Microstructural properties within the amygdala and affiliated white matter tracts across adolescence
The amygdala is a heterogenous set of nuclei with widespread cortical connections that continues to develop postnatally with vital implications for emotional regulation. Using high-resolution anatomical and multi-shell diffusion MRI in conjunction with novel amygdala segmentation, cutting-edge tractography, and Neurite Orientation Dispersion and Density (NODDI) methods, the goal of the current study was to characterize age associations with microstructural properties of amygdala subnuclei and amygdala-related white matter connections across adolescence (N = 61, 26 males; ages of 8–22 years). We found age-related increases in the Neurite Density Index (NDI) in the lateral nucleus (LA), dorsal and intermediate divisions of the basolateral nucleus (BLDI), and ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL). Additionally, there were age-related increases in the NDI of the anterior commissure, ventral amygdalofugal pathway, cingulum, and uncinate fasciculus, with the strongest age associations in the frontal and temporal regions of these white matter tracts. This is the first study to utilize NODDI to show neurite density of basolateral amygdala subnuclei to relate to age across adolescence. Moreover, age-related differences were also notable in white matter microstructural properties along the anterior commissure and ventral amydalofugal tracts, suggesting increased bilateral amygdalae to diencephalon structural connectivity. As these basolateral regions and the ventral amygdalofugal pathways have been involved in associative emotional conditioning, future research is needed to determine if age-related and/or individual differences in the development of these microstructural properties link to socio-emotional functioning and/or risk for psychopathology.
© 2021 The Authors. Published by Elsevier Under a Creative Commons license - Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Received 27 April 2021, Revised 16 July 2021, Accepted 19 August 2021, Available online 24 August 2021. The authors thank all participating individuals and families in these studies. In addition, we would like to acknowledge Dr. Mimi Kim, Norma Martinez, Heather Ross, Christina Koppin, Michelle Canales, Kimberly Felix, Adam Mezher, and Eva Gabor for assisting with participant recruitment and data collection as part of various studies that contributed data to this project. Computation for the work described in this paper was supported by the University of Southern California's Center for High-Performance Computing (hpcc.usc.edu). Financial support was provided by the National Institutes of Health under award numbers: K01 MH1087610, R03 HD090308, the Neuroimaging Core of a Conte Center grant (5P50MH094258), P41EB015922, and the Predoctoral Training Grant in Environmental Genomics (T32ES013678); the Diabetes & Obesity Research Institute (DORI) with funding from the Stewart Clifton Endowment; and the Southern California Clinical and Translational Science Institute (SC CTSI) Pilot Funding Program grant UL1TR001855. The funding sources had no involvement in study design; data collection, analysis, and interpretation; writing the report; or the decision to submit the article for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the DORI or the Stewart Clifton Endowment. CRediT authorship contribution statement. Anisa Azad: Conceptualization, Formal analysis, Writing – original draft, Validation, Visualization. Ryan P. Cabeen: Methodology, Visualization, Writing – review & editing. Farshid Sepehrband: Methodology, Writing – review & editing. Robert Kim: Data curation, Writing – review & editing. Claire E. Campbell: Data curation, Methodology, Writing – original draft. Kirsten Lynch: Methodology, Writing – review & editing. J. Michael Tyszka: Methodology, Writing – review & editing. Megan M. Herting: Funding acquisition, Conceptualization, Investigation, Methodology, Supervision, Project administration, Writing – original draft. Declaration of Competing Interest: None. Data availability statement: Due to the nature of the study, the data are not publicly available as participants of this study did not agree for their data to be shared publicly. The data that support the findings of this study are available on request from the corresponding author, MMH, but will require a formal sharing agreement.
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