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Neurodevelopmental Disorders of the Cerebellum: Autism Spectrum Disorder

  • Mehnosh Toback
  • Kambiz Zangeneh
  • Tabrez J. Siddiqui
  • Hassan MarzbanEmail author
Chapter
Part of the Contemporary Clinical Neuroscience book series (CCNE)

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an incidence of 1 in 68 children. Cerebellar abnormalities have been observed in many ASD patients. The cerebellum is an elaborate brain region critically important for motor learning and coordination of movement, and increasing lines of evidence indicate that the cerebellum also contributes to emotion and cognition. In this chapter, we will review the genetic and environmental factors that may cause cerebellar deficits in ASD patients. Structural and functional cerebellar abnormalities based on neuroimaging and histopathological studies and current approaches to management will be discussed.

Keywords

Cerebellum Neurodevelopmental disorders Motor skills Language Cognition Autism spectrum disorder 

References

  1. 1.
    Millon T. On the history and future study of personality and its disorders. Annu Rev Clin Psychol. 2012;8:1–19. PubMed PMID: 22035244.PubMedCrossRefGoogle Scholar
  2. 2.
    Tonge BJ, Dissanayake C, Brereton AV. Autism: fifty years on from Kanner. J Paediatr Child Health. 1994;30(2):102–7. PubMed PMID: 8198840.PubMedCrossRefGoogle Scholar
  3. 3.
    Volkmar FR, McPartland JC. From Kanner to DSM-5: autism as an evolving diagnostic concept. Annu Rev Clin Psychol. 2014;10:193–212. PubMed PMID: 24329180.PubMedCrossRefGoogle Scholar
  4. 4.
    Olmsted D, Blaxill M. Leo Kanner’s mention of 1938 in his report on autism refers to his first patient. J Autism Dev Disord. 2016;46(1):340–1. PubMed PMID: 26231203.CrossRefGoogle Scholar
  5. 5.
    Barahona-Correa JB, Filipe CN. A concise history of Asperger syndrome: the short reign of a troublesome diagnosis. Front Psychol. 2015;6:2024. PubMed PMID: 26834663. Pubmed Central PMCID: 4725185.PubMedCrossRefGoogle Scholar
  6. 6.
    Won H, Mah W, Kim E. Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses. Front Mol Neurosci. 2013;6:19. PubMed PMID: 23935565. Pubmed Central PMCID: 3733014.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Hampson DR, Blatt GJ. Autism spectrum disorders and neuropathology of the cerebellum. Front Neurosci. 2015;9:420. PubMed PMID: 26594141. Pubmed Central PMCID: 4635214.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum. 2012;11(3):777–807. PubMed PMID: 22370873. Pubmed Central PMCID: 3677555.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Mosconi MW, Wang Z, Schmitt LM, Tsai P, Sweeney JA. The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders. Front Neurosci. 2015;9:296. PubMed PMID: 26388713. Pubmed Central PMCID: 4555040.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Hagmeyer S, Mangus K, Boeckers TM, Grabrucker AM. Effects of trace metal profiles characteristic for autism on synapses in cultured neurons. Neural Plast. 2015;2015:985083. PubMed PMID: 25802764. Pubmed Central PMCID: 4352758.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Ismail MM, Keynton RS, Mostapha MM, ElTanboly AH, Casanova MF, Gimel’farb GL, et al. Studying autism spectrum disorder with structural and diffusion magnetic resonance imaging: a survey. Front Hum Neurosci. 2016;10:211. PubMed PMID: 27242476. Pubmed Central PMCID: 4862981.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Vuong HE, Hsiao EY. Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry. 2016;81:411–23. PubMed PMID:27773355.PubMedCrossRefGoogle Scholar
  13. 13.
    Rogers TD, McKimm E, Dickson PE, Goldowitz D, Blaha CD, Mittleman G. Is autism a disease of the cerebellum? Integr Clin Pre-Clin Res Front Syst Neurosci. 2013;7:15. PubMed PMID: 23717269. Pubmed Central PMCID: 3650713.Google Scholar
  14. 14.
    Wallace GL, Dankner N, Kenworthy L, Giedd JN, Martin A. Age-related temporal and parietal cortical thinning in autism spectrum disorders. Brain J Neurol. 2010;133(Pt 12):3745–54. PubMed PMID: 20926367. Pubmed Central PMCID: 2995883.CrossRefGoogle Scholar
  15. 15.
    Lainhart JE, Piven J, Wzorek M, Landa R, Santangelo SL, Coon H, et al. Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry. 1997;36(2):282–90. PubMed PMID: 9031582.PubMedCrossRefGoogle Scholar
  16. 16.
    Herbert MR, Ziegler DA, Deutsch CK, O’Brien LM, Kennedy DN, Filipek PA, et al. Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis. Brain J Neurol. 2005;128(Pt 1):213–26. PubMed PMID: 15563515.Google Scholar
  17. 17.
    Schumann CM, Bloss CS, Barnes CC, Wideman GM, Carper RA, Akshoomoff N, et al. Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. J Neurosci: Off J Soc Neurosci. 2010;30(12):4419–27. PubMed PMID: 20335478. Pubmed Central PMCID: 2859218.CrossRefGoogle Scholar
  18. 18.
    Wolff JJ, Gu H, Gerig G, Elison JT, Styner M, Gouttard S, et al. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry. 2012;169(6):589–600. PubMed PMID: 22362397. Pubmed Central PMCID: 3377782.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011;306(18):2001–10. PubMed PMID: 22068992.PubMedCrossRefGoogle Scholar
  20. 20.
