title: A Winding Road: Alzheimer's Disease Increases Circuitous Functional Connectivity Pathways.
abstract: Neuroimaging has been successful in characterizing the pattern of cerebral atrophy that accompanies the progression of Alzheimer's disease (AD). Examination of functional connectivity, the strength of signal synchronicity between brain regions, has gathered pace as another way of understanding changes to the brain that are associated with AD. It appears to have good sensitivity and detect effects that precede cognitive decline, and thus offers the possibility to understand the neurobiology of the disease in its earliest phases. However, functional connectivity analyzes to date generally consider only the strongest connections, with weaker links ignored. This proof-of-concept study compared patients with mild-to-moderate AD (N = 11) and matched control individuals (N = 12) based on functional connectivities derived from blood-oxygenation level dependent (BOLD) sensitive functional MRI acquired during resting wakefulness. All positive connectivities irrespective of their strength were included. Transitive closures of the resulting connectome were calculated that classified connections as either direct or indirect. Between-group differences in the proportion of indirect paths were observed. In AD, there was broadly increased indirect connectivity across greater spatial distances. Furthermore, the indirect pathways in AD had greater between-subject topological variance than controls. The prevailing characterization of AD as being a disconnection syndrome is refined by the observation that direct links between regions that are impaired are perhaps replaced by an increase in indirect functional pathways that is only detectable through inclusion of connections across the entire range of connection strengths.
authors.affiliation: Department of Psychiatry, University of Cambridge Cambridge, UK ; Cambridge and Peterborough Foundation NHS Trust Cambridge, UK ; MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge Cambridge, UK.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Department of Psychiatry, University of Cambridge Cambridge, UK.
authors.forename: Tiago
authors.initials: T
authors.lastname: Simas
authors.affiliation: Department of Psychiatry, University of Cambridge Cambridge, UK.
authors.forename: Shayanti
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge Cambridge, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Tait
authors.affiliation: Department of Psychiatry, University of Cambridge Cambridge, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge Cambridge, UK ; Wolfson Brain Imaging Centre, University of Cambridge Cambridge, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Williams
authors.affiliation: MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge Cambridge, UK ; Department of Clinical Neurosciences, University of Cambridge Cambridge, UK.
authors.forename: James B
authors.initials: JB
authors.lastname: Rowe
authors.affiliation: Department of Psychiatry, University of Cambridge Cambridge, UK ; Cambridge and Peterborough Foundation NHS Trust Cambridge, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
keywords: Alzheimer disease; connectome; functional connectivity; neuroimaging; semi metricity; transitivity