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Towards a neuroanatomy of autism: A systematic review and meta-analysis of structural magnetic resonance imaging studies

Published online by Cambridge University Press:  16 April 2020

Andrew C. Stanfield ,
Andrew M. McIntosh ,
Michael D. Spencer ,
Ruth Philip ,
Sonia Gaur  and
Stephen M. Lawrie
Andrew C. Stanfield*
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK
Andrew M. McIntosh
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK
Michael D. Spencer
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK
Ruth Philip
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK
Sonia Gaur
Affiliation:
2790 Skypark Drive, Suite 307, Torrance, CA90505, USA
Stephen M. Lawrie
Affiliation:
Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK
*
∗Corresponding author. Tel.: +44 (0)131 537 6265; fax: +44 (0)131 537 6291. E-mail address: [email protected] (A.C. Stanfield).
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Abstract

Background

Structural brain abnormalities have been described in autism but studies are often small and contradictory. We aimed to identify which brain regions can reliably be regarded as different in autism compared to healthy controls.

Method

A systematic search was conducted for magnetic resonance imaging studies of regional brain size in autism. Data were extracted and combined using random effects meta-analysis. The modifying effects of age and IQ were investigated using meta-regression.

Results

The total brain, cerebral hemispheres, cerebellum and caudate nucleus were increased in volume, whereas the corpus callosum area was reduced. There was evidence for a modifying effect of age and IQ on the cerebellar vermal lobules VI–VII and for age on the amygdala.

Conclusions

Autism may result from abnormalities in specific brain regions and a global lack of integration due to brain enlargement. Inconsistencies in the literature partly relate to differences in the age and IQ of study populations. Some regions may show abnormal growth trajectories.

Keywords

AutismMRIMeta-analysis
Type
Review
Information
European Psychiatry , Volume 23 , Issue 4 , June 2008 , pp. 289 - 299
Copyright
Copyright © European Psychiatric Association 2008

