Poster #60 - Multimodal brain imaging in infant primates predicts the later development of anxious temperament

• In Event: 2-055 - Poster Session 06
  In Poster Session: PS 06 Section - Developmental Psychopathology

Integrative Statement

Anxiety disorders directly impact the lives of nearly 1 in 5 people, accounting for substantial worldwide suffering and disability. Extreme childhood shyness, or anxious temperament (AT), is a major risk factor for the later development of pathological anxiety and comorbid depressive and substance use disorders. Here, we use a nonhuman primate model of AT to understand the neurobiology underlying this early-life risk. Leveraging the same neuroimaging measures routinely used in human studies, we explored the predictive nature of functional and structural brain imaging measures in newborn monkeys on the later expression of AT. Specifically, we collected imaging data from 33 infant rhesus monkeys (~2 weeks of age, 22 female), including deformation-based morphometry (DBM) to quantify brain volume, resting-state fMRI to measure functional connectivity of the central nucleus of the amygdala (Ce), and fluorodeoxyglucose (FDG)-PET to quantify threat-related glucose metabolism. When four months old, the monkeys were tested in the Human Intruder Paradigm to assess threat responsivity and to examine individual differences in AT. All imaging data were preprocessed and aligned to a study-specific template using standard co-registration techniques. Voxelwise multiple regression analyses were conducted to examine the prospective relationship between each imaging modality (DBM, fMRI & FDG-PET) and the AT phenotype, while controlling for variation in each of the other modalities and sex. The resulting 3D statistical maps were thresholded at t = 3.022 (p < 0.005, uncorrected). The preliminary analyses demonstrate that orbitofrontal cortex (OFC) volume, quantified as the LogJacobain determinant of the transformation to standard template space, measured at 2 weeks of age was inversely associated with the expression of AT at 4 months. Functional connectivity between the Ce and the dorsolateral prefrontal cortex (dlPFC) at 2 weeks of age was also inversely associated with the expression of AT at 4 months. Additionally, amygdala glucose metabolism measured at 2-weeks was positively associated with the expression of AT at 4 months. A hierarchical regression was computed examining the extent to which amygdala metabolism, Ce-dlPFC connectivity and OFC volume at 2 weeks of age accounted for similar or non-overlapping variance in AT at 4-months of age. Results demonstrate that these 3 modalities share 14.2% of the variance in AT. Together, approximately 50% of the variance can be explained by the unique and shared components of these measures as they relate to AT (R^2 = 0.533, p = 0.000198). These primate developmental data offer a rare glimpse into the early-life brain dispositions that are associated with the later risk to develop pathological anxiety. The data also address the value of using multimodal imaging measures to predict the development of psychopathology and provide potential neural targets for novel early-life interventions with the hope of preventing life-long disability in at-risk children.

Authors

• Jonathan Oler, University of Wisconsin-Madison
  Presenting Author

• Douglas Dean, University of Wisconsin-Madison
  Non-Presenting Author

• Marissa Riedel, University of Wisconsin - Madison
  Non-Presenting Author

• Eva Fekete, University of Wisconsin-Madison
  Non-Presenting Author

• Victoria Elam, University of Wisconsin - Madison
  Non-Presenting Author

• Brendon Nacewicz, University of Wisconsin-Madison
  Non-Presenting Author

• Patrick Roseboom, University of Wisconsin-Madison
  Non-Presenting Author

• Xiaojue Zhou, University of California, Irvine
  Non-Presenting Author

• Andrew Fox, University of California, Davis
  Non-Presenting Author

• Do Tromp, University of Wisconsin-Madison
  Non-Presenting Author

• Rasmus Birn, University of Wisconsin-Madison
  Non-Presenting Author

• Andrew Alexander, University of Wisconsin-Madison
  Non-Presenting Author

• Richard Davidson, University of Wisconsin-Madison
  Non-Presenting Author

• Ned Kalin, University of Wisconsin-Madison
  Non-Presenting Author