title: Intrinsic inter-network brain dysfunction correlates with symptom dimensions in late-life depression.
abstract: Prior studies have demonstrated dysfunctions within the core neurocognitive networks (the executive control [ECN], default mode [DMN] and salience [SN] networks) in late-life depression (LLD). Whether inter-network dysfunctional connectivity is present in LLD, and if such disruptions are associated with core symptom dimensions is unknown. A cross-sectional resting-state functional connectivity magnetic resonance imaging investigation was conducted of LLD (n = 39) and age- and gender-equated healthy comparison (HC) (n = 29) participants. Dual regression independent component analysis approach was used to identify components that represented the ECN, DMN and SN. The intrinsic inter-network connectivity was compared between LLD and HC participants and the relationship of inter-network connectivity abnormalities with dimensional measures was examined. Relative to HC participants, LLD subjects showed decreased inter-network connectivity between the bilateral ECN and default mode subcortical (thalamus, basal ganglia and ventral striatum) networks, and the left ECN and SN insula component; and increased inter-network connections between the left ECN and posterior DMN and salience (dorsal anterior cingulate) network components. Distinct inter-network connectivity abnormalities correlated with depression and anxiety severity, and executive dysfunction in LLD participants. LLD subjects also showed pronounced intra-network connectivity differences within the ECN, whereas fewer but significant DMN and SN disruptions were also detected. Investigating the intrinsic inter-network functional connectivity could provide a mechanistic framework to better understand the neural basis that underlies core symptom dimensions in LLD. Inter-network connectivity measures have the potential to be neuroimaging biomarkers of symptom dimensions comprising LLD, and may assist in developing symptom-specific treatment algorithms.
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, WI, USA; Department of Biophysics, Medical College of Wisconsin, WI, USA. Electronic address: wli@mcw.edu.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Radiology, Medical College of Wisconsin, WI, USA. Electronic address: yangwang@mcw.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, WI, USA. Electronic address: ward@mcw.edu.
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Ward
authors.affiliation: Department of Neurology, Medical College of Wisconsin, WI, USA. Electronic address: pantuono@mcw.edu.
authors.forename: Piero G
authors.initials: PG
authors.lastname: Antuono
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, WI, USA; Department of Biophysics, Medical College of Wisconsin, WI, USA. Electronic address: sjli@mcw.edu.
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, WI, USA. Electronic address: jgoveas@mcw.edu.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Goveas
mesh_terms: D000203:Activities of Daily Living / Q000523:psychology; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology*; D003863:Depression / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology / Q000523:psychology; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric
keywords: Brain networks; ICA; Inter-network; Late-life depression; Resting-state functional connectivity; Symptom dimensions