title: Interferon-α acutely impairs whole-brain functional connectivity network architecture - A preliminary study.
abstract: Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis C infection. Though clinically effective, IFN-α rapidly impairs mood, motivation and cognition, effects that can appear indistinguishable from major depression and provide powerful empirical support for the inflammation theory of depression. Though inflammation has been shown to modulate activity within discrete brain regions, how it affects distributed information processing and the architecture of whole brain functional connectivity networks have not previously been investigated. Here we use a graph theoretic analysis of resting state functional magnetic resonance imaging (rfMRI) to investigate acute effects of systemic interferon-alpha (IFN-α) on whole brain functional connectivity architecture and its relationship to IFN-α-induced mood change. Twenty-two patients with Hepatitis-C infection, initiating IFN-α-based therapy were scanned at baseline and 4h after their first IFN-α dose. The whole brain network was parcellated into 110 cortical and sub-cortical nodes based on the Oxford-Harvard Atlas and effects assessed on higher-level graph metrics, including node degree, betweenness centrality, global and local efficiency. IFN-α was associated with a significant reduction in global network connectivity (node degree) (p=0.033) and efficiency (p=0.013), indicating a global reduction of information transfer among the nodes forming the whole brain network. Effects were similar for highly connected (hub) and non-hub nodes, with no effect on betweenness centrality (p>0.1). At a local level, we identified regions with reduced efficiency of information exchange and a sub-network with decreased functional connectivity after IFN-α. Changes in local and particularly global functional connectivity correlated with associated changes in mood measured on the Profile of Mood States (POMS) questionnaire. IFN-α rapidly induced a profound shift in whole brain network structure, impairing global functional connectivity and the efficiency of parallel information exchange. Correlations with multiple indices of mood change support a role for global changes in brain functional connectivity architecture in coordinated behavioral responses to IFN-α.
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy; IRCCS, Fondazione don Carlo Gnocchi, Milan, Italy; Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, UK.
authors.forename: Ottavia
authors.initials: O
authors.lastname: Dipasquale
authors.affiliation: Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, UK.
authors.forename: Ella A
authors.initials: EA
authors.lastname: Cooper
authors.affiliation: Department of Gastroenterology, Brighton & Sussex University Hospitals, Brighton, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Tibble
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK; Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
authors.affiliation: IRCCS, Fondazione don Carlo Gnocchi, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baglio
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Baselli
authors.affiliation: Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, UK; Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
authors.affiliation: Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, UK; Sackler Centre for Consciousness Science, University of Sussex, Falmer, UK; Sussex Partnership NHS Foundation Trust, Brighton, UK. Electronic address: n.harrison@bsms.ac.uk.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Harrison
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D016898:Interferon-alpha
keywords: Brain network; Cytokine; Functional connectivity; Graph theory; Inflammation; Interferon-α; Resting state fMRI