White matter microstructure of the extended limbic system in male and female youth with conduct disorder.

BACKGROUND: Previous studies of conduct disorder (CD) have reported structural and functional alterations in the limbic system. However, the white matter tracts that connect limbic regions have not been comprehensively studied. The uncinate fasciculus (UF), a tract connecting limbic to prefrontal regions, has been implicated in CD. However, CD-related alterations in other limbic tracts, such as the cingulum and the fornix, have not been investigated. Furthermore, few studies have examined the influence of sex and none have been adequately powered to test whether the relationship between CD and structural connectivity differs by sex. We examined whether adolescent males and females with CD exhibit differences in structural connectivity compared with typically developing controls. METHODS: We acquired diffusion-weighted magnetic resonance imaging data from 101 adolescents with CD (52 females) and 99 controls (50 females). Data were processed for deterministic spherical deconvolution tractography. Virtual dissections of the UF, the three subdivisions of the cingulum [retrosplenial cingulum (RSC), parahippocampal and subgenual cingulum], and the fornix were performed and measures of fractional anisotropy (FA) and hindrance-modulated orientational anisotropy (HMOA) were analysed. RESULTS: The CD group had lower FA and HMOA in the right RSC tract relative to controls. Importantly, these effects were moderated by sex - males with CD significantly lower FA compared to male controls, whereas CD and control females did not differ. CONCLUSIONS: Our results highlight the importance of considering sex when studying the neurobiological basis of CD. Sex differences in RSC connectivity may contribute to sex differences in the clinical presentation of CD.

Investigating the Influences of Language Delay and/or Familial Risk for Dyslexia on Brain Structure in 5-Year-Olds.

Early language delay has often been associated with atypical language/literacy development. Neuroimaging studies further indicate functional disruptions during language and print processing in school-age children with a retrospective report of early language delay. Behavioral data of 114 5-year-olds with a retrospective report of early language delay in infancy (N = 34) and those without (N = 80) and with a familial risk for dyslexia and those without are presented. Behaviorally, children with a retrospective report of early language delay exhibited reduced performance in language/reading-related measures. A voxel-based morphometry analysis in a subset (N = 46) demonstrated an association between reduced gray matter volume and early language delay in left-hemispheric middle temporal, occipital, and frontal regions. Alterations in middle temporal cortex in children with a retrospective report of early language delay were observed regardless of familial risk for dyslexia. Additionally, while children with isolated familial risk for dyslexia showed gray matter reductions in temporoparietal and occipitotemporal regions, these effects were most profound in children with both risk factors. An interaction effect of early language delay and familial risk was revealed in temporoparietal, occipital, and frontal cortex. Our findings support a cumulative effect of early behavioral and genetic risk factors on brain development and may ultimately inform diagnosis/treatment.

Prefrontal cortical thickness, emotion regulation strategy use and COVID-19 mental health.

Coronavirus disease 2019 (COVID-19) and associated restrictions have been linked to negative mental health outcomes across the globe. Cognitive emotion regulation strategies, neurally supported by prefrontal and limbic regions, constitute means to mitigate negative affects resulting from adverse life experiences. Variations in cognitive emotion regulation strategy use, anxiety, and depression were assessed in 43 adults (31♀/12♂, age = 35.14 ± 9.20 years) during the first months following COVID-19 onset and at the end of 2020 (seven assessments). Direct and indirect effects of emotion regulatory brain structures assessed prior to the pandemic and emotion regulation strategy use during the pandemic were assessed in relation to mental well-being. Varying levels of anxiety and depression were observed. While adaptive emotion regulation strategies were most frequently employed, maladaptive strategies explained the highest variation in anxiety and depression scores. The effectiveness of specific emotion regulation strategies varied. Momentary emotion regulation strategy use mediated the association between cortical thickness in right lateral prefrontal cortex assessed prior to the pandemic and mental health during the pandemic. Early mental health measures impacted later mental well-being. Maladaptive strategies have a negative effect on mental health during prolonged stress as induced by pandemics, providing possible targets for intervention.

Mother-child similarity in brain morphology: A comparison of structural characteristics of the brain's reading network.

