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. 2021:32:102789.
doi: 10.1016/j.nicl.2021.102789. Epub 2021 Aug 21.

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

Ya Chai  1 , José R Chimelis-Santiago  1 , Kristy A Bixler  1 , Matthew Aalsma  2 , Meichen Yu  3 , Leslie A Hulvershorn  4
Affiliations

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

Ya Chai et al. Neuroimage Clin. 2021.

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.

Keywords: Adolescence; Externalizing disorders; Frontal-striatal Connectivity; Impulsivity; Resting-state Functional Connectivity; Sex Differences.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Seed-based functional connectivity differences between boys and girls. Significantly greater connectivity was found a) between bilateral ventral striatum (VS) seed and bilateral medial superior frontal gyrus (mSFG), anterior cingulate cortex (ACC), medial frontal cortex (mFC) in boys compared to girls; b) between left middle frontal gyrus (L.MFG) seed and bilateral mSFG, ACC, mFC and c) between left medial prefrontal cortex (L.mPFC) seed and left middle frontal gyrus (L.MFG), left superior frontal gyrus (L.SFG) in girls relative to boys. Images were displayed at a threshold of uncorrected p < 0.001, with cluster size > 30 voxels.
Fig. 2
Fig. 2
Seed-cluster functional connectivity analysis for sex differences. Functional connectivity between bilateral VS seed and bilateral mSFG/ACC/mFC was greater in boys than girls. The connectivity between L.MFG seed and bilateral mSFG/ACC/mFC and between L.mPFC seed and L.MFG/SFG was negative (anti-correlations) in boys as compared to girls. Error bars represent standard errors of the mean. *** p < 0.001. VS: ventral striatum; mSFG: medial superior frontal gyrus; ACC: anterior cingulate cortex; mFC: medial frontal cortex; L.mPFC: left medial prefrontal cortex; L.MFG/SFG: left middle frontal gyrus/superior frontal gyrus.
Fig. 3
Fig. 3
The scatter plots showed the Pearson’s (r) and Spearman’s (rho) correlation between functional connectivity values and UPPS-P-C subscale scores. Only in boys, connectivity between L.mPFC and L.MFG/SFG positively correlated with lack of premeditation (3a) and negative urgency (3b). The p values were not corrected for multiple comparisons. L.mPFC: left medial prefrontal cortex; L.MFG/SFG: left middle frontal gyrus/superior frontal gyrus; FC: functional connectivity. Black lines: boys and girls pooling together; Blue dots/lines: boys; Red dots/lines: girls. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
See this image and copyright information in PMC

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