Skip to main content

Advertisement

SpringerLink
Log in

Ferdinando Rossi Lecture: the Cerebellar Cognitive Affective Syndrome—Implications and Future Directions

  • Review
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

The notion that the cerebellum is devoted exclusively to motor control has been replaced by a more sophisticated understanding of its role in neurological function, one that includes cognition and emotion. Early clinical reports, as well as physiological and behavioral studies in animal models, raised the possibility of a nonmotor role for the cerebellum. Anatomical studies demonstrate cerebellar connectivity with the distributed neural circuits linked with autonomic, sensorimotor, vestibular, associative and limbic/paralimbic brain areas. Identification of the cerebellar cognitive affective syndrome in adults and children underscored the clinical relevance of the role of the cerebellum in cognition and emotion. It opened new avenues of investigation into higher order deficits that accompany the ataxias and other cerebellar diseases, as well as the contribution of cerebellar dysfunction to neuropsychiatric and neurocognitive disorders. Brain imaging studies demonstrate the complexity of cerebellar functional topography, revealing a double representation of the sensorimotor cerebellum in the anterior lobe and lobule VIII and a triple cognitive representation in the cerebellar posterior lobe, as well as representation in the cerebellum of the intrinsic connectivity networks identified in the cerebral hemispheres. This paradigm shift in thinking about the cerebellum has been advanced by the theories of dysmetria of thought and the universal cerebellar transform, harmonizing the dual anatomic realities of homogeneously repeating cerebellar cortical microcircuitry set against the heterogeneous and topographically arranged cerebellar connections with extracerebellar structures. This new appreciation of the cerebellar incorporation into circuits that subserve cognition and emotion enables deeper understanding and improved care of our patients with cerebellar ataxias and novel cerebellar-based approaches to therapy in neuropsychiatry.

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

Similar content being viewed by others

References

  1. Schmahmann JD. The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev. 2010;20(3):236–60.

    Article  PubMed  Google Scholar 

  2. Schmahmann JD. The cerebellum and cognition. Neurosci Lett. 2019;688:62–75.

    Article  CAS  PubMed  Google Scholar 

  3. Schmahmann JD. Emotional disorders and the cerebellum: neurobiological substrates, neuropsychiatry, and therapeutic implications. Handb Clin Neurol. 2021;183:109–54.

    Article  PubMed  Google Scholar 

  4. Schmahmann JD, Guell X, Stoodley CJ, Halko MA. The theory and neuroscience of cerebellar cognition. Annu Rev Neurosci. 2019;42:337–64.

    Article  CAS  PubMed  Google Scholar 

  5. Koziol LF, Budding D, Andreasen N, et al. Consensus paper: the cerebellum’s role in movement and cognition. Cerebellum. 2014;13(1):151–77.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Adamaszek M, D’Agata F, Ferrucci R, et al. Consensus paper: cerebellum and emotion. Cerebellum. 2017;16(2):552–76.

    Article  CAS  PubMed  Google Scholar 

  7. Mariën P, Ackermann H, Adamaszek M, et al. Consensus paper: language and the cerebellum: an ongoing enigma. Cerebellum. 2014;13(3):386–410.

    PubMed  PubMed Central  Google Scholar 

  8. Baumann O, Borra RJ, Bower JM, et al. Consensus paper: the role of the cerebellum in perceptual processes. Cerebellum. 2015;14(2):197–220.

    Article  PubMed  Google Scholar 

  9. Bodranghien F, Bastian A, Casali C, et al. Consensus paper: revisiting the symptoms and signs of cerebellar syndrome. Cerebellum. 2016;15(3):369–91.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Argyropoulos GPD, van Dun K, Adamaszek M, et al. The cerebellar cognitive affective/Schmahmann syndrome: a task force paper. Cerebellum. 2020;19(1):102–25.

    Article  CAS  PubMed  Google Scholar 

  11. Van Overwalle F, Manto M, Cattaneo Z, et al. Consensus paper: cerebellum and social cognition. Cerebellum. 2020;19(6):833–68.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Flourens P. Recherches expérimentales sur les propriétés et les fonctions du système nerveux dans les animaux vertébrés. Paris: Crevot; 1824.

