Abstract
We examined the brain organization for language and auditory functions in five high-functioning autistic and five normal adults, using [15O]-water positron emission tomography (PET). Cerebral blood flow was studied for rest, listening to tones, and listening to, repeating, and generating sentences. The autism group (compared to the control group) showed (a) reversed hemispheric dominance during verbal auditory stimulation; (b) a trend towards reduced activation of auditory cortex during acoustic stimulation; and (c) reduced cerebellar activation during nonverbal auditory perception and possibly expressive language. These results are compatible with findings of cerebellar anomalies and may suggest a tendency towards atypical dominance for language in autism.
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REFERENCES
Akshoomoff, N. A., & Courchesne, E. (1992). A new role for the cerebellum in cognitive operations. Behavioral Neuroscience, 106, 731–8.
Akshoomoff, N. A., Courchesne, E., Press, G. A., & Iragui, V. (1992). Contribution of the cerebellum to neuropsychological functioning: evidence from a case of cerebellar degenerative disorder. Neuropsychologia, 30, 315–328.
Allen, G., Buxton, R. B., Wong, E. C., & Courchesne, E. (1997). Attentional activation of the cerebellum independent of motor involvement. Science, 275, 1940–1943.
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington DC: Author.
Anderson, G. M. (1994). Studies on the neurochemistry of autism. In M. L. Bauman & T. L. Kemper (Eds.), The Neurobiology of autism (pp. 227–241). Baltimore: Johns Hopkins University Press.
Aram, D. M., & Eisele, J. A. (1994). Intellectual stability in children with unilateral brain lesions. Neuropsychologia, 32, 85–95.
Arin, D., Bauman, M. L., & Kemper, T. L. (1991). The distribution of Purkinje cell loss in the cerebellum in autism. Neurology, 41, 307.
Bachevalier, J., & Merjanian, P. M. (1994). The contribution of medial temporal lobe structures in infantile autism: a neurobehavioral study in primates. In M. L. Bauman & T. L. Kemper (Eds.), The neurobiology of autism (pp. 146–169). Baltimore: Johns Hopkins, University Press.
Bailey, A., Phillips, W., & Rutter, M. (1996). Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. Journal of Child Psychology & Psychiatry & Allied Disciplines, 37, 89–126.
Bauman, M., & Kemper, T. L. (1985). Histoanatomic observations of the brain in early infantile autism. Neurology, 35, 866–875.
Baumann, M. L., & Kemper, T. L. (1994). Neuroanatomic observations of the brain inautism. In M. L. Bauman & T. L. Kemper (Eds.), The neurobiology of autism (pp. 119–145). Baltimore: Johns Hopkins University Press.
Bishop, D. V. (1989). Autism, Asperger's syndrome and semantic-pragmatic disorder: where are the boundaries? British Journal of Disorders of Communication, 24, 107–121.
Boller, F., & Vignolo, L. A. (1966). Latent sensory aphasia in hemispheric-damaged patients: an experimental study with the token test. Brain, 89, 815–831.
Bower, J. M. (1995). The cerebellum as sensory acquisition controller. Human Brain Mapping, 2, 255–256.
Bruneau, N., Dourneau, M. C., Garreau, B., Pourcelot, L., & Lelord, G. (1992). Blood flow response to auditory stimulations in normal, mentally retarded, and autistic children: A preliminary transcranial Doppler ultrasonographic study of the middle cerebral arteries. Biological Psychiatry, 32, 691–699.
Buchsbaum, M. S., Siegel, B. V., Wu, J. C., Hazlett, E., Sicotte, N., Haier, R., Tanguay, P., Asarnow, R., Cadorette, T., Donoghue, D., Lagunas-Solar, M., Lott, I., Paek, J., & Sabalesky, D. (1992). Brief report: Attention performance in autism and regional brain metabolic rate assessed by positron emission tomography. Journal of Autism and Developmental Disorders, 22, 115–125.
Cantor, D. S., Thatcher, R. W., Hrybyk, M., & Kaye, H. (1986). Computerized EEG analyses of autistic children. Journal of Autism and Developmental Disorders, 16, 169–187.