    Sudarov A. Defining the role of cerebellar Purkinje cells in autism spectrum disorders. Cerebellum. 2013;12(6):950–5. PubMed PMID: 23703312. Pubmed Central PMCID: 3795842.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Taylor MJ, Doesburg SM, Pang EW. Neuromagnetic vistas into typical and atypical development of frontal lobe functions. Front Hum Neurosci. 2014;8:453. PubMed PMID: 24994980. Pubmed Central PMCID: 4061489.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Ecker C, Bookheimer SY, Murphy DG. Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan. Lancet Neurol. 2015;14(11):1121–34. PubMed PMID: 25891007.PubMedCrossRefGoogle Scholar
  23. 23.
    D’Mello AM, Stoodley CJ. Cerebro-cerebellar circuits in autism spectrum disorder. Front Neurosci. 2015;9:408. PubMed PMID: 26594140. Pubmed Central PMCID: 4633503.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Basson MA, Wingate RJ. Congenital hypoplasia of the cerebellum: developmental causes and behavioral consequences. Front Neuroanat. 2013;7:29. PubMed PMID: 24027500. Pubmed Central PMCID: 3759752.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Palmen SJ, van Engeland H, Hof PR, Schmitz C. Neuropathological findings in autism. Brain J Neurol. 2004;127(Pt 12):2572–83. PubMed PMID: 15329353.CrossRefGoogle Scholar
  26. 26.
    Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31(3):137–45. PubMed PMID: 18258309.PubMedCrossRefGoogle Scholar
  27. 27.
    Whitney ER, Kemper TL, Bauman ML, Rosene DL, Blatt GJ. Cerebellar Purkinje cells are reduced in a subpopulation of autistic brains: a stereological experiment using calbindin-D28k. Cerebellum. 2008;7(3):406–16. PubMed PMID: 18587625.PubMedCrossRefGoogle Scholar
  28. 28.
    Geschwind DH, Levitt P. Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol. 2007;17(1):103–11. PubMed PMID: 17275283.PubMedCrossRefGoogle Scholar
  29. 29.
    Dolen G, Sahin M. Editorial: essential pathways and circuits of autism pathogenesis. Front Neurosci. 2016;10:182. PubMed PMID: 27199644. Pubmed Central PMCID: 4844597.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    ten Donkelaar HJ, Lammens M, Wesseling P, Thijssen HO, Renier WO. Development and developmental disorders of the human cerebellum. J Neurol. 2003;250(9):1025–36. PubMed PMID: 14504962.PubMedCrossRefGoogle Scholar
  31. 31.
    Bolduc ME, Limperopoulos C. Neurodevelopmental outcomes in children with cerebellar malformations: a systematic review. Dev Med Child Neurol. 2009;51(4):256–67. PubMed PMID: 19191827.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Limperopoulos C. Autism spectrum disorders in survivors of extreme prematurity. Clin Perinatol. 2009;36(4):791–805. vi. PubMed PMID: 19944836.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang SS, Kloth AD, Badura A. The cerebellum, sensitive periods, and autism. Neuron. 2014;83(3):518–32. PubMed PMID: 25102558. Pubmed Central PMCID: 4135479.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Bolduc ME, Du Plessis AJ, Sullivan N, Khwaja OS, Zhang X, Barnes K, et al. Spectrum of neurodevelopmental disabilities in children with cerebellar malformations. Dev Med Child Neurol. 2011;53(5):409–16. PubMed PMID: 21418200.PubMedCrossRefGoogle Scholar
  35. 35.
    Geschwind DH, State MW. Gene hunting in autism spectrum disorder: on the path to precision medicine. Lancet Neurol. 2015;14(11):1109–20. PubMed PMID: 25891009. Pubmed Central PMCID: 4694565.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Ishii K, Kubo KI, Nakajima K. Reelin and neuropsychiatric disorders. Front Cell Neurosci. 2016;10:229. PubMed PMID: 27803648. Pubmed Central PMCID: 5067484.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Barnard RA, Pomaville MB, O’Roak BJ. Mutations and modeling of the chromatin remodeler CHD8 define an emerging autism etiology. Front Neurosci. 2015;9:477. PubMed PMID: 26733790. Pubmed Central PMCID: 4681771.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Sadakata T, Shinoda Y, Sato A, Iguchi H, Ishii C, Matsuo M, et al. Mouse models of mutations and variations in autism spectrum disorder-associated genes: mice expressing Caps2/Cadps2 copy number and alternative splicing variants. Int J Environ Res Public Health. 2013;10(12):6335–53. PubMed PMID: 24287856. Pubmed Central PMCID: 3881117.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Roppongi RT, Karimi B, Siddiqui TJ. Role of LRRTMs in synapse development and plasticity. Neurosci Res. 2016;116:18–28. PubMed PMID: 27810425.PubMedCrossRefGoogle Scholar
  40. 40.
    Sudhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature. 2008;455(7215):903–11. PubMed PMID: 18923512. Pubmed Central PMCID: 2673233.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Sala C, Vicidomini C, Bigi I, Mossa A, Verpelli C. Shank synaptic scaffold proteins: keys to understanding the pathogenesis of autism and other synaptic disorders. J Neurochem. 2015;135(5):849–58. PubMed PMID: 26338675.PubMedCrossRefGoogle Scholar
  42. 42.
    Baig DN, Yanagawa T, Tabuchi K. Distortion of the normal function of synaptic cell adhesion molecules by genetic variants as a risk for autism spectrum disorders. Brain Res Bull. 2017;129:82–90. PubMed PMID: 27743928.PubMedCrossRefGoogle Scholar
  43. 43.
    Li X, Zou H, Brown WT. Genes associated with autism spectrum disorder. Brain Res Bull. 2012;88(6):543–52. PubMed PMID: 22688012.PubMedCrossRefGoogle Scholar
  44. 44.
