Skip to main content
SpringerLink
Log in

Autism Spectrum Disorders and Ataxia

  • Living reference work entry
  • First Online:
Handbook of the Cerebellum and Cerebellar Disorders

  • 90 Accesses

Abstract

Autism is a neurodevelopmental disorder characterized by pervasive deficits in language, behavior, and cognition. Pathology exists throughout the brains of subjects with autism including the cerebellum. These abnormalities include changes in cerebellar and vermal volume, changes in pyramidal cell density, and changes in gray and white matter. Additionally, a number of brain markers associated with GABAergic function, brain development, inflammation, oxidative stress, immune system function, and apoptosis have shown altered expression in the cerebellum of subjects with autism. Initially, it was thought that cerebellar pathology contributed mainly to impaired motor function in autism. Over the past 20 years, however, there has been an increased understanding that the cerebellum is involved in emotional processing, cognition, and other higher brain functions, many of which are impaired in autism. Ataxia, or abnormal gait, is often accompanied by degeneration of the cerebellum. Moreover, similar to autism, ataxia is often associated with deficits in executive function, emotional processing, and cognition. The purpose of this chapter is to summarize findings of cerebellar pathology in autism and how cerebellar pathology may contribute to the behavioral and cognitive aspects of autism and ataxia.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Abrahams BS, Geschwind DH (2010) Connecting genes to brain in autism spectrum disorders. Arch Neurol 67:395–399

    PubMed  PubMed Central  Google Scholar 

  • Adusei DC, Pacey LK, Chen D et al (2010) Early developmental alterations in GABAergic protein expression in fragile X knockout mice. Neuropharmacology 59:167–171

    CAS  PubMed  Google Scholar 

  • Åhsgren I, Baldwin I, Goetzinger-Falk C et al (2005) Ataxia, autism, and the cerebellum: a clinical study of 32 individuals with congenital ataxia. Dev Med Child Neurol 47:193–198

    PubMed  Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5®). American Psychiatric Association, Washington, DC

    Google Scholar 

  • Araghi-Niknam M, Fatemi SH (2003) Levels of Bcl-2 and P53 are altered in superior frontal and cerebellar cortices of autistic subjects. Cell Mol Neurobiol 23:945–952

    CAS  PubMed  Google Scholar 

  • Argyropoulos GPD, van Dun K, Adamaszek M et al (2020) The cerebellar cognitive affective/Schmahmann syndrome: a task force paper. Cerebellum 19(1):102–125

    CAS  PubMed  Google Scholar 

  • Bailey A, Luthert P, Dean A et al (1998) Clinicopathological study of autism. Brain 121:889–905

    PubMed  Google Scholar 

  • Bauman ML, Kemper TL (1985) Histoanatomic observations of the brain in early infantile autism. Neurology 35:866–874

    CAS  PubMed  Google Scholar 

  • Bauman ML, Kemper TL (2003) The neuropathology of autism spectrum disorders: what have we learned? Novartis Found Symp 251:112–122; discussion 22–28, 281–297

    PubMed  Google Scholar 

  • Bauman ML, Kemper TL (2005) Structural brain anatomy in autism: what is the evidence? In: Bauman ML, Kemper TL (eds) The neurobiology of autism. Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Bedogni F, Hodge RD, Nelson BR et al (2010) Autism susceptibility candidate 2 (Auts2) encodes a nuclear protein expressed in developing brain regions implicated in autism neuropathology. Gene Expr Patterns 10:9–15

    CAS  PubMed  Google Scholar 

  • Bongmba OY, Martinez LA, Elhardt ME et al (2011) Modulation of dendritic spines and synaptic function by Rac1: a possible link to fragile X syndrome pathology. Brain Res 1399:79–95

    CAS  PubMed  PubMed Central  Google Scholar 

  • Braat S, D’Hulst C, Huelens I et al (2015) The GABAA receptor is an FMRP target with therapeutic potential in fragile X syndrome. Cell Cycle 14:2985–2995

