Contributions of Cerebellar White Matter Microstructure to Social Difficulty in Nonverbal Learning Disability


Emerging evidence suggests that the cerebellum may contribute to variety of cognitive capacities, including social cognition. Nonverbal learning disability (NVLD) is characterized by visual-spatial and social impairment. Recent functional neuroimaging studies have shown that children with NVLD have altered cerebellar resting-state functional connectivity, which is associated with various symptom domains. However, little is known about cerebellar white matter microstructure in NVLD and whether it contributes to social deficits. Twenty-seven children (12 with NVLD, 15 typically developing (TD)) contributed useable diffusion tensor imaging data. Tract-based spatial statistics (TBSS) were used to quantify fractional anisotropy (FA) in the cerebellar peduncles. Parents completed the Child Behavior Checklist, providing a measure of social difficulty. Children with NVLD had greater fractional anisotropy in the left and right inferior cerebellar peduncle. Furthermore, right inferior cerebellar peduncle FA was associated with social impairment as measured by the Child Behavior Checklist Social Problems subscale. Finally, the association between NVLD diagnosis and greater social impairment was mediated by right inferior cerebellar peduncle FA. These findings provide additional evidence that the cerebellum contributes both to social cognition and to the pathophysiology of NVLD.

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  1. 1.

    Margolis AE, Broitman J, Davis JM, Alexander L, Hamilton A, Liao Z, Banker S, Thomas L, Ramphal B, Salum GA, Merikangas K, Goldsmith J, Paus T, Keyes K, Milham MP. Estimated prevalence of nonverbal learning disability among North American children and adolescents. JAMA Network Open. 2020;3:e202551.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Banker SM, Pagliaccio D, Ramphal B, Thomas L, Dranovsky A, Margolis AE. Altered structure and functional connectivity of the hippocampus are associated with social and mathematical difficulties in nonverbal learning disability. Hippocampus 2020: n/a.

  3. 3.

    Banker SM, Ramphal B, Pagliaccio D, Thomas L, Rosen E, Sigel AN, Zeffiro T, Marsh R, Margolis AE. Spatial network connectivity and spatial reasoning ability in children with nonverbal learning disability. Sci Rep. 2020;10:561.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Margolis AE, Pagliaccio D, Thomas L, Banker S, Marsh R. Salience network connectivity and social processing in children with nonverbal learning disability or autism spectrum disorder. Neuropsychology. 2019;33:135–43.

    Article  PubMed  Google Scholar 

  5. 5.

    Van Overwalle F, Manto M, Cattaneo Z, Clausi S, Ferrari C, Gabrieli JDE, Guell X, Heleven E, Lupo M, Ma Q, Michelutti M, Olivito G, Pu M, Rice LC, Schmahmann JD, Siciliano L, Sokolov AA, Stoodley CJ, van Dun K, Vandervert L, Leggio M. Consensus paper: cerebellum and social cognition. The Cerebellum. 2020.

    Article  PubMed  Google Scholar 

  6. 6.

    Semrud-Clikeman M, Walkowiak J, Wilkinson A, Minne EP. Direct and indirect measures of social perception, behavior, and emotional functioning in children with Asperger’s disorder, nonverbal learning disability, or ADHD. J Abnorm Child Psychol. 2010;38:509–19.

    Article  PubMed  Google Scholar 

  7. 7.

    Heleven E, van Dun K, Van Overwalle F. The posterior cerebellum is involved in constructing social action sequences: an fMRI study. Sci Rep. 2019;9:11110.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Van Overwalle F, Ma Q, Heleven E. The posterior crus II cerebellum is specialized for social mentalizing and emotional self-experiences: a meta-analysis. Soc Cogn Affect Neurosci. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Olivito G, Lupo M, Laghi F, Clausi S, Baiocco R, Cercignani M, Bozzali M, Leggio M. Lobular patterns of cerebellar resting-state connectivity in adults with autism spectrum disorder. Eur J Neurosci. 2018;47:729–35.

    Article  PubMed  Google Scholar 

  10. 10.

    Stoodley CJ, D’Mello AM, Ellegood J, Jakkamsetti V, Liu P, Nebel MB, Gibson JM, Kelly E, Meng F, Cano CA, Pascual JM, Mostofsky SH, Lerch JP, Tsai PT. Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice. Nat Neurosci. 2017;20:1744–51.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    D’Mello AM, Crocetti D, Mostofsky SH, Stoodley CJ. Cerebellar gray matter and lobular volumes correlate with core autism symptoms. Neuroimage Clin. 2015;7:631–9.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Shukla DK, Keehn B, Lincoln AJ, Müller RA. White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study. J Am Acad Child Adolesc Psychiatry. 2010;49(1269–78):78.e1-2.

