Individual Variability in Performance Reflects Selectivity of the Multiple Demand Network among Children and Adults.

Executive function (EF) is essential for humans to effectively engage in cognitively demanding tasks. In adults, EF is subserved by frontoparietal regions in the multiple demand (MD) network, which respond to various cognitively demanding tasks. However, children initially show poor EF and prolonged development. Do children recruit the same network as adults? Is it functionally and connectionally distinct from adjacent language cortex, as in adults? And is this activation or connectivity dependent on age or ability? We examine task-dependent (spatial working memory and passive language tasks) and resting state functional data in 44 adults (18-38 years, 68% female) and 37 children (4-12 years, 35% female). Subject-specific functional ROIs (ss-fROIs) show bilateral MD network activation in children. In both children and adults, these MD ss-fROIs are not recruited for linguistic processing and are connectionally distinct from language ss-fROIs. While MD activation was lower in children than in adults (even in motion- and performance-matched groups), both showed increasing MD activation with better performance, especially in right hemisphere ss-fROIs. We observe this relationship even when controlling for age, cross-sectionally and in a small longitudinal sample of children. These data suggest that the MD network is selective to cognitive demand in children, is distinct from adjacent language cortex, and increases in selectivity as performance improves. These findings show that neural structures subserving domain-general EF emerge early and are sensitive to ability even in children. This research advances understanding of how high-level human cognition emerges and could inform interventions targeting cognitive control.SIGNIFICANCE STATEMENT This study provides evidence that young children already show differentiated brain network organization between regions that process cognitive demand and language. These data support the hypothesis that children recruit a similar network as adults to process cognitive demand; and despite immature characteristics, children's selectivity looks more adult-like as their executive function ability increases. Mapping early stages of network organization furthers our understanding of the functional architecture underlying domain-general executive function. Determining typical variability underlying cognitive processing across developmental periods helps establish a threshold for executive dysfunction. Early markers of dysfunction are necessary for effective early identification, prevention, and intervention efforts for individuals struggling with deficits in processing cognitive demand.

Maltreatment history and reasons for self-injurious behavior among adolescents engaged in non-suicidal self-injury versus adolescents who attempted suicide.

OBJECTIVE: Self-injurious behavior (SIB) is a significant public health concern in the United States, especially among adolescents with histories of maltreatment. This study compared maltreatment characteristics and reasons for SIB between three homogenous samples of adolescents with either: (1) non-suicidal self-injury (NSSI); (2) suicide attempt/s (SA), and (3) typically developing controls (TDC). METHOD: Participants (N = 124) aged 13-17 years completed questionnaires about their maltreatment and SIB histories. RESULTS: Maltreatment rates were as follows: 90% NSSI group, 76% SA group, and 40% TDC group. Adolescents in the NSSI group reported significantly higher rates of emotional neglect compared to the SA group. Maltreated adolescents in the NSSI and SA groups reported the same top three SIB reasons: (1) get rid of bad feelings, (2) mental state at the time, and (3) problems with family. However, maltreated NSSI participants were significantly more likely to engage in SIB for emotion regulation reasons than maltreated SA participants, who were more likely to engage in SIB for interpersonal reasons. Physical neglect and physical abuse also arose as significant predictors of specific SIB reasons. CONCLUSIONS: Our findings help elucidate the maltreatment profiles and reasons for SIB among adolescents engaged in NSSI or SA. Specific maltreatment experiences may also influence the reasons why adolescents engaged in SIB.

Relationship between cognitive flexibility and subsequent course of mood symptoms and suicidal ideation in young adults with childhood-onset bipolar disorder.