    Cotney J, Muhle RA, Sanders SJ, Liu L, Willsey AJ, Niu W, et al. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nat Commun. 2015;6:6404. PubMed PMID: 25752243. Pubmed Central PMCID: 4355952.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Willsey AJ, Sanders SJ, Li M, Dong S, Tebbenkamp AT, Muhle RA, et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell. 2013;155(5):997–1007. PubMed PMID: 24267886. Pubmed Central PMCID: 3995413.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Sakamoto I, Kishida S, Fukui A, Kishida M, Yamamoto H, Hino S, et al. A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation. J Biol Chem. 2000;275(42):32871–8. PubMed PMID: 10921920.PubMedCrossRefGoogle Scholar
  47. 47.
    O’Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. 2012;485(7397):246–50. PubMed PMID: 22495309. Pubmed Central PMCID: 3350576.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Hormozdiari F, Penn O, Borenstein E, Eichler EE. The discovery of integrated gene networks for autism and related disorders. Genome Res. 2015;25(1):142–54. PubMed PMID: 25378250. Pubmed Central PMCID: 4317170.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Fatemi SH. The role of Reelin in pathology of autism. Mol Psychiatry. 2002;7(9):919–20. PubMed PMID: 12399938.PubMedCrossRefGoogle Scholar
  50. 50.
    Persico AM, D’Agruma L, Maiorano N, Totaro A, Militerni R, Bravaccio C, et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry. 2001;6(2):150–9. PubMed PMID: 11317216.PubMedCrossRefGoogle Scholar
  51. 51.
    Zhang H, Liu X, Zhang C, Mundo E, Macciardi F, Grayson DR, et al. Reelin gene alleles and susceptibility to autism spectrum disorders. Mol Psychiatry. 2002;7(9):1012–7. PubMed PMID: 12399956.PubMedCrossRefGoogle Scholar
  52. 52.
    Skaar DA, Shao Y, Haines JL, Stenger JE, Jaworski J, Martin ER, et al. Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiatry. 2005;10(6):563–71. PubMed PMID: 15558079.PubMedCrossRefGoogle Scholar
  53. 53.
    Dutta S, Guhathakurta S, Sinha S, Chatterjee A, Ahmed S, Ghosh S, et al. Reelin gene polymorphisms in the Indian population: a possible paternal 5′UTR-CGG-repeat-allele effect on autism. Am J Med Genet Part B Neuropsychiatr Genet: Off Publ Int Soc Psychiatr Genet. 2007;144B(1):106–12. PubMed PMID: 16941662.CrossRefGoogle Scholar
  54. 54.
    Chudley AE. Genetic landmarks through philately – autism spectrum disorders: a genetic update. Clin Genet. 2004;65(5):352–7. PubMed PMID: 15099341.PubMedCrossRefGoogle Scholar
  55. 55.
    Fatemi SH, Stary JM, Halt AR, Realmuto GR. Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum. J Autism Dev Disord. 2001;31(6):529–35. PubMed PMID: 11814262.PubMedCrossRefGoogle Scholar
  56. 56.
    Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998;281(5381):1322–6. PubMed PMID: 9735050.PubMedCrossRefGoogle Scholar
  57. 57.
    de Bergeyck V, Nakajima K, Lambert de Rouvroit C, Naerhuyzen B, Goffinet AM, Miyata T, et al. A truncated Reelin protein is produced but not secreted in the ‘Orleans’ reeler mutation (Reln[rl-Orl]). Brain Res Mol Brain Res. 1997;50(1–2):85–90. PubMed PMID: 9406921.PubMedCrossRefGoogle Scholar
  58. 58.
    Lacor PN, Grayson DR, Auta J, Sugaya I, Costa E, Guidotti A. Reelin secretion from glutamatergic neurons in culture is independent from neurotransmitter regulation. Proc Natl Acad Sci U S A. 2000;97(7):3556–61. PubMed PMID: 10725375. Pubmed Central PMCID: 16278.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Fatemi SH, Stary JM, Egan EA. Reduced blood levels of reelin as a vulnerability factor in pathophysiology of autistic disorder. Cell Mol Neurobiol. 2002;22(2):139–52. PubMed PMID: 12363196.PubMedCrossRefGoogle Scholar
  60. 60.
    Boukhtouche F, Brugg B, Wehrle R, Bois-Joyeux B, Danan JL, Dusart I, et al. Induction of early Purkinje cell dendritic differentiation by thyroid hormone requires RORalpha. Neural Dev. 2010;5:18. PubMed PMID: 20663205. Pubmed Central PMCID: 2918593.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Hamilton BA, Frankel WN, Kerrebrock AW, Hawkins TL, FitzHugh W, Kusumi K, et al. Disruption of the nuclear hormone receptor RORalpha in staggerer mice. Nature. 1996;379(6567):736–9. PubMed PMID: 8602221.PubMedCrossRefGoogle Scholar
  62. 62.
    Wang Y, Billon C, Walker JK, Burris TP. Therapeutic effect of a synthetic RORalpha/gamma agonist in an animal model of autism. ACS Chem Neurosci. 2016;7(2):143–8. PubMed PMID: 26625251. Pubmed Central PMCID: 4759619.PubMedCrossRefGoogle Scholar
  63. 63.
    Huh JR, Leung MW, Huang P, Ryan DA, Krout MR, Malapaka RR, et al. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORgammat activity. Nature. 2011;472(7344):486–90. PubMed PMID: 21441909. Pubmed Central PMCID: 3172133.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Nguyen A, Rauch TA, Pfeifer GP, Hu VW. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J: Off Publ Fed Am Soc Exp Biol. 2010;24(8):3036–51. PubMed PMID: 20375269. Pubmed Central PMCID: 2909294.CrossRefGoogle Scholar
  65. 65.
    Devanna P, Vernes SC. A direct molecular link between the autism candidate gene RORa and the schizophrenia candidate MIR137. Sci Rep. 2014;4:3994. PubMed PMID: 24500708. Pubmed Central PMCID: 3915307.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Boukhtouche F, Doulazmi M, Frederic F, Dusart I, Brugg B, Mariani J. RORalpha, a pivotal nuclear receptor for Purkinje neuron survival and differentiation: from development to ageing. Cerebellum. 2006;5(2):97–104. PubMed PMID: 16818384.PubMedCrossRefGoogle Scholar
  67. 67.