BACKGROUND: Substantial evidence acknowledges the complex gene-environment interplay impacting brain development and learning. Intergenerational neuroimaging allows the assessment of familial transfer effects on brain structure, function and behavior by investigating neural similarity in caregiver-child dyads. METHODS: Neural similarity in the human reading network was assessed through well-used measures of brain structure (i.e., surface area (SA), gyrification (lG), sulcal morphology, gray matter volume (GMV) and cortical thickness (CT)) in 69 mother-child dyads (children's age~11 y). Regions of interest for the reading network included left-hemispheric inferior frontal gyrus, inferior parietal lobe and fusiform gyrus. Mother-child similarity was quantified by correlation coefficients and familial specificity was tested by comparison to random adult-child dyads. Sulcal morphology analyses focused on occipitotemporal sulcus interruptions and similarity was assessed by chi-square goodness of fit. RESULTS: Significant structural brain similarity was observed for mother-child dyads in the reading network for lG, SA and GMV (r = 0.349/0.534/0.542, respectively), but not CT. Sulcal morphology associations were non-significant. Structural brain similarity in lG, SA and GMV were specific to mother-child pairs. Furthermore, structural brain similarity for SA and GMV was higher compared to CT. CONCLUSION: Intergenerational neuroimaging techniques promise to enhance our knowledge of familial transfer effects on brain development and disorders.

Early and late neural correlates of mentalizing: ALE meta-analyses in adults, children and adolescents.

The ability to understand mental states of others is referred to as mentalizing and enabled by our Theory of Mind. This social skill relies on brain regions comprising the mentalizing network as robustly observed in adults but also in a growing number of developmental studies. We summarized and compared neuroimaging evidence in children/adolescents and adults during mentalizing using coordinate-based activation likelihood estimation meta-analyses to inform about brain regions consistently or differentially engaged across age categories. Adults (N = 5286) recruited medial prefrontal and middle/inferior frontal cortices, precuneus, temporoparietal junction and middle temporal gyri during mentalizing, which were functionally connected to bilateral inferior/superior parietal lobule and thalamus/striatum. Conjunction and contrast analyses revealed that children and adolescents (N = 479) recruit similar but fewer regions within core mentalizing regions. Subgroup analyses revealed an early continuous engagement of middle medial prefrontal cortex, precuneus and right temporoparietal junction in younger children (8-11 years) and adolescents (12-18 years). Adolescents additionally recruited the left temporoparietal junction and middle/inferior temporal cortex. Overall, the observed engagement of the medial prefrontal cortex, precuneus and right temporoparietal junction during mentalizing across all ages reflects an early specialization of some key regions of the social brain.

Psychophysiological responses to sadness in girls and boys with conduct disorder.

Reduced responsiveness to emotions is hypothesized to contribute to the development of conduct disorder (CD) in children and adolescents. Accordingly, blunted psychophysiological responses to emotions have been observed in boys with CD, but this has never been tested in girls. Therefore, this study compared psychophysiological responses to sadness in girls and boys with and without CD, and different clinical phenotypes of CD: with versus without limited prosocial emotions (LPE), and with versus without comorbid internalizing disorders (INT). Nine-hundred and 27 girls (427 CD, 500 controls) and 519 boys (266 CD, 253 controls) aged 9-18 years participated. Psychophysiological responses were measured while participants watched two validated sad film clips, specifically: heart rate (HR), respiratory sinus arrhythmia (RSA; indexing parasympathetic activity), preejection period (PEP; indexing sympathetic activity). Girls and boys with CD showed larger HR responses to sadness than controls. This effect was rendered nonsignificant, however, after controlling for covariates. We observed aberrant RSA responses to sadness in CD compared with controls. Similarly, we found a significant positive association between RSA responsivity and antisocial behavior when assessed dimensionally. The effects were very small, though. Results were similar for boys and girls. We found no evidence for emotional underresponsiveness in CD in the largest psychophysiological study to date in this field. More research is needed to explore whether this is specific to sadness or generalizes to other emotions. Furthermore, we recommend that studies on emotion processing in CD assess different physiological measures to help disentangle CD-related effects on sympathetic and parasympathetic activity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Eye gaze patterns and functional brain responses during emotional face processing in adolescents with conduct disorder.