Neurocognitive deficits, such as cognitive flexibility impairments, are common in bipolar disorder (BD) and predict poor academic, occupational, and functional outcomes. However, the association between neurocognition and illness trajectory is not well understood, especially across developmental transitions. This study examined cognitive flexibility and subsequent mood symptom and suicidal ideation (SI) course in young adults with childhood-onset BD-I (with distinct mood episodes) vs. BD-not otherwise specified (BD-NOS) vs. typically-developing controls (TDCs). Sample included 93 young adults (ages 18-30) with prospectively verified childhood-onset DSM-IV BD-I (n = 34) or BD-NOS (n = 15) and TDCs (n = 44). Participants completed cross-sectional neuropsychological tasks and clinical measures. Then participants with BD completed longitudinal assessments of mood symptoms and SI at 6-month intervals (M = 39.18 ± 16.57 months of follow-up data). Analyses included ANOVAs, independent-samples t tests, chi-square analyses, and multiple linear regressions. Participants with BD-I had significant deficits in cognitive flexibility and executive functioning vs. BD-NOS and TDCs, and impaired spatial working memory vs. TDCs only. Two significant BD subtype-by-cognitive flexibility interactions revealed that cognitive flexibility deficits were associated with subsequent percentage of time depressed and with SI in BD-I but not BD-NOS, regardless of other neurocognitive factors (full-scale IQ, executive functioning, spatial working memory) and clinical factors (current and prior mood and SI symptoms, age of BD onset, global functioning, psychiatric medications, comorbidity). Thus, cognitive flexibility may be an important etiological brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD-I, as this deficit appears to endure into young adulthood and is associated with worse prognosis for subsequent depression and SI.

Internalizing-externalizing comorbidity and regional brain volumes in the ABCD study.

Despite nonoverlapping diagnostic criteria, internalizing and externalizing disorders show substantial comorbidity. This comorbidity is attributable, at least in part, to transdiagnostic neuroaffective mechanisms. Both unipolar depression and externalizing disorders are characterized by structural and functional compromises in the striatum and its projections to the anterior cingulate cortex (ACC) and other frontal regions. Smaller volumes and dampened reward responding in these regions are associated with anhedonia and irritability - mood states that cut across the internalizing and externalizing spectra. In contrast, smaller amygdala volumes and dampened amygdala function differentiate externalizing disorders from internalizing disorders. Little is known, however, about associations between internalizing-externalizing comorbidity and brain volumes in these regions, or whether such patterns differ by sex. Using a transdiagnostic, research domain criteria (RDoC)-informed approach, we evaluate associations between heterotypic (Internalizing × Externalizing) symptom interactions and striatal, amygdalar, and ACC volumes among participants in the Adolescent Brain Cognitive Development study (N = 6,971, mean age 9.9 years, 51.6% female). Heterotypic symptoms were associated with ACC volumes for both sexes, over and above the main effects of internalizing and externalizing alone. However, heterotypic comorbidity was associated with larger ACC volumes for girls, but with smaller ACC volumes for boys. These findings suggest a need for further studies and transdiagnostic assessment by sex.

Maladaptive personality traits and the course of suicidal ideation in young adults with bipolar disorder: Cross-sectional and prospective approaches.

BACKGROUND: Childhood-onset bipolar disorder (BD) has considerable morbidity and mortality, including suicide. Many risk factors have been identified for suicidality, but the potential role of personality traits as assessed by a computer-assisted self-report measure remains unclear. AIMS: To address this gap in knowledge, we tested relations between pathological-range personality traits and suicidal ideation among young adults whose childhood-onset BD was prospectively confirmed by enrollment in the Course and Outcome of Bipolar Youth study (COBY) as children (n = 45) and a newly enrolled group of typically developing controls (TDCs; n = 52) both cross-sectionally and longitudinally after 1.5 years of follow up. MATERIALS & METHODS: Personality traits were assessed with the computerized Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2). RESULTS: Cross-sectionally, we found that participants with BD had elevated Suicide Proneness and Low Self-esteem versus TDCs at baseline. Furthermore, longitudinal analyses in the BD participants for whom we had 1.5 years of prospectively collected illness-course data showed that greater Suicide Proneness and Low Self-esteem prospectively predicted greater levels, shorter time until occurrence, and greater frequency of suicidal ideation during the follow-up. CONCLUSION: Our findings suggest the role of specific personality-related vulnerabilities in the course of BD that, pending replication, could contribute to development of interventions focused on personality traits among individuals with BD.

White matter correlates of cognitive flexibility in youth with bipolar disorder and typically developing children and adolescents.

Prior studies using behavioral tasks and neuroimaging have shown that children and adolescents with bipolar disorder (BD) have deficits in cognitive flexibility (CF)-defined as adaptation to changing rewards and punishments. However, no study, to our knowledge, has examined the white matter microstructural correlates of CF in youth with BD. To address this gap, we examined the relationship between CF assessed with the Cambridge Neuropsychological Testing Automated Battery (CANTAB)'s Intra-Extra Dimensional Set Shift task (ID/ED) and diffusion tensor imaging analyzed with FSL's preprocessing tools and Tract-Based Spatial Statistics (TBSS). We found a significantly different relationship between microstructural integrity of multiple white matter regions and CF performance in BD (n=28) and age-matched typically developing control (TDC) youths (n=26). Evaluation of the slopes of linear regressions in BD vs. TDC (ID/ED Simple Reversal error rate vs. fractional anisotropy) revealed significantly different slopes across the groups, indicating an aberrant relationship between CF and underlying white matter microstructure in youth with BD. These results underscore the importance of examining specific CF-neuroimaging relationships in BD youth. Future longitudinal studies could seek to define the white matter microstructural trajectories in BD vs. TDC, and relative to CF deficits and BD illness course.

Do styles of emotion dysregulation differentiate adolescents engaging in non-suicidal self-injury from those attempting suicide?

Emotion dysregulation is implicated in both suicide attempts (SA) and non-suicidal self-injury (NSSI). However, little is known about how emotion dysregulation may differ between adolescents who have made an SA from those engaged in NSSI. We sought to address this gap by comparing emotion dysregulation profiles across three homogenous groups of adolescents (1) SA-only (2) NSSI-only (3) and typically developing controls (TDCs). Mean comparisons suggest that adolescents with a history of NSSI reported significantly lower distress tolerance and higher emotional reactivity when compared to adolescents who made an SA. After controlling for shared variance across emotion dysregulation measures, parent report of affective lability was the only scale to uniquely distinguish between NSSI and SA groups. Accurately distinguishing emotion dysregulation patterns across self-injurious groups has practical implications towards assessment, treatment, course of illness, and prevention.

Preliminary analysis of resting state functional connectivity in young adults with subtypes of bipolar disorder.

BACKGROUND: A precision medicine approach to bipolar disorder (BD) requires greater knowledge of neural mechanisms, especially within the BD phenotype. The present study evaluated differences in resting state functional connectivity (RSFC) between young adults followed longitudinally since childhood with full-threshold type I BD (BD-I)-characterized by distinct manic episodes-or a more sub-syndromal presentation of BD (BD Not Otherwise Specified [BD-NOS]), compared to one another and to healthy controls (HC). Independent Components Analysis (ICA), a multivariate data-driven method, and dual regression were used to explore whether connectivity within resting state networks (RSNs) differentiated the groups, especially for characteristic fronto-limbic alterations in BD. METHODS: Young adults (ages 18-30) with BD-I (n = 28), BD-NOS (n = 14), and HCs (n = 52) underwent structural and RSFC neuroimaging. ICA derived 30 components from RSFC data; a subset of these components, representing well-characterized RSNs, was used for between-group analyses. RESULTS: Participants with BD-I had significantly greater connectivity strength between the executive control network and right caudate vs. HCs. Participants with BD-NOS had significantly greater connectivity strength between the sensorimotor network and left precentral gyrus vs. HCs, which was significantly related to psychiatric symptoms. LIMITATIONS: Limitations included small BD-NOS sample size and variation in BD mood state and medication status. CONCLUSIONS: Results for BD-I participants support prior findings of fronto-limbic alterations characterizing BD. Alterations in the sensorimotor network for adults with BD-NOS aligns with the small but growing body of evidence that sensorimotor network alterations may represent a marker for vulnerability to BD. Further study is required to evaluate specificity.

Corrigendum: Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With ADHD Symptom Severity in Children.

[This corrects the article on p. 90 in vol. 12, PMID: 29593515.].

Cognitive performance of youth with primary generalized anxiety disorder versus primary obsessive-compulsive disorder.

