Dataset Information

Sex-specific frontal-striatal connectivity differences among adolescents with externalizing disorders.

ABSTRACT:

Background

Sex-specific neurobiological underpinnings of impulsivity in youth with externalizing disorders have not been well studied. The only report of functional connectivity (FC) findings in this area demonstrated sex differences in fronto-subcortical connectivity in youth with attention-deficit/hyperactivity disorder (ADHD).

Methods

The current study used functional magnetic resonance imaging(fMRI) to examine sex differences in resting-state seed-based FC, self-rated impulsivity, and their interactions in 11-12-year-old boys (n = 43) and girls (n = 43) with externalizing disorders. Generalized linear models controlling for pubertal development were used. Seeds were chosen in the ventral striatum, medial prefrontal cortex, middle frontal gyrus and amygdala.

Results

Impulsivity scores were greater in boys than girls (p < 0.05). Boys showed greater positive connectivity within a ventromedial prefrontal-ventral striatal network. In addition, boys demonstrated weaker connectivity than girls within two medial-lateral prefrontal cortical networks. However, only boys showed greater medial-lateral prefrontal connectivity correlated with greater impulsivity.

Conclusions

The findings provide evidence supporting sex differences in both ventral striatal-ventromedial prefrontal and medial-lateral prefrontal functional networks in youth with externalizing disorders. These important networks are thought to be implicated in impulse control. Medial-lateral prefrontal connectivity may represent a male-specific biomarker of impulsivity.

SUBMITTER: Chai Y

PROVIDER: S-EPMC8405840 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:OBJECTIVE:Early adverse childhood experiences (ACEs) have been linked to the development of both internalizing and externalizing psychopathology. In our prior work, we found that ACEs predicted reductions in the volume of the inferior frontal gyrus (IFG), a brain region important for impulse control and emotion regulation. Here we tested the hypothesis that ACEs might influence child behavioral outcomes through an impact on IFG functional connectivity, which may influence impulsive or risk-taking behavior. METHOD:We examined the effects of prospectively assessed ACEs on IFG connectivity in childhood, and their relationship to the trajectory of subsequent psychopathology from late school age and early adolescence, using data from an 11-year longitudinal study of children starting in preschool that included 3 waves of resting state functional connectivity across childhood and early adolescence. RESULTS:ACEs predicted functional connectivity of both left and right IFG. Multi-level modeling of symptoms across 3 waves of assessments indicated that more ACEs predicted both internalizing and externalizing symptoms. However, altered IFG connectivity specifically predicted greater externalizing symptoms over time in middle childhood and early adolescence, as compared to internalizing symptoms. Longitudinal modeling indicating that the relationships between externalizing and functional connectivity were maintained across 3 waves of functional connectivity assessment. CONCLUSION:These findings underscore the relationship of ACEs to later psychopathology, and suggest that connectivity of the IFG, a region known to play an important role in impulse control and emotion regulation, may play a key role in the risk trajectory of ACEs to externalizing problems. However, further work is needed to understand whether these relationships reflect a direct effect of ACEs or whether ACEs are a marker for other environmental or genetic factors that may also influence brain development and behavior.

Project description:BackgroundExternalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs.MethodsMulti-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6-18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined.ResultsNo significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results.ConclusionsThe current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations.