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

Abstract

In addition to cerebellar degeneration symptoms, patients with spinocerebellar ataxia type 3 (SCA3) exhibit extensive involvements with damage in the prefrontal cortex. A network model has been proposed for investigating the structural organization and functional mechanisms of clinical brain disorders. For neural degenerative diseases, a cortical feature-based structural connectivity network can locate cortical atrophied regions and indicate how their connectivity and functions may change. The brain network of SCA3 has been minimally explored. In this study, we investigated this network by enrolling 48 patients with SCA3 and 48 healthy subjects. A novel three-dimensional fractal dimension-based network was proposed to detect differences in network parameters between the groups. Copula correlations and modular analysis were then employed to categorize and construct the structural networks. Patients with SCA3 exhibited significant lateralized atrophy in the left supratentorial regions and significantly lower modularity values. Their cerebellar regions were dissociated from higher-level brain networks, and demonstrated decreased intra-modular connectivity in all lobes, but increased inter-modular connectivity in the frontal and parietal lobes. Our results suggest that the brain networks of patients with SCA3 may be reorganized in these regions, with the introduction of certain compensatory mechanisms in the cerebral cortex to minimize their cognitive impairment syndrome.

Magnetic Resonance Imaging and Its Clinical Correlation in Spinocerebellar Ataxia Type 3: A Systematic Review

“…Finally, we included a total of 29 articles in this review. Twenty papers examined structural MRI [volumetric: n = 12 (Bürk et al, 1996;Etchebehere et al, 2001;Yoshizawa et al, 2003;Liang et al, 2009;Schulz et al, 2010;Camargos et al, 2011;D'Abreu et al, 2011;Ogawa et al, 2012;De Rezende et al, 2015;Nunes et al, 2015;Rezende et al, 2018;Jao et al, 2019b), voxel-based morphometry (VBM): n = 8 (Schulz et al, 2010;D'Abreu et al, 2012;Guimarães et al, 2013;Lopes et al, 2013;Kang et al, 2014;Hernandez-Castillo et al, 2017;Peng et al, 2019;Guo et al, 2020), and surface analysis: n = 4 (De Nunes et al, 2015;Rezende et al, 2018;Arruda et al, 2020)], seven papers examined MRS (Lei et al, 2011;Lirng et al, 2012;Wang et al, 2012;Lopes et al, 2013;Chen et al, 2014;Adanyeguh et al, 2015;Peng et al, 2019), and ten papers examined DTI (Guimarães et al, 2013;Lopes et al, 2013;Kang et al, 2014;Nunes et al, 2015;Wu et al, 2017;Rezende et al, 2018;Jao et al, 2019a;Peng et al, 2019;Meira et al, ...…”

Alteration of the Intra- and Inter-Lobe Connectivity of the Brain Structural Network in Normal Aging

“…Module 1 in the middle-aged group contains 14 frontal nodes, 3 temporal nodes, 3 parietal nodes, and 2 occipital nodes. Module 1 contained four bilateral nodes (highlighted with underlining in Table 3 ) of the frontal lobe (CACg(L,R), CMF(L,R), Tr(L,R) and PreC(L,R)) which mainly correspond to regions associated with cognitive and executive functions [ 26 , 34 ]. Module 2 comprises 14 regions, including the frontal, temporal, parietal, and occipital lobes, which are mainly related to sensorimotor, visual, and spatial functions.…”

“…Module 2 comprises 14 regions, including the frontal, temporal, parietal, and occipital lobes, which are mainly related to sensorimotor, visual, and spatial functions. Module 3 comprises 13 nodes in the frontal, temporal, and parietal lobes, including parahippocampal (PaH), superior temporal (SM), and supramarginal (SM) regions, which may be related to mnemonic and emotional functions [ 26 ]. We found that modules 1, 2, and 4 have at least one pair of bilateral node links, and the network modularity ( Q ) value for the middle-aged group was 0.2307.…”

“…A cortical feature-based network, including the thickness [ 20 ], volume [ 21 ], and surface area [ 22 ], can highlight the anatomical connection between parcellated regions in neural degenerative diseases, such as dementia [ 23 ], multiple sclerosis [ 24 ], and Alzheimer’s disease [ 25 ]. Recently, we proposed a novel three-dimensional FD-based brain structural network to detect intra- and inter-modular connectivity alterations in brain lobes of spinocerebellar ataxia type 3 (SCA3) [ 26 ]. First, the FD can accurately assess the significantly atrophied, parcellated cortical regions.…”

“…First, the FD can accurately assess the significantly atrophied, parcellated cortical regions. Second, the constructed network was revealed precisely, presenting the intra- and inter-modular connectivity of each brain lobe and the alterations between healthy individuals and patients with SCA3 [ 26 ]. In neurodegenerative disease or normal aging, monitoring brain structural network changes may be beneficial in understanding the pathophysiology and enabling the possibility of preventing or modifying progressive neurodegeneration.…”