Mapping the Alzheimer’s Brain with Connectomics

State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University Beijing, China.
Frontiers in Psychiatry 01/2011; 2:77. DOI: 10.3389/fpsyt.2011.00077
Source: PubMed


Alzheimer's disease (AD) is the most common form of dementia. As an incurable, progressive, and neurodegenerative disease, it causes cognitive and memory deficits. However, the biological mechanisms underlying the disease are not thoroughly understood. In recent years, non-invasive neuroimaging and neurophysiological techniques [e.g., structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, and EEG/MEG] and graph theory based network analysis have provided a new perspective on structural and functional connectivity patterns of the human brain (i.e., the human connectome) in health and disease. Using these powerful approaches, several recent studies of patients with AD exhibited abnormal topological organization in both global and regional properties of neuronal networks, indicating that AD not only affects specific brain regions, but also alters the structural and functional associations between distinct brain regions. Specifically, disruptive organization in the whole-brain networks in AD is involved in the loss of small-world characters and the re-organization of hub distributions. These aberrant neuronal connectivity patterns were associated with cognitive deficits in patients with AD, even with genetic factors in healthy aging. These studies provide empirical evidence to support the existence of an aberrant connectome of AD. In this review we will summarize recent advances discovered in large-scale brain network studies of AD, mainly focusing on graph theoretical analysis of brain connectivity abnormalities. These studies provide novel insights into the pathophysiological mechanisms of AD and could be helpful in developing imaging biomarkers for disease diagnosis and monitoring.

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Available from: Yong He, Sep 07, 2014
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    • "Full pathologic criteria for AD have been observed post mortem in 25% to 67% of the brains of elderly individuals with no indication of cognitive impairment prior to death [9, 70–72]. Certain AD patients show increased functional connectivity within frontal sectors as well as between frontal, thalamic, and striatal regions, which in turn suggests the presence of compensatory mechanisms aimed at coping with large-scale disconnection [67]. Generally speaking, in AD, variability across individuals in cerebral metabolic patterns is at least partly related to strategies of compensations aiming at optimizing the efficacy of key processes in a context of progressive decimation of resources [66]. "
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    ABSTRACT: The phenomenon of cognitive resilience, that is, the dynamical preservation of normal functions despite neurological disorders, demonstrates that cognition can be highly robust to devastating brain injury. Here, cognitive resilience is considered across a range of neurological conditions. Simple computational models of structure-function relationships are used to discuss hypotheses about the neural mechanisms of resilience. Resilience expresses functional redundancies in brain networks and suggests a process of dynamic rerouting of brain signals. This process is underlined by a global renormalization of effective connectivity, capable of restoring information transfer between spared brain structures via alternate pathways. Local mechanisms of synaptic plasticity mediate the renormalization at the lowest level of implementation, but it is also driven by top-down cognition, with a key role of self-awareness in fostering resilience. The presence of abstraction layers in brain computation and networking is hypothesized to account for the renormalization process. Future research directions and challenges are discussed regarding the understanding and control of resilience based on multimodal neuroimaging and computational neuroscience. The study of resilience will illuminate ways by which the brain can overcome adversity and help inform prevention and treatment strategies. It is relevant to combating the negative neuropsychological impact of aging and fostering cognitive enhancement.
    Full-text · Article · Sep 2014
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    • "In the first category, studies mainly focus on network dysfunction perspective of neurodegenerative diseases using graph theoretical analysis [Buldu et al., 2011; He and Evans, 2010; Xie and He, 2011], to demonstrate the topological differences of the brain networks between patients and NC. While these studies in general support the hypothesis of disconnection syndrome in AD and MCI, they cannot be automatically used to discriminate MCI and AD from NC at individual level [Seeley et al., 2009; Supekar et al., 2008; Wang et al., 2007]. "
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    ABSTRACT: Recently, brain connectivity networks have been used for classification of Alzheimer's disease and mild cognitive impairment (MCI) from normal controls (NC). In typical connectivity-networks-based classification approaches, local measures of connectivity networks are first extracted from each region-of-interest as network features, which are then concatenated into a vector for subsequent feature selection and classification. However, some useful structural information of network, especially global topological information, may be lost in this type of approaches. To address this issue, in this article, we propose a connectivity-networks-based classification framework to identify accurately the MCI patients from NC. The core of the proposed method involves the use of a new graph-kernel-based approach to measure directly the topological similarity between connectivity networks. We evaluate our method on functional connectivity networks of 12 MCI and 25 NC subjects. The experimental results show that our proposed method achieves a classification accuracy of 91.9%, a sensitivity of 100.0%, a balanced accuracy of 94.0%, and an area under receiver operating characteristic curve of 0.94, demonstrating a great potential in MCI classification, based on connectivity networks. Further connectivity analysis indicates that the connectivity of the selected brain regions is different between MCI patients and NC, that is, MCI patients show reduced functional connectivity compared with NC, in line with the findings reported in the existing studies. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Jul 2014 · Human Brain Mapping
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    • "These methods have been used to examine the structural consequences of neurological disorders (Guye et al., 2010; Martin, 2012; Xie and He, 2012) as well as the relationship between structure and function (Honey et al., 2007, 2009; Hagmann et al., 2008). "
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    ABSTRACT: Recent interest in human brain connectivity has led to the application of graph theoretical analysis to human brain structural networks, in particular white matter connectivity inferred from diffusion imaging and fiber tractography. While these methods have been used to study a variety of patient populations, there has been less examination of the reproducibility of these methods. A number of tractography algorithms exist and many of these are known to be sensitive to user-selected parameters. The methods used to derive a connectivity matrix from fiber tractography output may also influence the resulting graph metrics. Here we examine how these algorithm and parameter choices influence the reproducibility of proposed graph metrics on a publicly available test-retest dataset consisting of 21 healthy adults. The dice coefficient is used to examine topological similarity of constant density subgraphs both within and between subjects. Seven graph metrics are examined here: mean clustering coefficient, characteristic path length, largest connected component size, assortativity, global efficiency, local efficiency, and rich club coefficient. The reproducibility of these network summary measures is examined using the intraclass correlation coefficient (ICC). Graph curves are created by treating the graph metrics as functions of a parameter such as graph density. Functional data analysis techniques are used to examine differences in graph measures that result from the choice of fiber tracking algorithm. The graph metrics consistently showed good levels of reproducibility as measured with ICC, with the exception of some instability at low graph density levels. The global and local efficiency measures were the most robust to the choice of fiber tracking algorithm.
    Full-text · Article · May 2014 · Frontiers in Neuroinformatics
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