BACKGROUND: Conduct disorder (CD) is characterized by severe aggressive and antisocial behavior. Initial evidence suggests neural deficits and aberrant eye gaze pattern during emotion processing in CD; both concepts, however, have not yet been studied simultaneously. The present study assessed the functional brain correlates of emotional face processing with and without consideration of concurrent eye gaze behavior in adolescents with CD compared to typically developing (TD) adolescents. METHODS: 58 adolescents (23CD/35TD; average age = 16 years/range = 14-19 years) underwent an implicit emotional face processing task. Neuroimaging analyses were conducted for a priori-defined regions of interest (insula, amygdala, and medial orbitofrontal cortex) and using a full-factorial design assessing the main effects of emotion (neutral, anger, fear), group and the interaction thereof (cluster-level, p < .05 FWE-corrected) with and without consideration of concurrent eye gaze behavior (i.e., time spent on the eye region). RESULTS: Adolescents with CD showed significant hypo-activations during emotional face processing in right anterior insula compared to TD adolescents, independent of the emotion presented. In-scanner eye-tracking data revealed that adolescents with CD spent significantly less time on the eye, but not mouth region. Correcting for eye gaze behavior during emotional face processing reduced group differences previously observed for right insula. CONCLUSIONS: Atypical insula activation during emotional face processing in adolescents with CD may partly be explained by attentional mechanisms (i.e., reduced gaze allocation to the eyes, independent of the emotion presented). An increased understanding of the mechanism causal for emotion processing deficits observed in CD may ultimately aid the development of personalized intervention programs.

Neural correlates of theory of mind in children and adults using CAToon: Introducing an open-source child-friendly neuroimaging task.

Theory of Mind (ToM) or mentalizing is a basic social skill which is characterized by our ability of perspective-taking and the understanding of cognitive and emotional states of others. ToM development is essential to successfully navigate in various social contexts. The neural basis of mentalizing is well-studied in adults, however, less evidence exists in children. Potential reasons are methodological challenges, including a lack of age-appropriate fMRI paradigms. We introduce a novel child-friendly and open-source ToM fMRI task, for which accuracy and performance were evaluated behaviorally in 60 children ages three to nine (32♂). Furthermore, 27 healthy young adults (14♂; mean = 25.41 years) and 33 children ages seven to thirteen (17♂; mean = 9.06 years) completed the Cognitive and Affective Theory of Mind Cartoon task (CAToon;www.jacobscenter.uzh.ch/en/research/developmental_neuroscience/downloads/catoon.html) during a fMRI session. Behavioral results indicate that children of all ages can solve the CAToon task above chance level, though reliable performance is reached around five years. Neurally, activation increases were observed for adults and children in brain regions previously associated with mentalizing, including bilateral temporoparietal junction, temporal gyri, precuneus and medial prefrontal/orbitofrontal cortices. We conclude that CAToon is suitable for developmental neuroimaging studies within an fMRI environment starting around preschool and up.

Mental well-being during the first months of Covid-19 in adults and children: behavioral evidence and neural precursors.

Pandemics such as the Covid-19 pandemic have shown to impact our physical and mental well-being, with particular challenges for children and families. We describe data from 43 adults (31♀, ages = 22-51; 21 mothers) and 26 children (10♀, ages = 7-17 years) including pre-pandemic brain function and seven assessment points during the first months of the pandemic. We investigated (1) changes in child and adult well-being, (2) mother-child associations of mental well-being, and (3) associations between pre-pandemic brain activation during mentalizing and later fears or burden. In adults the prevalence of clinically significant anxiety-levels was 34.88% and subthreshold depression 32.56%. Caregiver burden in parents was moderately elevated. Overall, scores of depression, anxiety, and caregiver burden decreased across the 11 weeks after Covid-19-onset. Children's behavioral and emotional problems during Covid-19 did not significantly differ from pre-pandemic levels and decreased during restrictions. Mothers' subjective burden of care was associated with children's emotional and behavioral problems, while depression levels in mothers were related to children's mood. Furthermore, meeting friends was a significant predictor of children's mood during early restrictions. Pre-pandemic neural correlates of mentalizing in prefrontal regions preceded later development of fear of illnesses and viruses in all participants, while temporoparietal activation preceded higher subjective burden in mothers.

Atypical Dorsolateral Prefrontal Activity in Female Adolescents With Conduct Disorder During Effortful Emotion Regulation.

