Neural systems underlying reward cue processing in early adolescence: The role of puberty and pubertal hormones

Abstract

Affective neuroscience research suggests that maturational changes in reward circuitry during adolescence present opportunities for new learning, but likely also contribute to increases in vulnerability for psychiatric disorders such as depression and substance abuse. Basic research in animal models and human neuroimaging has made progress in understanding the normal development of reward circuitry in adolescence, yet, few functional neuroimaging studies have examined puberty-related influences on the functioning of this circuitry. The goal of this study was to address this gap by examining the extent to which striatal activation and cortico-striatal functional connectivity to cues predicting upcoming rewards would be positively associated with pubertal status and levels of pubertal hormones (dehydroepiandrosterone, testosterone, estradiol). Participants included 79 adolescents (10-13 year olds; 47 girls) varying in pubertal status who performed a novel reward cue processing task during fMRI. Pubertal maturation was assessed using sex-specific standardized composite measures based on Tanner staging (self-report and clinical assessment) and scores from the Pubertal Development Scale. These composite measures were computed to index overall pubertal maturation as well as maturation of the adrenal and gonadal axes separately for boys and girls. Basal levels of circulating pubertal hormones were measured using immunoassays from three samples collected weekly upon awakening across a three-week period. Results indicated greater striatal activation and functional connectivity between nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC) to reward cue (vs. no reward cue) on this task. Also, girls with higher levels of estradiol showed reduced activation in left and right caudate and greater NAcc-putamen connectivity. Girls with higher levels of testosterone showed greater NAcc connectivity with the anterior cingulate cortex and the insula. There were no significant associations in boys. Findings suggest that patterns of activation and connectivity in cortico-striatal regions are associated with reward cue processing, particularly in girls. Longitudinal follow-up neuroimaging studies are needed to fully characterize puberty-specific effects on the development of these neural regions and how such changes may contribute to pathways of risk or resilience in adolescence.

Keywords: Cortico-striatal regions; Pubertal hormones; Puberty; Reward cue processing; Sex differences; fMRI.

Figure 1.

Illustration of the Gopher Reward Processing task.

Figure 2.

Task-related neural activation and functional connectivity. Panel A highlights regional activation to Reward cue>No reward cue in bilateral regions of the nucleus accumbens (NAcc), putamen, and left insula. Voxelwise threshold p<.001, with family-wise correction p<.05 and a cluster threshold of 23 voxels. Panel B highlights functional connectivity to Reward cue>No Reward cue between the NAcc as a seed region [6 mm sphere around the coordinates 12, 8, −6 (right hemisphere) −12, 8, −6 (left hemisphere) (Silverman et al., 2015)] and two regions in rostral anterior cingulate cortex (rACC) [peak coordinates: Left rACC (x, y, z: −4, 30, 0) and Right rACC (x, y, z: 4, 34, −8)]. Voxelwise threshold p<.001, with family-wise correction p<.05 and a cluster threshold of 22 voxels. Statistical maps are overlaid on the skull stripped Colin brain (ch2better.nii). R=right.

Figure 3.

Results from regression analyses with estradiol in girls. A) Statistical map from regression analysis for Reward cue>No reward cue with levels of estradiol (log Empirical Bayes) in girls depicting a significant cluster in right caudate (peak coordinates x=16, y=4, z=20; T=4.14; k=34 voxels). Voxelwise threshold p<.001, with family-wise correction p<.05 and a cluster threshold of 23 voxels. B) Scatterplot illustrating negative association between girls’ level of estradiol (log Empirical Bayes) and neural activation in right caudate. EB = Empirical Bayes.

Figure 4.

Results from gPPI analyses with estradiol in girls. A) Depiction of functional connectivity to Reward cue>No reward cue between nucleus accumbens as a seed region [6 mm sphere around the coordinates x=12, y=8, z=−6 (right hemisphere); x= −12, y=8, z=−6 (left hemisphere) (Silverman et al., 2015)] and the right putamen (peak coordinates x=20, y=10, z=2; T=4.01; k=36 voxels. Voxelwise threshold p<.001, with family-wise correction p<.05 and a cluster threshold of 22 voxels. B) Scatterplot illustrating a positive association between girls’ level of estradiol (log Empirical Bayes) and gPPI eigenvariates extracted from the peak voxel of the cluster of the right putamen. gPPI = generalized psychophysiological interaction; EB = Empirical Bayes.

Figure 5.

Results from gPPI analyses with testosterone in girls. A) Depiction of functional connectivity to Reward cue>No reward cue between nucleus accumbens as a seed region [6 mm sphere around the coordinates x=12, y=8, z=−6 (right hemisphere); x= −12, y=8, z=−6 (left hemisphere) (Silverman et al., 2015)] and Ai) the left rACC (peak coordinates: x=−2, y=36, z=24; T=5.22; k=48 voxels) as well as Aii) the right anterior insula (peak coordinates: x=44, y=22, z=−4; T=4.07; k=41 voxels). Voxelwise threshold p<.001, with family-wise correction p<.05 and a cluster threshold of 22 voxels. B) Scatterplot illustrating a positive association between girls’ level of testosterone (log Empirical Bayes) and gPPI eigenvariates extracted from the peak voxel of the cluster of the Bi) left rostral anterior cingulate cortex and the Bii) right anterior insula. gPPI = generalized psychophysiological interaction; NAcc = nucleus accumbens; rACC = rostral anterior cingulate cortex; EB = Empirical Bayes.