Fig. 6.

Brainstem region functional connectivity for high-risk subjects (HR) vs age- and demographically matched healthy comparison subjects (HCS). Given the somewhat unexpected amygdala-brainstem connectivity finding, driven by the HR group, we compared connectivity patterns for the identified brainstem region between HR subjects and a subset of age- and demographically matched HCS. This was especially important given concerns that this finding may be related to brain maturation (rather than a risk factor for developing schizophrenia or psychiatric illness more broadly). This follow-up analysis was also important to better understand other possible circuits involved in elevated amygdala-brainstem connectivity patterns found for the HR group. Therefore, we identified a subset of HCS matched to the HR group across all demographic variables, but most importantly age (mean = 19.95, SD = 4.58). (a and b) We computed an independent samples t-test between the HR group and the age-matched HCS using the identified brainstem region as a seed. Type I error corrected results revealed elevated amygdala connectivity in the HR group, given that this is a partially circular analysis (red arrows). However, the analysis also revealed reduced connectivity between the brainstem region and frontoparietal cortical regions for HR subjects relative to age-matched HCS. This analysis is partially circular and should be interpreted as qualitative to better understand the source of the amygdala-brainstem connectivity alterations in the HR group. That is, we identified the brainstem region with the between-group F-test (figure 2), which we used here to compare HR subjects relative to a specific subgroup of age-matched controls. Independence concerns notwithstanding, this post hoc analysis revealed prefrontal clusters that may contribute to altered amygdala-brainstem coupling pattern identified for the HR group. Perhaps most importantly, this age-matched follow-up analysis provides a further validity check, showing that age alone did not drive the reported amygdala-brainstem effects in the HR group.