Skip to main content

Advertisement

SpringerLink
Log in

Characterization of Cerebellar Atrophy and Resting State Functional Connectivity Patterns in Sporadic Adult-Onset Ataxia of Unknown Etiology (SAOA)

  • Original Paper
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Sporadic adult-onset ataxia of unknown etiology (SAOA) is a non-genetic neurodegenerative disorder of the cerebellum of unknown cause which manifests with progressive ataxia without severe autonomic failure. Although SAOA is associated with cerebellar degeneration, little is known about the specific cerebellar atrophy pattern in SAOA. Thirty-seven SAOA patients and 49 healthy controls (HCs) were included at two centers. We investigated the structural and functional characteristics of SAOA brains using voxel-based morphometry (VBM) and resting-state functional imaging (rs-fMRI). In order to examine the functional consequence of structural cerebellar alterations, the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and then assessed their relation with disease severity, disease duration, and age of onset within these regions. Group differences were investigated using two-sample t tests, controlling for age, gender, site, and the total intracranial volume. The VBM analysis revealed a significant, mostly bilateral reduction of local gray matter (GM) volume in lobules I–V, V, VI, IX, X, and vermis VIII a/b in SAOA patients, compared with HCs. The GM volume loss in these regions was significantly associated with disease severity, disease duration, and age of onset. The disease-related atrophy regions did not show any functional alternations compared with HCs but were functionally characterized by high ALFF and poor DC compared with intact cerebellar regions. Our data revealed volume reduction in SAOA in cerebellar regions that are known to be involved in motor and somatosensory processing, corresponding with the clinical phenotype of SAOA. Our data suggest that the atrophy occurs in those cerebellar regions which are characterized by high ALFF and poor DC. Further studies have to show if these findings are specific for SAOA, and if they can be used to predict disease progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Notes

  1. https://www.fil.ion.ucl.ac.uk/spm/software/spm12

References

  1. Abele M, Minnerop M, Urbach H, Specht K, Klockgether T. Sporadic adult onset ataxia of unknown etiology: a clinical, electrophysiological and imaging study. J Neurol. 2007;254(10):1384–9.

    Article  CAS  PubMed  Google Scholar 

  2. Giordano I, Harmuth F, Jacobi H, Paap B, Vielhaber S, Machts J, et al. Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia. Neurology. 2017;89(10):1043–9.

    Article  PubMed  Google Scholar 

  3. Klockgether T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol. 2010;9(1):94–104.

    Article  CAS  PubMed  Google Scholar 

  4. Ota S, Tsuchiya K, Anno M, Niizato K, Akiyama H. Distribution of cerebello-olivary degeneration in idiopathic late cortical cerebellar atrophy: clinicopathological study of four autopsy cases. Neuropathology. 2008;28(1):43–50.

    Article  PubMed  Google Scholar 

  5. Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. NeuroImage. 2006;33(1):127–38.

    Article  PubMed  Google Scholar 

  6. Zang YF, He Y, Zhu CZ, Cao QJ, Sui MQ, Liang M, et al. Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain and Development. 2007;29(2):83–91.

    Article  PubMed  Google Scholar 

  7. Zuo XN, Di Martino A, Kelly C, Shehzad ZE, Gee DG, Klein DF, et al. The oscillating brain: complex and reliable. NeuroImage. 2010;49(2):1432–45.

    Article  PubMed  Google Scholar 

  8. Buckner RL, Sepulcre J, Talukdar T, Krienen FM, Liu H, Hedden T, et al. Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer’s disease. J Neurosci. 2009;29(6):1860–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zuo XN, Ehmke R, Mennes M, Imperati D, Castellanos FX, Sporns O, et al. Network centrality in the human functional connectome. Cereb Cortex. 2012;22(8):1862–75.

    Article  PubMed  Google Scholar 

  10. Premi E, Cauda F, Costa T, Diano M, Gazzina S, Gualeni V, et al. Looking for neuroimaging markers in frontotemporal lobar degeneration clinical trials: a multi-voxel pattern analysis study in granulin disease. J Alzheimers Dis. 2016;51(1):249–62.

