Introduction

Belonging to a group of neurodegenerative diseases, the spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia subtype with slowly progressive degenerative disorders that affect the cerebellum and cerebellar pathways. This study aimed to investigate the abnormal regional homogeneity (ReHo) of the brain in patients with SCA3.

Methods

Seventeen SCA3 patients and seventeen age-, sex- and education-matched healthy controls (HC) were prospectively recruited into this study. MR data of all subjects were acquired by the use of a 3.0T scanner (GE, Discovery MR750, Milwaukee, United States) with an 8-channel head coil. Acquisition parameters for resting-state functional magnetic resonance imaging (rs-fMRI) with a single-shot gradient recalled echo-planar imaging sequence: slice thickness=3.5 mm, slice spacing=0.7 mm, repetition time (TR)=2,000 ms, echo time (TE)=30 ms, flip angle=90°, matrix=64×64, field of view (FOV)=224×224 mm², number of excitations (NEX)=1, 34 slices and 240 phases. 3D T1WI structural images were reconstructed via three-dimensional fast spoiled gradient-echo sequences (3D FSPGR): slice thickness=1.0 mm, TR=6.7 ms, TE=min full, matrix=256×256, FOV=256×256 mm², NEX=1. Data preprocessing, ReHo map generating and visualizing were done in the DPABI toolbox (v5.1) and SUIT¹ toolbox (v3.4) based on MATLAB (R2020a). Two sample t-test was used in exploring the ReHo differences between the SCA3 group and the HC group. The Gaussian random field (GRF) method was performed for multiple comparison corrections, with voxel-level P < 0.005 and cluster-level P < 0.05. Then, correlations between the Scale for Assessment and Rating of Ataxia (SARA) as well as the International Cooperative Ataxia Rating Scale (ICARS) scores and the ReHo values of abnormal brain regions for SCA3 group were analyzed respectively by using Pearson’s correlation in SPSS software (v26.0).

Results

There were no significant differences in age, sex, and education level between the SCA3 group and the HC group (P>0.05) (Table 1). Significant group differences in ReHo values among the two groups were observed mainly in two clusters (Figure 1, 2A and Table 2). In Cluster 1 for the left cerebellum (e.g. declive, tuber semi-lunar lobule, etc.), especially in the Left VI, Left Crus I and Left Crus II of SUIT space, the ReHo values for SCA3 group were significantly lower than those for HC group (Figure 2B). On the contrary, compared to HC group, the SCA3 group showed significant increased ReHo values in the limbic lobe, temporal lobe, superior temporal gyrus, middle temporal pole, uncus, amygdala, putamen, parahippocampal and frontal lobe, gathered as Cluster 2, of the right cerebrum (Figure 2C). However, there was no significant correlation between altered ReHo values and SARA scores (Figure 3A) as well as ICARS scores (Figure 3B) in Cluster 1. Furthermore, altered ReHo values showed a strong correlation with SARA scores (Figure 3C) and a moderate correlation with ICARS scores (Figure 3D) in Cluster 2.

Discussion and Conclusion

As an analysis method of rs-fMRI, ReHo can quantify the local brain function and reflect the time synchronization of regional neural activities². The results indicate that the asynchronized neural activities happened within the specific regions of the left cerebellum and right cerebrum may be the neuroimaging characteristics of SCA3. Furthermore, in Cluster 1 of the left cerebellum, the abnormal cerebellar areas such as declive and tuber were found critical for controlling postural balance, saccadic eye movements and coordination. However, different from the most common characteristics like cerebellar atrophy in SCA3, the volumes of declive and tuber were revealed larger among sportspeople³. It is also worth noting that between the two clinical ataxia scores, the SARA⁴ scores performed a stronger positive correlation of ReHo values in Cluster 2 than the ICARS scores did. Therefore, the altered ReHo value can serve as a functional marker for reflecting the severity of the SCA3 symptoms.