Cerebellar Crus I and Crus II Structure and Excitation/Inhibition Balance in Autism Spectrum Disorder

This publication is included in the Autistic Autism Scholarship Project. one author of this publication is identified as autistic in the project.

About the autistic author marker

Hegarty, J. P., Komaki, H., Gu, M., Young, K., Ogbonnaya, N., Spielman, D. M., & Hardan, A. Y. (2026). Cerebellar Crus I and Crus II Structure and Excitation/Inhibition Balance in Autism Spectrum Disorder. Journal of Autism and Developmental Disorders. https://doi.org/10.1007/s10803-026-07529-4

Publication date: 8 Oct 2026 Added to AutiHub: 10 Oct 2026 Type: Article Article language: English

This publication is integrated into AutiHub through:

Authors

Publication authors
7
Publication authors identified as autistic
1 / 7 (14.3%)

Abstract

PURPOSE: Cerebro-cerebellar network dynamics are highly implicated in autism spectrum disorder (ASD), particularly the posterolateral cerebellar hemispheres. Cellular alterations in the cerebellum are also consistently reported in post-mortem research, suggesting potential impacts on the balance between excitatory glutamatergic (Glu) and inhibitory GABAergic signaling (E/I). Emerging evidence further indicates that the cerebellum supports multiple cognitive and behavioral domains associated with the diagnostic criteria for ASD. METHODS: The current study collected structural T1-weighted MRI and novel 1H MR spectroscopy data (MEGA-SPECIAL) to examine neurometabolites of Glu and GABA from the cerebellar hemispheres of autistic (n=13) and neurotypical children (n =16). We also explored preliminary comparisons with autistic adolescents (n=7) and assessed relationships for social communication, restricted and repetitive behaviors, and sensory processing differences. RESULTS: Crus I and II were significantly thinner in autistic children compared to neurotypical children. While there were no significant group differences in the subset of participants with quality neurometabolite measurements, p > 0.05, there were salient relationships between E/I, cerebellar structure, and core ASD domains. Thinner Crus I grey matter and smaller Crus II volume were correlated with higher E/I, especially for Glu in left Crus I and right Crus II. Morphometric properties and E/I were also associated with self-injurious and other restricted and repetitive behaviors. CONCLUSION: Our preliminary findings are limited by the small sample size but suggest a potential relationship between cerebellar structure, the balance of excitation-inhibition in cerebro-cerebellar networks, and the core domains of autism spectrum disorder.

Bibliography cited by this reference

Cited references are imported from external metadata sources when they are available. The list may be partial.

Cited bibliography overview

These indicators describe the bibliography cited by this publication. An author name is counted each time it appears in one cited reference, so the same person can be counted more than once. Names not yet linked to an author already present in AutiHub are treated as unknown, not as non-autistic. Last computed: 17 Oct 2026 01:01.

