Microstructural MRI Basis of the Cognitive Functions in Patients with Spinocerebellar Ataxia Type 2

Abstract

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum. The particular atrophy pattern results in some typical clinical features mainly including motor deficits. In addition, the presence of cognitive impairments, involving language, visuospatial and executive functions, has been also shown in SCA2 patients and it is now widely accepted as a feature of the disease. The aim of the study is to investigate the microstructural patterns and the anatomo-functional substrate that could account for the cognitive symptomatology observed in SCA2 patients. In the present study, diffusion tensor imaging (DTI) based-tractography was performed to map the main cerebellar white matter (WM) bundles, such as Middle and Superior Cerebellar Peduncles, connecting cerebellum with higher order cerebral regions. Damage-related diffusivity measures were used to determine the pattern of pathological changes of cerebellar WM microstructure in patients affected by SCA2 and correlated with the patients' cognitive scores. Our results provide the first evidence that WM diffusivity is altered in the presence of the cerebellar cortical degeneration associated with SCA2 thus resulting in a cerebello-cerebral dysregulation that may account for the specificity of cognitive symptomatology observed in patients.

Neuroimaging Biomarkers in SCA2 Gene Carriers

“…Generally, modifications of diffusion properties in the brain of SCA2 gene carriers correlated with ataxia severity [9,17,20,21], cognitive scores [22] and disease duration [17]. Morphometry [13,23] ( Figure 5) and diffusion MR [23,24] in small size longitudinal studies documented progression of neurodegeneration in terms of accelerated volume loss and microstructural changes in SCA2 compared to age matched healthy control subjects.…”

“…Diffusion MR imaging, using regions of interest, histogram analyses or tractography or tract-based spatial statistics, allows one to quantitatively measure the symmetric distributed microstructural damage of the T2 hyperintense or normal white matter in the brainstem, cerebellar peduncles, cerebellum and corticospinal tracts of SCA2 gene carriers [9,17,[19][20][21][22][23] (Figure 4). Additional areas of increased diffusivity and decreased fractional anisotropy can be observed in the thalamus, corpus callosum and cerebral hemispheric white matter [17,20,21,23].…”

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

“…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]. Network-based statistics reveals that altered internodal connectivity between the CB posterior lobe and the cerebral cortex correlated with assessments of cognition and emotion, consistent with the view that CB dysfunction in SCA2 affects cerebral regions at a distance and that the clinical symptoms may be related to connectivity changes in both the cerebral and CB nodes of motor and nonmotor cerebro-CB circuits [104].…”

Structural cerebellar correlates of cognitive functions in spinocerebellar ataxia type 2

“…Impaired cognitive performance, involving language, executive, visuospatial and sequencing functions has also been found in patients with cerebellar atrophy [4][5], a condition characterized by diffuse degeneration of the cerebellar cortex, which is regarded as the central computational integrator of the cerebellar system [6]. Throughout the cerebellar cortex, the information ultimately converges on Purkinje neurons and is then funneled out through the neurons of the deep cerebellar nuclei (DCN), the sole output of the cerebellar cortex.…”