    Google Scholar 

  13. Schmahmann JD. A brief history of the cerebellum. In: Gruol D, Koibuchi N, Manto M, Molinari M, Schmahmann JD, Shen Y. (eds) Essentials of cerebellum and cerebellar disorders. Springer, Cham. 2016, pp 5–20. https://doi.org/10.1007/978-3-319-24551-5_2.

  14. Holmes G. The cerebellum of man (Hughlings Jackson memorial lecture). Brain. 1939;62:1–30.

    Article  Google Scholar 

  15. Zanatta A, Cherici C, Bargoni A, et al. Vincenzo Malacarne (1744–1816) and the first description of the human cerebellum. Cerebellum. 2008;17(4):461–4.

    Article  Google Scholar 

  16. Schmahmann JD. An emerging concept. The cerebellar contribution to higher function. Arch Neurol. 1991;48(11):178–87.

    Article  Google Scholar 

  17. Schmahmann JD. From movement to thought: anatomic substrates of the cerebellar contribution to cognitive processing. Hum Brain Mapp. 1996;4(3):174–98.

    Article  CAS  PubMed  Google Scholar 

  18. Schmahmann JD. Dysmetria of thought. Clinical consequences of cerebellar dysfunction on cognition and affect. Trends Cogn Sci. 1998;2:362–70.

    Article  CAS  PubMed  Google Scholar 

  19. Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci. 2004;16(3):367–78.

    Article  PubMed  Google Scholar 

  20. Guell X, Hoche F, Schmahmann JD. Metalinguistic deficits in patients with cerebellar dysfunction: empirical support for the dysmetria of thought theory. Cerebellum. 2015;14:50–8.

    Article  PubMed  Google Scholar 

  21. Schmahmann JD. The role of the cerebellum in affect and psychosis. J Neurolinguistics. 2000;13:189–214.

    Article  Google Scholar 

  22. Schmahmann JD, Pandya DN. The cerebrocerebellar system. In: Schmahmann JD, editor. Cerebellum and cognition. San Diego: Academic Press. Int Rev Neurobiol. 1997;41:31–60.

  23. Middleton FA, Strick PL. Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. Science. 1994;266:458–61.

    Article  CAS  PubMed  Google Scholar 

  24. Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci. 2003;23:8432–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Haines DE, Dietrichs E, Mihailoff GA, McDonald EF. The cerebellar-hypothalamic axis: basic circuits and clinical observations. Int Rev Neurobiol. 1997;41:83–107.

    Article  CAS  PubMed  Google Scholar 

  26. Bostan AC, Dum RP, Strick PL. The basal ganglia communicate with the cerebellum. Proc Natl Acad Sci U S A. 2010;107(18):8452–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Caligiore D, Pezzulo G, Baldassarre G, et al. Consensus paper: towards a systems-level view of cerebellar function: the interplay between cerebellum, basal ganglia, and cortex. Cerebellum. 2017;16(1):203–29.

    Article  PubMed  Google Scholar 

  28. Silveri MC. Contribution of the cerebellum and the basal ganglia to language production: speech, word fluency, and sentence construction-evidence from pathology. Cerebellum. 2021;20(2):282–94.

    Article  PubMed  Google Scholar 

  29. Pisano TJ, Dhanerawala ZM, Kislin M, et al. Homologous organization of cerebellar pathways to sensory, motor, and associative forebrain. Cell Rep. 2021;36(12):109721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wagner MJ, Kim TH, Savall J, Schnitzer MJ, Luo L. Cerebellar granule cells encode the expectation of reward. Nature. 2017;544(7648):96–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Carta I, Chen CH, Schott AL at al. Cerebellar modulation of the reward circuitry and social behavior. Science. 2019;363(6424):eaa0581.

  32. Fujita H, Kodama T, du Lac S. Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis. Elife. 2020;8(9):e58613.

    Article  Google Scholar 

  33. Tsai PT, Hull C, Chu Y, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. 2012;488(7413):647–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kelly E, Meng F, Fujita H, et al. Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits. Nat Neurosci. 2020;23(9):1102–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain. 1998;121(4):561–79.

