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.