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References

APA. Diagnostic and statistical manual of mental disorders. 4th ed.Washington, DC: American Psychiatric Association; 1994.Google Scholar
Kanner, L.Problems of nosology and psychodynamics of early infantile autism. Am J Orthopsychiatry 1949;19:416–426.CrossRefGoogle ScholarPubMed
Courchesne, E.Yeung-Courchesne, R.Press, G.A.Hesselink, J.R.Jernigan, T.L.Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med 1988;318(21):1349–1354.CrossRefGoogle ScholarPubMed
Hashimoto, T.Tayama, M.Murakawa, K.Yoshimoto, T.Miyazaki, M.Harada, M.et al.Development of the brainstem and cerebellum in autistic patients. J Autism Dev Disord 1995;25(1):1–18.CrossRefGoogle ScholarPubMed
Hardan, A.Y.Minshew, N.J.Harenski, K.Keshavan, M.S.Posterior fossa magnetic resonance imaging in autism. J Am Acad Child Adolescent Psychiatry 2001;40(6):666–672.CrossRefGoogle ScholarPubMed
Kleiman, M.D.Neff, S.Rosman, N.The brain in infantile autism: are posterior fossa structures abnormal?. Neurology 1992;42(4):753–760.CrossRefGoogle ScholarPubMed
Kaufmann, W.E.Cooper, K.L.Mostofsky, S.H.Capone, G.T.Kates, W.R.Newschaffer, C.J.et al.Specificity of cerebellar vermian abnormalities in autism: a quantitative magnetic resonance imaging study. J Child Neurol 2003;18(7):463–470.CrossRefGoogle ScholarPubMed
Piven, J.Saliba, K.Bailey, J.Arndt, S.An MRI study of autism: the cerebellum revisited. Neurology 1997;49(2):546–551 (see comment)CrossRefGoogle ScholarPubMed
Sparks, B.F.Friedman, S.D.Shaw, D.W.Aylward, E.H.Echelard, D.Artru, A.A.et al.Brain structural abnormalities in young children with autism spectrum disorder. Neurology 2002;59(2):184–192 (see comment)CrossRefGoogle ScholarPubMed
Kates, W.R.Burnette, C.P.Eliez, S.Strunge, L.A.Kaplan, D.Landa, R.et al.Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism. Am J Psychiatry 2004;161(3):539–546.CrossRefGoogle ScholarPubMed
Courchesne, E.Karns, C.M.Davis, H.R.Ziccardi, R.Carper, R.A.Tigue, Z.D.et al.Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 2001;57(2):245–254.CrossRefGoogle Scholar
Aylward, E.H.Minshew, N.J.Field, K.Sparks, B.F.Singh, N.Effects of age on brain volume and head circumference in autism. Neurology 2002;59(2):175–183.CrossRefGoogle ScholarPubMed
Piven, J.Arndt, S.Bailey, J.Havercamp, S.Andreasen, N.C.Palmer, P.An MRI study of brain size in autism. Am J Psychiatry 1995;152(8):1145–1149.Google ScholarPubMed
Schumann, C.M.Hamstra, J.Goodlin-Jones, B.L.Lotspeich, L.J.Kwon, H.Buonocore, M.H.et al.The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci 2004;24(28):6392–6401.CrossRefGoogle Scholar
Di Martino, A.Castellanos, F.X.Functional neuroimaging of social cognition in pervasive developmental disorders: a brief review. Ann N Y Acad Sci 2003;1008:256–260.CrossRefGoogle ScholarPubMed
Pierce, K.Muller, R.A.Ambrose, J.Allen, G.Courchesne, E.Face processing occurs outside the fusiform ‘face area’ in autism: evidence from functional MRI. Brain 2001;124(Pt 10):2059–2073.CrossRefGoogle ScholarPubMed
Haznedar, M.M.Buchsbaum, M.S.Wei, T.C.Hof, P.R.Cartwright, C.Bienstock, C.A.et al.Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry 2000;157(12):1994–2001.CrossRefGoogle ScholarPubMed
Howard, M.A.Cowell, P.E.Boucher, J.Broks, P.Mayes, A.Farrant, A.et al.Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism. Neuroreport 2000;11(13):2931–2935.CrossRefGoogle ScholarPubMed
Brambilla, P.Hardan, A.di Nemi, S.U.Perez, J.Soares, J.C.Barale, F.Brain anatomy and development in autism: review of structural MRI studies. Brain Res Bull 2003;61(6):557–569.CrossRefGoogle ScholarPubMed
Cody, H.Pelphrey, K.Piven, J.Structural and functional magnetic resonance imaging of autism. Int J Dev Neurosci 2002;20(3-5):421–438.CrossRefGoogle ScholarPubMed
Redcay, E.Courchesne, E.When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biol Psychiatry 2005;58(1):1–9.CrossRefGoogle ScholarPubMed