    Article  PubMed  Google Scholar 

  36. Levisohn L, Cronin-Golomb A, Schmahmann JD. Neuropsychological consequences of cerebellar tumor resection in children: cerebellar cognitive affective syndrome in a pediatric population. Brain. 2000;123:1041–50.

    Article  PubMed  Google Scholar 

  37. Manto M, Mariën P. Schmahmann’s syndrome - identification of the third cornerstone of clinical ataxiology. Cerebellum. 2015;2:2.

    Article  Google Scholar 

  38. Hoche F, Guell X, Sherman JC, et al. Cerebellar contribution to social cognition. Cerebellum. 2016;15:732–43.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum. 2007;6:254–67.

    Article  PubMed  Google Scholar 

  40. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–76.

    Article  CAS  PubMed  Google Scholar 

  41. Tedesco AM, Chiricozzi FR, Clausi S, Lupo M, Molinari M, Leggio MG. The cerebellar cognitive profile. Brain. 2011;134(Pt 12):3672–86.

    Article  PubMed  Google Scholar 

  42. Ahmadian N, van Baarsen K, van Zandvoort M, Robe PA. The cerebellar cognitive affective syndrome-a meta-analysis. Cerebellum. 2019;18(5):941–50.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hoche F, Guell X, Vangel MG, Sherman JC, Schmahmann JD. The cerebellar cognitive affective/Schmahmann syndrome scale. Brain. 2018;141(1):248–70.

    Article  PubMed  Google Scholar 

  44. Rodríguez-Labrada R, Batista-Izquierdo A, González-Melix Z, et al. Cognitive decline is closely associated with ataxia severity in spinocerebellar ataxia type 2: a validation study of the Schmahmann Syndrome Scale. Cerebellum. 2022;21(3):391–403.

    Article  PubMed  Google Scholar 

  45. Gudrunardottir T, Morgan AT, Lux AL, et al. Iceland Delphi Group. Consensus paper on post-operative pediatric cerebellar mutism syndrome: the Iceland Delphi results. Childs Nerv Syst. 2016;32(7):1195–203.

    Article  PubMed  Google Scholar 

  46. Albazron FM, Bruss J, Jones RM, et al. Pediatric postoperative cerebellar cognitive affective syndrome follows outflow pathway lesions. Neurology. 2019;93(16):e1561–71.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Schmahmann JD, Doyon J, McDonald D, et al. Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space. Neuroimage. 1999;10(3 Pt 1):233–60.

    Article  CAS  PubMed  Google Scholar 

  48. Schmahmann JD, Doyon J, Toga A, et al. MRI atlas of the human cerebellum. San Diego: Academic Press; 2000.

    Google Scholar 

  49. Larsell O, Jansen J. The comparative anatomy and histology of the cerebellum. The human cerebellum, cerebellar connections, and cerebellar cortex. 1972. Univ. Minnesota Press, Minneapolis.

  50. Diedrichsen J, Balsters JH, Flavell J, et al. A probabilistic MR atlas of the human cerebellum. Neuroimage. 2009;46(1):39–46.

    Article  PubMed  Google Scholar 

  51. Stoodley CJ, MacMore JP, Makris N, Sherman JC, Schmahmann JD. Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke. Neuroimage Clin. 2016;12:765–75.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage. 2009;44(2):489–501.

    Article  PubMed  Google Scholar 

  53. Stoodley CJ, Valera EM, Schmahmann JD. Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. Neuroimage. 2012;59:1560–70.

    Article  PubMed  Google Scholar 

  54. Guell X, Gabrieli JDE, Schmahmann JD. Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort. Neuroimage. 2018;172:437–49.

    Article  PubMed  Google Scholar 

  55. King M, Hernandez-Castillo CR, Poldrack RA, et al. Functional boundaries in the human cerebellum revealed by a multi-domain task battery. Nat Neurosci. 2019;22(8):1371–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Buckner RL, Krienen FM, Castellanos A, et al. The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:2322–45.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Habas C, Kamdar N, Nguyen D, et al. Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci. 2009;29(26):8586–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. O’Reilly JX, Beckmann CF, Tomassini V, Ramnani N, Johansen-Berg H. Distinct and overlapping functional zones in the cerebellum defined by resting state functional connectivity. Cereb Cortex. 2010;20(4):953–65.