    Article  CAS  PubMed  Google Scholar 

  11. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Schmitz-Hubsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006;66(11):1717–20.

    Article  CAS  PubMed  Google Scholar 

  13. Jessen F, Spottke A, Boecker H, Brosseron F, Buerger K, Catak C, et al. Design and first baseline data of the DZNE multicenter observational study on predementia Alzheimer’s disease (DELCODE). Alzheimers Res Ther. 2018;10(1):15.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004;23(Suppl 1):S208–19.

    Article  PubMed  Google Scholar 

  15. Ashburner J. A fast diffeomorphic image registration algorithm. NeuroImage. 2007;38(1):95–113.

    Article  PubMed  Google Scholar 

  16. Dagli MS, Ingeholm JE, Haxby JV. Localization of cardiac-induced signal change in fMRI. NeuroImage. 1999;9(4):407–15.

    Article  CAS  PubMed  Google Scholar 

  17. Windischberger C, Langenberger H, Sycha T, Tschernko EM, Fuchsjager-Mayerl G, Schmetterer L, et al. On the origin of respiratory artifacts in BOLD-EPI of the human brain. Magn Reson Imaging. 2002;20(8):575–82.

    Article  PubMed  Google Scholar 

  18. Friston KJ, Williams S, Howard R, Frackowiak RS, Turner R. Movement-related effects in fMRI time-series. Magn Reson Med. 1996;35(3):346–55.

    Article  CAS  PubMed  Google Scholar 

  19. Wang J, Wang X, Xia M, Liao X, Evans A, He Y. GRETNA: a graph theoretical network analysis toolbox for imaging connectomics. Front Hum Neurosci. 2015;9:386.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Samson M, Claassen DO. Neurodegeneration and the cerebellum. Neurodegener Dis. 2017;17(4–5):155–65.

    Article  PubMed  Google Scholar 

  21. Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BT. The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106(5):2322–45.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Grodd W, Hulsmann E, Lotze M, Wildgruber D, Erb M. Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization. Hum Brain Mapp. 2001;13(2):55–73.

    Article  CAS  PubMed  Google Scholar 

  23. Reetz K, Dogan I, Rolfs A, Binkofski F, Schulz JB, Laird AR, et al. Investigating function and connectivity of morphometric findings--exemplified on cerebellar atrophy in spinocerebellar ataxia 17 (SCA17). NeuroImage. 2012;62(3):1354–66.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mottolese C, Richard N, Harquel S, Szathmari A, Sirigu A, Desmurget M. Mapping motor representations in the human cerebellum. Brain J Neurol. 2013;136(Pt 1):330–42.

    Article  Google Scholar 

  25. Klockgether T, Schroth G, Diener HC, Dichgans J. Idiopathic cerebellar ataxia of late onset: natural history and MRI morphology. J Neurol Neurosurg Psychiatry. 1990;53(4):297–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Baloh RW, Yee RD, Honrubia V. Late cortical cerebellar atrophy. Clinical and oculographic features. Brain J Neurol. 1986;109(Pt 1):159–80.

    Article  Google Scholar 

  27. Klockgether T. Sporadic adult-onset ataxia. Handb Clin Neurol. 2018;155:217–25.

    Article  PubMed  Google Scholar 

  28. Gellersen HM, Guo CC, O’Callaghan C, Tan RH, Sami S, Hornberger M. Cerebellar atrophy in neurodegeneration-a meta-analysis. J Neurol Neurosurg Psychiatry. 2017;88(9):780–8.

    Article  PubMed  Google Scholar 

  29. Shin H, Lee DK, Lee JM, Huh YE, Youn J, Louis ED, et al. Atrophy of the cerebellar vermis in essential tremor: segmental volumetric MRI analysis. Cerebellum. 2016;15(2):174–81.

