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Cognitive and behavioural genetics
The cerebellum and embodied semantics: evidence from a case of genetic ataxia due to STUB1 mutations
  1. Adolfo M García1,2,3,
  2. Sofía Abrevaya1,2,
  3. Giselle Kozono1,
  4. Indira García Cordero1,
  5. Marta Córdoba4,
  6. Marcelo Andrés Kauffman4,5,6,
  7. Ricardo Pautassi7,
  8. Edinson Muñoz8,
  9. Lucas Sedeño1,2,
  10. Agustín Ibáñez1,2,9,10,11
  1. 1Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Cognitive and Translational Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina
  2. 2National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina
  3. 3Faculty of Elementary and Special Education (FEEyE), National University of Cuyo (UNCuyo), Mendoza, Argentina
  4. 4Neurogenetics Unit, Hospital JM Ramos Mejía, Buenos Aires, Argentina
  5. 5Instituto de Biología Celular y Neurociencias Eduardo de Robertis, Buenos Aires, Argentina
  6. 6School of Medicine, University of Buenos Aires, National Scientific and Technical Research Council, Buenos Aires, Argentina
  7. 7Instituto Ferreyra (INIMEC, CONICET, UNC), National University of Córdoba, Córdoba, Argentina
  8. 8Facultad de Humanidades, Departamento de Lingüística y Literatura, Universidad de Santiago de Chile, Santiago, Chile
  9. 9Universidad Autónoma del Caribe, Barranquilla, Colombia
  10. 10Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibáñez, Santiago, Chile
  11. 11Centre of Excellence in Cognition and its Disorders, Australian Research Council (ARC), Sydney, Australia
  1. Correspondence to Dr Agustín Ibáñez, Institute of Cognitive and Translational Neuroscience and National Scientific and Technical Research Council, Pacheco de Melo 1860, C1126AAB Buenos Aires, Argentina; aibanez{at}ineco.org.ar

https://doi.org/10.1136/jmedgenet-2016-104148

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    Abundant research on lexicosemantic processing indicates that damage to movement-related regions (the motor and premotor cortices, Broca's area and the basal ganglia1) distinctively impairs processing of action verbs, that is, verbs denoting bodily motion. Moreover, such deficits could be hereditary,2 suggesting an association with genetic factors. We, thus, hypothesised that genetically based deterioration of other motor regions could involve similar impairments. In particular, through a combination of structural and functional MRI (fMRI) with genetic and behavioural analysis, this case study indicates that distinctive action-verb deficits can also be linked to genetic mutations affecting the cerebellum, a key motor hub implicated in balance, posture and movement coordination. Accordingly, in line with the embodied cognition framework, our data illuminate a potential functional specialisation of the cerebellum within the lexicosemantic domain.

    To test our hypothesis, we profited from access to a unique case of genetic ataxia and assessed action-verb processing together with cerebellar atrophy and related functional connectivity. The patient is a 26-year-old, Spanish-speaking male, with 13 years of education and a normal score (26/30) on the Montreal Cognitive Assessment (MoCA). He was diagnosed with cerebellar ataxia plus myoclonus, and exome sequencing revealed novel compound heterozygous mutations in the STUB1 gene3 (see online supplementary appendix e-1). His condition is characterised by severe dysarthria, action and postural tremor in the upper limbs, abnormalities of manual and facial movements and progressive disturbances of balance and gait.

    supplementary appendices

    [jmedgenet-2016-104148supp_appendices.pdf]

    The patient's neurocognitive profile was compared with that of six healthy male participants with no history of neuropsychiatric conditions. This sample had a mean age of 24.17 (SD=2.48), an average of 15 (SD=1.55) years of education and a mean score of 26.67 (SD=1.51) on the MoCA. Crawford's modified two-tailed t-tests (see online supplementary appendix e-2) showed that the patient and the controls were comparable in all these …

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    Footnotes

    • AMG and SA are the first authors.

    • Contributors AMG: study concept and design, analysis and interpretation of data, manuscript writing; SA: acquisition and analysis of data, manuscript writing; GK, IGC: acquisition and analysis of data; MC, RP, EM: critical revision of manuscript for intellectual content; MAK: study supervision, critical revision of manuscript for intellectual content; LS: analysis and interpretation of data, critical revision of manuscript for intellectual content; AI: study concept and design, study supervision, critical revision of manuscript for intellectual content.

    • Funding This work was partially supported by grants from National Scientific and Technical Research Council, CONICYT/FONDECYT Regular (1130920), FONCyT-PICT (grants 2012-0412 and 2012-1309), FONDAP 15150012 and INECO Foundation.

    • Competing interests None.

    • Ethics approval INECO Foundation.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Our data are fully original and available for sharing. No data from the study has been excluded from this manuscript.