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NA-MIC Project Weeks

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Long-COVID and the Brain White Matter

Key Investigators

Presenter location: In-person

Project Description

About 10% of COVID-19 survivors experience long-lasting symptoms known as long-COVID. The debilitating symptoms of PASC impact patient’s health-related quality of life, earnings, caretaking activities for loved ones, and healthcare costs. There is no proven cure for PASC. Amongst the variable sequelae of long-COVID, the neuropsychiatric subtype of long-COVID (neuro-long-COVID) is characterized by fatigue, cognitive impairments, and pro-inflammatory cytokines. Our research project aims to understand how changes in the brain, specifically the white matter, contribute to the symptoms of the neuropsychiatric subtype of long-COVID.

We are particularly interested in the brain white matter fiber system that we term the dorsal vagal complex-corticolimbic fiber system (DVC-CLFS; Kikinis et al., in press). This fiber system interconnects cortical, paralimbic, limbic, and autonomic brain regions. It integrates them with bodily organs via the brainstem and the vagal nerve. The DVC-CLFS underlies brain-immune interactions and involves several centers in the brainstem. The principal fiber tract in the DVC-CFLS is the medial forebrain bundle (MFB).

While we have previously reconstructed the MFB, our new approach allows us to rebuild the streamlines reaching the brainstem. Using the Harvard Oxford Atlas (HOA, Rushmore et al., 2020), we will use whole brain tractography from 10 patients with long-COVID to select the Medial Forebrain Bundle (MFB) at its entire extension.

As part of the project, we will demonstrate the method reconstructing new fiber tracts using 3dSlicer. We will offer tutorial of 3DSlicer of segmentation, reconstruction of brain white matter streamlines to new users.


  1. To test and apply a semi-automated approach to delineate a fiber tracts that reach the brain stem. Tractography in the brain stem is challenging as most fibers run parallel and very close to each other. Additionally, the nuclei of the brainstem from which tracts originate and are difficult to visualize.
  2. Give a tutorial of 3DSlicer segmentation and reconstruction of brain white matter streamlines, specially those connecting the thalamus, cerebellum, pons and frontal cortex.

Approach and Plan

  1. We will use diffusion and structural MRI, specifically whole brain tractography and T1 images, from 10 patients with long-COVID to select the Medial Forebrain Bundle (MFB) at its entire extension to the brainstem.

Progress and Next Steps

  1. We were able to reconstruct the MFB of eight cases. 1st picture.
  2. We successfully taught how to use 3DSlicer segmentation and tractography settings. 2nd picture.


Screenshot 2024-02-01 at 3 40 38 PM tracts

No response

Background and References