Structural cerebellar correlates of cognitive functions in spinocerebellar ataxia type 2

Abstract

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum and characterized by a typical motor syndrome. In addition, the presence of cognitive impairment is now widely acknowledged as a feature of SCA2. Given the extensive connections between the cerebellum and associative cerebral areas, it is reasonable to hypothesize that cerebellar neurodegeneration associated with SCA2 may impact on the cerebellar modulation of the cerebral cortex, thus resulting in functional impairment. The aim of the present study was to investigate and quantitatively map the pattern of cerebellar gray matter (GM) atrophy due to SCA2 neurodegeneration and to correlate that with patients' cognitive performances. Cerebellar GM maps were extracted and compared between SCA2 patients (n = 9) and controls (n = 33) by using voxel-based morphometry. Furthermore, the relationship between cerebellar GM atrophy and neuropsychological scores of the patients was assessed. Specific cerebellar GM regions were found to be affected in patients. Additionally, GM loss in cognitive posterior lobules (VI, Crus I, Crus II, VIIB, IX) correlated with visuospatial, verbal memory and executive tasks, while additional correlations with motor anterior (V) and posterior (VIIIA, VIIIB) lobules were found for the tasks engaging motor and planning components. Our results provide evidence that the SCA2 neurodegenerative process affects the cerebellar cortex and that MRI indices of atrophy in different cerebellar subregions may account for the specificity of cognitive symptomatology observed in patients, as result of a cerebello-cerebral dysregulation.

The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper

“…Neuroimaging in the hereditary ataxias reveals that atrophy in different CB subregions may account for the specificity of cognitive symptoms. In patients with SCA2, atrophy in the cognitive CB in the posterior lobe (lobules VI, Crus I, Crus II, VIIB, and IX) correlated with impaired visuospatial, verbal memory, and executive function, whereas atrophy in the motor CB (lobule V in the anterior lobe; lobules VIIIA and VIIIB of the posterior lobe) correlated with motor deficits and impaired motor planning [214]. CB atrophy was also associated with altered diffusivity of the middle and superior CB peduncles, the main cerebro-CB afferent and efferent white matter tracts, respectively, indicating that cerebro-CB dysregulation may account for the CCAS in SCA2 [215].…”

Voxel‐based meta‐analysis of gray and white matter volume abnormalities in spinocerebellar ataxia type 2

“…The atrophy in cerebellar lobule Crus II of cerebellum also plays a role in cognitive impairments, which has been reported (Stoodley & Schmahmann, 2010). A latest study assessed the relationship between cerebellar GM atrophy and neuropsychological scores of the SCA2 patients and demonstrated GM loss in posterior lobules including lobule VI, VIIB, Crus I/II correlated with visuospatial, verbal memory, and executive tasks (Olivito et al., 2018). All these findings above indicated that the atrophy of lobule VI/VII and Crus I/II detected in the current meta‐analysis accounted for cognitive impairments in SCA2.…”

“…Voxel‐based morphometry (VBM), a processing technique of magnetic resonance imaging (MRI) that can detect regional morphological changes in the whole brain, has been commonly used to evaluate gray matter (GM) and white matter (WM) volume abnormalities in SCA2 patients (Brenneis, Bosch, Schocke, Wenning, & Poewe, 2003; D'Agata, Caroppo, Boghi et al., 2011; Goel et al., 2011; Hernandez‐Castillo et al., 2015; Jacobi et al., 2013; Mercadillo et al., 2014; Nave, Ginestroni, Tessa, Cosottini et al., 2008; Nave, Ginestroni, Tessa, Salvatore et al., 2008; Olivito et al., 2018). However, the findings of these studies are variable and conflicting.…”

“…However, the findings of these studies are variable and conflicting. Some studies reported regional cerebral atrophy in frontal, parietal, and temporal lobes (Brenneis et al., 2003; Goel et al., 2011; Hernandez‐Castillo et al., 2015; Mercadillo et al., 2014; Nave, Ginestroni, Tessa, Salvatore et al., 2008), while some studies found brain volume reductions limited in the infratentorial regions such as cerebellum and pons (D'Agata, Caroppo, Boghi et al., 2011; Jacobi et al., 2013; Nave, Ginestroni, Tessa, Cosottini et al., 2008; Olivito et al., 2018). The atrophy of mesencephalon and thalamus was also detected in a few studies (Brenneis et al., 2003; Nave, Ginestroni, Tessa, Salvatore et al., 2008), and significant parahippocampal atrophy was demonstrated in one study (Mercadillo et al., 2014).…”

“…Previous neuropathological findings have shown extensive atrophy of cerebellum, brainstem, basal ganglia, and frontal lobes in SCA2 patients (Estrada, Galarraga, Orozco, Nodarse, & Auburger, 1999;Martin et al, 1994), but these postmortem studies may not well reflect abnormalities in vivo or the central nervous system alteration with the disease progression. Voxel-based morphometry (VBM), a processing technique of magnetic resonance imaging (MRI) that can detect regional morphological changes in the whole brain, has been commonly used to evaluate gray matter (GM) and white matter (WM) volume abnormalities in SCA2 patients (Brenneis, Bosch, Schocke, Wenning, & Poewe, 2003;D'Agata, Caroppo, Boghi et al, 2011;Goel et al, 2011;Hernandez-Castillo et al, 2015;Jacobi et al, 2013;Mercadillo et al, 2014;Nave, Ginestroni, Tessa, Cosottini et al, 2008;Olivito et al, 2018). However, the findings of these studies are variable and conflicting.…”