title: Prefrontal vulnerabilities and whole brain connectivity in aging and depression.
abstract: Studies exploring the underpinnings of age-related neurodegeneration suggest fronto-limbic alterations that are increasingly vulnerable in the presence of disease including late life depression. Less work has assessed the impact of this specific vulnerability on widespread brain circuitry. Seventy-nine older adults (healthy controls=45; late life depression=34) completed translational tasks shown in non-human primates to rely on fronto-limbic networks involving dorsolateral (Self-Ordered Pointing Task) or orbitofrontal (Object Alternation Task) cortices. A sub-sample of participants also completed diffusion tensor imaging for white matter tract quantification (uncinate and cingulum bundle; n=58) and whole brain tract-based spatial statistics (n=62). Despite task associations to specific white matter tracts across both groups, only healthy controls demonstrated significant correlations between widespread tract integrity and cognition. Thus, increasing Object Alternation Task errors were associated with decreasing fractional anisotropy in the uncinate in late life depression; however, only in healthy controls was the uncinate incorporated into a larger network of white matter vulnerability associating fractional anisotropy with Object Alternation Task errors using whole brain tract-based spatial statistics. It appears that the whole brain impact of specific fronto-limbic vulnerabilities in aging may be eclipsed in the presence of disease-specific neuropathology like that seen in late life depression.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, 1601W Taylor St, MC912, Chicago, IL 60601, USA. mlamar@psych.uic.edu
authors.forename: Melissa
authors.initials: M
authors.lastname: Lamar
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Charlton
authors.forename: Olusola
authors.initials: O
authors.lastname: Ajilore
authors.forename: Aifeng
authors.initials: A
authors.lastname: Zhang
authors.forename: Shaolin
authors.initials: S
authors.lastname: Yang
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Barrick
authors.forename: Emma
authors.initials: E
authors.lastname: Rhodes
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000704:Analysis of Variance; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003863:Depression / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000473:pathology*