Cited references
60
With a DOI
54
Without a DOI, from raw bibliography text
6
3 / 60 (5.0%) cited references include at least one author identified as autistic.
References with data to complete
2 / 60 (3.3%)
References with detected author names
59 / 60 (98.3%)
Without detected author names
1
Without a structured title
2
Without a stable identifier
6
References with raw author names still to review
1
References with external metadata lookup issues
1
These indicators apply to cited references displayed on this page, after technical duplicates have been merged. A reference without a DOI can still support author statistics when a title and author names are available.
Author names detected in the cited bibliography
393
From DOI or external metadata
393
From validated raw bibliography text
0
Raw names already validated
0
Raw names still to review
1
77 / 393 (19.6%) names are linked to an author already present in AutiHub. 316 / 393 (80.4%) names are not yet linked.
Names linked to a person identified as autistic
3 / 393 (0.8%)
Calculated across all author names detected in the cited bibliography. Among names linked to an author already present in AutiHub: 3 / 77 (3.9%). Distinct people identified as autistic: 1 / 354 (0.3%).
  1. Stephen W. Provencher (2001). Automatic quantitation of localized in vivo 1 H spectra with LCModel . NMR in Biomedicine, 14(4), 260. Wiley.
    Type: Article DOI: 10.1002/nbm.698 OpenAlex: https://openalex.org/W1730237872
    Crossref OpenAlex
  2. T. M. Achenbach , T. M. Ruffle (2000). The Child Behavior Checklist and Related Forms for Assessing Behavioral/Emotional Problems and Competencies . Pediatrics in Review, 21(8), 265. American Academy of Pediatrics (AAP).
    Crossref OpenAlex
  3. Anila M. D'Mello , Catherine J. Stoodley (2015). Cerebro-cerebellar circuits in autism spectrum disorder . Frontiers in Neuroscience, 9, 40. Frontiers Media SA.
    Crossref OpenAlex
  4. David G. Amaral , Cynthia Mills Schumann , Christine Wu Nordahl (2008). Neuroanatomy of autism . Trends in Neurosciences, 31(3), 137. Elsevier BV.
    Crossref OpenAlex
  5. Catherine Lord , Michael Rutter , Ann Le Couteur (1994). Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders . Journal of Autism and Developmental Disorders, 24(5), 659. Springer Science and Business Media LLC.
    Crossref OpenAlex
  6. Y Aoki , K Kasai , H Yamasue (2012). Age-related change in brain metabolite abnormalities in autism: a meta-analysis of proton magnetic resonance spectroscopy studies . Translational Psychiatry, 2(1), e69. Springer Science and Business Media LLC.
    Crossref OpenAlex
  7. C STOODLEY , J SCHMAHMANN (2009). Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies . NeuroImage, 44(2), 489. Elsevier BV.
    Crossref OpenAlex
  8. Tiffany Bell , Mehak Stokoe , Ashley D. Harris (2021). Macromolecule suppressed GABA levels show no relationship with age in a pediatric sample . Scientific Reports, 11(1), 722-722. Springer Science and Business Media LLC.
    Crossref OpenAlex
  9. Catherine J. Stoodley , Eve M. Valera , Jeremy D. Schmahmann (2012). Functional topography of the cerebellum for motor and cognitive tasks: An fMRI study . NeuroImage, 59(2), 1560. Elsevier BV.
    Crossref OpenAlex
  10. Yoav Benjamini , Yosef Hochberg (1995). Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing . Journal of the Royal Statistical Society. Series b, Statistical Methodology, 57(1), 289. Oxford University Press (OUP).
    Crossref OpenAlex
  11. Christine Wu Nordahl , Tony J. Simon , Cynthia Zierhut , Marjorie Solomon , Sally J. Rogers , David G. Amaral (2008). Brief Report: Methods for Acquiring Structural MRI Data in Very Young Children with Autism Without the Use of Sedation . Journal of Autism and Developmental Disorders, 38(8), 1581. Springer Science and Business Media LLC.
    Crossref OpenAlex
  12. Fréderique Bonnet‐Brilhault , Toky A. Rajerison , Christian Paillet , Marie Guimard‐Brunault , Agathe Saby , Laura Ponson et al. (2018). Autism is a prenatal disorder: Evidence from late gestation brain overgrowth . Autism Research, 11(12), 1635. Wiley.