Chiron, C., Jambaqué, I., Nabbout, R., Lounes, R., Syrota, A., & Dulac, O. (1997). The right brain hemisphere is dominant in human infants. Brain, 120, 1057–1065.
Chiron, C., Leboyer, M., Leon, F., Jambaqué, I., Nuttin, C., & Syrota, A. (1995). SPECT of the brain in childhood autism: Evidence for a lack of normal hemispheric asymmetry. Developmental Medicine and Child Neurology, 37, 849–860.
Chugani, D. C., Muzik, O., Rothermel, R. D., Behen, M. E., Chakraborty, P. K., Mangner, T. J., da Silva, E. A., & Chugani, H. T. (1997). Altered serotonin synthesis in the dentato-thalamo-cortical pathway in autistic boys. Annals of Neurology, 41, 666–669.
Ciaranello, A. L., & Ciaranello, R. D. (1995). The neurobiology of infantile autism. Annual Review of Neuroscience, 18, 101–128.
Ciesielski, K. T., Knight, J. E., Prince, R. J., Harris, R. J., & Handmaker, S. D. (1995). Event-related potentials in cross-modal divided attention in autism. Neuropsychologia, 33, 225–246.
Cook, E. H., Courchesne, R., Lord, C., Cox, N. J., Yan, S., Lincoln, A., Haas, R., Courchesne, E., & Leventhal, B. L. (1997). Evidence of linkage between the serotonin transporter and autistic disorder. Molecular Psychiatry, 2, 247–250.
Courchesne, E. (1995). Infantile autism [Parts 1 & 2]. International Pediatrics, 10, 141–165.
Courchesne, E. (1997). Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism. Current Opinion in Neurobiology, 7, 269–278.
Courchesne, E., Press, G. A., & Yeung-Courchesne, R. (1993). Parietal lobe abnormalities detected with MR in patients with infantile autism. American Journal of Roentgenology, 160, 387–393.
Courchesne, E., Townsend, J., & Saitoh, O. (1994). The brain in infantile autism: posteria fossa structures are abnormal. Neurology, 44, 214–223.
Courchesne, E., Townsend, J., & Saitoh, O. (1995). The cerebellum and autism. Neurology, 45, 399–401.
Courchesne, E., Yeung-Courchesne, R., Press, G. A., Hesselink, J. R., & Jernigan, T. L. (1988). Hypoplasia of cerebellar vermal lobules VI and VII in autism. New England Journal of Medicine, 318, 1349–1354.
D'Amato, R. J., Blue, M. E., Largent, B. L., Lynch, D. R., Ledbetter, D. J., Molliver, M. E., & Snyder, S. H. (1987). Ontogeny of the serotonergic projection to rat neocortex: Transient expression of a dense innervation to primary sensory areas. Paper presented at the Proceedings of the National Academy of Sciences (U.S.A.).
Damasio, A. R., & Maurer, R. G. (1978). A neurological model for childhood autism. Archives of Neurology, 35, 777–786.
Dawson, G., Finley, C., Phillips, S., Galpert, L. (1986). Hemispheric specialization and the language abilities of autistic children. Child Development, 57, 1440–1453.
Dawson, G., Finley, C., Phillips, S., & Lewy, A. (1989). A comparison of hemispheric asymmetries in speech-related brain potentials of autistic and dysphasic children. Brain and Language, 37, 26–41.
De Volder, A. G., Bol, A., Michel, C., Cogneau, M., & Goffinet, A. M. (1987). Brain glucose metabolism in children with the autistic syndrome: positron emission analysis. Brain & Development, 9, 581–587.
Devinsky, O., Morrell, M. J., & Vogt, B. A. (1995). Contributions of anterior cingulate cortex to behaviour. Brain, 118, 279–306.
Egaas, B., Courchesne, E., & Saitoh, O. (1995). Reduced size of corpus callosum in autism. Archives of Neurology, 52, 794–801.
Fein, D., Humes, M., Kaplan, E., Lucci, D., & Waterhouse, L. (1984). The question of left hemisphere dysfunction in infantile autism. Psychological Bulletin, 95, 258–281.
