The Maturation of Functional Network Connectivity Supporting Emotion Regulation before Adolescence

725 

Abstract Submission 

Ekomobong Eyoh^1,2, Kody DeGolier², Elina Thomas³, Trevor Day¹, Maryam Mahmoudi^2,4, Katharina Pittner⁵, Martin Bauer⁵, Fiona O'Donovan⁵, Claudia Buss⁵, Eric Feczko^2,6, Joel Nigg⁷, Jed Elison^1,2, Damien Fair^1,2,6, Alice Graham⁷, Oscar Miranda Dominguez^2,6

¹Institute of Child Development, University of Minnesota, Minneapolis, MN, ²Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, ³Earlham College, Richmond, IN, ⁴Department of Pediatrics, University of Minnesota, Minneapolis, MN, ⁵Charité – Universitätsmedizin Berlin, Berlin, Germany, ⁶Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, ⁷Oregon Health and Science University, Portland, OR

Ekomobong Eyoh, MPH  
Institute of Child Development, University of Minnesota|Masonic Institute for the Developing Brain, University of Minnesota
Minneapolis, MN|Minneapolis, MN

Kody DeGolier, MS  
Masonic Institute for the Developing Brain, University of Minnesota
Minneapolis, MN

Elina Thomas, PhD  
Earlham College
Richmond, IN

Trevor Day  
Institute of Child Development, University of Minnesota
Minneapolis, MN

Maryam Mahmoudi, PhD  
Masonic Institute for the Developing Brain, University of Minnesota|Department of Pediatrics, University of Minnesota
Minneapolis, MN|Minneapolis, MN

Katharina Pittner  
Charité – Universitätsmedizin Berlin
Berlin, Germany

Martin Bauer  
Charité – Universitätsmedizin Berlin
Berlin, Germany

Fiona O'Donovan  
Charité – Universitätsmedizin Berlin
Berlin, Germany

Claudia Buss  
Charité – Universitätsmedizin Berlin
Berlin, Germany

Eric Feczko  
Masonic Institute for the Developing Brain, University of Minnesota|Department of Pediatrics, University of Minnesota Medical School
Minneapolis, MN|Minneapolis, MN

Joel Nigg, PhD  
Oregon Health and Science University
Portland, OR

Jed Elison  
Institute of Child Development, University of Minnesota|Masonic Institute for the Developing Brain, University of Minnesota
Minneapolis, MN|Minneapolis, MN

Damien Fair  
Institute of Child Development, University of Minnesota|Masonic Institute for the Developing Brain, University of Minnesota|Department of Pediatrics, University of Minnesota Medical School
Minneapolis, MN|Minneapolis, MN|Minneapolis, MN

Alice Graham, PhD  
Oregon Health and Science University
Portland, OR

Oscar Miranda Dominguez  
Masonic Institute for the Developing Brain, University of Minnesota|Department of Pediatrics, University of Minnesota Medical School
Minneapolis, MN|Minneapolis, MN

Emotion regulation (ER) has been proposed as a transdiagnostic factor in the development of psychopathology and neurodevelopmental disorders (Aldao et al., 2016). The development of individual ER has been hypothesized to begin with co-regulation of stress between parents and infants which transitions into more self-mediated top-down control from frontal regions on subcortical regions in adolescence (Gee et al., 2014; Silvers, 2022). Understanding dynamic changes in ER and its supporting brain circuitry will yield insight into the typical development of this construct and help identify critical periods when perturbations in typical maturation are associated with increased risk for psychopathology and neurodevelopmental disorders. We hypothesize that left amygdala connectivity to other cortical and subcortical regions of the brain will be differentially associated with ER at different developmental stages.

We used high-quality data from a large sample representative of the US population (the Adolescent Brain Cognitive Development, ABCD, study, N=6900, age 9-11) to derive reproducible brain-behavior associations related to ER (Byington et al., 2023). Resulting models were used to calculate brain scores of ER in independent samples with individuals of different ages. To do this, we used subjects from the Baby Connectome Project (BCP) and infants from a study at the University of California – Irvine (UCI). First, the resting state functional connectivity of 6900 subjects from ABCD was parcellated according to the regions of interest (ROIs) designated by Gordon et al. (2016). Then, the correlation of the left amygdala with each other brain cortical and subcortical region was calculated. The resulting 351 connections were grouped into 14 networks as defined in Fig. 1A. ß-weights were generated by modeling the CBCL internalizing raw score as the weighted contribution of each connection when controlling for collection site, gender, race, and ethnicity (Figure 1B). The ß-weights were used to calculate polyneuro risk scores (PNRS, predicted scores of behavior given left amygdala connectivity) by network in 90 18-60-month-olds in the BCP and 54 1-month-olds in the UCI study. In addition, we calculated PNRSes for the ABCD sample using a split half approach, where one half of the ABCD subjects were used as the training sample to generate PNRSes in the other half and vice versa.
Differences in brain scores by network and across age were tested via repeated measures ANOVA using aggregated data from all three samples. Additionally, the interaction between network and age was tested to determine whether means were changing over time within each network. Median PNRSes per network by cohort were calculated and ranked from lowest to highest to map the change in the association between amygdala connectivity to networks and ER. Lower scores indicate better ER and higher scores indicate more ER difficulties.

Results of the ANOVA indicate that there is a significant difference in means by network (F = 43.184, p = <0.001) and an interaction between age and network (F =29.151, p<0.001). Thus, network PNRS means are different from one another, and mean scores differ by network across age. Large changes in rank occurred in the ReT (UCI: 10, BCP: 12, ABCD: 2) and Sal (UCI: 13, BCP: 13, ABCD: 4). Generally, scores across networks become more negative over time, indicating that amygdala connectivity to other regions results in better regulation as children get older. This was not the case for all networks as amygdala connectivity to the cingulo-parietal network was consistently indicative of higher emotion dysregulation. These transitions are denoted in Figure 2 (top panels).

The results yield evidence that changes in network connectivity to the left amygdala are associated with changes in ER across infancy to early adolescence. Further inquiry into the ways in which the Sal and ReT networks differentially modulate ER across childhood is needed.

Emotion and Motivation Other ¹

Early life, Adolescence, Aging ²

fMRI Connectivity and Network Modeling

Task-Independent and Resting-State Analysis

Development

Emotions

FUNCTIONAL MRI

Modeling

PEDIATRIC

Sub-Cortical

Other - emotion regulation; functional network connectivity