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brunberg JA, Jacquemont S, Hagerman RJ (2002) Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction. AJNR Am J Neuroradiol 23:1757–1766

    PubMed  Google Scholar 

  • Burk K, Bosch S, Globas C et al (2001) Executive dysfunction in spinocerebellar ataxia type 1. Eur Neurol 46:43–48

    CAS  PubMed  Google Scholar 

  • Burk K, Globas C, Bosch S et al (2003) Cognitive deficits in spinocerebellar ataxia type 1:2 and 3. J Neurol 250:207–211

    CAS  PubMed  Google Scholar 

  • Ceman S, O’Donnell WT, Reed M et al (2003) Phosphorylation influences the translation state of FMRP-associated polyribosomes. Hum Mol Genet 12:3295–3305

    CAS  PubMed  Google Scholar 

  • Centers for Disease Control and Prevention (CDC) (2020) https://www.cdc.gov/media/releases/2020/p0326-autism-prevalence-rises.html

  • Chauhan A, Audhya T, Chauhan V (2012) Brain region-specific glutathione redox imbalance in autism. Neurochem Res 37:1681–1691

    CAS  Google Scholar 

  • Cipriano R, Patton JT, Mayo LD et al (2010) Inactivation of p53 signaling by p73 or PTEN ablation results in a transformed phenotype that remains susceptible to nutilin-3 mediated apoptosis. Cell Cycle 9:1373–1379

    CAS  PubMed  Google Scholar 

  • Courchesne E, Yeung-Courchesne R, Press GA et al (1988) Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med 318:1349–1354

    CAS  PubMed  Google Scholar 

  • Courchesne E, Townsend J, Saitoh O (1994) The brain in infantile autism: posterior fossa structures are abnormal. Neurology 44:214–223

    CAS  PubMed  Google Scholar 

  • Courchesne E, Karns CM, Davis HR et al (2001) Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 57:245–254

    CAS  PubMed  Google Scholar 

  • Cousins SL, Hoey SE, Anne Stephenson F et al (2009) Amyloid precursor protein 695 associates with assembled NR2A- and NR2B-containing NMDA receptors to result in the enhancement of their cell surface delivery. J Neurochem 111:1501–1513

    CAS  PubMed  Google Scholar 

  • Crooks R, Mitchell T, Thom M (2000) Patterns of cerebellar atrophy in patients with chronic epilepsy; a quantitative neuropathological study. Epilepsy Res 41:63–73

    CAS  PubMed  Google Scholar 

  • Cupolillo D, Hoxha E, Faralli A et al (2016) Autistic-like traits and cerebellar dysfunction in Purkinje cell PTEN knock-out mice. Neuropsychopharmacology 41:1457–1466

    PubMed  Google Scholar 

  • D’Hulst C, De Geest N, Reeve SP et al (2006) Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res 1121:238–245

    PubMed  Google Scholar 

  • D’Mello AM, Crocetti D, Mostofsky SH et al (2015) Cerebellar gray matter in lobular volumes correlate with core autism symptoms. Neuroimage Clin 7:631–639

    PubMed  PubMed Central  Google Scholar 

  • Didonna A, Opal P (2016) Advances in sequencing technologies for understanding hereditary ataxias. JAMA Neurol 73:1485–1490

    PubMed  PubMed Central  Google Scholar 

  • El Idrissi A, Ding XH, Scalia J et al (2005) Decreased GABAA receptor expression in the seizure-prone fragile X mouse. Neurosci Lett 377:141–146

    PubMed  Google Scholar 

  • El-Fishawy P, State MW (2010) The genetics of autism: key issues, recent findings, and clinical implications. Psychiatr Clin North Am 33:83–105

    PubMed  PubMed Central  Google Scholar 

  • Fatemi SH, Halt AR, Realmuto G et al (2002a) Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol 22:171–175

    PubMed  Google Scholar 

  • Fatemi SH, Halt A, Stary J et al (2002b) Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in parietal and cerebellar cortices of autistic subjects. Biol Psychiatry 52:805–810