    Gold DA, Gent PM, Hamilton BA. ROR alpha in genetic control of cerebellum development: 50 staggering years. Brain Res. 2007;1140:19–25. PubMed PMID: 16427031.PubMedCrossRefGoogle Scholar
  68. 68.
    Liu A, Losos K, Joyner AL. FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. Development. 1999;126(21):4827–38. PubMed PMID: 10518499.PubMedGoogle Scholar
  69. 69.
    Kuemerle B, Gulden F, Cherosky N, Williams E, Herrup K. The mouse Engrailed genes: a window into autism. Behav Brain Res. 2007;176(1):121–32. PubMed PMID: 17055592. Pubmed Central PMCID: 2791532.PubMedCrossRefGoogle Scholar
  70. 70.
    Benayed R, Choi J, Matteson PG, Gharani N, Kamdar S, Brzustowicz LM, et al. Autism-associated haplotype affects the regulation of the homeobox gene, ENGRAILED 2. Biol Psychiatry. 2009;66(10):911–7. PubMed PMID: 19615670. Pubmed Central PMCID: 2783416.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Fernandes BS, Berk M, Turck CW, Steiner J, Goncalves CA. Decreased peripheral brain-derived neurotrophic factor levels are a biomarker of disease activity in major psychiatric disorders: a comparative meta-analysis. Mol Psychiatry. 2014;19(7):750–1. PubMed PMID: 24342989.PubMedCrossRefGoogle Scholar
  72. 72.
    Qin XY, Feng JC, Cao C, Wu HT, Loh YP, Cheng Y. Association of peripheral blood levels of brain-derived neurotrophic factor with autism spectrum disorder in children: a systematic review and meta-analysis. JAMA Pediatr. 2016;170(11):1079–86. PubMed PMID: 27654278.PubMedCrossRefGoogle Scholar
  73. 73.
    Sato A, Sekine Y, Saruta C, Nishibe H, Morita N, Sato Y, et al. Cerebellar development transcriptome database (CDT-DB): profiling of spatio-temporal gene expression during the postnatal development of mouse cerebellum. Neural Netw: Off J Int Neural Netw Soc. 2008;21(8):1056–69. PubMed PMID: 18603407.CrossRefGoogle Scholar
  74. 74.
    Sadakata T, Furuichi T. Developmentally regulated Ca2+−dependent activator protein for secretion 2 (CAPS2) is involved in BDNF secretion and is associated with autism susceptibility. Cerebellum. 2009;8(3):312–22. PubMed PMID: 19238500.PubMedCrossRefGoogle Scholar
  75. 75.
    Sadakata T, Washida M, Iwayama Y, Shoji S, Sato Y, Ohkura T, et al. Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients. J Clin Invest. 2007;117(4):931–43. PubMed PMID: 17380209. Pubmed Central PMCID: 1821065.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2):185–8. PubMed PMID: 10508514.PubMedCrossRefGoogle Scholar
  77. 77.
    Ertan G, Arulrajah S, Tekes A, Jordan L, Huisman TA. Cerebellar abnormality in children and young adults with tuberous sclerosis complex: MR and diffusion weighted imaging findings. J Neuroradiol J Neuroradiol. 2010;37(4):231–8. PubMed PMID: 20381146.PubMedCrossRefGoogle Scholar
  78. 78.
    Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. 2012;488(7413):647–51. PubMed PMID: 22763451. Pubmed Central PMCID: 3615424.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Wagner MJ, Kim TH, Savall J, Schnitzer MJ, Luo L. Cerebellar granule cells encode the expectation of reward. Nature. 2017;544:96–100. PubMed PMID: 28321129.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Folstein SE, Rosen-Sheidley B. Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet. 2001;2(12):943–55. PubMed PMID: 11733747.PubMedCrossRefGoogle Scholar
  81. 81.
    Grabrucker AM. Environmental factors in autism. Front Psych. 2012;3:118. PubMed PMID: 23346059. Pubmed Central PMCID: 3548163.Google Scholar
  82. 82.
    Cheh MA, Millonig JH, Roselli LM, Ming X, Jacobsen E, Kamdar S, et al. En2 knockout mice display neurobehavioral and neurochemical alterations relevant to autism spectrum disorder. Brain Res. 2006;1116(1):166–76. PubMed PMID: 16935268.PubMedCrossRefGoogle Scholar
  83. 83.
    Lee MH, Kim M, Lee BH, Kim JH, Kang KS, Kim HL, et al. Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver. Toxicol Appl Pharmacol. 2008;226(3):271–84. PubMed PMID: 17963808.PubMedCrossRefGoogle Scholar
  84. 84.
    Cole TB, Fisher JC, Burbacher TM, Costa LG, Furlong CE. Neurobehavioral assessment of mice following repeated postnatal exposure to chlorpyrifos-oxon. Neurotoxicol Teratol. 2012;34(3):311–22. PubMed PMID: 22425525. Pubmed Central PMCID: 3367041.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Krishnan K, Mitra NK, Yee LS, Yang HM. A comparison of neurotoxicity in cerebellum produced by dermal application of chlorpyrifos in young and adult mice. J Neural Transm. 2012;119(3):345–52. PubMed PMID: 21922192.PubMedCrossRefGoogle Scholar
  86. 86.
    Abou-Donia MB, Khan WA, Dechkovskaia AM, Goldstein LB, Bullman SL, Abdel-Rahman A. In utero exposure to nicotine and chlorpyrifos alone, and in combination produces persistent sensorimotor deficits and Purkinje neuron loss in the cerebellum of adult offspring rats. Arch Toxicol. 2006;80(9):620–31. PubMed PMID: 16482470.PubMedCrossRefGoogle Scholar
  87. 87.