Fein, D., Waterhouse, L., Lucci, D., & Snyder, D. (1985). Cognitive subtypes in developmentally disabled children: A pilot study. Journal of Autism and Developmental Disorders, 15, 77–95.
Fiez, J. A., Tallal, P., Raichle, M. E., Miezin, F. M., Katz, W. F., & Petersen, S. E. (1995). PET studies of auditory and phonological processing: Effects of stimulus characteristics and task demands. Journal of Cognitive Neuroscience, 7, 357–375.
Filipek, P. A. (1995). Quantitative magnetic resonance imaging in autism: The cerebellar vermis. Current Opinion in Neurology, 8, 134–138.
Friston, K. J., Frith, C. D., Liddle, P. F., & Frackowiak, R. S. J. (1991). Comparing functional (PET) images: The assessment of significant change. Journal of Cerebral Blood Flow and Metabolism, 11, 690–699.
Gaffney, G. R., Tsai, L. Y., Kuperman, S., & Minchin, S. (1987). Cerebellar structure in autism. American Journal of Diseases of Children, 141, 1330–1332.
George, M. S., Costa, D. C., Kouris, K., Ring, H. A., & Ell, P. J. (1992). Cerebral blood flow abnormalities in adults with infantile autism. Journal of Nervous and Mental Disease, 180, 413–417.
Gilliam, J. E. (1995). Gilliam Autism Rating Scales. Austin, TX: Pro-Ed.
Gordon, M. (1991). Gordon Diagnostic System-Model-III-R. Dewitt, NY: Gordon Systems.
Hallett, M., Lebiedowska, M. K., Thomas, S. L., Stanhope, S. J., Denckla, M. B., & Rumsey, J. (1993). Locomotion of autistic adults. Archives of Neurology, 50, 1304–1308.
Happé, F., Ehlers, S., Fletcher, P. C., Frith, U., Johansson, M., Gillberg, C., Dolan, R. J., Frackowiak, R. S. J., & Frith, C. D. (1996). ‘Theory of mind’ in the brain. Evidence from a PET scan study of Asperger syndrome. NeuroReport, 8, 197–201.
Hashimoto, T., Tayama, M., Murakawa, K., Yoshimoto, T., Miyazaki, M., Harada, M., & Kuroda, Y. (1995). Development of the brainstem and cerebellum in autistic patients. Journal of Autism and Developmental Disorders, 25, 1–18.
Haznedar, M. M., Buchsbaum, M. S., Metzger, M., Solimando, A., Spiegel-Cohen, J., & Hollander, E. (1997). Anterior cingulate gyrus volume and glucose metabolism in autistic disorder. American Journal of Psychiatry, 154, 1047–1050.
Heaton, R. K., Chelune, G. J., Talley, J. L., Kay, J. G., & Curtiss, G. (1993). Wisconsin Card Sort Test Manual-Revised and expanded. Odessa, FL: Psychological Assessment Resources.
Herold, S., Frackowiak, R. S. J., Le Couteur, A., Rutter, M., & Howlin, P. (1988). Cerebral blood flow and metabolism of oxygen and glucose in young autistic adults. Psychological Medicine, 18, 823–831.
Hier, D. B., Lemay, M., & Rosenberger, P. B. (1979). Autism and unfavorable left-right asymmetries of the brain. Journal of Autism and Developmental Disorders, 9, 154–179.
Hoffmann, W. L., & Prior, M. R. (1982). Neuropsychological dimensions of autism in children: A test of the hemispheric dysfunction hypothesis. Journal of Clinical Neuropsychology, 4, 27–41.
Holttum, J. R., Minshew, N. J., Sanders, R. S., & Phillips, N. E. (1992). Magnetic resonance imaging of the posterior fossa in autism. Biological Psychiatry, 32, 1091–1101.
Horwitz, B., Rumsey, J. M., Grady, C. L., & Rapoport, S. I. (1988). The cerebral metabolic landscape in autism: Intercorrelations of regional glucose utilization. Archives of Neurology, 45, 749–755.
Khorram-Sefat, D., Dierks, T., & Hacker, H. (1996). Cerebellar activation during music listening. Neuroimage, 3, S312.