Hedges, L.V.Oklin, I.Statistical methods for meta-analysis. Orlando, FL: Academic Press; 1985.Google Scholar
DerSimonian, R.Laird, N.Meta-analysis in clinical trials. Control Clin Trials 1986;7(3):177–188.CrossRefGoogle ScholarPubMed
Higgins, J.P.Thompson, S.G.Deeks, J.J.Altman, D.G.Measuring inconsistency in meta-analyses. Br Med J 2003;327(7414):557–560.CrossRefGoogle ScholarPubMed
Akshoomoff, N.Lord, C.Lincoln, A.J.Courchesne, R.Y.Carper, R.A.Townsend, J.et al.Outcome classification of preschool children with autism spectrum disorders using MRI brain measures. J Am Acad Child Adolescent Psychiatry 2004;43(3):349–357.CrossRefGoogle ScholarPubMed
Carper, R.A.Courchesne, E.Inverse correlation between frontal lobe and cerebellum sizes in children with autism. Brain 2000;123(Pt 4):836–844.CrossRefGoogle ScholarPubMed
Carper, R.A.Moses, P.Tigue, Z.D.Courchesne, E.Cerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage 2002;16(4):1038–1051.CrossRefGoogle ScholarPubMed
Ciesielski, K.T.Harris, R.J.Hart, B.L.Pabst, H.F.Cerebellar hypoplasia and frontal lobe cognitive deficits in disorders of early childhood. Neuropsychologia 1997;35(5):643–655.CrossRefGoogle ScholarPubMed
Courchesne, E.Saitoh, O.Yeung-Courchesne, R.Press, G.A.Lincoln, A.J.Haas, R.H.et al.Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging. Am J Roentgenol 1994;162(1):123–130.CrossRefGoogle ScholarPubMed
Egaas, B.Courchesne, E.Saitoh, O.Reduced size of corpus callosum in autism. Arch Neurol 1995;52(8):794–801.CrossRefGoogle ScholarPubMed
Elia, M.Manfre, L.Ferri, R.Musumeci, S.A.Panerai, S.Bottitta, M.et al.Brain morphometry and psychobehavioural measures in autistic low- functioning subjects. Riv Neuroradiol 1997;10(4):431–436.CrossRefGoogle Scholar
Gaffney, G.R.Kuperman, S.Tsai, L.Y.Minchin, S.Hassanein, K.M.Midsagittal magnetic resonance imaging of autism. Br J Psychiatry 1987;151:831–833.CrossRefGoogle ScholarPubMed
Gaffney, G.R.Kuperman, S.Tsai, L.Y.Minchin, S.Morphological evidence for brainstem involvement in infantile autism. Biol Psychiatry 1988;24(5):578–586.CrossRefGoogle ScholarPubMed
Garber, H.J.Ritvo, E.R.Chiu, L.C.Griswold, V.J.Kashanian, A.Freeman, B.J.et al.A magnetic resonance imaging study of autism: normal fourth ventricle size and absence of pathology. Am J Psychiatry 1989;146(4):532–534.Google ScholarPubMed
Garber, H.J.Ritvo, E.R.Magnetic resonance imaging of the posterior fossa in autistic adults. Am J Psychiatry 1992;149(2):245–247 (see comment)Google ScholarPubMed
Girgis, R.R.Minshew, N.J.Melhem, N.M.Nutche, J.J.Keshavan, M.S.Hardan, A.Y.Volumetric alterations of the orbitofrontal cortex in autism. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:41–45.CrossRefGoogle ScholarPubMed
Hardan, A.Y.Minshew, N.J.Keshavan, M.S.Corpus callosum size in autism. Neurology 2000;55(7):1033–1036 (erratum appears in Neurology 2000;55(9):1425)CrossRefGoogle ScholarPubMed
Hardan, A.Y.Minshew, N.J.Mallikarjuhn, M.Keshavan, M.S.Brain volume in autism. J Child Neurol 2001;16(6):421–424.CrossRefGoogle ScholarPubMed
Hardan, A.Y.Kilpatrick, M.Keshavan, M.S.Minshew, N.J.Motor performance and anatomic magnetic resonance imaging (MRI) of the basal ganglia in autism. J Child Neurol 2003;18(5):317–324.CrossRefGoogle ScholarPubMed
Hardan, A.Y.Jou, R.J.Keshavan, M.S.Varma, R.Minshew, N.J.Increased frontal cortical folding in autism: a preliminary MRI study. Psychiatry Res 2004;131(3):263–268.CrossRefGoogle ScholarPubMed
Hardan, A.Y.Muddasani, S.Vemulapalli, M.Keshavan, M.S.Minshew, N.J.An MRI study of increased cortical thickness in autism. Am J Psychiatry 2006;163(7):1290–1292.CrossRefGoogle ScholarPubMed
Hazlett, H.C.Poe, M.D.Gerig, G.Smith, R.G.Piven, J.Cortical gray and white brain tissue volume in adolescents and adults with autism. Biol Psychiatry 2006;59(1):1–6.CrossRefGoogle ScholarPubMed
Haznedar, M.M.Buchsbaum, M.S.Hazlett, E.A.LiCalzi, E.M.Cartwright, C.Hollander, E.Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders. Am J Psychiatry 2006;163(7):1252–1263.CrossRefGoogle ScholarPubMed
Herbert, M.R.Ziegler, D.A.Deutsch, C.K.O'Brien, L.M.Lange, N.Bakardjiev, A.et al.Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 126Pt 52003 1182–1192.CrossRefGoogle ScholarPubMed
Holttum, J.R.Minshew, N.J.Sanders, R.S.Phillips, N.E.Magnetic resonance imaging of the posterior fossa in autism. Biol Psychiatry 1992;32(12):1091–1101.CrossRefGoogle ScholarPubMed
Hsu, M.Yeung-Courchesne, R.Courchesne, E.Press, G.A.Absence of magnetic resonance imaging evidence of pontine abnormality in infantile autism. Arch Neurol 1991;48(11):1160–1163.CrossRefGoogle ScholarPubMed
Levitt, J.G.Blanton, R.Capetillo-Cunliffe, L.Guthrie, D.Toga, A.McCracken, J.T.Cerebellar vermis lobules VIII–X in autism. Prog Neuropsychopharmacol Biol Psychiatry 1999;23(4):625–633.CrossRefGoogle ScholarPubMed
Lotspeich, L.J.Kwon, H.Schumann, C.M.Fryer, S.L.Goodlin-Jones, B.L.Buonocore, M.H.et al.Investigation of neuroanatomical differences between autism and Asperger syndrome. Arch Gen Psychiatry 2004;61(3):291–298 (erratum appears in Arch Gen Psychiatry 2004;61(6):606)CrossRefGoogle ScholarPubMed
McAlonan, G.M.Cheung, V.Cheung, C.Suckling, J.Lam, G.Y.Tai, K.S.et al.Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism. Brain 2005;128(Pt 2):268–276.CrossRefGoogle ScholarPubMed
Pierce, K.Courchesne, E.Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism. Biol Psychiatry 2001;49(8):655–664 (see comment)CrossRefGoogle ScholarPubMed
Piven, J.Nehme, E.Simon, J.Barta, P.Pearlson, G.Folstein, S.E.Magnetic resonance imaging in autism: measurement of the cerebellum, pons, and fourth ventricle. Biol Psychiatry 1992;31(5):491–504.CrossRefGoogle ScholarPubMed
Piven, J.Arndt, S.Bailey, J.Andreasen, N.Regional brain enlargement in autism: a magnetic resonance imaging study. J Am Acad Child Adolescent Psychiatry 1996;35(4):530–536.CrossRefGoogle ScholarPubMed
Piven, J.Bailey, J.Ranson, B.J.Arndt, S.No difference in hippocampus volume detected on magnetic resonance imaging in autistic individuals. J Autism Dev Disord 1998;28(2):105–110 (erratum appears in J Autism Dev Disord 1998;28(3):271)CrossRefGoogle ScholarPubMed
Rojas, D.C.Smith, J.A.Benkers, T.L.Camou, S.L.Reite, M.L.Rogers, S.J.Hippocampus and amygdala volumes in parents of children with autistic disorder. Am J Psychiatry 2004;161(11):2038–2044.CrossRefGoogle ScholarPubMed
Sears, L.L.Vest, C.Mohamed, S.Bailey, J.Ranson, B.J.Piven, J.An MRI study of the basal ganglia in autism. Prog Neuropsychopharmacol Biol Psychiatry 1999;23(4):613–624.CrossRefGoogle ScholarPubMed
Townsend, J.Courchesne, E.Covington, J.Westerfield, M.Harris, N.S.Lyden, P.et al.Spatial attention deficits in patients with acquired or developmental cerebellar abnormality. J Neurosci 1999;19(13):5632–5643.CrossRefGoogle ScholarPubMed
Tsatsanis, K.D.Rourke, B.P.Klin, A.Volkmar, F.R.Cicchetti, D.Schultz, R.T.Reduced thalamic volume in high-functioning individuals with autism. Biol Psychiatry 2003;53(2):121–129.CrossRefGoogle ScholarPubMed
Vidal, C.N.Nicolson, R.DeVito, T.J.Hayashi, K.M.Geaga, J.A.Drost, D.J.et al.Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity. Biol Psychiatry 2006;60(3):218–225.CrossRefGoogle ScholarPubMed
Lord, C.Rutter, M.Le Couteur, A.Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994;24(5):659–685.CrossRefGoogle ScholarPubMed
Lord, C.Risi, S.Lambrecht, L.Cook, E.H. Jr.Leventhal, B.L.DiLavore, P.C.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):205–223.CrossRefGoogle ScholarPubMed
Volkmar, F.R.Cicchetti, D.V.Bregman, J.Cohen, D.J.Three diagnostic systems for autism: DSM-III, DSM-III-R, and ICD-10. J Autism Dev Disord 1992;22(4):483–492.CrossRefGoogle ScholarPubMed
Volkmar, F.R.Klin, A.Siegel, B.Szatmari, P.Lord, C.Campbell, M.et al.Field trial for autistic disorder in DSM-IV. Am J Psychiatry 1994;151(9):1361–1367.Google ScholarPubMed