    Article  Google Scholar 

  13. 13.

    Catani M, Jones DK, Daly E, Embiricos N, Deeley Q, Pugliese L, Curran S, Robertson D, Murphy DGM. Altered cerebellar feedback projections in Asperger syndrome. Neuroimage. 2008;41:1184–91.

    Article  PubMed  Google Scholar 

  14. 14.

    Hanaie R, Mohri I, Kagitani-Shimono K, Tachibana M, Azuma J, Matsuzaki J, Watanabe Y, Fujita N, Taniike M. Altered microstructural connectivity of the superior cerebellar peduncle is related to motor dysfunction in children with autistic spectrum disorders. Cerebellum. 2013;12:645–56.

    Article  PubMed  Google Scholar 

  15. 15.

    Sivaswamy L, Kumar A, Rajan D, Behen M, Muzik O, Chugani D, Chugani H. A diffusion tensor imaging study of the cerebellar pathways in children with autism spectrum disorder. J Child Neurol. 2010;25:1223–31.

    Article  PubMed  Google Scholar 

  16. 16.

    Brito AR, Vasconcelos MM, Domingues RC, Hygino da Cruz LC Jr, Rodrigues LS, Gasparetto EL, Calçada CA. Diffusion tensor imaging findings in school-aged autistic children. J Neuroimaging. 2009;19:337–43.

    Article  PubMed  Google Scholar 

  17. 17.

    Okugawa G, Nobuhara K, Minami T, Takase K, Sugimoto T, Saito Y, Yoshimura M, Kinoshita T. Neural disorganization in the superior cerebellar peduncle and cognitive abnormality in patients with schizophrenia: a diffusion tensor imaging study. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1408–12.

    Article  PubMed  Google Scholar 

  18. 18.

    Thomas AR, Lacadie C, Vohr B, Ment LR, Scheinost D. Fine motor skill mediates visual memory ability with microstructural neuro-correlates in cerebellar peduncles in prematurely born adolescents. Cereb Cortex. 2017;27:322–9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Davis K, Margolis AE, Thomas L, Huo Z, Marsh R. Amygdala sub-regional functional connectivity predicts anxiety in children with reading disorder. Dev Sci. 2018;21:e12631.

    Article  PubMed  Google Scholar 

  20. 20.

    Ramphal B, DeSerisy M, Pagliaccio D, Raffanello E, Rauh V, Tau G, Posner J, Marsh R, Margolis A. Associations between amygdala-prefrontal functional connectivity and age depend on neighborhood socioeconomic status. Cerebral Cortex Communications. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    He X, Liu W, Li X, Li Q, Liu F, Rauh VA, Yin D, Bansal R, Duan Y, Kangarlu A, Peterson BS, Xu D. Automated assessment of the quality of diffusion tensor imaging data using color cast of color-encoded fractional anisotropy images. Magn Reson Imaging. 2014;32:446–56.

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23:S208–19.

    Article  Google Scholar 

  23. 23.

    Andersson JLR, Sotiropoulos SN. An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. Neuroimage. 2016;125:1063–78.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Andersson JLR, Graham MS, Drobnjak I, Zhang H, Filippini N, Bastiani M. Towards a comprehensive framework for movement and distortion correction of diffusion MR images: within volume movement. Neuroimage. 2017;152:450–66.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 2006;31:1487–505.

    Article  PubMed  Google Scholar 

  26. 26.

    Mori S, Oishi K, Jiang H, Jiang L, Li X, Akhter K, Hua K, Faria AV, Mahmood A, Woods R, Toga AW, Pike GB, Neto PR, Evans A, Zhang J, Huang H, Miller MI, van Zijl P, Mazziotta J. Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. Neuroimage. 2008;40:570–82.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Wakana S, Caprihan A, Panzenboeck MM, Fallon JH, Perry M, Gollub RL, Hua K, Zhang J, Jiang H, Dubey P, Blitz A, van Zijl P, Mori S. Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage. 2007;36:630–44.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Achenbach T, Rescorla L. Manual for the ASEBA school-age forms & profiles: an integrated system of mult-informant assessment. Burlington: University of Vermont, Research Center for Children, Youth & Families; 2001.

    Google Scholar 

  29. 29.

    Constantino JN, Gruber CP. The Social Responsiveness Scale Manual. Los Angeles: Western Psychological Services; 2005.

    Google Scholar 

  30. 30.

    Pagliaccio D. scipub: Summarize Data for Scientific Publication R package version 1.1.0. Accessed 6 Jan 2021.

  31. 31.

    Jones DK, Knösche TR, Turner R. White matter integrity, fiber count, and other fallacies: the doʼs and donʼts of diffusion MRI. Neuroimage. 2013;73:239–54.