Le, H. T., Pardo, J. V., & Hu, X. (1998). 4 T-fMRI study of nonspatial shifting of selective attention: cerebellar and parietal contributions. Journal of Neurophysiology, 79, 1535–1548.
Le, H. T., Pardo, J., & Hu, X. (1996). Cerebellar activation in silent verbal generation using fMRI. Neuroimage, 3, S584.
Leiner, H. C., Leiner, A. L., & Dow, R. S. (1995). The underestimated cerebellum. Human Brain Mapping, 2, 244–254.
Lezak, M. D. (1995). Neuropsychological assessment (3rd ed.). New York: Oxford University Press.
Lincoln, A. J., Courchesne, E., Harms, L., & Allen, M. (1995). Sensory modulation of auditory stimuli in children with autism and receptive developmental language disorder: Event-related brain potential evidence. Journal of Autism and Developmental Disorders, 25, 521–539.
Marriage, J., & Barnes, N. M. (1995). Is central hyperacusis a symptom of 5-hydroxytryptamine (5-HT) dysfunction? Journal of Laryngology and Otology, 109, 915–921.
McDougle, C. J., Naylor, S. T., Cohen, D. J., Volkmar, F. R., Heninger, G. R., & Price, L. H. (1996). A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Archives of General Psychiatry, 53, 1001–1008.
McKelvey, J. R., Lambert, R., Mottron, L., & Shevell, M. I. (1995). Right-hemisphere dysfunction in Asperger's syndrome. Journal of Child Neurology, 10, 310–314.
Minoshima, S., Koeppe, R. A., Fessler, J. A., Mintun, M. A., Berger, K. L., Taylor, S. F., & Kuhl, D. E. (1993). Integrated and automated data analysis method for neuronal activation studies using 16O-water PET. In K. Uemura, N. Lassen, T. Jones, & I. Kanno (Eds.), Quantification of brain function (pp. 409–415). New York: Elsevier.
Minoshima, S., Koeppe, R. A., Frey, K. A., & Kuhl, D. E. (1994). Anatomic standardization: linear scaling and nonlinear warping of functional brain images. Journal of Nuclear Medicine, 35, 1528–1537.
Minshew, N. J. (1994). In vivo neuroanatomy of autism: neuroimaging studies. In M. L. Bauman & T. L. Kemper (Eds.), The neurobiology of autism (pp. 66–85). Baltimore: Johns Hopkins University Press.
Mountz, J. M., Tolbert, L. C., Lill, D. W., Katholi, C. R., & Liu, H. G. (1995). Functional deficits in autistic disorder: Characterization by technetium-99m-HMPAO and SPECT. Journal of Nuclear Medicine, 36, 1156–1162.
Müller, R.-A., Rothermel, R. D., Behen, M. E., Muzik, O., Mangner, T. J., Chakraborty, P. K., & Chugani, H. T. (1997). Receptive and expressive language activations for sentences: A PET study. Neuroreport, 8, 3767–3770.
Murakami, J. W., Courchesne, E., Press, G. A., Yeung-Courchesne, R., & Hesselink, J. R. (1989). Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism. Archives of Neurology, 46, 689–694.
Nass, R., & Stiles, J. (1996). Neurobehavioral consequences of congenital focal lesions. In Y. Frank (Ed.). Pediatric behavioral neurology (pp. 149–178). Boca Raton, FL: CRC Press.
Novick, B., Vaughan, H. G., Jr., Kurtzberg, D., & Simson, R. (1980). An electrophysiologic indication of auditory processing defects in autism. Psychiatry Research, 3, 107–114.
Ogawa, T., Sugiyama, A., Ishiwa, S., Suzuki, M., Ishihara, T., & Sato, K. (1982). Ontogenic development of EEG-asymmetry in early infantile autism. Brain & Development, 4, 439–49.
Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh Inventory. Neuropsychologia, 9, 97–113.
Ozonoff, S., & Miller, J. N. (1996). An exploration of right-hemisphere contributions to the pragmatic impairments of autism. Brain & Language, 52, 411–34.
Ozonoff, S., Rogers, S. J., & Pennington, B. F. (1991). Asperger's syndrome: Evidence of an empirical distinction from high-functioning autism. Journal of Child Psychology and Psychiatry, 32, 1107–1122.
