Clarifying the role of Cortico-Cortical and Amygdalo-Cortical brain dysconnectivity associated with Conduct Problems

Abstract

A recent meta-analysis of resting-state functional connectivity studies revealed that individuals exhibiting antisocial behaviors or conduct problems may show disrupted brain connectivity in networks underpinning socio-affective and attentional processes. However, studies included in the meta-analysis generally rely on small sample sizes and substantially differ in terms of psychometric scales and neuroimaging methodologies. Therefore, we aimed to identify reliable functional brain connectivity alterations associated with severity of conduct problems using a large sample of adolescents and two measures of conduct problems. In a sample of 1416 children and adolescents, mass-univariate analyses of connectivity measures between 333 cortical parcels were conducted to examine the relationship between resting-state functional cortical-cortical connectome and the severity of conduct problems using the Child Behavior Checklist (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). At a liberal threshold, results showed that the functional brain connectivity significantly associated with conduct problems largely differ between the two scales. Indeed, only 21 pairs of brain regions overlapped between the CBCL and SDQ. Permutation feature importance of these 21 brain connectivity measures revealed that connectivity between precentral/postcentral gyri and lateral prefrontal cortex (both ventral and dorsal) were the most important features in explaining variance in conduct problems. The current study highlights that psychometric measures may yield distinct functional connectivity results. Moreover, severity of conduct problems in children and adolescents was mainly associated with deficient functional connectivity of somatomotor and ventral attention networks indicating potential alterations in motor, cognitive and reward processes.

Keywords: Antisocial behaviors; Conduct disorder; Functional connectivity; Somatomotor.

Fig. 1

Associations between cortico-cortical connectivity and Conduct Problems across different scales. A. Weight (F-value) of each significant (p < 0.005) cortico-cortical connectivity across 13 networks of the Gordon (333 parcels, Gordon et al., 2015) after 5,000 random subsampling using 90 % of the sample in association with Conduct Problems scales derived from the Child Behavior Checklist (CP-CBCL) and the Strengths and Difficulties Questionnaire (CP-SDQ). B. Connectivity positively and negatively associated with Conduct Problems that intersected between the CBCL and SDQ (Red edges = positive associations; Blue edges = negative associations). C. Adjacency matrix showing significant within- and between-network connectivity results associated (Red = Positively; Blue = Negatively) with CP. D. Feature importance (R² score with Standard Deviation) in association with severity of Conduct Problems for the Child Behavior Checklist (CP-CBCL) and the Strengths and Difficulties Questionnaire (CP-SDQ). Permutation importance was conducted by permutating each of the 21 cortico-cortical brain connectivity in a multivariate linear regression 100 times on a test set (20 % of the data) repeated 1,000 using Monte-Carlo cross-validation. Red dots = brain connectivity positively associated with CP; Blue dots = brain connectivity negatively associated with CP. Darker colors = CBCL & Lighter colors = SDQ. Please refer to Table 1 for more detailed information about brain connectivity. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Relationship between functional brain connectivity associated with Conduct Problems and other psychopathologies. Please refer to Table 1 for complete list of brain connectivity measure. Red lines = Positive associations with conduct problems; Blue lines = Negative associations with conduct problems. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Circular layout displaying the relationship between the behavioral domains significantly associated with functional brain connectivity. Red graph = brain connectivity positively related to CP. Blue Graph = brain connectivity negatively related to CP. Thicker line represents larger number of connected behavioral categories across pairs of brain connectivity. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)