BACKGROUND: Conduct disorder (CD), which is characterized by severe aggressive and antisocial behavior, is linked to emotion processing and regulation deficits. However, the neural correlates of emotion regulation are yet to be investigated in adolescents with CD. Furthermore, it remains unclear whether CD is associated with deficits in emotional reactivity, emotion regulation, or both. METHODS: We used functional magnetic resonance imaging to study effortful emotion regulation by cognitive reappraisal in 59 female adolescents 15 to 18 years of age (30 with a CD diagnosis and 29 typically developing (TD) control adolescents). RESULTS: Behaviorally, in-scanner self-report ratings confirmed successful emotion regulation within each group individually but significant group differences in emotional reactivity and reappraisal success when comparing the groups (CD < TD). Functional magnetic resonance imaging results revealed significantly lower activation in left dorsolateral prefrontal cortex and angular gyrus in CD compared with TD adolescents during emotion regulation, but no group differences for emotional reactivity. Furthermore, connectivity between left dorsolateral prefrontal cortex and the bilateral putamen, right prefrontal cortex, and amygdala was reduced in CD compared with TD adolescents during reappraisal. Callous-unemotional traits were unrelated to neural activation, but these traits correlated negatively with behavioral reports of emotional reactivity. CONCLUSIONS: Our results demonstrate reduced prefrontal brain activity and functional connectivity during effortful emotion regulation in female adolescents with CD. This sheds light on the neural basis of the behavioral deficits that have been reported previously. Future studies should investigate whether cognitive interventions are effective in enhancing emotion-regulation abilities and/or normalizing prefrontal and temporoparietal activity in female adolescents with CD.

White Matter Microstructure in Youths With Conduct Disorder: Effects of Sex and Variation in Callous Traits.

OBJECTIVE: Studies using diffusion tensor imaging (DTI) to investigate white matter (WM) microstructure in youths with conduct disorder (CD) have reported disparate findings. We investigated WM alterations in a large sample of youths with CD, and examined the influence of sex and callous-unemotional (CU) traits. METHOD: DTI data were acquired from 124 youths with CD (59 female) and 174 typically developing (TD) youths (103 female) 9 to 18 years of age. Tract-based spatial statistics tested for effects of diagnosis and sex-by-diagnosis interactions. Associations with CD symptoms, CU traits, a task measuring impulsivity, and the impact of comorbidity, and age- and puberty-related effects were examined. RESULTS: Youths with CD exhibited higher axial diffusivity in the corpus callosum and lower radial diffusivity and mean diffusivity in the anterior thalamic radiation relative to TD youths. Female and male youths with CD exhibited opposite changes in the left hemisphere within the internal capsule, fornix, posterior thalamic radiation, and uncinate fasciculus. Within the CD group, CD symptoms and callous traits exerted opposing influences on corpus callosum axial diffusivity, with callous traits identified as the unique clinical feature predicting higher axial diffusivity and lower radial diffusivity within the corpus callosum and anterior thalamic radiation, respectively. In an exploratory analysis, corpus callosum axial diffusivity partially mediated the association between callous traits and impulsive responses to emotional faces. Results were not influenced by symptoms of comorbid disorders, and no age- or puberty-related interactions were observed. CONCLUSION: WM alterations within the corpus callosum represent a reliable neuroimaging marker of CD. Sex and callous traits are important factors to consider when examining WM in CD.

Altered Neuronal Responses During an Affective Stroop Task in Adolescents With Conduct Disorder.

Conduct disorder (CD) is a psychiatric disorder of childhood and adolescence which has been linked to deficient emotion processing and regulation. The behavioral and neuronal correlates targeting the interaction of emotion processing and response inhibition are still under investigation. Whole-brain event-related fMRI was applied during an affective Stroop task in 39 adolescents with CD and 39 typically developing adolescents (TD). Participants were presented with an emotional stimulus (negative/neutral) followed by a Stroop task with varying cognitive load (congruent/incongruent/blank trials). fMRI analysis included standard preprocessing, region of interest analyses (amygdala, insula, ventromedial prefrontal cortex) and whole-brain analyses based on a 2(group) × 2(emotion) × 3(task) full-factorial ANOVA. Adolescents with CD made significantly more errors, while reaction times did not significantly differ compared to TD. Additionally, we observed a lack of downregulation of left amygdala activity in response to incongruent trials and increased anterior insula activity for CD relative to TD during affective Stroop task processing [cluster-level family-wise error-corrected (p < 0.05)]. Even though no three-way interaction (group × emotion × task) interaction was detected, the findings presented still provide evidence for altered neuronal underpinnings of the interaction of emotion processing and response inhibition in CD. Moreover, our results may corroborate previous evidence of emotion dysregulation as a core dysfunction in CD. Future studies shall focus on investigating the interaction of emotion processing and response inhibition in CD subgroups (e.g., variations in callous-unemotional traits, impulsivity, or anxiety).

