Single-Subject Grey Matter Graphs in Alzheimer's Disease

Beijing Normal University, China
PLoS ONE (Impact Factor: 3.23). 09/2013; 8(3):e58921. DOI: 10.1371/journal.pone.0058921
Source: PubMed


Coordinated patterns of cortical morphology have been described as structural graphs and previous research has demonstrated that properties of such graphs are altered in Alzheimer's disease (AD). However, it remains unknown how these alterations are related to cognitive deficits in individuals, as such graphs are restricted to group-level analysis. In the present study we investigated this question in single-subject grey matter networks. This new method extracts large-scale structural graphs where nodes represent small cortical regions that are connected by edges when they show statistical similarity. Using this method, unweighted and undirected networks were extracted from T1 weighted structural magnetic resonance imaging scans of 38 AD patients (19 female, average age 72±4 years) and 38 controls (19 females, average age 72±4 years). Group comparisons of standard graph properties were performed after correcting for grey matter volumetric measurements and were correlated to scores of general cognitive functioning. AD networks were characterised by a more random topology as indicated by a decreased small world coefficient (p = 3.53×10(-5)), decreased normalized clustering coefficient (p = 7.25×10(-6)) and decreased normalized path length (p = 1.91×10(-7)). Reduced normalized path length explained significantly (p = 0.004) more variance in measurements of general cognitive decline (32%) in comparison to volumetric measurements (9%). Altered path length of the parahippocampal gyrus, hippocampus, fusiform gyrus and precuneus showed the strongest relationship with cognitive decline. The present results suggest that single-subject grey matter graphs provide a concise quantification of cortical structure that has clinical value, which might be of particular importance for disease prognosis. These findings contribute to a better understanding of structural alterations and cognitive dysfunction in AD.

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Available from: Betty M Tijms,
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    • "For example, areas involved in visual processing grow in a coordinated way (Andrews et al., 1997; Voss and Zatorre, 2015). In Alzheimer's disease (AD), such gray matter networks become disorganized (He et al., 2008; Li et al., 2012; Tijms et al., 2013a; Yao et al., 2010), and these disruptions have been associated with cognitive dysfunction (Tijms et al., 2013a, 2014). This suggests that gray matter networks capture pathologically relevant information. "
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    ABSTRACT: Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (Aβ42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Aβ42 levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal Aβ42 < 550 pg/mL). Degree, clustering coefficient, and path length were computed at whole brain level and for 90 anatomical areas. Associations between continuous Aβ42 CSF levels and single-subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower Aβ42 CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p < 0.05). These results suggest that mostly within the normal spectrum of amyloid, lower Aβ42 levels can be related to gray matter networks disruptions.
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    • "Wee et al. and Dai et al. have expressed similar views [40] [41], which calculate the thickness network via exponential function. These studies of individual structural network construction fail to take into account vertex-based information, which we suppose may arguably represent more detailed information [42] [43]. Also, we hypothesize that the selection of correlation calculation function could significantly affect the connectivity strength. "
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    ABSTRACT: Brain network occupies an important position in representing abnormalities in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Currently, most studies only focused on morphological features of regions of interest without exploring the interregional alterations. In order to investigate the potential discriminative power of a morphological network in AD diagnosis and to provide supportive evidence on the feasibility of an individual structural network study, we propose a novel approach of extracting the correlative features from magnetic resonance imaging, which consists of a two-step approach for constructing an individual thickness network with low computational complexity. Firstly, multi-distance combination is utilized for accurate evaluation of between-region dissimilarity; and then the dissimilarity is transformed to connectivity via calculation of correlation function. An evaluation of the proposed approach has been conducted with 189 normal controls, 198 MCI subjects, and 163 AD patients using machine learning techniques. Results show that the observed correlative feature suggests significant promotion in classification performance compared with cortical thickness, with accuracy of 89.88% and area of 0.9588 under receiver operating characteristic curve. We further improved the performance by integrating both thickness and apolipoprotein E ɛ4 allele information with correlative features. New achieved accuracies are 92.11% and 79.37% in separating AD from normal controls and AD converters from non-converters, respectively. Differences between using diverse distance measurements and various correlation transformation functions are also discussed to explore an optimal way for network establishment.
    Journal of Alzheimer's disease: JAD 10/2015; 48(4). DOI:10.3233/JAD-150311 · 4.15 Impact Factor
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    • "nto the data . We have calibrated our data with the use of a phantom , but the possibility that there was still some noise left in the images cannot be fully dismissed . At this point an unresolved issue in graph theory is how to best compare networks of different sizes ( Fornito et al . , 2010 ; Hayasaka and Laurienti , 2010 ; Li et al . , 2011 ; Tijms et al . , 2013 ; van Wijk et al . , 2010 ; Zalesky et al . , 2010b ) . We have analysed grey matter graphs in native space segmentations in order to preserve inter - individual variability , since earlier studies suggest that such inter - individual differences in cortical shape have functional relevance ( Bohbot et al . , 2007 ; Mechelli et al . , 20"
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    ABSTRACT: Grey matter brain networks are disrupted in schizophrenia, but it is still unclear at which point during the development of the illness these disruptions arise and whether these can be associated with behavioural predictors of schizophrenia. We investigated if single-subject grey matter networks were disrupted in a sample of people at familial risk of schizophrenia. Single-subject grey matter networks were extracted from structural MRI scans of 144 high risk subjects, 32 recent-onset patients and 36 healthy controls. The following network properties were calculated: size, connectivity density, degree, path length, clustering coefficient, betweenness centrality and small world properties. People at risk of schizophrenia showed decreased path length and clustering in mostly prefrontal and temporal areas. Within the high risk sample, the path length of the posterior cingulate cortex and the betweenness centrality of the left inferior frontal operculum explained 81% of the variance in schizotypal cognitions, which was previously shown to be the strongest behavioural predictor of schizophrenia in the study. In contrast, local grey matter volume measurements explained 48% of variance in schizotypy. The present results suggest that single-subject grey matter networks can quantify behaviourally relevant biological alterations in people at increased risk for schizophrenia before disease onset. Copyright © 2015 Elsevier B.V. All rights reserved.
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