differences in EA. Based on previous research on the relationship between EA and both emotion conceptualization and visceromotor control processes, we tested two hypotheses in a sample of 26 healthy participants: that higher EA would be predicted by greater cortical thickness within (1) regions of the default mode network (DMN; linked with conceptualization processes), and/or (2) regions of the limbic network (linked with affect generation and visceromotor control processes). A non-significant correlation was found between EA and cortical thickness in the DMN. In contrast, a significant positive correlation was observed between EA and cortical thickness within the limbic network. These findings suggest that the structural integrity of cortical regions involved in the generation of affective bodily reactions may play a more important role in explaining differences in EA than previously thought.

A Shared Multivariate Brain-Behavior Relationship in a Transdiagnostic Sample of Adolescents.

BACKGROUND: Internalizing and externalizing psychopathology typically present in early childhood and can have negative implications on general functioning and quality of life. Prior work has linked increased psychopathology symptoms with altered brain structure. Multivariate analysis such as partial least squares correlation can help identify patterns of covariation between brain regions and psychopathology symptoms. This study examined the relationship between gray matter volume (GMV) and psychopathology symptoms in adolescents with various psychiatric diagnoses. METHODS: Structural magnetic resonance imaging data were collected from 490 participants with various internalizing and externalizing diagnoses (197 female/293 male; age = 14.68 ± 2.35 years; IQ = 104.05 ± 13.11). Cortical and subcortical volumes were parcellated using the Desikan-Killiany atlas. Partial least squares correlation was used to identify multivariate linear relationships between GMV and the Strength and Difficulties Questionnaire difficulties domains (emotional, peer, conduct, and hyperactivity issues). Resampling approaches were used to determine significance (permutation test), stability (bootstrap resampling), and reproducibility (split-half resampling) of identified relationships. RESULTS: We found a significant, stable, and largely reproducible dimension that linked lower Strength and Difficulties Questionnaire scores (less impairment) across all difficulties domains with greater widespread GMV (singular value = 1.17, accounts for 87.1% of the covariance; p < .001). This dimension emphasized the relationship between lower conduct problems and greater GMV in frontotemporal regions. CONCLUSIONS: Our results indicate that the most significant and stable brain-behavior relationship in a transdiagnostic sample is a domain-general relationship, linking lower psychopathology symptom scores to greater global GMV. This finding suggests that a shared brain-behavior relationship may be present across adolescents with and without clinically significant psychopathology symptoms.

Neural correlates of automatic emotion regulation and their association with suicidal ideation in adolescents during the first 90-days of residential care.

BACKGROUND: Suicide is the second leading cause of death for adolescents in the United States. However, relatively little is known about the forms of atypical neuro-cognitive function that are correlates of suicidal ideation (SI). One form of cognitive/affective function that, when dysfunctional, is associated with SI is emotion regulation. However, very little work has investigated the neural correlates of emotion dysregulation in adolescents with SI. METHODS: Participants (N = 111 aged 12-18, 32 females, 31 [27.9%] reporting SI) were recruited shortly after their arrival at a residential care facility where they had been referred for behavioral and mental health problems. Daily reports of SI were collected during the participants' first 90-days in residential care. Participants were presented with a task-fMRI measure of emotion regulation - the Affective Number Stroop task shortly after recruitment. Participants were divided into two groups matched for age, sex and IQ based on whether they demonstrated SI. RESULTS: Participants who demonstrated SI showed increased recruitment of regions including dorsomedial prefrontal cortex/supplemental motor area and parietal cortex during task (congruent and incongruent) relative to view trials in the context of emotional relative to neutral distracters. CONCLUSIONS: Participants with SI showed increased recruitment of regions implicated in executive control during the performance of a task indexing automatic emotion regulation. Such data might suggest a relative inefficiency in the recruitment of these regions in individuals with SI.

Neuroimaging alterations of the suicidal brain and its relevance to practice: an updated review of MRI studies.

Suicide is a leading cause of death in the United States. Historically, scientific inquiry has focused on psychological theory. However, more recent studies have started to shed light on complex biosignatures using MRI techniques, including task-based and resting-state functional MRI, brain morphometry, and diffusion tensor imaging. Here, we review recent research across these modalities, with a focus on participants with depression and Suicidal Thoughts and Behavior (STB). A PubMed search identified 149 articles specific to our population of study, and this was further refined to rule out more diffuse pathologies such as psychotic disorders and organic brain injury and illness. This left 69 articles which are reviewed in the current study. The collated articles reviewed point to a complex impairment showing atypical functional activation in areas associated with perception of reward, social/affective stimuli, top-down control, and reward-based learning. This is broadly supported by the atypical morphometric and diffusion-weighted alterations and, most significantly, in the network-based resting-state functional connectivity data that extrapolates network functions from well validated psychological paradigms using functional MRI analysis. We see an emerging picture of cognitive dysfunction evident in task-based and resting state fMRI and network neuroscience studies, likely preceded by structural changes best demonstrated in morphometric and diffusion-weighted studies. We propose a clinically-oriented chronology of the diathesis-stress model of suicide and link other areas of research that may be useful to the practicing clinician, while helping to advance the translational study of the neurobiology of suicide.

