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Loss of Intrinsic Organization of Cerebellar Networks in Spinocerebellar Ataxia Type 1: Correlates with Disease Severity and Duration

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Abstract

The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of cerebellar degenerative disorders, characterized by progressive gait unsteadiness, hand incoordination, and dysarthria. The mutational mechanism in SCA1, a dominantly inherited form of SCA, consists of an expanded trinucleotide CAG repeat. In SCA1, there is loss of Purkinje cells, neuronal loss in dentate nucleus, olives, and pontine nuclei. In the present study, we sought to apply intrinsic functional connectivity analysis combined with diffusion tensor imaging to define the state of cerebellar connectivity in SCA1. Our results on the intrinsic functional connectivity in lateral cerebellum and thalamus showed progressive organizational changes in SCA1 noted as a progressive increase in the absolute value of the correlation coefficients. In the lateral cerebellum, the anatomical organization of functional clusters seen as parasagittal bands in controls is lost, changing to a patchy appearance in SCA1. Lastly, only fractional anisotropy in the superior peduncle and changes in functional organization in thalamus showed a linear dependence to duration and severity of disease. The present pilot work represents an initial effort describing connectivity biomarkers of disease progression in SCA1. The functional changes detected with intrinsic functional analysis and diffusion tensor imaging suggest that disease progression can be analyzed as a disconnection syndrome.

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Notes

  1. Anatomically [21], the lateral cerebellum included the following lobules: V lat (culmen inferior), VI lat (simplex), VIIA_Crus I/1,2 (superior semilunar lobule), VIIA_Crus II/1,2 (inferior semilunar lobule), VIIB lat (paramedian/gracilis), VIIIA lat (biventer, pars copularis), and VIIIB lat (biventer, pars paraflocculus dorsalis).

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Acknowledgments

We want to thank Mr. R. Lyons for technical help in performing the scan sessions, Ms. N. Sansone for assisting in the generation of anatomical ROIs, and Ms. N. Lobo for assisting in primary MRI analysis. Special thanks go to Dr. Christian Hansel for his valuable comments. The work was supported by grants from the Center for Integrative Neuroscience and Neuroengineering Research (CINNR), NIH RO1-NS-54942, and the James McDonnell Foundation (NRG group).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, MC 2030, The University of Chicago Hospitals, Chicago, IL, USA

    Ana Solodkin, E. Elinor Chen & Christopher M. Gomez

  2. School of Physics and Astronomy, Tel-Aviv University, Tel Aviv, Israel

    Eitan Peri & Eshel Ben-Jacob

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  1. Ana Solodkin
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  2. Eitan Peri
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Solodkin, A., Peri, E., Chen, E.E. et al. Loss of Intrinsic Organization of Cerebellar Networks in Spinocerebellar Ataxia Type 1: Correlates with Disease Severity and Duration. Cerebellum 10, 218–232 (2011). https://doi.org/10.1007/s12311-010-0214-5

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