    Moore SJ, Turnpenny P, Quinn A, Glover S, Lloyd DJ, Montgomery T, et al. A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet. 2000;37(7):489–97. PubMed PMID: 10882750. Pubmed Central PMCID: 1734633.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Khan VR, Brown IR. The effect of hyperthermia on the induction of cell death in brain, testis, and thymus of the adult and developing rat. Cell Stress Chaperones. 2002;7(1):73–90. PubMed PMID: 11892990. Pubmed Central PMCID: 514805.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Maroni P, Bendinelli P, Tiberio L, Rovetta F, Piccoletti R, Schiaffonati L. In vivo heat-shock response in the brain: signalling pathway and transcription factor activation. Brain Res Mol Brain Res. 2003;119(1):90–9. PubMed PMID: 14597233.PubMedCrossRefGoogle Scholar
  90. 90.
    Dean SL, Wright CL, Hoffman JF, Wang M, Alger BE, McCarthy MM. Prostaglandin E2 stimulates estradiol synthesis in the cerebellum postnatally with associated effects on Purkinje neuron dendritic arbor and electrophysiological properties. Endocrinology. 2012;153(11):5415–27. PubMed PMID: 23054057. Pubmed Central PMCID: 3473195.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Johnson RT. Effects of viral infection on the developing nervous system. N Engl J Med. 1972;287(12):599–604. PubMed PMID: 4560094.PubMedCrossRefGoogle Scholar
  92. 92.
    Atladottir HO, Thorsen P, Ostergaard L, Schendel DE, Lemcke S, Abdallah M, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord. 2010;40(12):1423–30. PubMed PMID: 20414802.PubMedCrossRefGoogle Scholar
  93. 93.
    Shi L, Fatemi SH, Sidwell RW, Patterson PH. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci: Off J Soc Neurosci. 2003;23(1):297–302. PubMed PMID: 12514227.CrossRefGoogle Scholar
  94. 94.
    Beraki S, Aronsson F, Karlsson H, Ogren SO, Kristensson K. Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice. Mol Psychiatry. 2005;10(3):299–308. PubMed PMID: 15241434.PubMedCrossRefGoogle Scholar
  95. 95.
    Asp L, Beraki S, Kristensson K, Ogren SO, Karlsson H. Neonatal infection with neurotropic influenza A virus affects working memory and expression of type III Nrg1 in adult mice. Brain Behav Immun. 2009;23(6):733–41. PubMed PMID: 19362585.PubMedCrossRefGoogle Scholar
  96. 96.
    Shi L, Smith SE, Malkova N, Tse D, Su Y, Patterson PH. Activation of the maternal immune system alters cerebellar development in the offspring. Brain Behav Immun. 2009;23(1):116–23. PubMed PMID: 18755264. Pubmed Central PMCID: 2614890.PubMedCrossRefGoogle Scholar
  97. 97.
    Luna RA, Savidge TC, Williams KC. The brain-gut-microbiome axis: what role does it play in autism spectrum disorder? Curr Dev Disord Rep. 2016;3(1):75–81. PubMed PMID: 27398286. Pubmed Central PMCID: 4933016.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Mazurek MO, Vasa RA, Kalb LG, Kanne SM, Rosenberg D, Keefer A, et al. Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders. J Abnorm Child Psychol. 2013;41(1):165–76. PubMed PMID: 22850932.PubMedCrossRefGoogle Scholar
  99. 99.
    Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105(5):755–64. PubMed PMID: 20974015.PubMedCrossRefGoogle Scholar
  100. 100.
    Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108(38):16050–5. PubMed PMID: 21876150. Pubmed Central PMCID: 3179073.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Flores-Pajot MC, Ofner M, Do MT, Lavigne E, Villeneuve PJ. Childhood autism spectrum disorders and exposure to nitrogen dioxide, and particulate matter air pollution: a review and meta-analysis. Environ Res. 2016;151:763–76. PubMed PMID: 27609410.PubMedCrossRefGoogle Scholar
  102. 102.
    Aavani T, Rana SA, Hawkes R, Pittman QJ. Maternal immune activation produces cerebellar hyperplasia and alterations in motor and social behaviors in male and female mice. Cerebellum. 2015;14(5):491–505. PubMed PMID: 25863812.PubMedCrossRefGoogle Scholar
  103. 103.
    Gottfried C, Bambini-Junior V, Francis F, Riesgo R, Savino W. The impact of neuroimmune alterations in autism spectrum disorder. Front Psych. 2015;6:121. PubMed PMID: 26441683. Pubmed Central PMCID: 4563148.Google Scholar
  104. 104.
    Verkhratsky A, Rodriguez JJ, Parpura V. Neuroglia in ageing and disease. Cell Tissue Res. 2014;357(2):493–503. PubMed PMID: 24652503.PubMedCrossRefGoogle Scholar
  105. 105.
    Murphy CM, Wilson CE, Robertson DM, Ecker C, Daly EM, Hammond N, et al. Autism spectrum disorder in adults: diagnosis, management, and health services development. Neuropsychiatr Dis Treat. 2016;12:1669–86. PubMed PMID: 27462160. Pubmed Central PMCID: 4940003.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Johnston K, Dittner A, Bramham J, Murphy C, Knight A, Russell A. Attention deficit hyperactivity disorder symptoms in adults with autism spectrum disorders. Autism Res: Off J Int Soc Autism Res. 2013;6(4):225–36. PubMed PMID: 23788522.CrossRefGoogle Scholar
  107. 107.
    Russell AJ, Murphy CM, Wilson E, Gillan N, Brown C, Robertson DM, et al. The mental health of individuals referred for assessment of autism spectrum disorder in adulthood: a clinic report. Autism Int J Res Pract. 2016;20(5):623–7. PubMed PMID: 26471427.CrossRefGoogle Scholar
  108. 108.
