PMID- 34107770 OWN - NLM STAT- MEDLINE DCOM- 20220519 LR - 20230502 IS - 2158-0022 (Electronic) IS - 2158-0014 (Print) IS - 2158-0014 (Linking) VI - 12 IP - 4 DP - 2022 May TI - Altered White Matter Tracts in the Somatosensory, Salience, Motor, and Default Mode Networks in 7-Year-Old Children Living with Human Immunodeficiency Virus: A Tractographic Analysis. PG - 302-319 LID - 10.1089/brain.2020.0948 [doi] AB - Introduction: Even with the increased access and early initiation of combination antiretroviral therapy, children with perinatally acquired human immunodeficiency virus (CPHIV) continue to demonstrate white matter alterations. Children perinatally HIV-exposed, but uninfected (CHEU) alike show differences in white matter integrity compared with children who are HIV-unexposed and uninfected (CHUU). Objectives: Mapping white matter connections that link gray matter regions that form resting-state (RS) functional networks may demonstrate whether structural and functional connectivity alterations in HIV infection and exposure may be related. We hypothesized reduced structural connectivity in CPHIV within the default mode network (DMN), visual, ventral DMN (vDMN), somatosensory, salience, auditory, motor, executive, basal ganglia, and posterior DMN (pDMN). We also hypothesized that CHEU will have increased structural connectivity compared with CHUU in the vDMN, somatosensory, pDMN, dorsal attention, salience, auditory, motor and basal ganglia. Methods: Study participants were 61 seven-year-old CPHIV and 46 age-matched children who are HIV uninfected (CHU) (19 CHEU). We used diffusion tensor imaging-based tractography to investigate white matter connections that link gray matter regions within RS functional networks. Results: We found altered white matter integrity in the somatosensory, salience, default mode, and motor networks of CPHIV compared with CHU. The superior temporal cortex, superior frontal cortex, and putamen were affected in all four networks and have also been reported to demonstrate morphological alterations in the same cohort. In CHEU, white matter integrity was higher in the visual network, pDMN, and motor network compared with CHUU. Conclusion: Our results suggest that altered white matter integrity may influence gray matter morphology and functional network alterations. Impact statement The long-term effects of human immunodeficiency virus (HIV) and exposure on the developing brain in the combination antiretroviral therapy era are still not well known. We use diffusion tensor imaging-based tractography to explore these effects on white matter connections that link gray matter regions within functional networks. Our findings provide a context for HIV-associated white matter and connectivity abnormalities. FAU - Madzime, Joanah AU - Madzime J AUID- ORCID: 0000-0002-9165-0599 AD - Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa. AD - Neurosciences Institute, University of Cape Town, Cape Town, South Africa. FAU - Holmes, Martha AU - Holmes M AD - Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa. AD - Neurosciences Institute, University of Cape Town, Cape Town, South Africa. FAU - Cotton, Mark F AU - Cotton MF AD - Family Centre for Research with Ubuntu, Department of Pediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa. FAU - Laughton, Barbara AU - Laughton B AD - Family Centre for Research with Ubuntu, Department of Pediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa. FAU - van der Kouwe, Andre J W AU - van der Kouwe AJW AD - Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa. AD - Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts, USA. FAU - Meintjes, Ernesta M AU - Meintjes EM AD - Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa. AD - Neurosciences Institute, University of Cape Town, Cape Town, South Africa. AD - Cape Universities Body Imaging Centre, University of Cape Town, Cape Town, South Africa. FAU - Jankiewicz, Marcin AU - Jankiewicz M AD - Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa. AD - Neurosciences Institute, University of Cape Town, Cape Town, South Africa. AD - Cape Universities Body Imaging Centre, University of Cape Town, Cape Town, South Africa. LA - eng GR - HHSN272200800014C/AI/NIAID NIH HHS/United States GR - R01 HD099846/HD/NICHD NIH HHS/United States GR - R01 DC015984/DC/NIDCD NIH HHS/United States GR - R01 HD071664/HD/NICHD NIH HHS/United States GR - R21 MH096559/MH/NIMH NIH HHS/United States GR - R21 MH108346/MH/NIMH NIH HHS/United States GR - ZIC MH002888/ImNIH/Intramural NIH HHS/United States GR - U19 AI053217/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20210823 PL - United States TA - Brain Connect JT - Brain connectivity JID - 101550313 SB - IM MH - Brain/diagnostic imaging MH - Brain Mapping MH - Child MH - Diffusion Tensor Imaging MH - HIV MH - *HIV Infections/diagnostic imaging MH - Humans MH - Magnetic Resonance Imaging MH - *White Matter/diagnostic imaging PMC - PMC9131360 OTO - NOTNLM OT - HIV OT - brain injuries OT - children OT - diffusion tensor imaging OT - maternal exposure OT - tractography COIS- No competing financial interests exist. EDAT- 2021/06/11 06:00 MHDA- 2022/05/20 06:00 PMCR- 2023/05/01 CRDT- 2021/06/10 05:31 PHST- 2021/06/11 06:00 [pubmed] PHST- 2022/05/20 06:00 [medline] PHST- 2021/06/10 05:31 [entrez] PHST- 2023/05/01 00:00 [pmc-release] AID - 10.1089/brain.2020.0948 [pii] AID - 10.1089/brain.2020.0948 [doi] PST - ppublish SO - Brain Connect. 2022 May;12(4):302-319. doi: 10.1089/brain.2020.0948. Epub 2021 Aug 23.