Sorg, C. et al. Selective changes of resting-state networks in individuals at risk for Alzheimer's disease. Proc. Natl Acad. Sci. USA 104, 18760-18765

Department of Psychiatry, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2007; 104(47):18760-5. DOI: 10.1073/pnas.0708803104
Source: PubMed


Alzheimer's disease (AD) is a neurodegenerative disorder that prominently affects cerebral connectivity. Assessing the functional connectivity at rest, recent functional MRI (fMRI) studies reported on the existence of resting-state networks (RSNs). RSNs are characterized by spatially coherent, spontaneous fluctuations in the blood oxygen level-dependent signal and are made up of regional patterns commonly involved in functions such as sensory, attention, or default mode processing. In AD, the default mode network (DMN) is affected by reduced functional connectivity and atrophy. In this work, we analyzed functional and structural MRI data from healthy elderly (n = 16) and patients with amnestic mild cognitive impairment (aMCI) (n = 24), a syndrome of high risk for developing AD. Two questions were addressed: (i) Are any RSNs altered in aMCI? (ii) Do changes in functional connectivity relate to possible structural changes? Independent component analysis of resting-state fMRI data identified eight spatially consistent RSNs. Only selected areas of the DMN and the executive attention network demonstrated reduced network-related activity in the patient group. Voxel-based morphometry revealed atrophy in both medial temporal lobes (MTL) of the patients. The functional connectivity between both hippocampi in the MTLs and the posterior cingulate of the DMN was present in healthy controls but absent in patients. We conclude that in individuals at risk for AD, a specific subset of RSNs is altered, likely representing effects of ongoing early neurodegeneration. We interpret our finding as a proof of principle, demonstrating that functional brain disorders can be characterized by functional-disconnectivity profiles of RSNs.

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    • "In AD , FC decreased between the right hippocampus and a set of regions including DMN and increased between the left hippocampus and the right lateral PFC . Sorg et al . ( 2007 ) HC , aMCI Resting No task DMN activity showed reductions in aMCI . The FC between both hippocampi and the PCC of the DMN was present in healthy controls but absent in patients ."
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    • "The same is true in the case of depression, where abnormal DMN activity and functional connectivity correlate with depressive rumination and symptom severity (Greicius et al., 2007; Berman et al., 2010; Sheline et al., 2010a). Many studies have now established this relationship between DMN-related abnormalities and psychological symptoms such as depressive rumination (Greicius, 2008; Broyd et al., 2009; Sheline et al., 2009; Fox, 2010; Whitfield-Gabrieli and Ford, 2012), feelings of hopelessness (Grimm et al., 2008), mind wandering (Mason et al., 2007), and poor cognitive performance (Weissman et al., 2006; Sorg et al., 2007; Sheline and Raichle, 2013) further intimating the role of the DMN in mental illness. "
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    • "Nearly all the functional regions highlighted were located directly adjacent to fiber tracts that exhibited high or moderate sensitivity. Most of these regions have been reported to show altered functional connectivity measures in AD or MCI [Buckner et al., 2009; Minati et al., 2014; Sorg et al., 2007; Tijms et al., 2013; Wee et al., 2012]. "
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