Impaired Efficiency and Resilience of Structural Network in Spinocerebellar Ataxia Type 3

Abstract

Background: Recent studies have shown that the patients with spinocerebellar ataxia type 3 (SCA3) may not only have disease involvement in the cerebellum and brainstem but also in the cerebral regions. However, the relations between the widespread degenerated brain regions remains incompletely explored.Methods: In the present study, we investigate the topological properties of the brain networks of SCA3 patients (n = 40) constructed based on the correlation of three-dimensional fractal dimension values. Random and targeted attacks were applied to measure the network resilience of normal and SCA3 groups.Results: The SCA3 networks had significantly smaller clustering coefficients (P < 0.05) and global efficiency (P < 0.05) but larger characteristic path length (P < 0.05) than the normal controls networks, implying loss of small-world features. Furthermore, the SCA3 patients were associated with reduced nodal betweenness (P < 0.001) in the left supplementary motor area, bilateral paracentral lobules, and right thalamus, indicating that the motor control circuit might be compromised.Conclusions: The SCA3 networks were more vulnerable to targeted attacks than the normal controls networks because of the effects of pathological topological organization. The SCA3 revealed a more sparsity and disrupted structural network with decreased values in the largest component size, mean degree, mean density, clustering coefficient, and global efficiency and increased value in characteristic path length. The cortico-cerebral circuits in SCA3 were disrupted and segregated into occipital-parietal (visual-spatial cognition) and frontal-pre-frontal (motor control) clusters. The cerebellum of SCA3 were segregated from cerebellum-temporal-frontal circuits and clustered into a frontal-temporal cluster (cognitive control). Therefore, the disrupted structural network presented in this study might reflect the clinical characteristics of SCA3.

Non-invasive Transcranial Electrical Stimulation in Movement Disorders

“…Is there any threshold of neurodegeneration beyond which applying tES is not reasonable? (Wu et al, 2018). What would be the realistic expectation after tES?…”

“…There is emerging evidence of network-level dysfunction in many neurological disorders. Movement disorders such as Parkinson's disease (PD) (de Schipper et al, 2018), dystonia (Schirinzi et al, 2018), tremor (Benito-León et al, 2015), and ataxia (Falcon et al, 2016;Wu et al, 2018) may fit very well within this construct of network dysfunction to explain the pathophysiology and phenotypes. This paradigm shift of suggesting that the movement disorders are a result of dysfunction in multilevel, interconnected complex cortico-subcortical network rather than only being restricted to the basal ganglia has opened the possibility of modifying that network noninvasively by delivering electromagnetic stimulation.…”

Intra- and Inter-Modular Connectivity Alterations in the Brain Structural Network of Spinocerebellar Ataxia Type 3

“…The reorganization and increased inter-modular connectivity of the supratentorial networks may have resulted from the plasticity of the brain in attempting to compensate for function loss in the cerebellum. Moreover, our previous study evidenced that the SCA3 networks were globally more vulnerable to targeted attacks than the normal controls networks because of the effects of pathological topological organization [ 33 ]. The SCA3 analysis revealed a sparser and disrupted structural network with decreased values in the largest component size, mean degree, mean density, clustering coefficient and global efficiency and increased value in characteristic path length [ 33 ].…”

“…Moreover, our previous study evidenced that the SCA3 networks were globally more vulnerable to targeted attacks than the normal controls networks because of the effects of pathological topological organization [ 33 ]. The SCA3 analysis revealed a sparser and disrupted structural network with decreased values in the largest component size, mean degree, mean density, clustering coefficient and global efficiency and increased value in characteristic path length [ 33 ]. While in the present study, we used modular analysis of network, and focused local effect between different lobes.…”

Non‐invasive electrical stimulation in patients with neurodegenerative ataxia and spasticity: A systematic review and meta‐analysis of randomized controlled trials

“…Furthermore, it may provide new information regarding brain physiology as well as enhance neural plasticity in neurodegenerative ataxia and spasticity, without exposing the patients to the risks associated with invasive therapies such as deep brain stimulation [6‐8]. NES is especially promising given the emerging evidence of network‐level disturbances, consequences of degenerative changes in the cerebellum and basal ganglia [9,10].…”