    CAS  PubMed  Google Scholar 

  • Fatemi SH, Snow AV, Stary JM et al (2005) Reelin signaling is impaired in autism. Biol Psychiatry 57:777–787

    CAS  PubMed  Google Scholar 

  • Fatemi SH, Reutiman TJ, Folsom TD et al (2009a) GABA(A) receptor downregulation in brains of subjects with autism. J Autism Dev Disord 39:223–230

    Google Scholar 

  • Fatemi SH, Folsom TD, Reutiman TJ et al (2009b) Expression of GABA(B) receptors is altered in brains of subjects with autism. Cerebellum 8:64–69

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fatemi SH, Reutiman TJ, Folsom TD et al (2010) mRNA and protein levels for GABAAalpha4, alpha5, beta1 and GABABR1 receptors are altered in brains from subjects with autism. J Autism Dev Disord 40:743–750

    PubMed  PubMed Central  Google Scholar 

  • Fatemi SH, Folsom TD, Kneeland RE et al (2011) Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism. Anat Rec 294:1635–1645

    CAS  Google Scholar 

  • Fatemi SH, Aldinger KA, Ashwood P et al (2012) Consensus paper: pathological role of the cerebellum in autism. Cerebellum 11:777–807

    PubMed  PubMed Central  Google Scholar 

  • Fatemi SH, Folsom TD, Kneeland RE et al (2013) Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex. Mol Autism 4:21

    PubMed  PubMed Central  Google Scholar 

  • Fatemi SH, Reutiman TJ, Folsom TD et al (2014) Downregulation of GABAA receptor protein subunits α6, β2, δ, ε, γ2, θ, and ρ2 in superior frontal cortex of subjects with autism. J Autism Dev Disord 44:1833–1845

    PubMed  Google Scholar 

  • Filley CM, Brown MS, Onderko K et al (2015) White matter disease and cognitive impairment in FMR1 premutation carriers. Neurology 84:2146–2152

    PubMed  PubMed Central  Google Scholar 

  • Forster E, Tielsch A, Saum B et al (2002) Reelin, disabled 1, and beta 1 integrins are required for the formation of the radial glial scaffold in the hippocampus. Proc Natl Acad Sci U S A 99:13178–13183

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gantois I, Vandescompele J, Speleman F et al (2006) Expression profiling suggests underexpression of the GABAA receptor subunit delta in the fragile X knockout mouse model. Neurobiol Dis 21:346–357

    CAS  PubMed  Google Scholar 

  • Garrard P, Martin NH, Giunti P et al (2008) Cognitive and social cognitive functioning in spinocerebellar ataxia. J Neurol 255:398–405

    CAS  PubMed  Google Scholar 

  • Globas C, Bosch S, Zuhlke C et al (2003) The cerebellum and cognition. Intellectual function in spinocerebellar ataxia type 6 (SCA6). J Neurol 250:1482–1487

    CAS  PubMed  Google Scholar 

  • Gottwald B, Wilde B, Mihajlovic Z et al (2004) Evidence for distinct cognitive deficits after focal cerebellar lesions. J Neurol Neurosurg Psychiatry 75:1124–1131

    Google Scholar 

  • Gu F, Chauhan V, Chauhan A (2013) Impaired synthesis and antioxidant defense of glutathione in the cerebellum of autistic subjects: alterations in the activities and protein expression of glutathione-related enzymes. Free Radic Biol Med 65:488–496

    CAS  PubMed  Google Scholar 

  • Haas RH, Townsend J, Courchesne E et al (1996) Neurological abnormalities in infantile autism. J Child Neurol 11:84–92

    CAS  PubMed  Google Scholar 

  • Hagerman RJ (1996) Physical and behavioral phenotype. In: Hagerman RJ, Cronister A (eds) Diagnosis, treatment, and research. The Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Hagerman RJ, Ono MY, Hagerman PJ (2005) Recent advances in fragile X: a model for autism and neurodegeneration. Curr Opin Psychiatry 18:490–496

