Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19

Kuaikuai Duan; Enrico Premi; Andrea Pilotto; Viviana Cristillo; Alberto Benussi; Ilenia Libri; Marcello Giunta; H Jeremy Bockholt; Jingyu Liu; Riccardo Campora; Alessandro Pezzini; Roberto Gasparotti; Mauro Magoni; Alessandro Padovani; Vince D Calhoun

doi:10.1016/j.ynstr.2021.100326

Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19

Neurobiol Stress. 2021 May:14:100326. doi: 10.1016/j.ynstr.2021.100326. Epub 2021 Apr 13.

Authors

Kuaikuai Duan^{1

2}, Enrico Premi^{3

4}, Andrea Pilotto⁴, Viviana Cristillo⁴, Alberto Benussi⁴, Ilenia Libri⁴, Marcello Giunta⁴, H Jeremy Bockholt², Jingyu Liu^{2

5}, Riccardo Campora⁶, Alessandro Pezzini⁴, Roberto Gasparotti⁶, Mauro Magoni³, Alessandro Padovani⁴, Vince D Calhoun^{1

2

5

7}

Affiliations

¹ Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, USA.
² Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia Institute of Technology, Georgia State University, Emory University, Atlanta, USA.
³ Stroke Unit, Azienda Socio Sanitaria Territoriale Spedali Civili, Spedali Civili Hospital, Brescia, Italy.
⁴ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Italy.
⁵ Department of Computer Science, Georgia State University, Atlanta, USA.
⁶ Neuroradiology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
⁷ Department of Psychology, Computer Science, Neurosciences, Mathematics & Statistics, Georgia State University, Atlanta, USA.

Abstract

COVID-19, the infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. It dramatically affects people's health and daily life. Neurological complications are increasingly documented for patients with COVID-19. However, the effect of COVID-19 on the brain is less studied, and existing quantitative neuroimaging analyses of COVID-19 were mainly based on the univariate voxel-based morphometry analysis (VBM) that requires corrections for a large number of tests for statistical significance, multivariate approaches that can reduce the number of tests to be corrected have not been applied to study COVID-19 effect on the brain yet. In this study, we leveraged source-based morphometry (SBM) analysis, a multivariate extension of VBM, to identify changes derived from computed tomography scans in covarying gray matter volume patterns underlying COVID-19 in 120 neurological patients (including 58 cases with COVID-19 and 62 patients without COVID-19 matched for age, gender and diseases). SBM identified that lower gray matter volume (GMV) in superior/medial/middle frontal gyri was significantly associated with a higher level of disability (modified Rankin Scale) at both discharge and six months follow-up phases even when controlling for cerebrovascular diseases. GMV in superior/medial/middle frontal gyri was also significantly reduced in patients receiving oxygen therapy compared to patients not receiving oxygen therapy. Patients with fever presented significant GMV reduction in inferior/middle temporal gyri and fusiform gyrus compared to patients without fever. Patients with agitation showed GMV reduction in superior/medial/middle frontal gyri compared to patients without agitation. Patients with COVID-19 showed no significant GMV differences from patients without COVID-19 in any brain region. Results suggest that COVID-19 may affect the frontal-temporal network in a secondary manner through fever or lack of oxygen.

Keywords: COVID-19; Computed tomography; Frontal-temporal network; Gray matter volume; Source-based morphometry.

Grants and funding

RF1 AG063153/AG/NIA NIH HHS/United States