Disruption of visual and motor connectivity in spinocerebellar ataxia type 7.
Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant neurodegenerative disorder characterized by progressive ataxia and retinal dystrophy. It is caused by a CAG trinucleotide expansion in the ataxin7 gene. Anatomical studies have shown severe cerebellar degeneration and region-specific neocortical atrophy in SCA7 patients. However, the impact of the neurodegeneration on the functional integration of the remaining tissue is still unknown. The aim of this study was to examine functional connectivity abnormalities in areas with significant gray matter atrophy in SCA7 patients and their relationship with number of CAG repeats. Using a combination of voxel-based morphometry and resting-state fMRI, we studied 26 genetically confirmed SCA7 patients and aged-matched healthy controls. In SCA7 patients we found reduced functional interaction between the cerebellum and the middle and superior frontal gyri, disrupted functional connectivity between the visual and motor cortices, and increased functional coordination between atrophied areas of the cerebellum and a range of visual cortical areas compared with healthy controls. The degree of mutation expansion showed a negative effect on both the functional interaction between the right anterior cerebellum and the left superior frontal gyrus and the connectivity between the right anterior cerebellum and left parahippocampal gyrus. We found abnormal functional connectivity patterns, including both hypo- and hyperconnectivity, compared with controls. These abnormal patterns show reasonable association with the severity of gene mutation. Our findings suggest that aberrant changes are prevalent in both motor and visual systems, adding significantly to our understanding of the pathophysiology of SCA7.
Instituto de Neuroetologia, Universidad Veracruzana, Xalapa, Mexico; Department of Radiology and BRIC, University of North Carolina, Chapel Hill, North Carolina, USA.
Carlos R
CR
Hernandez-Castillo
Sarael
S
Alcauter
Victor
V
Galvez
Fernando A
FA
Barrios
Petra
P
Yescas
Adriana
A
Ochoa
Lizbeth
L
Garcia
Rosalinda
R
Diaz
Wei
W
Gao
Juan
J
Fernandez-Ruiz
D000328:Adult; D001284:Atrophy / Q000503:physiopathology; D002531:Cerebellum / Q000503:physiopathology*; D004525:Efferent Pathways / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D020754:Spinocerebellar Ataxias / Q000503:physiopathology*; D014795:Visual Pathways / Q000503:physiopathology*
frontocerebellar network; functional connectivity; motor network; spinocerebellar ataxia 7; visual network