title: Default Mode Connectivity in Youth With Perinatally Acquired HIV.
abstract: Youth with perinatally acquired human immunodeficiency virus (PHIV+) survive longer with combination antiretroviral therapy, but remain at risk for poor cognitive outcomes. We evaluated whether markers of HIV disease severity relate to default mode resting-state functional connectivity in PHIV+ youth. We conducted resting-state functional neuroimaging and cognitive testing in a subset of 40 PHIV+ youth recruited from a single study site of the Adolescent Master Protocol study conducted by the Pediatric HIV/AIDS Cohort Study (PHACS) network. Current and past HIV disease severity measures (nadir CD4 lymphocyte percentages and peak HIV RNA plasma levels) were obtained from medical charts. We evaluated associations of both HIV disease severity measures and cognitive functioning with between- and within- default mode network (DMN) connectivity using Analysis of Functional NeuroImaging multiple regression analyses, controlling for multiple comparisons. Of the 40 youth, 31 (mean age = 16.5 years) with minimal motion during scans were included. We observed global alterations in DMN within- and between-network connectivity, with significant associations between disease severity and DMN BOLD correlations. Furthermore, patterns of connectivity with the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) that varied as a function of peak HIV RNA were found to predict processing speed ability. Alterations in within- and between-network DMN connectivity in PHIV+ youth may reflect global reorganization of the DMN; this could lead to compensatory alterations in both the within- and between-connectivity of large-scale networks, which may ultimately relate to known cognitive processing difficulties in PHIV+ youth.
authors.affiliation: From the Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA (MMH, KAU, PG, ERS); Department of Biostatistics, Harvard School of Public Health, Boston, MA (PLW, YH); Feinberg School of Medicine, Northwestern University, Chicago, IL (KM, RY, JC, LW); Department of Neurosciences, Division of Pediatric Neurology, University of California San Diego, La Jolla, CA (SN); Tulane University School of Medicine, New Orleans, LA (RVD); and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA (ERS).
authors.forename: Megan M
authors.initials: MM
authors.lastname: Herting
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Uban
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Prapti
authors.initials: P
authors.lastname: Gautam
authors.forename: Yanling
authors.initials: Y
authors.lastname: Huo
authors.forename: Kathleen
authors.initials: K
authors.lastname: Malee
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: John
authors.initials: J
authors.lastname: Csernansky
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Sharon
authors.initials: S
authors.lastname: Nichols
authors.forename: Russell
authors.initials: R
authors.lastname: Van Dyke
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sowell
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000503:physiopathology*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012367:RNA, Viral / Q000097:blood*; D014888:Wechsler Scales; D055815:Young Adult
chemical_list: D015415:Biomarkers; D012367:RNA, Viral