    Fournier KA, Hass CJ, Naik SK, Lodha N, Cauraugh JH. Motor coordination in autism spectrum disorders: a synthesis and meta-analysis. J Autism Dev Disord. 2010;40(10):1227–40. PubMed PMID: 20195737.PubMedCrossRefGoogle Scholar
  109. 109.
    Becker EB, Stoodley CJ. Autism spectrum disorder and the cerebellum. Int Rev Neurobiol. 2013;113:1–34. PubMed PMID: 24290381.PubMedCrossRefGoogle Scholar
  110. 110.
    Hilton CL, Zhang Y, Whilte MR, Klohr CL, Constantino J. Motor impairment in sibling pairs concordant and discordant for autism spectrum disorders. Autism Int J Res Pract. 2012;16(4):430–41. PubMed PMID: 22013131. Pubmed Central PMCID: 4222044.CrossRefGoogle Scholar
  111. 111.
    Gowen E, Hamilton A. Motor abilities in autism: a review using a computational context. J Autism Dev Disord. 2013;43(2):323–44. PubMed PMID: 22723127.PubMedCrossRefGoogle Scholar
  112. 112.
    Zwaigenbaum L, Bryson S, Garon N. Early identification of autism spectrum disorders. Behav Brain Res. 2013;251:133–46. PubMed PMID: 23588272.PubMedCrossRefGoogle Scholar
  113. 113.
    Landa R, Garrett-Mayer E. Development in infants with autism spectrum disorders: a prospective study. J Child Psychol Psychiatry. 2006;47(6):629–38. PubMed PMID: 16712640.PubMedCrossRefGoogle Scholar
  114. 114.
    Gernsbacher MA, Sauer EA, Geye HM, Schweigert EK, Hill GH. Infant and toddler oral- and manual-motor skills predict later speech fluency in autism. J Child Psychol Psychiatry. 2008;49(1):43–50. PubMed PMID: 17979963. Pubmed Central PMCID: 4123528.PubMedCrossRefGoogle Scholar
  115. 115.
    Bhat AN, Galloway JC, Landa RJ. Relation between early motor delay and later communication delay in infants at risk for autism. Infant Behav Dev. 2012;35(4):838–46. PubMed PMID: 22982285. Pubmed Central PMCID: 3538350.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Papadopoulos N, McGinley J, Tonge B, Bradshaw J, Saunders K, Murphy A, et al. Motor proficiency and emotional/behavioural disturbance in autism and Asperger’s disorder: another piece of the neurological puzzle? Autism Int J Res Pract. 2012;16(6):627–40. PubMed PMID: 21949004.CrossRefGoogle Scholar
  117. 117.
    Jones V, Prior M. Motor imitation abilities and neurological signs in autistic children. J Autism Dev Disord. 1985;15(1):37–46. PubMed PMID: 3980428.PubMedCrossRefGoogle Scholar
  118. 118.
    Ecker C, Rocha-Rego V, Johnston P, Mourao-Miranda J, Marquand A, Daly EM, et al. Investigating the predictive value of whole-brain structural MR scans in autism: a pattern classification approach. NeuroImage. 2010;49(1):44–56. PubMed PMID: 19683584.PubMedCrossRefGoogle Scholar
  119. 119.
    Stanfield AC, McIntosh AM, Spencer MD, Philip R, Gaur S, Lawrie SM. Towards a neuroanatomy of autism: a systematic review and meta-analysis of structural magnetic resonance imaging studies. Eur Psychiatry J Assoc Eur Psychiatr. 2008;23(4):289–99. PubMed PMID: 17765485.CrossRefGoogle Scholar
  120. 120.
    Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD, et al. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology. 2001;57(2):245–54. PubMed PMID: 11468308.PubMedCrossRefGoogle Scholar
  121. 121.
    Hallahan B, Daly EM, McAlonan G, Loth E, Toal F, O’Brien F, et al. Brain morphometry volume in autistic spectrum disorder: a magnetic resonance imaging study of adults. Psychol Med. 2009;39(2):337–46. PubMed PMID: 18775096.PubMedCrossRefGoogle Scholar
  122. 122.
    Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res. 2011;1380:138–45. PubMed PMID: 20920490. Pubmed Central PMCID: 4500507.PubMedCrossRefGoogle Scholar
  123. 123.
    Murakami JW, Courchesne E, Press GA, Yeung-Courchesne R, Hesselink JR. Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism. Arch Neurol. 1989;46(6):689–94. PubMed PMID: 2730382.PubMedCrossRefGoogle Scholar
  124. 124.
    Hodge SM, Makris N, Kennedy DN, Caviness VS Jr, Howard J, McGrath L, et al. Cerebellum, language, and cognition in autism and specific language impairment. J Autism Dev Disord. 2010;40(3):300–16. PubMed PMID: 19924522. Pubmed Central PMCID: 3771698.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Cheung C, Chua SE, Cheung V, Khong PL, Tai KS, Wong TK, et al. White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism. J Child Psychol Psychiatry. 2009;50(9):1102–12. PubMed PMID: 19490309.PubMedCrossRefGoogle Scholar
  126. 126.
    Bauman M, Kemper TL. Histoanatomic observations of the brain in early infantile autism. Neurology. 1985;35(6):866–74. PubMed PMID: 4000488.PubMedCrossRefGoogle Scholar
  127. 127.
    Whitney ER, Kemper TL, Rosene DL, Bauman ML, Blatt GJ. Density of cerebellar basket and stellate cells in autism: evidence for a late developmental loss of Purkinje cells. J Neurosci Res. 2009;87(10):2245–54. PubMed PMID: 19301429. Pubmed Central PMCID: 2760265.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Courchesne E. Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism. Curr Opin Neurobiol. 1997;7(2):269–78. PubMed PMID: 9142760.PubMedCrossRefGoogle Scholar
  129. 129.
