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Graph theory analysis reveals how sickle cell disease impacts neural networks of patients with more severe disease.

ABSTRACT: Sickle cell disease (SCD) is a hereditary blood disorder associated with many life-threatening comorbidities including cerebral stroke and chronic pain. The long-term effects of this disease may therefore affect the global brain network which is not clearly understood. We performed graph theory analysis of functional networks using non-invasive fMRI and high resolution EEG on thirty-one SCD patients and sixteen healthy controls. Resting state data were analyzed to determine differences between controls and patients with less severe and more severe sickle cell related pain. fMRI results showed that patients with higher pain severity had lower clustering coefficients and local efficiency. The neural network of the more severe patient group behaved like a random network when performing a targeted attack network analysis. EEG results showed the beta1 band had similar results to fMRI resting state data. Our data show that SCD affects the brain on a global level and that graph theory analysis can differentiate between patients with different levels of pain severity.

SUBMITTER: Case M

PROVIDER: S-EPMC6411610 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Graph theory analysis reveals how sickle cell disease impacts neural networks of patients with more severe disease.

Case Michelle M Shirinpour Sina S Vijayakumar Vishal V Zhang Huishi H Datta Yvonne Y Nelson Stephen S Pergami Paola P Darbari Deepika S DS Gupta Kalpna K He Bin B

NeuroImage. Clinical 20181114

Sickle cell disease (SCD) is a hereditary blood disorder associated with many life-threatening comorbidities including cerebral stroke and chronic pain. The long-term effects of this disease may therefore affect the global brain network which is not clearly understood. We performed graph theory analysis of functional networks using non-invasive fMRI and high resolution EEG on thirty-one SCD patients and sixteen healthy controls. Resting state data were analyzed to determine differences between c ...[more]

PMID: 30477765

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Project description:In accordance with the physiological networks that underlie it, human cognition is characterized by both the segregation and interdependence of a number of cognitive domains. Cognition itself, therefore, can be conceptualized as a network of functions. A network approach to cognition has previously revealed topological differences in cognitive profiles between healthy and disease populations. The present study, therefore, used graph theory to determine variation in cognitive profiles across healthy aging and cognitive impairment. A comprehensive neuropsychological test battery was administered to 415 participants. This included three groups of healthy adults aged 18-39 (n = 75), 40-64 (n = 75), and 65 and over (n = 70) and three patient groups with either amnestic (n = 75) or non-amnestic (n = 60) mild cognitive impairment or Alzheimer's type dementia (n = 60). For each group, cognitive networks were created reflective of test-to-test covariance, in which nodes represented cognitive tests and edges reflected statistical inter-nodal significance (p < 0.05). Network metrics were derived using the Brain Connectivity Toolbox. Network-wide clustering, local efficiency and global efficiency of nodes showed linear differences across the stages of aging, being significantly higher among older adults when compared with younger groups. Among patients, these metrics were significantly higher again when compared with healthy older controls. Conversely, average betweenness centralities were highest in middle-aged participants and lower among older adults and patients. In particular, compared with controls, patients demonstrated a distinct lack of centrality in the domains of semantic processing and abstract reasoning. Network composition in the amnestic mild cognitive impairment group was similar to the network of Alzheimer's dementia patients. Using graph theoretical methods, this study demonstrates that the composition of cognitive networks may be measurably altered by the aging process and differentially impacted by pathological cognitive impairment. Network alterations characteristic of Alzheimer's disease in particular may occur early and be distinct from alterations associated with differing types of cognitive impairment. A shift in centrality between domains may be particularly relevant in identifying cognitive profiles indicative of underlying disease. Such techniques may contribute to the future development of more sophisticated diagnostic tools for neurodegenerative disease.

Project description:BackgroundAlthough a large body of knowledge about both brain structure and function has been gathered over the last decades, we still have a poor understanding of their exact relationship. Graph theory provides a method to study the relation between network structure and function, and its application to neuroscientific data is an emerging research field. We investigated topological changes in large-scale functional brain networks in patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) by means of graph theoretical analysis of resting-state EEG recordings. EEGs of 20 patients with mild to moderate AD, 15 FTLD patients, and 23 non-demented individuals were recorded in an eyes-closed resting-state. The synchronization likelihood (SL), a measure of functional connectivity, was calculated for each sensor pair in 0.5-4 Hz, 4-8 Hz, 8-10 Hz, 10-13 Hz, 13-30 Hz and 30-45 Hz frequency bands. The resulting connectivity matrices were converted to unweighted graphs, whose structure was characterized with several measures: mean clustering coefficient (local connectivity), characteristic path length (global connectivity) and degree correlation (network 'assortativity'). All results were normalized for network size and compared with random control networks.ResultsIn AD, the clustering coefficient decreased in the lower alpha and beta bands (p < 0.001), and the characteristic path length decreased in the lower alpha and gamma bands (p < 0.05) compared to controls. In FTLD no significant differences with controls were found in these measures. The degree correlation decreased in both alpha bands in AD compared to controls (p < 0.05), but increased in the FTLD lower alpha band compared with controls (p < 0.01).ConclusionWith decreasing local and global connectivity parameters, the large-scale functional brain network organization in AD deviates from the optimal 'small-world' network structure towards a more 'random' type. This is associated with less efficient information exchange between brain areas, supporting the disconnection hypothesis of AD. Surprisingly, FTLD patients show changes in the opposite direction, towards a (perhaps excessively) more 'ordered' network structure, possibly reflecting a different underlying pathophysiological process.

Dataset Information

Graph theory analysis reveals how sickle cell disease impacts neural networks of patients with more severe disease.

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Graph theory analysis reveals how sickle cell disease impacts neural networks of patients with more severe disease.

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