    Type: Article DOI: 10.1002/aur.2036 OpenAlex: https://openalex.org/W2902765223
    Crossref OpenAlex
  13. Amanda J. Khan , Aarti Nair , Christopher L. Keown , Michael C. Datko , Alan J. Lincoln , Ralph-Axel Müller (2015). Cerebro-cerebellar Resting-State Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder . Biological Psychiatry, 78(9), 625-634. Elsevier BV.
    Crossref OpenAlex
  14. Hu Cheng , Amanda Wang , Sharlene Newman , Ulrike Dydak (2021). An investigation of glutamate quantification with PRESS and MEGA‐PRESS . NMR in Biomedicine, 34(2), e4453-e4453. Wiley.
    Type: Article DOI: 10.1002/nbm.4453 OpenAlex: https://openalex.org/W3107226841
    Crossref OpenAlex
  15. S. Hossein Fatemi , Kimberly A. Aldinger , Paul Ashwood , Margaret Bauman , Charles D. Blaha , Gene J. Blatt et al. (2012). Consensus Paper: Pathological Role of the Cerebellum in Autism . The Cerebellum, 11(3), 777. Springer Science and Business Media LLC.
    Crossref OpenAlex
  16. Sarah V. Clark , Eric S. Semmel , Holly A. Aleksonis , Stephanie N. Steinberg , Tricia Z. King (2021). Cerebellar-Subcortical-Cortical Systems as Modulators of Cognitive Functions . Neuropsychology Review, 31(3), 422. Springer Science and Business Media LLC.
    Crossref OpenAlex
  17. Jaimie F. Veale (2014). Edinburgh Handedness Inventory – Short Form: A revised version based on confirmatory factor analysis . Laterality, 19(2), 164. Informa UK Limited.
    Crossref OpenAlex
  18. JN Constantino (2007). Social responsiveness scale (SRS) . Social responsiveness scale (SRS).
    Type: Other
    Crossref
  19. Catherine J. Stoodley (2014). Distinct regions of the cerebellum show gray matter decreases in autism, ADHD, and developmental dyslexia . Frontiers in Systems Neuroscience, 8, 92. Frontiers Media SA.
    Crossref OpenAlex
  20. Dario Cupolillo , Eriola Hoxha , Alessio Faralli , Annarita De Luca , Ferdinando Rossi , Filippo Tempia et al. (2016). Autistic-Like Traits and Cerebellar Dysfunction in Purkinje Cell PTEN Knock-Out Mice . Neuropsychopharmacology, 41(6), 1457. Springer Science and Business Media LLC.
    Crossref OpenAlex
  21. Ruth C.M. Philip , Maria R. Dauvermann , Heather C. Whalley , Katie Baynham , Stephen M. Lawrie , Andrew C. Stanfield (2012). A systematic review and meta-analysis of the fMRI investigation of autism spectrum disorders . Neuroscience and Biobehavioral Reviews, 36(2), 901. Elsevier BV.
    Crossref OpenAlex
  22. Tamer H. Hassan , Hadeel M. Abdelrahman , Nelly R. Abdel Fattah , Nagda M. El-Masry , Haitham M. Hashim , Khaled M. El-Gerby et al. (2013). Blood and brain glutamate levels in children with autistic disorder . Research in Autism Spectrum Disorders, 7(4), 541. Elsevier BV.
    Crossref OpenAlex
  23. W Dunn (1999). Short sensory profile . Short sensory profile.
    Type: Other
    Crossref
  24. Paul G. Mullins , David J. McGonigle , Ruth L. O'Gorman , NA Puts , Rishma Vidyasagar , C. John Evans et al. (2014). Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA . NeuroImage, 86, 43. Elsevier BV.
    Crossref OpenAlex
  25. Meng Gu , Ralph Hurd , Ralph Noeske , Laima Baltusis , Roeland Hancock , Matthew D. Sacchet et al. (2018). GABA editing with macromolecule suppression using an improved MEGA‐SPECIAL sequence . Magnetic Resonance in Medicine, 79(1), 41. Wiley.
    Crossref OpenAlex
  26. Catherine J. Stoodley , Jeremy D. Schmahmann (2010). Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing . Cortex, 46(7), 831. Elsevier BV.
    Crossref OpenAlex
  27. Kristen S. L. Lam , Michael G. Aman (2007). The Repetitive Behavior Scale-Revised: Independent Validation in Individuals with Autism Spectrum Disorders . Journal of Autism and Developmental Disorders, 37(5), 855. Springer Science and Business Media LLC.
    Crossref OpenAlex
  28. J. Schmahmann (1998). The cerebellar cognitive affective syndrome . Brain, 121(4), 561. Oxford University Press (OUP).