    PubMed  Google Scholar 

  • Hallahan B, Daly EM, McAlonan G et al (2009) Brain morphology volume in autistic spectrum disorder: a magnetic resonance imaging study of adults. Psychol Med 39:337–346

    CAS  PubMed  Google Scholar 

  • Hallet M, Lebiedowska MK, Thomas SL et al (1993) Locomotion of autistic adults. Arch Neurol 50:1304–1308

    Google Scholar 

  • Hampson DR, Blatt GJ (2015) Autism spectrum disorders and neuropathology of the cerebellum. Front Neurosci 9:420

    PubMed  PubMed Central  Google Scholar 

  • Hardan AY, Minshew NJ, Harenski K et al (2001) Posterior fossa magnetic resonance imaging in autism. J Am Acad Child Adolesc Psychiatry 40:666–672

    CAS  PubMed  Google Scholar 

  • Hazlett HC, Poe M, Gerig G et al (2005) Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch Gen Psychiatry 62:1366–1376

    PubMed  Google Scholar 

  • Herbert MR (2010) Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol 23:103–110

    PubMed  Google Scholar 

  • Herbert MR, Ziegler DA, Deutsch CK et al (2003) Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 126:1182–1192

    CAS  PubMed  Google Scholar 

  • Hessl D, Grigsby J (2016) Fragile X tremor/ataxia syndrome: another phenotype of the fragile X gene. Clin Neuropsychol 30:810–814

    PubMed  PubMed Central  Google Scholar 

  • Hoche F, Guell X, Sherman JC, Vangel MG, Schmahmann JD (2016) Cerebellar contribution to social cognition. Cerebellum 15(6):732–743

    PubMed  PubMed Central  Google Scholar 

  • Hoche F, Guell X, Vangel MG, Sherman JC, Schmahmann JD (2018) The cerebellar cognitive affective/Schmahmann syndrome scale. Brain 141(1):248–270

    PubMed  Google Scholar 

  • Holttum J, Minshew N, Sanders R (1992) Magnetic resonance imaging of the posterior fossa in autism. Biol Psychiatry 32:1091–1101

    CAS  PubMed  Google Scholar 

  • Hong A, Zhang A, Ke Y et al (2012) Downregulation of GABA(A) β subunits is transcriptionally controlled by Fmr1p. J Mol Neurosci 46:272–275

    CAS  PubMed  Google Scholar 

  • Innocent N, Cousins SL, Stephenson FA (2012) NMDA receptor/amyloid precursor protein interactions: a comparison between wild-type and amyloid precursor protein mutations associated with familial Alzheimer’s disease. Neurosci Lett 515:131–136

    CAS  PubMed  Google Scholar 

  • Jeong JW, Tiwari VN, Behen ME et al (2014) In vivo detection of reduced Purkinje cell fibers with diffusion MRI tractography in children with autistic spectrum disorders. Front Hum Neurosci 8:110

    PubMed  PubMed Central  Google Scholar 

  • Karatekin C, Lazareff JA, Asarnow RF (2000) Relevance of the cerebellar hemispheres for executive function. Pediatr Neurol 22:106–112

    CAS  PubMed  Google Scholar 

  • Kawaguchi Y, Okamoto T, Taniwaki M et al (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 8:221–227

    CAS  PubMed  Google Scholar 

  • Kawai Y, Takeda A, Abe Y et al (2004) Cognitive impairments in Machado-Joseph disease. Arch Neurol 61:1757–1760

    PubMed  Google Scholar 

  • Kelly RM, Strick PL (2003) Cerebellar loops with motor cortex and prefrontal cortex. J Neurosci 23:8432–8444

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kinney DK, Munir KM, Crowley DJ et al (2008) Prenatal stress and risk for autism. Neurosci Biobehav Rev 32:1519–1532

    PubMed  PubMed Central  Google Scholar 

  • Kleiman MD, Neff S, Rosman NP (1992) The brain in infantile autism: are posterior fossa structures abnormal? Neurology 42:753–760

