title: Are Structural Changes Induced by Lithium in the HIV Brain Accompanied by Changes in Functional Connectivity?
abstract: Lithium therapy has been shown to affect imaging measures of brain function and microstructure in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. The aim of this proof-of-concept study was to explore whether changes in brain microstructure also entail changes in functional connectivity. Functional MRI data of seven cognitively impaired HIV infected individuals enrolled in an open-label lithium study were included in the connectivity analysis. Seven regions of interest (ROI) were defined based on previously observed lithium induced microstructural changes measured by Diffusion Tensor Imaging. Generalized partial directed coherence (gPDC), based on time-variant multivariate autoregressive models, was used to quantify the degree of connectivity between the selected ROIs. Statistical analyses using a linear mixed model showed significant differences in the average node strength between pre and post lithium therapy conditions. Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity. Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention. Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks.
authors.affiliation: Department of Imaging Sciences, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Madalina E
authors.initials: ME
authors.lastname: Tivarus
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Pester
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehmann
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Imaging Sciences, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Leistritz
authors.affiliation: Department of Imaging Sciences, University of Rochester Medical Center, Rochester, New York, United States of America; Department of Neurology, University of Rochester Medical Center, Rochester New York, United States of America.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D063132:Connectome; D056324:Diffusion Tensor Imaging; D006801:Humans; D016651:Lithium Carbonate / Q000494:pharmacology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008570:Memory, Short-Term; D008959:Models, Neurological; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018697:Nootropic Agents; D016651:Lithium Carbonate