White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling

Abstract In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental...

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Autores principales:	Manoj K. Sarma, Amrita Pal, Margaret A. Keller, Tamara Welikson, Joseph Ventura, David E. Michalik, Karin Nielsen-Saines, Jaime Deville, Andrea Kovacs, Eva Operskalski, Joseph A. Church, Paul M. Macey, Bharat Biswal, M. Albert Thomas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c9addae8db674b8f91bcc9acd8f64955
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spelling	oai:doaj.org-article:c9addae8db674b8f91bcc9acd8f649552021-12-02T14:06:55ZWhite matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling10.1038/s41598-021-82587-52045-2322https://doaj.org/article/c9addae8db674b8f91bcc9acd8f649552021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82587-5https://doaj.org/toc/2045-2322Abstract In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.Manoj K. SarmaAmrita PalMargaret A. KellerTamara WeliksonJoseph VenturaDavid E. MichalikKarin Nielsen-SainesJaime DevilleAndrea KovacsEva OperskalskiJoseph A. ChurchPaul M. MaceyBharat BiswalM. Albert ThomasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manoj K. Sarma Amrita Pal Margaret A. Keller Tamara Welikson Joseph Ventura David E. Michalik Karin Nielsen-Saines Jaime Deville Andrea Kovacs Eva Operskalski Joseph A. Church Paul M. Macey Bharat Biswal M. Albert Thomas White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling
description	Abstract In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.
format	article
author	Manoj K. Sarma Amrita Pal Margaret A. Keller Tamara Welikson Joseph Ventura David E. Michalik Karin Nielsen-Saines Jaime Deville Andrea Kovacs Eva Operskalski Joseph A. Church Paul M. Macey Bharat Biswal M. Albert Thomas
author_facet	Manoj K. Sarma Amrita Pal Margaret A. Keller Tamara Welikson Joseph Ventura David E. Michalik Karin Nielsen-Saines Jaime Deville Andrea Kovacs Eva Operskalski Joseph A. Church Paul M. Macey Bharat Biswal M. Albert Thomas
author_sort	Manoj K. Sarma
title	White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling
title_short	White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling
title_full	White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling
title_fullStr	White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling
title_full_unstemmed	White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling
title_sort	white matter of perinatally hiv infected older youths shows low frequency fluctuations that may reflect glial cycling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c9addae8db674b8f91bcc9acd8f64955
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White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling

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