    CAS  PubMed  Google Scholar 

  • Krueger DD, Bear MF (2011) The mGluR theory of fragile X syndrome. In: Amaral DG, Dawson G, Geschwind DH (eds) Autism spectrum disorders. Oxford University Press, New York, pp 1239–1258

    Google Scholar 

  • Laurence JA, Fatemi SH (2005) Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects. Cerebellum 4:206–210

    CAS  PubMed  Google Scholar 

  • López-Mourelo O, Mur E, Madrigal I et al (2017) Social anxiety and autism spectrum traits among adult FMR1 premutation carriers. Clin Genet 91:111–114

    PubMed  Google Scholar 

  • Luque JM, Morante-Oria J, Fairen A (2003) Localization of ApoER2, VLDLR and Dab-1 in radial glia: groundwork for a new model of Reelin action during cortical development. Dev Brain Res 140:195–203

    CAS  Google Scholar 

  • Magliaro C, Cocito C, Bagatella S et al (2016) The number of Purkinje neurons and their topology in the cerebellar vermis of normal and reln haplodeficient mouse. Ann Anat 207:68–75

    PubMed  Google Scholar 

  • Manes F, Piven J, Vrancic D (1999) An MRI study of the corpus callosum and cerebellum in mentally retarded autistic individuals. J Neuropsychiatr Clin Neurosci 11:470–474

    CAS  Google Scholar 

  • Manto M (2005) The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum 4:2–6

    CAS  PubMed  Google Scholar 

  • Manto M, Marmolino D (2009) Cerebellar ataxias. Curr Opin Neurol 22:419–429

    PubMed  Google Scholar 

  • Martin LA, Goldowitz D, Mittleman G (2010) Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism. Eur J Neurosci 31:544–555

    PubMed  PubMed Central  Google Scholar 

  • McAlonan GM, Cheung V, Cheung C et al (2005) Mapping the brain in autism: a voxel-based MRI study of volumetric differences and intercorrelations in autism. Brain 128:268–276

    PubMed  Google Scholar 

  • Middleton FA, Strick PL (1994) Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive functioning. Science 266:458–461

    CAS  PubMed  Google Scholar 

  • Mostofsky SH, Powell SK, Simmonds DJ et al (2009) Decreased connectivity and cerebellar activity in autism during motor task performance. Brain 132:2413–2425

    PubMed  PubMed Central  Google Scholar 

  • Palmen SJ, van Engeland H, Hof PR et al (2004) Neuropathological findings in autism. Brain 127:2572–2583

    PubMed  Google Scholar 

  • Palmen SJ, Hulshoff Pol HE, Kemner C et al (2005) Increased gray-matter volume in medication-naïve high-functioning children with autism spectrum disorder. Psychol Med 35:561–570

    PubMed  Google Scholar 

  • Paulson HL (2009) The spinocerebellar ataxias. J Neuro-Oncol 23:227–237

    Google Scholar 

  • Peter S, Ten Brinke MM, Stedehouder J et al (2016) Dysfunctional cerebellar Purkinje cells contribute to autism-like behavior in Shank2-deficient mice. Nat Commun 7:12627

    CAS  PubMed  PubMed Central  Google Scholar 

  • Picelli A, Zuccher P, Tomelleri G et al (2017) Prognostic importance of lesion location on functional outcome in patients with cerebellar ischemic stroke: a prospective pilot study. Cerebellum 16:257–261

    PubMed  Google Scholar 

  • Piven J, Saliba K, Bailey J et al (1997) An MRI study of autism: the cerebellum revisited. Neurology 49:546–551

    CAS  PubMed  Google Scholar 

  • Pretto DI, Kumar M, Cao Z et al (2014) Reduced excitatory amino acid transporter 1 and metabotropic glutamate receptor 5 expression in the cerebellum of fragile X mental retardation gene 1 premutation carriers with fragile X-associated tremor/ataxia syndrome. Neurobiol Aging 35:1189–1197

