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Structural connectivity alterations in amyotrophic lateral sclerosis are modulated by the topology of the anatomical brain connectome
Silvia Basaia1, Federica Agosta1, Nilo Riva2, Edoardo G. Spinelli1, Yuri Falzone2, Adriano Chiò3, Andrea Falini4, Giancarlo Comi2, and Massimo Filippi1,2

1Neuroimaging Research Unit, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 2Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, 3ALS Center, ‘Rita Levi Montalcini’ Department of Neuroscience, University of Torino, Torino, Italy, 4Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

Synopsis

In this study, we used graph theory and connectomics to test whether the spatial patterning of structural brain alterations in amyotrophic lateral sclerosis (ALS) is modulated by the topology of the anatomical brain network. In the healthy subject connectome, brain regions of subsequent stages of ALS pathology are shown to be more closely interconnected (shorter topological distance) with the primary motor cortex (ALS epicenter) than regions of more distant stages. Altered structural connectivity was greater between closely connected regions. Axonal connections may influence the spatial spreading of pathology in ALS.

Introduction

Cerebral pathology in amyotrophic lateral sclerosis (ALS) has been long-recognized as widespread, despite the obvious clinical predilection for the motor network. Disease pathology in ALS has been suggested to progress in a regional and sequential pattern that permits recognition of successive pathological disease stages. In this study, we used graph theory and connectomics to test whether the spatial patterning of structural brain alterations in ALS is modulated by the topology of the anatomical brain network.

Methods

58 patients with ALS and 34 healthy controls underwent T1-weighted and diffusion tensor MRI. Graph analysis and connectomics were used to define the “healthy” connectome structure in healthy subjects and assessed global and local topological network properties in ALS patients. Regions of subsequent stages of ALS pathology were defined according to the recently proposed pathological propagation pattern.

Results

ALS patients showed reduced structural local efficiency and nodal strength of the sensorimotor network relative to controls. At the regional network level, ALS patients compared to controls showed structural alterations involving sensorimotor network and connections linking motor to basal ganglia and frontal regions. In the healthy subject connectome, brain regions of subsequent stages of ALS pathology are shown to be more closely interconnected (shorter topological distance) with the primary motor cortex (ALS epicenter) than regions of more distant stages. We also found a correlation between the topological distance between the epicenter and brain nodes of subsequent stages of pathology in healthy subjects and the structural connectivity (fractional anisotropy) between the same regions in ALS patients, such that more closely connected regions in healthy subjects exhibited more severe alterations of structural connectivity in ALS patients. In ALS patients, disease duration correlated significantly with the altered structural connectivity of the pathways that are involved at different stages.

Discussion

In ALS, graph analysis and connectomics represent a powerful approach to detect upper motor neuron degeneration, extra-motor brain changes and network disorganization associated with the disease. Altered structural connectivity was greater between closely connected regions.

Conclusions

Axonal connections may influence the spatial spreading of pathology in ALS.

Acknowledgements

Study supported by the Italian Ministry of Health (grant #RF-2011-02351193).

References

No reference found.
Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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