Callous-unemotional traits and brain structure: Sex-specific effects in anterior insula of typically-developing youths.

Callous-unemotional traits are characterized by a lack of empathy, a disregard for others' feelings and shallow or deficient affect, such as a lack of remorse or guilt. Neuroanatomical correlates of callous-unemotional traits have been demonstrated in clinical samples (i.e., adolescents with disruptive behavior disorders). However, it is unknown whether callous-unemotional traits are associated with neuroanatomical correlates within normative populations without clinical levels of aggression or antisocial behavior. Here we investigated the relationship between callous-unemotional traits and gray matter volume using voxel-based morphometry in a large sample of typically-developing boys and girls (N = 189). Whole-brain multiple regression analyses controlling for site, total intracranial volume, and age were conducted in the whole sample and in boys and girls individually. Results revealed that sex and callous-unemotional traits interacted to predict gray matter volume when considering the whole sample. This interaction was driven by a significant positive correlation between callous-unemotional traits and bilateral anterior insula volume in boys, but not girls. Insula gray matter volume explained 19% of the variance in callous-unemotional traits for boys. Our results demonstrate that callous-unemotional traits are related to variations in brain structure beyond psychiatric samples. This association was observed for boys only, underlining the importance of considering sex as a factor in future research designs. Future longitudinal studies should determine whether these findings hold over childhood and adolescence, and whether the neuroanatomical correlates of callous-unemotional traits are predictive of future psychiatric vulnerability. General scientific summary: This study suggests that callous-unemotional traits have a neuroanatomical correlate within typically developing boys, but not girls. Bilateral anterior insula volume explains up to 19% of the variance in callous-unemotional traits in boys.

Investigating the Neural Correlates of Emotion-Cognition Interaction Using an Affective Stroop Task.

The human brain has the capacity to integrate various sources of information and continuously adapts our behavior according to situational needs in order to allow a healthy functioning. Emotion-cognition interactions are a key example for such integrative processing. However, the neuronal correlates investigating the effects of emotion on cognition remain to be explored and replication studies are needed. Previous neuroimaging studies have indicated an involvement of emotion and cognition related brain structures including parietal and prefrontal cortices and limbic brain regions. Here, we employed whole brain event-related functional magnetic resonance imaging (fMRI) during an affective number Stroop task and aimed at replicating previous findings using an adaptation of an existing task design in 30 healthy young adults. The Stroop task is an indicator of cognitive control and enables the quantification of interference in relation to variations in cognitive load. By the use of emotional primes (negative/neutral) prior to Stroop task performance, an emotional variation is added as well. Behavioral in-scanner data showed that negative primes delayed and disrupted cognitive processing. Trials with high cognitive demand furthermore negatively influenced cognitive control mechanisms. Neuronally, the emotional primes consistently activated emotion-related brain regions (e.g., amygdala, insula, and prefrontal brain regions) while Stroop task performance lead to activations in cognition networks of the brain (prefrontal cortices, superior temporal lobe, and insula). When assessing the effect of emotion on cognition, increased cognitive demand led to decreases in neural activation in response to emotional stimuli (negative > neutral) within prefrontal cortex, amygdala, and insular cortex. Overall, these results suggest that emotional primes significantly impact cognitive performance and increasing cognitive demand leads to reduced neuronal activation in emotion related brain regions, and therefore support previous findings investigating emotion-cognition interaction in healthy adults. Moreover, emotion and cognition seem to be tightly related to each other, as indicated by shared neural networks involved in both of these processes. Emotion processing, cognitive control, and their interaction are crucial for healthy functioning and a lack thereof is related to psychiatric disorders such as, disruptive behavior disorders. Future studies may investigate the neural characteristics of children and adolescents with disruptive behavior disorders.