BACKGROUND: Despite gains made in the study of childhood anxiety, differential diagnosis remains challenging because of indistinct boundaries between disorders and high comorbidity. This is certainly true for generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) as they share multiple cognitive processes (e.g., rumination, intolerance of uncertainty, and increased attention to threat). Disentangling such cognitive characteristics and, subsequently, underlying mechanisms could serve to inform assessment and treatment practices, and improve prognoses. METHODS: The current study sought to compare the cognitive performance (working memory, visuospatial memory, planning ability/efficiency, and cognitive flexibility), indexed by the Cambridge Neuropsychological Automated Battery (CANTAB) among three nonoverlapping groups of youth: (1) those diagnosed with OCD (n = 28), (2) those diagnosed with GAD, not OCD (n = 34), and (3) typically-developing controls (TDC) (n = 65). RESULTS: Results showed that OCD and GAD youth demonstrated neurocognitive deficits in planning ability/efficiency, cognitive flexibility, and visual processing when compared to TDC, with potential diagnostic specificity such that youth with GAD or OCD had unique deficits compared to TDC and to one another. Specifically, youth with OCD demonstrated significantly impaired planning ability compared to youth in the GAD and TDS groups, whereas youth with GAD demonstrated greater cognitive inflexibility and delayed visual processing compared to youth in the OCD and TDC groups. CONCLUSIONS: Future studies should expand upon these findings with more comprehensive assessment of cognitive functioning by including self- and parent-report forms, and neuroimaging to link behavioral findings with subjective ratings and neurocircuitry. Altogether, data can then inform future assessment and treatment targets.

Developmental evaluation of family functioning deficits in youths and young adults with childhood-onset bipolar disorder.

BACKGROUND: Childhood-onset bipolar disorder (BD) is a serious condition that affects the patient and family. While research has documented familial dysfunction in individuals with BD, no studies have compared developmental differences in family functioning in youths with BD vs. adults with prospectively verified childhood-onset BD. METHODS: The Family Assessment Device (FAD) was used to examine family functioning in participants with childhood-onset BD (n = 116) vs. healthy controls (HCs) (n = 108), ages 7-30 years, using multivariate analysis of covariance and multiple linear regression. RESULTS: Participants with BD had significantly worse family functioning in all domains (problem solving, communication, roles, affective responsiveness, affective involvement, behavior control, general functioning) compared to HCs, regardless of age, IQ, and socioeconomic status. Post-hoc analyses suggested no influence for mood state, global functioning, comorbidity, and most medications, despite youths with BD presenting with greater severity in these areas than adults. Post-hoc tests eliminating participants taking lithium (n = 17) showed a significant diagnosis-by-age interaction: youths with BD had worse family problem solving and communication relative to HCs. LIMITATIONS: Limitations include the cross-sectional design, clinical differences in youths vs. adults with BD, ambiguity in FAD instructions, participant-only report of family functioning, and lack of data on psychosocial treatments. CONCLUSIONS: Familial dysfunction is common in childhood-onset BD and endures into adulthood. Early identification and treatment of both individual and family impairments is crucial. Further investigation into multi-level, family-based mechanisms underlying childhood-onset BD may clarify the role family factors play in the disorder, and offer avenues for the development of novel, family-focused therapeutic strategies.

Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With ADHD Symptom Severity in Children.

Atypical brain function in attention-deficit/hyperactivity disorder (ADHD) has been identified using both task-activation and functional connectivity fMRI approaches. Recent work highlights the potential for another measure derived from functional neuroimaging data, brain signal variability, to reveal insights into clinical conditions. Higher brain signal variability has previously been linked with optimal behavioral performance. At present, little is known regarding the relationship between resting-state brain signal variability and ADHD symptom severity. The current study examined the relationship between a measure of moment-to-moment brain signal variability called mean-square successive difference (MSSD) and ADHD symptomatology in a group of children (7-12 years old) with (n = 40) and without (n = 30) a formal diagnosis of ADHD. A categorical analysis comparing subjects with and without a clinical diagnosis of ADHD showed no differences in MSSD between groups. A dimensional analysis revealed a positive relationship between MSSD and overall ADHD symptom severity and inattention across children with and without an ADHD diagnosis. Specifically, this positive relationship was found in medial prefrontal areas comprising the default mode network. These results demonstrate a link between intrinsic brain signal variability and ADHD symptom severity that cuts across diagnostic categories, and point to a locus of dysfunction consistent with previous neuroimaging literature.