de Bildt, A.Sytema, S.Ketelaars, C.Kraijer, D.Mulder, E.Volkmar, F.et al.Interrelationship between Autism Diagnostic Observation Schedule-Generic (ADOS-G), Autism Diagnostic Interview-Revised (ADI-R), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) classification in children and adolescents with mental retardation. J Autism Dev Disord 2004;34(2):129–137.CrossRefGoogle ScholarPubMed
Bishop, D.V.Norbury, C.F.Exploring the borderlands of autistic disorder and specific language impairment: a study using standardised diagnostic instruments. J Child Psychol Psychiatry 2002;43(7):917–929.CrossRefGoogle ScholarPubMed
Ventola, P.E.Kleinman, J.Pandey, J.Barton, M.Allen, S.Green, J.et al.Agreement among four diagnostic instruments for autism spectrum disorders in toddlers. J Autism Dev Disord 2006;36(7):839–847.CrossRefGoogle ScholarPubMed
Chakrabarti, S.Fombonne, E.Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am J Psychiatry 2005;162(6):1133–1141.CrossRefGoogle ScholarPubMed
Courchesne, E.Townsend, J.Saitoh, O.The brain in infantile autism: posterior fossa structures are abnormal. Neurology 1994;44(2):214–223 (see comment)CrossRefGoogle ScholarPubMed
Spencer, M.D.Moorhead, T.W.Lymer, G.K.Job, D.E.Muir, W.J.Hoare, P.et al.Structural correlates of intellectual impairment and autistic features in adolescents. Neuroimage 2006;33(4):1136–1144.CrossRefGoogle ScholarPubMed
Hazlett, H.C.Poe, M.Gerig, G.Smith, R.G.Provenzale, J.Ross, A.et al.Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch Gen Psychiatry 2005;62(12):1366–1376.CrossRefGoogle ScholarPubMed
de Bruin, E.I.Verheij, F.Ferdinand, R.F.WISC-R subtest but no overall VIQ-PIQ difference in Dutch children with PDD-NOS. J Abnorm Child Psychol 2006;34(2):263–271.CrossRefGoogle ScholarPubMed
Siegel, D.J.Minshew, N.J.Goldstein, G.Wechsler IQ profiles in diagnosis of high-functioning autism. J Autism Dev Disord 1996;26(4):389–406.CrossRefGoogle ScholarPubMed
Bailey, A.Luthert, P.Dean, A.Harding, B.Janota, I.Montgomery, M.et al.A clinicopathological study of autism. Brain 1998;121(Pt 5):889–905.CrossRefGoogle ScholarPubMed
Casanova, M.F.Buxhoeveden, D.P.Switala, A.E.Roy, E.Minicolumnar pathology in autism. Neurology 2002;58(3):428–432.CrossRefGoogle ScholarPubMed
Herbert, M.R.Large brains in autism: the challenge of pervasive abnormality. Neuroscientist 2005;11(5):417–440.CrossRefGoogle ScholarPubMed
Middleton, F.A.Strick, P.L.Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Brain Res Rev 2000;31(2-3):236–250.CrossRefGoogle ScholarPubMed
Schmahmann, J.D.Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 2004;16(3):367–378.CrossRefGoogle ScholarPubMed
Hollander, E.Anagnostou, E.Chaplin, W.Esposito, K.Haznedar, M.M.Licalzi, E.et al.Striatal volume on magnetic resonance imaging and repetitive behaviors in autism. Biol Psychiatry 2005;58(3):226–232.CrossRefGoogle ScholarPubMed
van den Heuvel, O.A.Veltman, D.J.Groenewegen, H.J.Cath, D.C.van Balkom, A.J.van Hartskamp, J.et al.Frontal-striatal dysfunction during planning in obsessive-compulsive disorder. Arch Gen Psychiatry 2005;62(3):301–309.CrossRefGoogle ScholarPubMed
Chakos, M.H.Lieberman, J.A.Bilder, R.M.Borenstein, M.Lerner, G.Bogerts, B.et al.Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am J Psychiatry 1994;151(10):1430–1436.Google ScholarPubMed
Lee, K.H.Farrow, T.F.Spence, S.A.Woodruff, P.W.Social cognition, brain networks and schizophrenia. Psychol Med 2004;34(3):391–400.CrossRefGoogle Scholar
Shaw, P.Lawrence, E.J.Radbourne, C.Bramham, J.Polkey, C.E.David, A.S.The impact of early and late damage to the human amygdala on ‘theory of mind’ reasoning. Brain 2004;127(Pt 7):1535–1548.CrossRefGoogle ScholarPubMed
Munson, J.Dawson, G.Abbott, R.Faja, S.Webb, S.J.Friedman, S.D.et al.Amygdalar volume and behavioral development in autism. Arch Gen Psychiatry 2006;63(6):686–693.CrossRefGoogle ScholarPubMed
Hardan, A.Y.Girgis, R.R.Adams, J.Gilbert, A.R.Keshavan, M.S.Minishew, N.J.Abnormal brain size effect on the thalamus in autism. Psychiatry Res Neuroimaging 2006;147(2–3):145–151.CrossRefGoogle ScholarPubMed
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