    Article  PubMed  Google Scholar 

  59. Halko MA, Farzan F, Eldaief MC, Schmahmann JD, Pascual-Leone A. Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network. J Neurosci. 2014;34(36):12049–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Farzan F, Pascual-Leone A, Schmahmann JD, Halko M. Enhancing the temporal complexity of distributed brain networks with patterned cerebellar stimulation. Sci Rep. 2016;6:23599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Demirtas-Tatlidede A, Freitas C, Cromer JR, et al. Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia. Schizophr Res. 2010;124(1–3):91–100.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Brady RO Jr, Gonsalvez I, Lee I, Öngür D, et al. Cerebellar-prefrontal network connectivity and negative symptoms in schizophrenia. Am J Psychiatry. 2019;176(7):512–20.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Guo CC, Tan R, Hodges JR, Hu X, Sami S, Hornberger M. Network-selective vulnerability of the human cerebellum to Alzheimer’s disease and frontotemporal dementia. Brain. 2016;139(Pt 5):1527–38.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Schmahmann JD. Cerebellum in Alzheimer’s disease and frontotemporal dementia: not a silent bystander. Brain. 2016;139(Pt 5):1314–8.

    Article  PubMed  Google Scholar 

  65. Jacobs HIL, Hopkins DA, Mayrhofer HC, et al. The cerebellum in Alzheimer’s disease: evaluating its role in cognitive decline. Brain. 2018;141(1):37–47.

    Article  PubMed  Google Scholar 

  66. Wolpert DM, Miall RC, Kawato M. Internal models in the cerebellum. Trends Cogn Sci. 1998;2(9):338–47.

    Article  CAS  PubMed  Google Scholar 

  67. Ebner TJ. Cerebellum and internal models. In: Manto M, Schmahmann JD, Rossi F, Gruol DL, Koibuchi N. (eds) Handbook of the cerebellum and cerebellar disorders. 2013: 1279–1295. Springer, Dordrecht.

  68. Ito M. Control of mental activities by internal models in the cerebellum. Nat Rev Neurosci. 2008;9(4):304–13.

    Article  CAS  PubMed  Google Scholar 

  69. Land MF. Do we have an internal model of the outside world? Philos Trans R Soc Lond B Biol Sci. 2014;369(1636):20130045.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Falcon A. Aristotle on causality, in Edward N Zalta (ed.), The Stanford Encyclopedia of Philosophy, Spring 2022.

  71. Guell X, Schmahmann J. Cerebellar functional anatomy: a didactic summary based on human fMRI evidence. Cerebellum. 2020;19(1):1–5.

    Article  PubMed  Google Scholar 

  72. Xue A, Kong R, Yang Q, et al. The detailed organization of the human cerebellum estimated by intrinsic functional connectivity within the individual. J Neurophysiol. 2021;125(2):358–84.

    Article  PubMed  Google Scholar 

  73. Schmahmann JD, Pandya DN. Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems. Cortex. 2008;44(8):1037–66.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Whiting BA, Barton RA. The evolution of the cortico-cerebellar complex in primates: anatomical connections predict patterns of correlated evolution. J Hum Evol. 2003;44(1):3–10.

    Article  CAS  PubMed  Google Scholar 

  75. Parvizi J. Corticocentric myopia: old bias in new cognitive sciences. Trends Cogn Sci. 2009;13(8):354–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Supported in part by the MINDLink Foundation and the National Ataxia Foundation. The assistance of Jason MacMore is greatly appreciated.

Author information

Authors and Affiliations

  1. Ataxia Center, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Suite 2000, Boston, MA, 02114, USA

    Jeremy D. Schmahmann

Authors
  1. Jeremy D. Schmahmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeremy D. Schmahmann.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schmahmann, J.D. Ferdinando Rossi Lecture: the Cerebellar Cognitive Affective Syndrome—Implications and Future Directions. Cerebellum 22, 947–953 (2023). https://doi.org/10.1007/s12311-022-01456-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-022-01456-7

Search

Navigation