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RESEARCH ARTICLE
Combined T1-weighted MRI and diffusion MRI tractography of paraventricular, locus coeruleus, and dorsal vagal complex connectivity in brainstem-hypothalamic nuclei
Nikos Makris1,2,3,4,5,6,7†* ,
Poliana Hartung Toppa6† ,
Richard J. Rushmore1,5,6† ,
Kayley Haggerty6 ,
George Papadimitriou6 ,
Stuart Tobet7,8 ,
Yogesh Rathi1,6 ,
Marek Kubicki1,6,7,9 ,
Edward Yeterian6,10 ,
Agustin Castañeyra-Perdomo3 ,
Jill M. Goldstein2,7,11
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1
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115,
United States
2
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114,
United States
3
Anatomy and Physiology Area, Department of Basic Medical Sciences, Faculty of Health Sciences, University of La Laguna, San Cristobal de La Laguna 38000, Tenerife,
Spain
4
Department of Cognitive, Social and Organizational Psychology, Faculty of Health Sciences, University of La Laguna, University Institute of Neuroscience, San Cristobal de La Laguna 38000, Tenerife,
Spain
5
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118,
United States
6
Center for Morphometric Analysis, Department of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129,
United States
7
Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114,
United States
8
Department of Biomedical Sciences, School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523,
United States
9
Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115,
United States
10
Department of Psychology, Colby College, Waterville, Maine 04901,
United States
11
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114,
United States
JBM 2024 , 11(4), e99010036;
https://doi.org/10.14440/jbm.2024.0043
Submitted: 24 July 2024 | Revised: 7 September 2024 | Accepted: 8 October 2024 | Published: 22 November 2024
© 2024 by the Journal of Biological Methods published by POL Scientific. Licensee POL Scientific, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract
Background: Current multimodal neuroimaging plays a critical role in studying clinical conditions such as cardiovascular disease, major depression, and other disorders related to chronic stress. These conditions involve the brainstem-hypothalamic network, specifically the locus coeruleus (LC), dorsal vagal complex (DVC), and paraventricular nucleus (PVN) of the hypothalamus, collectively referred to as the “DVC-LC-PVN circuitry.” This circuitry is strongly associated with the norepinephrine (NE) and epinephrine (E) neurotransmitter systems, which are implicated in the regulation of key autonomic functions, such as cardiovascular and respiratory control, stress response, and cognitive and emotional behaviors. Objectives: To develop a methodology for delineating the DVC-LC-PVN circuitry in the human brain using multimodal neuroimaging. Methods: We combined structural T1-weighted morphometric magnetic resonance imaging (MRI) and diffusion MRI-based tractography to map the DVC-LC-PVN circuitry in the human brain. This methodology was applied to a pilot sample of brain datasets from five healthy adult subjects obtained from the publicly available Human Connectome Project repository and to one post-mortem human dataset. Results: The DVC-LC-PVN circuitry was delineated in vivo in five human subjects and one ultra-high resolution post-mortem dataset, allowing for refined anatomical observations. Conclusion: NE and E neurotransmitter systems engender substantial interest in both basic and clinical neuroscience due to their roles in the regulation of key autonomic functions, such as cardiovascular and respiratory control, stress responses, and cognitive and emotional behaviors. As demonstrated in this study, multimodal neuroimaging techniques provide a valuable approach for mapping small brainstem and hypothalamic structures and complex circuitries such as the DVC-LC-PVN circuitry.
Keywords
Diffusion magnetic resonance imaging
Dorsal vagal complex
Locus coeruleus
Major depressive disorder
Paraventricular nucleus of the hypothalamus
Funding
We would like to acknowledge the following grants for their support: R01MH112748 (MRK, NM, RJR), R01AG042512 (MRK, NM), K24MH116366, R01MH132610, R01MH125860 (NM), R21NS136960 (RJR, NM), and R01NS125307 (RJR, NM). In addition, work on this manuscript was supported by ORWH-NIMH U54 MH118919 (JMG & SAT, mPIs).
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Conflict of interest
Jill M. Goldstein serves on the scientific advisory board of, and holds equity interest in, Cala Health (a neuromodulation company). Jill M. Goldstein’s interests are managed by MGH and MassGeneral Brigham HealthCare in accordance with their conflict of interest policies. However, the work presented in this study was conducted before this relationship, and thus no conflict of interest exists. The other authors declare they have no competing interest.