Microstructural White Matter Alterations in the Corpus Callosum of Girls With Conduct Disorder.

OBJECTIVE: Diffusion tensor imaging (DTI) studies in adolescent conduct disorder (CD) have demonstrated white matter alterations of tracts connecting functionally distinct fronto-limbic regions, but only in boys or mixed-gender samples. So far, no study has investigated white matter integrity in girls with CD on a whole-brain level. Therefore, our aim was to investigate white matter alterations in adolescent girls with CD. METHOD: We collected high-resolution DTI data from 24 girls with CD and 20 typically developing control girls using a 3T magnetic resonance imaging system. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed for whole-brain as well as a priori-defined regions of interest, while controlling for age and intelligence, using a voxel-based analysis and an age-appropriate customized template. RESULTS: Whole-brain findings revealed white matter alterations (i.e., increased FA) in girls with CD bilaterally within the body of the corpus callosum, expanding toward the right cingulum and left corona radiata. The FA and MD results in a priori-defined regions of interest were more widespread and included changes in the cingulum, corona radiata, fornix, and uncinate fasciculus. These results were not driven by age, intelligence, or attention-deficit/hyperactivity disorder comorbidity. CONCLUSION: This report provides the first evidence of white matter alterations in female adolescents with CD as indicated through white matter reductions in callosal tracts. This finding enhances current knowledge about the neuropathological basis of female CD. An increased understanding of gender-specific neuronal characteristics in CD may influence diagnosis, early detection, and successful intervention strategies.

Temporal dynamics of early visual word processing - Early versus late N1 sensitivity in children and adults.

In the course of reading development children become familiar with letter strings and learn to distinguish between lexical and non-lexical items. In previous studies, the N1 component of the ERP was shown to reflect print tuning but also to be sensitive to lexical effects. It remains unclear, however, whether these two aspects of orthographic processing occur at the same time or in different time windows during the lengthy N1 component. Moreover, it is unclear whether these processes develop late or occur already at early stages of literacy acquisition and whether this is similar for native languages and languages acquired later in life. To address these questions, 27 children were tested longitudinally, i.e. before (mean: 7.6 years) and after one year of classroom-based English instruction. Additionally, 22 adult speakers of English as a foreign language (mean: 25.1 years) were investigated. A 128-channel EEG was recorded while participants performed a one-back task with native German words, English words, pseudowords and false-font strings. The event-related EEG analysis of early and late N1 phases revealed early effects related to print tuning and late effects related to lexical processing in the native, but not in the second language of adult readers. In the absence of lexicality effects in children, print tuning effects were found across both early and late N1 segments. The temporally distinct N1 sensitivities to print and lexicality reflect temporal dynamics of visual word processing, which seem to depend on reading expertise or maturation.

Structural and Functional Alterations in Right Dorsomedial Prefrontal and Left Insular Cortex Co-Localize in Adolescents with Aggressive Behaviour: An ALE Meta-Analysis.

Recent neuroimaging work has suggested that aggressive behaviour (AB) is associated with structural and functional brain abnormalities in processes subserving emotion processing and regulation. However, most neuroimaging studies on AB to date only contain relatively small sample sizes. To objectively investigate the consistency of previous structural and functional research in adolescent AB, we performed a systematic literature review and two coordinate-based activation likelihood estimation meta-analyses on eight VBM and nine functional neuroimaging studies in a total of 783 participants (408 [224AB/184 controls] and 375 [215 AB/160 controls] for structural and functional analysis respectively). We found 19 structural and eight functional foci of significant alterations in adolescents with AB, mainly located within the emotion processing and regulation network (including orbitofrontal, dorsomedial prefrontal and limbic cortex). A subsequent conjunction analysis revealed that functional and structural alterations co-localize in right dorsomedial prefrontal cortex and left insula. Our results are in line with meta-analytic work as well as structural, functional and connectivity findings to date, all of which make a strong point for the involvement of a network of brain areas responsible for emotion processing and regulation, which is disrupted in AB. Increased knowledge about the behavioural and neuronal underpinnings of AB is crucial for the development of novel and implementation of existing treatment strategies. Longitudinal research studies will have to show whether the observed alterations are a result or primary cause of the phenotypic characteristics in AB.