Reduced Grey Matter Volume in Adolescents with Conduct Disorder: A Region-of-Interest Analysis Using Multivariate Generalized Linear Modeling.

Background: Conduct disorder (CD) involves a group of behavioral and emotional problems that usually begins during childhood or adolescence. Structural brain alterations have been observed in CD, including the amygdala, insula, ventrolateral and medial prefrontal cortex, anterior cingulate cortex, and fusiform gyrus. The current study developed a multivariate generalized linear model (GLM) to differentiate adolescents with CD from typically developing (TD) adolescents in terms of grey matter volume (GMV). Methods: The whole-brain structural MRI data were collected from 96 adolescents with CD (mean age = years; mean IQ = ; 63 males) and 90 TD individuals (mean age = years; mean IQ = ; 59 males) matched on age, IQ, and sex. Region-wise GMV was extracted following whole-brain parcellation into 68 cortical and 14 subcortical regions for each participant. A multivariate GLM was developed to predict the GMV of the pre-hypothesized regions-of-interest (ROIs) based on CD diagnosis, with intracranial volume, age, sex, and IQ serving as the covariate. Results: A diagnosis of CD was a significant predictor for GMV in the right pars orbitalis, right insula, right superior temporal gyrus, left fusiform gyrus, and left amygdala (F(1, 180) = 5.460 - 10.317, p < 0.05, partial eta squared = 0.029 - 0.054). The CD participants had smaller GMV in these regions than the TD participants (MCD - MTD = [-614.898] mm3 - [-53.461] mm3). Conclusions: Altered GMV within specific regions may serve as a biomarker for the development of CD in adolescents. Clinical work can potentially target these biomarkers to treat adolescents with CD.

Reduced grey matter volume in adolescents with conduct disorder: a region-of-interest analysis using multivariate generalized linear modeling.

BACKGROUND: Conduct disorder (CD) involves a group of behavioral and emotional problems that usually begins during childhood or adolescence. Structural brain alterations have been observed in CD, including the amygdala, insula, ventrolateral and medial prefrontal cortex, anterior cingulate cortex, and fusiform gyrus. The current study developed a multivariate generalized linear model (GLM) to differentiate adolescents with CD from typically developing (TD) adolescents in terms of grey matter volume (GMV). METHODS: The whole-brain structural MRI data were collected from 96 adolescents with CD (mean age = [Formula: see text] years; mean IQ = [Formula: see text]; 63 males) and 90 TD individuals (mean age = [Formula: see text] years; mean IQ = [Formula: see text]; 59 males) matched on age, IQ, and sex. Region-wise GMV was extracted following whole-brain parcellation into 68 cortical and 14 subcortical regions for each participant. A multivariate GLM was developed to predict the GMV of the pre-hypothesized regions-of-interest (ROIs) based on CD diagnosis, with intracranial volume, age, sex, and IQ serving as the covariate. RESULTS: A diagnosis of CD was a significant predictor for GMV in the right pars orbitalis, right insula, right superior temporal gyrus, left fusiform gyrus, and left amygdala (F(1, 180) = 5.460-10.317, p < 0.05, partial eta squared = 0.029-0.054). The CD participants had smaller GMV in these regions than the TD participants (MCD-MTD = [- 614.898] mm3-[- 53.461] mm3). CONCLUSIONS: Altered GMV within specific regions may serve as a biomarker for the development of CD in adolescents. Clinical work can potentially target these biomarkers to treat adolescents with CD.

Association Between Aggression and Differential Functional Activity of Neural Regions Implicated in Retaliation.

OBJECTIVE: The goal of the current study was to determine the extent to which atypical neural responsiveness during retaliation is associated with observed aggression in youth in residential care. METHOD: This functional magnetic resonance imaging study involved 83 adolescents (56 male and 27 female; mean age, 16.18 years) in residential care performing a retaliation task. Of the 83 adolescents, 42 displayed aggressive behavior within the first 3 months of residential care, whereas 41 did not. During the retaliation task, participants were offered either fair or unfair divisions of $20 pots (allocation phase) and could either accept the offer or reject it, and, by spending $1, $2, or $3, punish the partner (retaliation phase). RESULTS: The study's main findings were that aggressive adolescent showed the following: reduced down-regulation of activity within regions involved in representing the expected value of choice options (left ventromedial prefrontal cortex and left posterior cingulate cortex) as a function of offer unfairness and retaliation level; and reduced recruitment of regions implicated in response control (right inferior frontal gyrus and bilateral anterior insular cortex) and associated fronto-parietal regions as a function of retaliation level. The aggressive adolescents were also significantly more likely to have been aggressive prior to residential care and showed a strong trend for increased retaliation on the task. CONCLUSION: We suggest that individuals with a greater propensity for aggression show reduced representation of the negative consequences of retaliation and associated reduced recruitment of regions potentially involved in over-ruling these negative consequences to engage in retaliation. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex balance in the selection of non-human subjects. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.