Although not surviving correction for multiple comparisons h

Although not surviving correction for multiple comparisons, high levels of both guilt and shame-proneness were associated with attenuated dmPFC cortical thinning with age. The involvement of the dmPFC in shame is consistent with hypotheses and with previous fMRI study findings (Roth et al., 2014). The role of dmPFC development in both guilt and shame may reflect maturation of other-relevant social-cognitive processes like perspective-taking, which have been ascribed to functioning of this region (Bzdok et al., 2013). High levels of shame-proneness were also associated with attenuated PCC and precuneus thickness with age in males, which might suggest a gender-specific association with shame-proneness and development of self-referential processing (Harrison et al., 2008). Given that these results did not survive correction for multiple comparisons, their interpretation warrants caution and replication in future work. Further, our findings suggest that for some AZD1152 regions, measures of developmental change may be more sensitive to, or may reveal more complex associations with, guilt- and shame-proneness than do measures of absolute brain structure. Our findings highlight the fact that cross-sectional studies that include adolescents and young adults spanning wide age ranges may produce anomalous findings if they do not consider the marked development of the brain during this period. While we have provided evidence for the importance of brain development in understanding the propensity to experience guilt and shame, an important limitation of this work is that it is not longitudinal, and thus, we can only make inferences about developmental processes based on age differences. Future longitudinal work is needed in order to make inferences about intra-individual change. Questionnaire measures of guilt- and shame-proneness were collected on average 9 months after MRI scans, however, these measures are designed to assess stable traits, and time between scan and questionnaire completion was not significantly correlated with guilt- or shame-proneness or any ROI measure (all p\'s>0.23), suggesting that this time difference did not introduce any measureable bias. Non-interpersonal types of guilt (e.g., existential guilt, societal guilt) were not investigated and thus, we cannot comment on neurodevelopmental correlates of guilt more broadly. While results for shame were found to be independent of depressive symptoms, we did not investigate other factors (e.g., temperamental shyness or inhibition) that may better explain the associations between shame and brain structure. Finally, the study may have been under-powered to see significant effects in some hypothesized ROIs. Further, exclusion of individuals with lifetime psychiatric disorder likely reduced variance and hence power. It is of note that most of the effects identified (corrected and uncorrected) can be classified as approximately medium in size (Cohen, 1992). Further research with larger, and more representative sample sizes is warranted.
Acknowledgments This work was supported by a National Health and Medical Research Council of Australia (NHMRC) Project Grant to BJH (ID: 1064643). BJH was supported by a NHMRC Clinical Career Development Fellowship (ID: 628509). SW was supported by a NHMRC Biomedical Career Development Fellowship (ID: 1007716). We thank Dr. Rebecca Kerestes and Ms Katerina Stephanou for their assistance with data collection. We also thank staff from the Sunshine Hospital Medical Imaging Department (Western Health, Melbourne) for their contribution to Helper virus work.
Introduction The hippocampus is critical for episodic memory in adults (e.g., Aggleton and Brown, 2006; Cabeza and Nyberg, 2000; Davachi et al., 2003; Eichenbaum et al., 2007; Ranganath et al., 2004; Scoville and Milner, 1957; Yonelinas et al., 2005; see Spaniol et al., 2009 for review). Developmental changes in hippocampal structure and function have been shown to be related to improvement in episodic memory in school-aged children and adolescents (e.g., DeMaster et al., 2014; DeMaster and Ghetti, 2012; Ghetti et al., 2010; Ofen et al., 2007; Østby et al., 2012; see Ghetti and Bunge, 2012 for review). Overall, these studies suggest positive correlations exist between hippocampal volume and delayed recall and that changes in hippocampal function (as measured by task-based fMRI) contribute to age-related improvements in episodic memory. However, relatively little is known about how the hippocampus is related to memory development earlier in life. This gap is particularly unfortunate since behavioral studies have consistently identified early childhood (4–6 years) as a time of rapid improvement in episodic memory (e.g.,. Bauer et al., 2012; Drummey and Newcombe, 2002; Sluzenski et al., 2006; Riggins, 2014). Theoretical arguments have been made proposing how developmental changes in the hippocampus may be related to the development of episodic memory ability during early childhood (e.g., Jabès and Nelson, 2015; Lavenex and Lavenex, 2013; Riggins, 2012; Serres, 2001), however, this association has not been empirically examined in human children. This gap is likely due to the multiple challenges associated with acquiring functional neuroimaging measures in young children. To overcome these challenges and address this gap in the literature, the present research examined relations between resting-state functional connectivity and behavioral measures of episodic memory ability assessed outside the scanner in 4- and 6-year-old children.