Abstract
IntroductionWe aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3).Methods17 genetically-confirmed SCA3 patients and 16 controls underwent structural MRI and static resting-state [18F]‑Fluoro‑deoxyglucose Positron Emission Tomography (FDG-PET) imaging. A SCA3-related pattern (SCA3-RP) was identified using a multivariate method (scaled subprofile model and principal component analysis (SSM PCA)). Participants were evaluated with the Scale for Assessment and Rating of Ataxia (SARA) and with neuropsychological examination including tests for language, executive dysfunction, memory, and information processing speed. The relationships between SCA3-RP expression and clinical scores were explored. Voxel based morphology (VBM) was applied on MRI-T1 images to assess possible correlations between FDG reduction and grey matter atrophy.ResultsThe SCA3-RP disclosed relative hypometabolism of the cerebellum, caudate nucleus and posterior parietal cortex, and relatively increased metabolism in somatosensory areas and the limbic system. This topography, which was not explained by regional atrophy, correlated significantly with ataxia (SARA) scores (ρ = 0.72; P = 0.001). SCA3 patients showed significant deficits in executive function and information processing speed, but only letter fluency correlated with SCA3-RP expression (ρ = 0.51; P = 0.04, uncorrected for multiple comparisons).ConclusionThe SCA3 metabolic profile reflects network-level alterations which are primarily associated with the motor features of the disease. Striatum decreases additional to cerebellar hypometabolism underscores an intrinsic extrapyramidal involvement in SCA3. Cerebellar-posterior parietal hypometabolism together with anterior parietal (sensory) cortex hypermetabolism may reflect a shift from impaired feedforward to compensatory feedback processing in higher-order motor control. The demonstrated SCA3-RP provides basic insight in cerebral network changes in this disease.
Highlights
We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3)
The SCA3-related pattern (SCA3-RP) was characterized by relative hypometabolism in the cerebellar hemispheres and vermis, the brainstem, caudate nucleus, and the posterior parietal cortex
Increased metabolism was found in the cerebellar peduncles, the amygdala, hippocampus/parahippocampal gyrus, orbitofrontal cortex, insula, the anterior and middle cingulate gyrus and the somatosensory cortex
Summary
We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3). Results: The SCA3-RP disclosed relative hypometabolism of the cerebellum, caudate nucleus and posterior parietal cortex, and relatively increased metabolism in somatosensory areas and the limbic system This topography, which was not explained by regional atrophy, correlated significantly with ataxia (SARA) scores (ρ = 0.72; P = 0.001). The obtained FDG-PET (as well as perfusion SPECT) data are commonly analyzed with univariate models which have consistently demonstrated cerebellar hypo-activity, but showed variable results regarding the involvement of extra-cerebellar structures such as the NeuroImage: Clinical 19 (2018) 90–97 brainstem (Soong et al, 1997; Soong and Liu, 1998; Wullner et al, 2005; Wang et al, 2007), thalamus (Wullner et al, 2005), lentiform nucleus (Wang et al, 2007), limbic lobe (Wang et al, 2007; Braga-Neto et al, 2012a), and occipital cortex (Soong et al, 1997; Soong and Liu, 1998; Braga-Neto et al, 2012a). With the scaled subprofile model with principal component analysis (SSM PCA) (Spetsieris and Eidelberg, 2011) disease-specific patterns have been identified in several neurodegenerative disorders (Meles et al, 2017; Niethammer and Eidelberg, 2012)
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