    CAS  PubMed  Google Scholar 

  • Ravizza SM, McCormick CA, Schlerf JE et al (2006) Cerebellar damage produces selective deficits in verbal working memory. Brain 129:306–320

    PubMed  Google Scholar 

  • Redfern RE, Daou MC, Li L et al (2010) A mutant form of PTEN linked to autism. Protein Sci 19:1948–1956

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rinehart NJ, Tonge BJ, Iansek R et al (2006) Gait function in newly diagnosed children with autism: cerebellar and basal ganglia related motor disorder. Dev Med Child Neurol 48:819–824

    PubMed  Google Scholar 

  • Ritvo ER, Freeman BJ, Scheibel AB et al (1986) Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC autopsy research report. Am J Psychiatry 146:862–866

    Google Scholar 

  • Riva D, Giorgi C (2000) The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumors. Brain 123:1051–1061

    PubMed  Google Scholar 

  • Rodriguez-Revenga L, Madrigal I, Pagonabarraga J (2009) Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur J Hum Genet 17:1359–1362

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rojas DC, Peterson E, Winterrowd E et al (2006) Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms. BMC Psychiatry 6:56

    PubMed  PubMed Central  Google Scholar 

  • Rose S, Melnyk S, Pavliv O et al (2012) Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2:e134

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ruano L, Melo C, Silva MC et al (2014) The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 42:174–183

    PubMed  Google Scholar 

  • Rustan OG, Folsom TD, Yousefi MK et al (2013) Phosphorylated fragile X mental retardation protein at serine 499, is reduced in cerebellar vermis and superior frontal cortex of subjects with autism: implications for fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling. Mol Autism 4:41

    PubMed  PubMed Central  Google Scholar 

  • Sajdel-Sulkowska EM, Lipinski B, Windhom H et al (2008) Oxidative stress in autism: cerebellar 3-nitrotyrosine levels. Am J Biochem Biothechnol 4:73–84

    CAS  Google Scholar 

  • Sajdel-Sulkowska EM, Xu M, Koibuchi N (2009) Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism. Cerebellum 8:366–372

    CAS  PubMed  Google Scholar 

  • Salman MS, Tsai P (2016) The role of the pediatric cerebellum in motor functions, cognition and behavior: a clinical perspective. Neuroimaging Clin N Am 26:317–329

    PubMed  PubMed Central  Google Scholar 

  • Schmahmann JD (2010) 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 20:236–260

    PubMed  Google Scholar 

  • Schmahmann JD, Pandya DN (1989) Anatomical investigation of projections to the basis pontis from posterior parietal association cortices in rhesus monkey. J Comp Neurol 289:53–73

    CAS  PubMed  Google Scholar 

  • Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579

    PubMed  Google Scholar 

  • Schmahmann JD, Weilburg JB, Sherman JC (2007) The neuropsychiatry of the cerebellum – insights from the clinic. Cerebellum 6:254–267

    PubMed  Google Scholar 

  • Scott RB, Stoodley CJ, Anslow P et al (2001) Lateralized cognitive deficits in children following cerebellar lesions. Dev Med Child Neurol 43:685–691

    CAS  PubMed  Google Scholar 

  • Scott JA, Schumann CM, Goodlin-Jones BL et al (2009) A comprehensive volumetric analysis of the cerebellum in children and adolescents with autism spectrum disorder. Autism Res 2:246–257

    PubMed  PubMed Central  Google Scholar 

  • Sheikh AM, Malik M, Wen G et al (2010a) BDNF-AKT-Bcl2 antiapoptotic signaling pathway is compromised in the brain of autistic subjects. J Neurosci Res 88:2641–2647

    CAS  PubMed  Google Scholar 

  • Sheikh AM, Li X, Wen G et al (2010b) Cathepsin D and apoptosis related proteins are elevated in the brain of autistic subjects. Neuroscience 165:363–370

