Anorexia Nervosa: Brain White Matter Correlates of Autonomic Cardiac Dysfunction

Poster No:

388 

Submission Type:

Abstract Submission 

Authors:

Feliberto De La Cruz1, Andy Schumann1, Katrin Rieger1, Jon H. Legarreta2, Yuqian Chen2, Ryan Zurrin2, Tashrif Billah2, Nicholas Kim2, Owen Borders2, Nikos Makris2, Yogesh Rathi2, Marek Kubicki2, Lauren O’Donnell2, Karl-Jürgen Bär1, Zora kikinis2

Institutions:

1Jena University Hospital, Jena, Germany, 2Brigham and Women's Hospital, Harvard Medical School, Boston, MA

First Author:

Feliberto De La Cruz  
Jena University Hospital
Jena, Germany

Co-Author(s):

Andy Schumann  
Jena University Hospital
Jena, Germany
Katrin Rieger  
Jena University Hospital
Jena, Germany
Jon Haitz Legarreta  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Yuqian Chen  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Ryan Zurrin  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Tashrif Billah  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Nicholas Kim  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Owen Borders  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Nikos Makris  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Yogesh Rathi  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Marek Kubicki  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Lauren O’Donnell  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA
Karl-Jürgen Bär  
Jena University Hospital
Jena, Germany
Zora kikinis  
Brigham and Women's Hospital, Harvard Medical School
Boston, MA

Introduction:

In anorexia nervosa, autonomic dysfunction, driven by a parasympathetic–sympathetic imbalance and typically manifested as a lower heart rate, is a common yet frequently overlooked condition. In a recent study, we identified functional alterations within the central autonomic network as key neural correlates of autonomic dysfunction in young women with anorexia nervosa ⁠⁠(de la Cruz et al., 2023)⁠. However, the white matter architecture underlying this functional network and its relationship to autonomic dysfunction remains unexplored. Specifically, no studies have examined the white matter pathway connecting two critical autonomic centers: the ventromedial prefrontal cortex (vmPFC) and the dorsal vagal complex (DVC). This study aims to identify, for the first time, structural changes in the vmPFC-DVC neurocircuitry and investigate their connection to autonomic dysfunction in anorexia nervosa.

Methods:

We recruited twenty-one acute patients with anorexia nervosa and twenty-five healthy controls, matched by age, education- and gender. Each participant underwent two diffusion-weighted MRI scans with opposing phase-encoding directions and parameters: 96 axial slices, 1.5 mm³ voxels, TR/TE = 3318/87 ms, 8 volumes with b=0s/mm2, 16 volumes with b=800s/mm2, 32 volumes with b=1600s/mm2, and 48 volumes with b=2500s/mm2. We preprocessed the diffusion MRI data using the Psychiatry Neuroimaging Laboratory pipeline (Billah & Bouix, 2020)⁠, which included axis alignment, centering, Gibbs ringing removal and eddy current, and head motion correction. Next, we performed whole-brain tractography using a multi-tensor unscented Kalman filter method (Malcolm et al., 2010)⁠⁠. Regions-of-interest were defined for the vmPFC and DVC, with the latter manually delineated by a neuroanatomist. We then calculated fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) within the streamlines connecting the two regions. Finally, we performed statistical analyses to compare these tensor metrics between the anorexia and control groups.
Supporting Image: figWcaption.png
 

Results:

Our analyses revealed significant (pFDR < 0.05) white matter changes in vmPFC-DVC fibers in patients with anorexia nervosa, with increased FA and AD compared to healthy controls (Fig. 1, top). RD did not differ significantly between groups. The FA profile along the vmPFC-DVC fibers revealed heterogeneity, with significant differences localized at the level of the ponto-midbrain junction where the fibers diverge to cross each hemisphere (Fig. 1, bottom). Furthermore, anorexia patients exhibited a greater number of streamlines in this pathway compared to controls.
In the control group, heart rate showed a negative correlation with RD (r=-0.41, p=0.04) and a positive trend with FA (r=0.36, p=0.06), indicating an association between white matter integrity and autonomic regulation. Conversely, no significant associations emerged between physiological indices and diffusion MRI metrics in the anorexia group, suggesting a potential decoupling of structural and functional autonomic processes in these patients.

Conclusions:

This study uncovers key structural alterations in the vmPFC-DVC white matter pathway in anorexia patients, characterized by increased FA and AD and a higher number of streamlines. These changes suggest disrupted autonomic network integrity, potentially contributing to the autonomic dysfunction observed in anorexia nervosa. In controls, correlations between heart rate and tensor metrics emphasize the link between structural connectivity and physiological regulation. The absence of such associations in anorexia nervosa suggests a decoupling of autonomic function from underlying white matter microstructure, which could contribute to the autonomic dysregulation observed in this group. These findings offer valuable insights into the neurobiological basis of anorexia nervosa, paving the way for more targeted interventions aimed at restoring autonomic balance.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1

Modeling and Analysis Methods:

Diffusion MRI Modeling and Analysis 2

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

White Matter Anatomy, Fiber Pathways and Connectivity

Keywords:

Brainstem
Eating Disorders
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Anorexia Nervosa, Autonomic Dysfunction, Dorsal Vagal Complex

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Other

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

Was this research conducted in the United States?

No

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Structural MRI
Diffusion MRI

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

Free Surfer
Other, Please list  -   https://github.com/pnlbwh/luigi-pnlpipe

Provide references using APA citation style.

Billah, T., & Bouix, S. (2020). A Luigi workflow joining individual modules of an MRI processing pipeline. https://doi.org/10.5281/zenodo.3666802

de la Cruz, F., Schumann, A., Suttkus, S., Helbing, N., & Bär, K. (2023). Dynamic changes in the central autonomic network of patients with anorexia nervosa. European Journal of Neuroscience, 57(9), 1597–1610. https://doi.org/10.1111/ejn.15969

Malcolm, J. G., Shenton, M. E., & Rathi, Y. (2010). Filtered multitensor tractography. IEEE Transactions on Medical Imaging, 29(9), 1664–1675. https://doi.org/10.1109/TMI.2010.2048121

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