    Nicot A, Lelievre V, Tam J, Waschek JA, DiCicco-Bloom E. Pituitary adenylate cyclase-activating polypeptide and sonic hedgehog interact to control cerebellar granule precursor cell proliferation. J Neurosci: Off J Soc Neurosci. 2002;22(21):9244–54. PubMed PMID: 12417650.CrossRefGoogle Scholar
  130. 130.
    DiCicco-Bloom E, Lord C, Zwaigenbaum L, Courchesne E, Dager SR, Schmitz C, et al. The developmental neurobiology of autism spectrum disorder. J Neurosci: Off J Soc Neurosci. 2006;26(26):6897–906. PubMed PMID: 16807320.CrossRefGoogle Scholar
  131. 131.
    Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67–81. PubMed PMID: 15546155.PubMedCrossRefGoogle Scholar
  132. 132.
    Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci: Off J Int Soc Dev Neurosci. 2005;23(2–3):183–7. PubMed PMID: 15749244.CrossRefGoogle Scholar
  133. 133.
    Skefos J, Cummings C, Enzer K, Holiday J, Weed K, Levy E, et al. Regional alterations in Purkinje cell density in patients with autism. PLoS One. 2014;9(2):e81255. PubMed PMID: 24586223. Pubmed Central PMCID: 3933333.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Fatemi SH, Halt AR, Realmuto G, Earle J, Kist DA, Thuras P, et al. Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol. 2002;22(2):171–5. PubMed PMID: 12363198.PubMedCrossRefGoogle Scholar
  135. 135.
    Vajda S, Vakser IA, Sternberg MJ, Janin J. Modeling of protein interactions in genomes. Proteins. 2002;47(4):444–6. PubMed PMID: 12001222.PubMedCrossRefGoogle Scholar
  136. 136.
    Catani M, Jones DK, Daly E, Embiricos N, Deeley Q, Pugliese L, et al. Altered cerebellar feedback projections in Asperger syndrome. NeuroImage. 2008;41(4):1184–91. PubMed PMID: 18495494.PubMedCrossRefGoogle Scholar
  137. 137.
    Shukla DK, Keehn B, Lincoln AJ, Muller 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(12):1269–78. 78 e1-2. PubMed PMID: 21093776. Pubmed Central PMCID: 3346956.PubMedPubMedCentralGoogle Scholar
  138. 138.
    Dum RP, Strick PL. An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. J Neurophysiol. 2003;89(1):634–9. PubMed PMID: 12522208.PubMedCrossRefGoogle Scholar
  139. 139.
    Eccles JC, Sasaki K, Strata P. Interpretation of the potential fields generated in the cerebellar cortex by a mossy fibre volley. Exp Brain Res. 1967;3(1):58–80. PubMed PMID: 6031000.PubMedGoogle Scholar
  140. 140.
    Percheron G, Francois C, Talbi B, Yelnik J, Fenelon G. The primate motor thalamus. Brain Res Brain Res Rev. 1996;22(2):93–181. PubMed PMID: 8883918.PubMedCrossRefGoogle Scholar
  141. 141.
    Leiner HC, Leiner AL, Dow RS. The human cerebro-cerebellar system: its computing, cognitive, and language skills. Behav Brain Res. 1991;44(2):113–28. PubMed PMID: 1751002.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Leiner HC, Leiner AL, Dow RS. Cognitive and language functions of the human cerebellum. Trends Neurosci. 1993;16(11):444–7. PubMed PMID: 7507614.PubMedCrossRefGoogle Scholar
  143. 143.
    Zuber BL, Stark L, Cook G. Microsaccades and the velocity-amplitude relationship for saccadic eye movements. Science. 1965;150(3702):1459–60. PubMed PMID: 5855207.PubMedCrossRefGoogle Scholar
  144. 144.
    Kase M, Miller DC, Noda H. Discharges of Purkinje cells and mossy fibres in the cerebellar vermis of the monkey during saccadic eye movements and fixation. J Physiol. 1980;300:539–55. PubMed PMID: 6770085. Pubmed Central PMCID: 1279371.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Grodd W, Hulsmann E, Lotze M, Wildgruber D, Erb M. Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization. Hum Brain Mapp. 2001;13(2):55–73. PubMed PMID: 11346886.PubMedCrossRefGoogle Scholar
  146. 146.
    Vaillancourt DE, Mayka MA, Corcos DM. Intermittent visuomotor processing in the human cerebellum, parietal cortex, and premotor cortex. J Neurophysiol. 2006;95(2):922–31. PubMed PMID: 16267114. Pubmed Central PMCID: 2366036.PubMedCrossRefGoogle Scholar
  147. 147.
    Spraker MB, Corcos DM, Kurani AS, Prodoehl J, Swinnen SP, Vaillancourt DE. Specific cerebellar regions are related to force amplitude and rate of force development. NeuroImage. 2012;59(2):1647–56. PubMed PMID: 21963915. Pubmed Central PMCID: 3230677.PubMedCrossRefGoogle Scholar
  148. 148.
    Neely KA, Coombes SA, Planetta PJ, Vaillancourt DE. Segregated and overlapping neural circuits exist for the production of static and dynamic precision grip force. Hum Brain Mapp. 2013;34(3):698–712. PubMed PMID: 22109998. Pubmed Central PMCID: 3292669.PubMedGoogle Scholar
  149. 149.
    Brisson J, Warreyn P, Serres J, Foussier S, Adrien-Louis J. Motor anticipation failure in infants with autism: a retrospective analysis of feeding situations. Autism Int J Res Pract. 2012;16(4):420–9. PubMed PMID: 22250193.CrossRefGoogle Scholar
  150. 150.