Petersen, S. E., Fox, P. T., Posner, M. I., Mintun, M., & Raichle, M. E. (1989). Positron emission tomographic studies of the processing of single words. Journal of Cognitive Neuroscience, 1, 153–170.
Piven, J., & Arndt, S. (1995). The cerebellum and autism. Neurology, 45, 398–402.
Piven, J., Arndt, S., Bailey, J., Havercamp, S., Andreasen, N. C., & Palmer, P. (1995). An MRI study of brain size in autism. American Journal of Psychiatry, 152, 1145–9.
Piven, J., Bailey, J., Ranson, B. J., & Arndt, S. (1997). An MRI study of the corpus callosum in autism. American Journal of Psychiatry, 154, 1051–1055.
Piven, J., Nehme, E., Simon, J., Barta, P., Pearlson, G., & Folstein, S. (1992). Magnetic resonance imaging in autism: Measurement of the cerebellum, pons, and fourth ventricle. Biological Psychiatry, 31, 491–504.
Piven, J., Saliba, K., Bailey, J., & Arndt, S. (1997). An MRI study of autism: The cerebellum revisited. Neurology, 49, 546–551.
Posner, M. I., & Petersen, S. E. (1990). The attention system of the human brain. Annual Review of Neuroscience, 13, 25–42.
Prior, M. R., & Bradshaw, J. L. (1979). Hemisphere functioning in autistic children. Cortex, 15, 73–81.
Raichle, M. E., Fiez, J. A., Videen, T. O., MacLeod, A.-M. K., Pardo, J. V., Fox, P. T., & Petersen, S. E. (1994). Practice-related changes in human brain functional anatomy during nonmotor learning. Cerebral Cortex, 4, 8–26.
Rapin, I. (1997). Autism. New England Journal of Medicine, 337, 97–104.
Rasmussen, T., & Milner, B. (1977). The role of early left brain injury in determining lateralization of cerebral speech functions. Annals of the New York Academy of Sciences, 299, 355–69.
Rimland, B., & Edelson, S. M. (1995). Brief report: A pilot study of auditory integration training in autism. Journal of Autism and Developmental Disorders, 25, 61–70.
Rosenbloom, S., Campbell, M., George, A. E., Kricheff, H., Taleporos, E., Anderson, L., Reuben, R. N., & Korein, J. (1984). High resolution CT scanning in infantile autism: a quantitative approach. Journal of the American Academy of Child Psychiatry, 23, 72–7.
Rumsey, J. M. (1996). Neuroimaging studies of autism. In G. R. Lyon & J. M. Rumsey (Eds.), Neuroimaging. A window to the neurological foundations of learning and behavior in children (pp. 119–146). Baltimore: Paul H. Brookes.
Rumsey, J. M., Creasey, H., Stepanek, J. S., Dorwart, R., Patronas, N., Hamburger, S. D., & Duara, R. (1988). Hemispheric asymmetries, fourth ventricular size, and cerebellar morphology in autism. Journal of Autism and Developmental Disorders, 18, 127–137.
Rumsey, J. M., Duara, R., Grady, C., Rapoport, L. J., Margolin, R. A., Rapoport, S. T., & Cutler, N. R. (1985). Brain metabolism in autism: Resting cerebral glucose utilization rates as measured with positron emission tomography. Archives of General Psychiatry, 42, 448–455.
Rumsey, J. M., & Hamburger, S. D. (1990). Neuropsychological divergence of high-level autism and severe dyslexia. Journal of Autism and Developmental Disorders, 20, 155–168.
Schmahmann, J. D. (Ed.) (1997). The Cerebellum and Cognition. San Diego: Academic Press.
Semel, E., Wiig, E. H., & Secord, W. (1987). Clinical evaluation of language fundamentals-revised. Psychological Corp.: Harcourt Brace Jovanovich.
Shields, J., Varley, R., Broks, P., & Simpson, A. (1996). Hemispheric function in developmental language disorders and high-level autism. Developmental Medicine & Child Neurology, 38, 473–486.