    CAS  PubMed  Google Scholar 

  • Sivaswamy L, Kumar A, Rajan D et al (2010) A diffusion tensor imaging study of the cerebellar pathways in children with autism spectrum disorder. J Child Neurol 25:1223–1231

    PubMed  Google Scholar 

  • Skefos J, Cummings C, Enzer K et al (2014) Regional alterations in Purkinje cell density in patients with autism. PLoS One 9:e81255

    PubMed  PubMed Central  Google Scholar 

  • Sparks BF, Friedman SD, Shaw DW, et al (2002) Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59:184–192

    Google Scholar 

  • Stanfield AC, McIntosh AM, Spencer MD et al (2008) Towards a neuroanatomy of autism: a systematic review and meta-analysis of structural magnetic resonance imaging studies. Eur Psychiatry 23:289–299

    PubMed  Google Scholar 

  • Starr EM, Berument SK, Tomlins M et al (2005) Brief report: autism in individuals with down syndrome. J Autism Dev Disord 35:665–673

    PubMed  Google Scholar 

  • Steinlin M, Styger M, Boltshauser E (1998) Non-progressive congenital ataxia with or without cerebellar hypoplasia: a review of 34 subjects. Dev Med Child Neurol 40:148–154

    CAS  PubMed  Google Scholar 

  • Stoodley CJ (2012) The cerebellum and cognition: evidence from functional imaging studies. Cerebellum 11:352–365

    PubMed  Google Scholar 

  • Stoodley CJ (2014) Distinct regions of the cerebellum show gray matter decreases in autism, ADHD, and developmental dyslexia. Front Syst Neurosci 8:92

    PubMed  PubMed Central  Google Scholar 

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

    PubMed  Google Scholar 

  • Stoodley CJ, MacMore JP, Makris N et al (2016) Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke. Neuroimage Clin 12:765–775

    PubMed  PubMed Central  Google Scholar 

  • Taroni F, DiDonato S (2004) Pathways to motor incoordination: the inherited ataxias. Nat Rev Neurosci 5:641–655

    CAS  PubMed  Google Scholar 

  • Tavano A, Grasso R, Gagliardi C et al (2007) Disorders of cognitive and affective development in cerebellar malformations. Brain 130:2646–2660

    PubMed  Google Scholar 

  • Toal F, Bloemen OJ, Deely Q, et al (2009) Psychosis and autism: magnetic resonance imaging study of brain anatomy. Br J Psychiatry 194:418–425

    Google Scholar 

  • Tsai PT, Hull C, Chu Y et al (2012) Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 488:647–651

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tuchman R, Rapin I (2002) Epilepsy in autism. Lancet Neurol 1:352–358

    PubMed  Google Scholar 

  • Varga EA, Pastore M, Prior T et al (2009) The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly. Genet Med 11:111–117

    PubMed  Google Scholar 

  • Vargas DL, Nascimbene C, Krishnan C et al (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57:67–81

    CAS  PubMed  Google Scholar 

  • Vedolin L, Gonzalez G, Souza CF et al (2013) Inherited cerebellar ataxia in childhood: a pattern recognition approach using brain MRI. AJNR Am J Neuroradiol 34:925–934

    CAS  PubMed  Google Scholar 

  • Wassmer E, Davies P, Whitehouse WP et al (2003) Clinical spectrum associated with cerebellar hypoplasia. Pediatr Neurol 28:347–351

    PubMed  Google Scholar 

  • Webb SJ, Sparks BF, Friedman SD, et al (2009) Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder. Psychiatry Res 172:61–67

    Google Scholar 

  • Wegiel J, Flory M, Kuchna I et al (2014a) Stereological study of the neuronal number and volume of 38 brain subdivisions of subjects diagnosed with autism reveals significant alterations restricted to the striatum, amygdala and cerebellum. Acta Neuropathol Commun 2:141

    PubMed  PubMed Central  Google Scholar 

  • Wegiel J, Flory M, Kuchna I et al (2014b) Brain-region-specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism. Acta Neuropathol Commun 2:28

