Selective changes of resting-state networks in individuals at risk for Alzheimer's disease

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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Available from: Claus Zimmer, Oct 04, 2015
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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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    ABSTRACT: Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment.
    Frontiers in Human Neuroscience 08/2015; 9:454. DOI:10.3389/fnhum.2015.00454 · 2.99 Impact Factor
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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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    ABSTRACT: Alzheimer's disease (AD) patients exhibit alterations in the functional connectivity between spatially segregated brain regions which may be related to both local gray matter (GM) atrophy as well as a decline in the fiber integrity of the underlying white matter tracts. Machine learning algorithms are able to automatically detect the patterns of the disease in image data, and therefore, constitute a suitable basis for automated image diagnostic systems. The question of which magnetic resonance imaging (MRI) modalities are most useful in a clinical context is as yet unresolved. We examined multimodal MRI data acquired from 28 subjects with clinically probable AD and 25 healthy controls. Specifically, we used fiber tract integrity as measured by diffusion tensor imaging (DTI), GM volume derived from structural MRI, and the graph-theoretical measures 'local clustering coefficient' and 'shortest path length' derived from resting-state functional MRI (rs-fMRI) to evaluate the utility of the three imaging methods in automated multimodal image diagnostics, to assess their individual performance, and the level of concordance between them. We ran the support vector machine (SVM) algorithm and validated the results using leave-one-out cross-validation. For the single imaging modalities, we obtained an area under the curve (AUC) of 80% for rs-fMRI, 87% for DTI, and 86% for GM volume. When it came to the multimodal SVM, we obtained an AUC of 82% using all three modalities, and 89% using only DTI measures and GM volume. Combined multimodal imaging data did not significantly improve classification accuracy compared to the best single measures alone. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 02/2015; 36(6). DOI:10.1002/hbm.22759 · 5.97 Impact Factor
    • "Default Mode Network (DMN), has been the object of particular attention due to its involvement in self-referential processes often affected in clinical conditions (e.g., depression; anxiety) such as evaluating the salience of internal and external cues, remembering the past, and planning the future. The significance of the DMN for contemporary models of mental illness has been empirically supported by findings on alterations of this network associated with different neuropsychiatry disorders (e.g., Buckner et al. 2008; Calhoun et al. 2009; Fox and Raichle 2007; Garrity et al. 2007; Greicius et al. 2007; Greicius et al. 2003; Raichle et al. 2001; Sorg et al. 2007; Whitfield-Gabrieli and Ford 2012). There is an increasing number of studies focused on DMN alterations in a wide range of clinical conditions as well as in normal psychological states with a diversity of methodological approaches: DMN connectivity at rest; transition from rest to externally-oriented tasks; alterations in the level of activity of specific regions of interest of the DMN either at rest or during specific emotional tasks (Berman et al. 2011; Kennedy and Courchesne 2008; Liao et al. 2010; Öngür et al. 2010; Uddin et al. 2008; Zhao et al. 2007; Zhou et al. 2007). "
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