    Cheng Y, Chou KH, Chen IY, Fan YT, Decety J, Lin CP. Atypical development of white matter microstructure in adolescents with autism spectrum disorders. NeuroImage. 2010;50(3):873–82. PubMed PMID: 20074650.PubMedCrossRefGoogle Scholar
  151. 151.
    Provost B, Lopez BR, Heimerl S. A comparison of motor delays in young children: autism spectrum disorder, developmental delay, and developmental concerns. J Autism Dev Disord. 2007;37(2):321–8. PubMed PMID: 16868847.PubMedCrossRefGoogle Scholar
  152. 152.
    Brian J, Bryson SE, Garon N, Roberts W, Smith IM, Szatmari P, et al. Clinical assessment of autism in high-risk 18-month-olds. Autism Int J Res Pract. 2008;12(5):433–56. PubMed PMID: 18805941.CrossRefGoogle Scholar
  153. 153.
    Van Waelvelde H, Oostra A, Dewitte G, Van Den Broeck C, Jongmans MJ. Stability of motor problems in young children with or at risk of autism spectrum disorders, ADHD, and or developmental coordination disorder. Dev Med Child Neurol. 2010;52(8):e174–8. PubMed PMID: 20132135.PubMedCrossRefGoogle Scholar
  154. 154.
    Solomon M, Ozonoff SJ, Cummings N, Carter CS. Cognitive control in autism spectrum disorders. Int J Dev Neurosci: Off J Int Soc Dev Neurosci. 2008;26(2):239–47. PubMed PMID: 18093787. Pubmed Central PMCID: 2695998.CrossRefGoogle Scholar
  155. 155.
    Middleton FA, Strick PL. Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies. Brain Cogn. 2000;42(2):183–200. PubMed PMID: 10744919.PubMedCrossRefGoogle Scholar
  156. 156.
    Schmahmann JD. From movement to thought: anatomic substrates of the cerebellar contribution to cognitive processing. Hum Brain Mapp. 1996;4(3):174–98. PubMed PMID: 20408197.PubMedCrossRefGoogle Scholar
  157. 157.
    Robbins TW, Roberts AC. Differential regulation of fronto-executive function by the monoamines and acetylcholine. Cereb Cortex. 2007;17(Suppl 1):i151–60. PubMed PMID: 17725997.PubMedCrossRefGoogle Scholar
  158. 158.
    Fallon JH, Riley JN, Moore RY. Substantia nigra dopamine neurons: separate populations project to neostriatum and allocortex. Neurosci Lett. 1978;7(2–3):157–62. PubMed PMID: 19605105.PubMedCrossRefGoogle Scholar
  159. 159.
    Huerta M, Lord C. Diagnostic evaluation of autism spectrum disorders. Pediatr Clin N Am. 2012;59(1):103–11. xi. PubMed PMID: 22284796. Pubmed Central PMCID: 3269006.CrossRefGoogle Scholar
  160. 160.
    Taylor LJ, Eapen V, Maybery MT, Midford S, Paynter J, Quarmby L, et al. Diagnostic evaluation for autism spectrum disorder: a survey of health professionals in Australia. BMJ Open. 2016;6(9):e012517. PubMed PMID: 27601502. Pubmed Central PMCID: 5020660.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Filipek PA, Accardo PJ, Ashwal S, Baranek GT, Cook EH Jr, Dawson G, et al. Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology. 2000;55(4):468–79. PubMed PMID: 10953176.PubMedCrossRefGoogle Scholar
  162. 162.
    Zwaigenbaum L, Bauman ML, Choueiri R, Kasari C, Carter A, Granpeesheh D, et al. Early intervention for children with autism spectrum disorder under 3 years of age: recommendations for practice and research. Pediatrics. 2015;136(Suppl 1):S60–81. PubMed PMID: 26430170.PubMedCrossRefGoogle Scholar
  163. 163.
    Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000;30(3):205–23. PubMed PMID: 11055457.PubMedCrossRefGoogle Scholar
  164. 164.
    Stone WL, Coonrod EE, Ousley OY. Brief report: screening tool for autism in two-year-olds (STAT): development and preliminary data. J Autism Dev Disord. 2000;30(6):607–12. PubMed PMID: 11261472.PubMedCrossRefGoogle Scholar
  165. 165.
    Wetherby AM, Allen L, Cleary J, Kublin K, Goldstein H. Validity and reliability of the communication and symbolic behavior scales developmental profile with very young children. J Speech Lang Hear Res: JSLHR. 2002;45(6):1202–18. PubMed PMID: 12546488.PubMedCrossRefGoogle Scholar
  166. 166.
    Kim SH, Lord C. Restricted and repetitive behaviors in toddlers and preschoolers with autism spectrum disorders based on the Autism Diagnostic Observation Schedule (ADOS). Autism Res: Off J Int Soc Autism Res. 2010;3(4):162–73. PubMed PMID: 20589716. Pubmed Central PMCID: 3005305.CrossRefGoogle Scholar
  167. 167.
    Listhaus AD, Freeman WR. Fluorescein angiography in patients with posterior uveitis. Int Ophthalmol Clin. 1990;30(4):297–308. PubMed PMID: 2228479.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Mehnosh Toback
    • 1
  • Kambiz Zangeneh
    • 2
  • Tabrez J. Siddiqui
    • 3
    • 4
  • Hassan Marzban
    • 5
    Email author
  1. 1.Foothills HospitalCalgaryCanada
  2. 2.Sina Laboratory BuildingArakIran
  3. 3.Department of Physiology and Pathophysiology, Max Rady College of MedicineUniversity of ManitobaWinnipegCanada
  4. 4.Neuroscience Research ProgramKleysen Institute for Advanced Medicine, Health Sciences CentreWinnipegCanada
  5. 5.Department of Human Anatomy and Cell Science, The Children’s Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health ScienceUniversity of ManitobaWinnipegCanada

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