    Crossref OpenAlex
  29. Catherine Limperopoulos , Haim Bassan , Kimberlee Gauvreau , Richard L. Robertson , Nancy R. Sullivan , Carol B. Benson et al. (2007). Does Cerebellar Injury in Premature Infants Contribute to the High Prevalence of Long-term Cognitive, Learning, and Behavioral Disability in Survivors? Pediatrics, 120(3), 584. American Academy of Pediatrics (AAP).
    Crossref OpenAlex
  30. Hollingshead, A. A. (1975). Four-factor index of social status. In Y. University (Ed.), Unpublished manuscript.
    Type: Other
    Crossref
  31. Dennis K. Kinney , Andrea M. Miller , David J. Crowley , Emerald Huang , Erika Gerber (2008). Autism Prevalence Following Prenatal Exposure to Hurricanes and Tropical Storms in Louisiana . Journal of Autism and Developmental Disorders, 38(3), 481. Springer Science and Business Media LLC.
    Crossref OpenAlex
  32. Hiromichi Ito , Kenji Mori , Masafumi Harada , Sonoka Hisaoka , Yoshihiro Toda , Tatsuo Mori et al. (2017). A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum . Journal of Child Neurology, 32(8), 731. SAGE Publications.
    Crossref OpenAlex
  33. Kalyani Kansal , Zhen Yang , Ann M. Fishman , Haris I. Sair , Sarah H. Ying , Bruno M. Jedynak et al. (2017). Structural cerebellar correlates of cognitive and motor dysfunctions in cerebellar degeneration . Brain, 140(3), 707. Oxford University Press (OUP).
    Crossref OpenAlex
  34. Joseph J. Volpe (2009). Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important . Journal of Child Neurology, 24(9), 1085. SAGE Publications.
    Crossref OpenAlex
  35. Daria Riva , Silvia Annunziata , Valeria Contarino , Alessandra Erbetta , Domenico Aquino , Sara Bulgheroni (2013). Gray Matter Reduction in the Vermis and CRUS-II Is Associated with Social and Interaction Deficits in Low-Functioning Children with Autistic Spectrum Disorders: a VBM-DARTEL Study . The Cerebellum, 12(5), 676. Springer Science and Business Media LLC.
    Crossref OpenAlex
  36. M. Mescher , H. Merkle , J. Kirsch , M. Garwood , R. Gruetter (1998). Simultaneousin vivo spectral editing and water suppression . NMR in Biomedicine, 11(6), 266. Wiley.
    Crossref OpenAlex
  37. Jeremy D. Schmahmann (2004). Disorders of the Cerebellum: Ataxia, Dysmetria of Thought, and the Cerebellar Cognitive Affective Syndrome . The Journal of Neuropsychiatry and Clinical Neurosciences, 16(3), 367. American Psychiatric Association Publishing.
    Crossref OpenAlex
  38. Catherine Lord (2012). Autism diagnostic observation schedule: ADOS-2 . Autism diagnostic observation schedule: ADOS-2.
    Type: Other
    Crossref
  39. Christine Wu Nordahl , Melissa Mello , Audrey M. Shen , Mark D. Shen , Laurie A. Vismara , Deana Li et al. (2016). Methods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation . Journal of Neurodevelopmental Disorders, 8(1), 1. Springer Science and Business Media LLC.
    Crossref OpenAlex
  40. Saša Peter , Michiel M. ten Brinke , Jeffrey Stedehouder , Claudia M. Reinelt , Bin Wu , Haibo Zhou et al. (2016). Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice . Nature Communications, 7(1), 12627-12627. Springer Science and Business Media LLC.
    Crossref OpenAlex
  41. Athanasia Metoki , Yin Wang , Ingrid R Olson (2022). The Social Cerebellum: A Large-Scale Investigation of Functional and Structural Specificity and Connectivity . Cerebral Cortex, 32(5), 987. Oxford University Press (OUP).
    Crossref OpenAlex
  42. Sergio Morell-Ortega , Marina Ruiz-Perez , Marien Gadea , Roberto Vivo-Hernando , Gregorio Rubio , Fernando Aparici et al. (2025). DeepCERES: A deep learning method for cerebellar lobule segmentation using ultra-high resolution multimodal MRI . NeuroImage, 308, 121063. Elsevier BV.
    Crossref OpenAlex
  43. EM Mullen (1995). Mullen scales of early learning . Mullen scales of early learning.
    Type: Other
    Crossref