Siegel, B. V., Jr., Asarnow, R., Tanguay, P., Call, J. D., Abel, L., Ho, A., Lou, I., & Buchsbaum, M. S. (1992). Regional cerebral glucose metabolism and attention in adults with a history of childhood autism. Journal of Neuropsychiatry & Clinical Neurosciences, 4, 406–414.
Silveri, M. C., Leggio, M. G., & Molinari, M. (1994). The cerebellum contributes to linguistic production: A case of agrammatic speech following a right cerebellar lesion. Neurology, 44, 2047–2050.
Szatmari, P., Archer, L., Fisman, S., Streiner, D. L., & Wilson, F. (1995). Asperger's syndrome and autism: differences in behavior, cognition, and adaptive functioning. Journal of the American Academy of Child & Adolescent Psychiatry, 34, 1662–1671.
Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain. Stuttgart, Germany: Georg Thieme.
Tanguay, P. E., & Edwards, R. M. (1982). Electrophysiological studies of autism: the whisper of the bang. Journal of Autism and Developmental Disorders, 12, 177–184.
Tanguay, P. E., Edwards, R. M., Buchwald, J., Schwafel, J., & Allen, V. (1982). Auditory brainstem evoked responses in autistic children. Archives of General Psychiatry, 39, 174–180.
Thach, W. T. (1996). On the specific role of the cerebellum in motor learning and cognition: clues from PET activation and lesion studies in man. Behavioral and Brain Sciences, 19, 411–431.
Townsend, J., Courchesne, E., & Egaas, B. (1996). Slowed orienting of covert visual-spatial attention in autism: specific deficits associated with cerebellar and parietal abnormality. Development and Psychopathology, 8, 563–584.
Tsai, L. Y. (1992). Diagnostic issues in high-functioning autism. In E. Schopler & G. Mesibov (Eds.), High-functioning individuals with autism (pp. 10–40). New York: Plenum Press.
Tsai, L. Y., Jacoby, C. G., Stewart, M. A., & Beisler, J. M. (1982). Unfavourable left-right asymmetries of the brain and autism: a question of methodology. British Journal of Psychiatry, 140, 312–319.
Tsai, L. Y., & Stewart, M. A. (1983). Morphological cerebral asymmetries in autistic children. Journal of Autism and Developmental Disorders, 13, 57–65.
Volkmar, F. R., Klin, A., Schultz, R., Bronen, R., Marans, W. D., Sparrow, S., & Cohen, D. J. (1996). Asperger's syndrome [clinical conference]. Journal of the American Academy of Child & Adolescent Psychiatry, 35, 118–123.
Williams, J. M. (1990). Memory Assessment Scales: A professional manual. Odessa, FL: Psychological Assessment Resources.
Wong, V., & Wong, S. N. (1991). Brainstem auditory evoked potential study in children with autistic disorder. Journal of Autism and Developmental Disorders, 21, 329–340.
Worsley, K. J., Evans, A. C., Marrett, S., & Neelin, P. (1992). A three-dimensional statistical analysis for CBF activation studies in human brain. Journal of Cerebral Blood Flow and Metabolism, 12, 900–918.
Yan, W., Wilson, C. C., & Haring, J. H. (1997). 5-HT1a receptors mediate the neurotrophic effects of serotonin on developing dentate granule cells. Developmental Brain Research, 98, 185–190.
Zilbovicius, M., Garreau, B., Samson, Y., Remy, P., Barthelemy, C., Syrota, A., & Lelord, G. (1995). Delayed maturation of the frontal cortex in childhood autism. American Journal of Psychiatry, 152, 248–252.
Zilbovicius, M., Garreau, B., Tzourio, N., Mazoyer, B., Bruck, B., Martinot, J.-L., Raynaud, C., Samson, Y., Syrota, A., & Lelord, G. (1992). Regional cerebral blood flow in childhood autism: A SPECT study. American Journal of Psychiatry, 149, 924–930.
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Müller, RA., Behen, M.E., Rothermel, R.D. et al. Brain Mapping of Language and Auditory Perception in High-Functioning Autistic Adults: A PET Study. J Autism Dev Disord 29, 19–31 (1999). https://doi.org/10.1023/A:1025914515203
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DOI: https://doi.org/10.1023/A:1025914515203