    Article  PubMed  Google Scholar 

  32. 32.

    Kitazawa S, Kimura T, Yin P-B. Cerebellar complex spikes encode both destinations and errors in arm movements. Nature. 1998;392:494–7.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Ebner TJ, Hewitt AL, Popa LS. What features of limb movements are encoded in the discharge of cerebellar neurons? Cerebellum (London, England). 2011;10:683–93.

    Article  Google Scholar 

  34. 34.

    Lang EJ, Apps R, Bengtsson F, Cerminara NL, De Zeeuw CI, Ebner TJ, Heck DH, Jaeger D, Jörntell H, Kawato M. The roles of the olivocerebellar pathway in motor learning and motor control. A consensus paper. Cerebellum. 2017;16:230–52.

    Article  Google Scholar 

  35. 35.

    Ohmae S, Medina JF. Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice. Nat Neurosci. 2015;18:1798–803.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Jossinger S, Mawase F, Ben-Shachar M, Shmuelof L. Locomotor adaptation is associated with microstructural properties of the inferior cerebellar peduncle. Cerebellum. 2020;19:370–82.

    Article  PubMed  Google Scholar 

  37. 37.

    Sokolov AA, Miall RC, Ivry RB. The cerebellum: adaptive prediction for movement and cognition. Trends Cogn Sci. 2017;21:313–32.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Van Overwalle F, Manto M, Leggio M, Delgado-García JM. The sequencing process generated by the cerebellum crucially contributes to social interactions. Med Hypotheses. 2019;128:33–42.

    Article  PubMed  Google Scholar 

  39. 39.

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

    Article  PubMed  Google Scholar 

  40. 40

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

    Article  Google Scholar 

  41. 41.

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

    CAS  Article  PubMed  Google Scholar 

  42. 42.

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

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Xu D, Liu T, Ashe J, Bushara KO. Role of the olivo-cerebellar system in timing. J Neurosci. 2006;26:5990–5.

    CAS  Article  Google Scholar 

  44. 44.

    Wu X, Ashe J, Bushara KO. Role of olivocerebellar system in timing without awareness. Proc Natl Acad Sci. 2011;108:13818.

    Article  PubMed  Google Scholar 

  45. 45.

    Jacobson GA, Rokni D, Yarom Y. A model of the olivo-cerebellar system as a temporal pattern generator. Trends Neurosci. 2008;31:617–25.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Liu T, Xu D, Ashe J, Bushara K. Specificity of inferior olive response to stimulus timing. J Neurophysiol. 2008;100:1557–61.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Mogan R, Fischer R, Bulbulia JA. To be in synchrony or not? A meta-analysis of synchronyʼs effects on behavior, perception, cognition and affect. J Exp Soc Psychol. 2017;72:13–20.

    Article  Google Scholar 

  48. 48.

    LaFrance M. Nonverbal synchrony and rapport: analysis by the cross-lag panel technique. Soc Psychol Q. 1979;42:66–70.

    Article  Google Scholar 

  49. 49.

    Miles LK, Nind LK, Macrae CN. The rhythm of rapport: interpersonal synchrony and social perception. J Exp Soc Psychol. 2009;45:585–9.

    Article  Google Scholar 

  50. 50.

    Hove MJ, Risen JL. Itʼs all in the timing: interpersonal synchrony increases affiliation. Soc Cogn. 2009;27:949–60.

    Article  Google Scholar 

  51. 51.

    Wang Y, Olson IR. The Original Social Network: white matter and social cognition. Trends Cogn Sci. 2018;22:504–16.

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Czekóová K, Zemánková P, Shaw DJ, Bareš M. Social cognition and idiopathic isolated cervical dystonia. J Neural Transm. 2017;124:1097–104.

    Article  PubMed  Google Scholar 

  53. 53.

    Kemp J, Berthel MC, Dufour A, Després O, Henry A, Namer IJ, Musacchio M, Sellal F. Caudate nucleus and social cognition: neuropsychological and SPECT evidence from a patient with focal caudate lesion. Cortex. 2013;49:559–71.

    Article  PubMed  Google Scholar 

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This work was supported by NIEHS grant K23ES026239 (to AEM), the NVLD Project (to AEM), and the Promise Project.

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Correspondence to Amy E. Margolis.

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Ramphal, B., Pagliaccio, D., Thomas, L.V. et al. Contributions of Cerebellar White Matter Microstructure to Social Difficulty in Nonverbal Learning Disability. Cerebellum (2021).

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  • Neurodevelopment
  • Neuroimaging
  • Diffusion tensor imaging
  • Cerebellum
  • Nonverbal learning disability