    Article  PubMed  Google Scholar 

  30. Morton SM, Bastian AJ. Cerebellar control of balance and locomotion. Neuroscientist. 2004;10(3):247–59.

    Article  PubMed  Google Scholar 

  31. Schmitt JE, Eliez S, Warsofsky IS, Bellugi U, Reiss AL. Enlarged cerebellar vermis in William’s syndrome. J Psychiatr Res. 2001;35(4):225–9.

    Article  CAS  PubMed  Google Scholar 

  32. Kheradmand A, Zee DS. Cerebellum and ocular motor control. Front Neurol. 2011;2:53.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Beh SC, Frohman TC, Frohman EM. Neuro-ophthalmic manifestations of cerebellar disease. Neurol Clin. 2014;32(4):1009–80.

    Article  PubMed  Google Scholar 

  34. Beh SC, Frohman TC, Frohman EM. Cerebellar control of eye movements. J Neuroophthalmol. 2017;37(1):87–98.

    Article  PubMed  Google Scholar 

  35. Rondi-Reig L, Paradis AL, Lefort JM, Babayan BM, Tobin C. How the cerebellum may monitor sensory information for spatial representation. Front Syst Neurosci. 2014;8:205.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Barmack NH. Central vestibular system: vestibular nuclei and posterior cerebellum. Brain Res Bull. 2003;60(5–6):511–41.

    Article  PubMed  Google Scholar 

  37. Glickstein M, Gerrits N, Kralj-Hans I, Mercier B, Stein J, Voogd J. Visual pontocerebellar projections in the macaque. J Comp Neurol. 1994;349(1):51–72.

    Article  CAS  PubMed  Google Scholar 

  38. Yakusheva TA, Blazquez PM, Chen A, Angelaki DE. Spatiotemporal properties of optic flow and vestibular tuning in the cerebellar nodulus and uvula. J Neurosci. 2013;33(38):15145–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Habas C, Kamdar N, Nguyen D, Prater K, Beckmann CF, Menon V, et al. Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci. 2009;29(26):8586–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Scharmuller W, Ille R, Schienle A. Cerebellar contribution to anger recognition deficits in Huntington’s disease. Cerebellum. 2013;12(6):819–25.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Berent S, Giordani B, Gilman S, Trask CL, Little RJ, Johanns JR, et al. Patterns of neuropsychological performance in multiple system atrophy compared to sporadic and hereditary olivopontocerebellar atrophy. Brain Cogn. 2002;50(2):194–206.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Research, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

    Xueyan Jiang, J. Faber, I. Giordano, Ch. Kindler, F. Jessen, A. Spottke, H. Boecker, T. Klockgether & L. Scheef

  2. Department of Neurology, University Hospital Bonn, Bonn, Germany

    J. Faber, I. Giordano, Ch. Kindler, A. Spottke & T. Klockgether

  3. German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany

    J. Machts, O. Speck, E. Düzel & St. Vielhaber

  4. Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany

    J. Machts, E. Düzel & St. Vielhaber

  5. Department of Neurology, University of Rostock, Rostock, Germany

    A. Dudesek & Ch. Kamm

  6. Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany

    F. Jessen

  7. Department of Radiology, University of Bonn, Bonn, Germany

    H. Boecker & L. Scheef

Authors
  1. Xueyan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Faber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Giordano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Machts
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ch. Kindler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Dudesek
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. O. Speck
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ch. Kamm
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. Düzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F. Jessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A. Spottke
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. St. Vielhaber
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. H. Boecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. T. Klockgether
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. L. Scheef
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xueyan Jiang.

Ethics declarations

The study was approved by the local ethics committees in Bonn and Magdeburg. All subjects provided written informed consent before participation.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 193 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, X., Faber, J., Giordano, I. et al. Characterization of Cerebellar Atrophy and Resting State Functional Connectivity Patterns in Sporadic Adult-Onset Ataxia of Unknown Etiology (SAOA). Cerebellum 18, 873–881 (2019). https://doi.org/10.1007/s12311-019-01072-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-019-01072-y

Keywords

Search

Navigation