  44. Catherine J. Stoodley , Anila M. D’Mello , Jacob Ellegood , Vikram Jakkamsetti , Pei Liu , Mary Beth Nebel et al. (2017). Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice . Nature Neuroscience, 20(12), 1744. Springer Science and Business Media LLC.
    Crossref OpenAlex
  45. Georg Oeltzschner , Helge J. Zöllner , Steve C.N. Hui , Mark Mikkelsen , Muhammad G. Saleh , Sofie Tapper et al. (2020). Osprey: Open-source processing, reconstruction & estimation of magnetic resonance spectroscopy data . Journal of Neuroscience Methods, 343, 108827. Elsevier BV.
    Crossref OpenAlex
  46. R. C. Oldfield (2013). Edinburgh Handedness Inventory . Journal of Abnormal Psychology. American Psychological Association (APA).
    Crossref OpenAlex
  47. Susanne Weigend , Sebastian C Holst , Valérie Treyer , Ruth L O’Gorman Tuura , Josefine Meier , Simon M Ametamey et al. (2019). Dynamic changes in cerebral and peripheral markers of glutamatergic signaling across the human sleep–wake cycle . Sleep, 42(11). Oxford University Press (OUP).
    Crossref OpenAlex
  48. Jennifer M. Phillips , Mirko Uljarević , Rachel K. Schuck , Salena Schapp , Elizabeth M. Solomon , Emma Salzman et al. (2019). Development of the Stanford Social Dimensions Scale: initial validation in autism spectrum disorder and in neurotypicals . Molecular Autism, 10(1), 1. Springer Science and Business Media LLC.
    Crossref OpenAlex
  49. Frank Van Overwalle , Mario Manto , Zaira Cattaneo , Silvia Clausi , Chiara Ferrari , John D. E. Gabrieli et al. (2020). Consensus Paper: Cerebellum and Social Cognition . The Cerebellum, 19(6), 833. Springer Science and Business Media LLC.
    Crossref OpenAlex
  50. GH Roid (2012). Contemporary intellectual assessment: Theories, tests, and issues . Contemporary intellectual assessment: Theories, tests, and issues, 249.
    Type: Other
    Crossref
  51. JL Rubenstein (2003). Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: Increased ratio of excitation/inhibition in key neural systems. Genes, Brain, and Behavior, 2(5), 255–267. https://doi.org/10 . 1046/j. 1601-183X. 2003. 00037.x Genes, Brain, and Behavior, 2(5), 255.
    Crossref
  52. Mirko Uljarević , Thomas W. Frazier , Booil Jo , Lawrence Scahill , Eric A. Youngstrom , Emily Spackman et al. (2023). Dimensional Assessment of Restricted and Repetitive Behaviors: Development and Preliminary Validation of a New Measure . Journal of the American Academy of Child & Adolescent Psychiatry, 62(5), 568-581. Elsevier BV.
    Crossref OpenAlex
  53. Kelly A. Shaw , Susan Williams , Mary E. Patrick , Miguel Valencia-Prado , Maureen S. Durkin , Ellen M. Howerton et al. (2025). Prevalence and Early Identification of Autism Spectrum Disorder Among Children Aged 4 and 8 Years — Autism and Developmental Disabilities Monitoring Network, 16 Sites, United States, 2022 . MMWR. Surveillance Summaries, 74(2), 1-22. Centers for Disease Control MMWR Office.
    Crossref OpenAlex
  54. Judith A.W. Westerhuis , Jeroen Dudink , Chris I. De Zeeuw , Cathrin B. Canto (2024). Critical Periods and Vulnerability of Cerebellar Development in Human and Rodent . Preprints.org. MDPI AG.
    Crossref OpenAlex
  55. Alice R Thomson , Hannah Hwa , Duanghathai Pasanta , Benjamin Hopwood , Helen Powell , Ross Lawrence et al. (2024). The developmental trajectory of 1H-MRS brain metabolites from childhood to adulthood . Cerebral Cortex, 34(3). Oxford University Press (OUP).
    Crossref OpenAlex
  56. Alice R. Thomson , Duanghathai Pasanta , Tomoki Arichi , NA Puts (2024). Neurometabolite differences in Autism as assessed with Magnetic Resonance Spectroscopy: A systematic review and meta-analysis . Neuroscience and Biobehavioral RevieWs, 162, 105728. Elsevier BV.
    Crossref OpenAlex
  57. Yu Wang , Aihua Cao , Jing Wang , He Bai , Tianci Liu , Chenxi Sun et al. (2025). Abnormalities in cerebellar subregions' volume and cerebellocerebral structural covariance in autism spectrum disorder . Autism Research, 18(1), 83. Wiley.
    Type: Article DOI: 10.1002/aur.3287 OpenAlex: https://openalex.org/W4406021311
    Crossref OpenAlex