    PubMed  PubMed Central  Google Scholar 

  • Whitney ER, Kemper TL, Bauman ML et al (2008a) Cerebellar Purkinje cells are reduced in a subpopulation of autistic brains: a stereological experiment using calbindin-D28k. Cerebellum 7:406–416

    CAS  PubMed  Google Scholar 

  • Whitney ER, Kemper TL, Rosene DL et al (2008b) Calbindin-D28k is a more reliable marker of human Purkinje cells than standard Nissl stains: a stereological experiment. J Neurosci Methods 168:42–47

    CAS  PubMed  Google Scholar 

  • Williams RS, Hauser LS, Parpura DP et al (1980) Autism and mental retardation: neuropathologic studies performed in four retarded persons with autistic behavior. Arch Neurol 37:749–753

    CAS  PubMed  Google Scholar 

  • Witnitzer M (2004) Autism and tuberous sclerosis. J Child Neurol 19:675–679

    Google Scholar 

  • Yip J, Soghomonian JJ, Blatt GJ (2007) Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications. Acta Neuropathol 113:559–568

    CAS  PubMed  Google Scholar 

  • Yip J, Soghomonian JJ, Blatt GJ (2008) Increased GAD67 mRNA expression in cerebellar interneurons in autism: implications for Purkinje cell dysfunction. J Neurosci Res 86:525–530

    CAS  PubMed  Google Scholar 

  • Yip J, Soghomonian JJ, Blatt GJ (2009) Decreased GAD65 mRNA levels in select subpopulations of neurons in cerebellar dentate nuclei in autism: an in situ hybridization study. Autism Res 2:50–59

    PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Kurup P, Xu J et al (2010) Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proc Natl Acad Sci U S A 107:19014–19019

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng T, Meng X, Wang J et al (2010) PTEN- and p53-mediated apoptosis and cell cycle arrest by FTY720 in gastric cancer cells and nude mice. J Cell Biochem 111:218–228

    CAS  PubMed  Google Scholar 

  • Zhuchenko O, Bailey J, Bonnen P et al (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α-1A-voltage dependent calcium channel. Nat Genet 15:62–69

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding from NIH (5R01HD052074-04 and 3R01HD052074-03S1) to SHF is gratefully acknowledged. SH Fatemi has also been supported by Bernstein Endowment in Adult Psychiatry and the Winston and Maxine Wallin Neuroscience Discovery Fund.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Division of Neuroscience Research, University of Minnesota, Minneapolis, MN, USA

    Timothy D. Folsom & S. Hossein Fatemi

  2. Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA

    S. Hossein Fatemi

Authors
  1. Timothy D. Folsom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Hossein Fatemi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Hossein Fatemi .

Editor information

Editors and Affiliations

  1. Bruxelles, Belgium

    Mario Manto

  2. Scripps Research Institute Dept. Neuropharmacology, La Jolla, CA, USA

    Donna Gruol

  3. Dept. Neurology, Harvard Medical School Massachusetts General Hospital, Boston, MA, USA

    Jeremy Schmahmann

  4. Gunma University Dept. Integrative Physiology, Maebashi, Gunma, Japan

    Noriyuki Koibuchi

  5. Dept Pathology & Immunology & Neuro, Baylor College of Medicine Dept Pathology & Immunology & Neuro, Houston, TX, USA

    Roy Sillitoe

Section Editor information

  1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Jeremy D. Schmahmann

  2. CHU-Charleroi, University of Mons, UMons, Charleroi, Belgium

    Mario U. Manto

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Folsom, T.D., Fatemi, S.H. (2020). Autism Spectrum Disorders and Ataxia. In: Manto, M., Gruol, D., Schmahmann, J., Koibuchi, N., Sillitoe, R. (eds) Handbook of the Cerebellum and Cerebellar Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-97911-3_87-2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-97911-3_87-2

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-97911-3

  • Online ISBN: 978-3-319-97911-3

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation