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Comparative Study
. 2024 Dec;30(12):e70171.
doi: 10.1111/cns.70171.

Gray Matter Asymmetry Alterations in Patients With Spinocerebellar Ataxia Type 3: A Voxel-Based Morphometric Comparison Study

Linfeng Shi  1 , Lan Ou  1 , Peiling Ou  1 , Lihua Deng  1 , Yonghua Huang  1 , Xingang Wang  1 , Li Gui  2 , Bijia Wang  2 , Limeng Dai  3 , Guolin Ma  4 , Jian Wang  1 , Chen Liu  1
Affiliations
Comparative Study

Gray Matter Asymmetry Alterations in Patients With Spinocerebellar Ataxia Type 3: A Voxel-Based Morphometric Comparison Study

Linfeng Shi et al. CNS Neurosci Ther. 2024 Dec.

Abstract

Aims: The aim of this study was to investigate the whole-brain asymmetry changes in spinocerebellar ataxia type 3 (SCA3) and their association with movement disorders.

Methods: Voxel-based morphometry (VBM) was used to assess asymmetry in gray matter (GM) volume in 83 genetically confirmed SCA3 patients and 83 sex- and age-matched healthy controls (HCs). The asymmetry index (AI) was analyzed for partial correlation with disease severity, as measured by the Scale for Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale (ICARS). Age, sex, and total intracranial volume (TIV) were included as covariates in the analysis.

Results: Asymmetry in GM analysis with SCA3 patients showed decreased leftward asymmetry in cerebellar lobules VIII and IX, the visual cortex, and the putamen, as well as decreased rightward asymmetry in the ventral lateral thalamus, as analyzed by VBM. The AI in the cerebellum, the visual cortex, and the putamen was positively correlated with SARA and ICARS scores, whereas the AI in the thalamus was negatively correlated with these scales.

Conclusion: SCA3 patients exhibit distinct patterns of asymmetrical changes in GM volume, which correlates with motor dysfunction. These changes in asymmetry may serve as potential biomarkers for early intervention in SCA3.

Trial registration: Chinese Clinical Trial Registry (ChiCTR): 1800019901, 2000039434.

Keywords: brain; brain asymmetry; gray matter; magnetic resonance imaging; spinocerebellar ataxia type 3.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
This figure provides a visual summary of the study's workflow, detailing each step from sample collection to data analysis.
FIGURE 2
FIGURE 2
Changes in gray matter asymmetry in patients with SCA3. (A) Regions with altered gray matter asymmetry in SCA3 patients compared to healthy controls; red indicates increased rightward asymmetry, whereas blue indicates decreased rightward asymmetry. The regions showing significant gray matter volume asymmetry changes include the cluster 1 (cerebellar lobules VIII and IX), cluster 2 (visual cortex), cluster 3 (putamen), and cluster 4 (ventral posterolateral thalamus).(B, C) Comparisons of asymmetry index (AI) in regions with significant differences. Positive AI values indicate rightward asymmetry, whereas negative AI values indicate leftward asymmetry.(D, E) Comparisons of mean gray matter volume in the left hemisphere in regions with significant differences. (F–G) Comparisons of mean gray matter volume in the right hemisphere in regions with significant differences.
FIGURE 3
FIGURE 3
Correlation of asymmetry index with motor and neuropsychological features in a SCA3 patient. The results are adjusted for age, sex, and total intracranial volume. The x‐axes represent the asymmetry index. The regions showing significant gray matter volume asymmetry changes include cluster 1 (cerebellar lobules VIII and IX), cluster 2 (visual cortex), cluster 3 (putamen), and cluster 4 (ventral posterolateral thalamus). ADL, activities of daily living; DST, digit span test; HAMD, Hamilton depression scale; IADL, instrumental activities of daily living; ICARs, International Cooperative Ataxia Rating Scale; MoCA, montreal cognitive assessment; RVR, rapid verbal retrieval; SARA, scale for the assessment and rating of ataxia;*p < 0.05, **p < 0.01, ***p < 0.001.
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