Skip to main content

Brainstem volumetric alterations in children with autism

  • R. J. Jou (a1), N. J. Minshew (a2), N. M. Melhem (a2), M. S. Keshavan (a3) and A. Y. Hardan (a4)...

Although several studies have examined brainstem volume in autism, results have been mixed and no investigation has specifically measured gray- and white-matter structures. The aim of this investigation was to assess gray- and white-matter volumes in children with autism.


Subjects included 22 right-handed, non-mentally retarded boys with autism and 22 gender- and age-matched controls. Magnetic resonance imaging (MRI) scans were obtained using a 1.5-T scanner and volumetric measurements were performed using the BRAINS2 software package. Gray- and white-matter volumes were measured using a semi-automated segmentation process.


There were no significant differences in age and total brain volume (TBV) between the two groups but full-scale IQ was higher in controls. A decrease in brainstem gray-matter volume was observed in the autism group before and after controlling for TBV. No significant differences were observed in white-matter volume. A significant relationship was observed between brainstem gray-matter volume and oral sensory sensitivity as measured by the Sensory Profile Questionnaire (SPQ).


Findings from this study are suggestive of brainstem abnormalities in autism involving gray-matter structures with evidence supporting the existence of a relationship between these alterations and sensory deficits. These results are consistent with previous investigations and support the existence of disturbances in brainstem circuitry thought to be implicated in the sensory dysfunction observed in autism.

Corresponding author
*Address for correspondence: A. Y. Hardan, M.D., Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, USA. (Email:
Hide All
APA (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association: Washington, DC.
Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P (1998). A clinicopathological study of autism. Brain 121, 889905.
Bandim JM, Ventura LO, Miller MT, Almeida HC, Costa AE (2003). Autism and Möbius sequence: an exploratory study of children in northeastern Brazil. Arquivos de Neuro-psiquiatria 61, 181185.
Bauman M, Kemper TL (1985). Histoanatomic observations of the brain in early infantile autism. Neurology 35, 866874.
Ciesielski KT, Harris RJ, Hart BL, Pabst HF (1997). Cerebellar hypoplasia and frontal lobe cognitive deficits in disorders of early childhood. Neuropsychologia 35, 643655.
Cody H, Pelphrey K, Piven J (2002). Structural and functional magnetic resonance imaging of autism. International Journal of Developmental Neuroscience 20, 421438.
Dunn W (1999). Sensory Profile. Psychological Corporation: San Antonio, TX.
Elia M, Ferri R, Musumeci SA, Panerai S, Bottitta M, Scuderi C (2000). Clinical correlates of brain morphometric features of subjects with low-functioning autistic disorder. Journal of Child Neurology 15, 504508.
Gaffney GR, Kuperman S, Tsai LY, Minchin S (1988). Morphological evidence for brainstem involvement in infantile autism. Biological Psychiatry 24, 578586.
Garber HJ, Ritvo ER (1992). Magnetic resonance imaging of the posterior fossa in autistic adults. American Journal of Psychiatry 149, 245247.
Happe FG (1994). Wechsler IQ profile and theory of mind in autism: a research note. Journal of Child Psychology and Psychiatry 35, 14611471.
Hardan AY, Minshew NJ, Harenski K, Keshavan MS (2001). Posterior fossa magnetic resonance imaging in autism. Journal of the American Academy of Child and Adolescent Psychiatry 40, 666672.
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, 118.
Herbert MR, Ziegler DA, Deutsch CK, O'Brien LM, Lange N, Bakardjiev A, Hodgson J, Adrien KT, Steele S, Makris N, Kennedy D, Harris GJ, Caviness VS (2003). Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain 126, 11821192.
Hobson RP (1991). Methodological issues for experiments on autistic individuals' perception and understanding of emotion. Journal of Child Psychology and Psychiatry 32, 11351158.
Hollingshead AB (1975). Four Factor Index of Social Status. Yale University Department of Sociology: New Haven, CT.
Hsu M, Yeung-Courchesne R, Courchesne E, Press GA (1991). Absence of magnetic resonance imaging evidence of pontine abnormality in infantile autism. Archives of Neurology 48, 11601163.
Jarrold C, Brock J (2004). To match or not to match? Methodological issues in autism-related research. Journal of Autism and Developmental Disorders 34, 8186.
Jastak S, Wilkinson JS (1985). The Wide Range Achievement Test-Revised. Jastak Associates: Wilmington, DE.
Joseph RM, Tager-Flusberg H, Lord C (2002). Cognitive profiles and social-communicative functioning in children with autism spectrum disorder. Journal of Child Psychology and Psychiatry 43, 807821.
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980988.
Kleiman MD, Neff S, Rosman NP (1992). The brain in infantile autism: are posterior fossa structures abnormal? Neurology 42, 753760.
Klin A (1993). Auditory brainstem responses in autism: brainstem dysfunction or peripheral hearing loss? Journal of Autism and Developmental Disorders 23, 1535.
Lord C, Rutter M, Goode S, Heemsbergen J, Jordan H, Mawhood L, Schopler E (1989). Autism Diagnostic Observation Schedule: a standardized observation of communicative and social behavior. Journal of Autism and Developmental Disorders 19, 185212.
Lord C, Rutter M, LeCouteur A (1994). Autism Diagnostic Interview – Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders 24, 659685.
Magnotta VA, Harris G, Andreasen NC, O'Leary DS, Yuh WT, Heckel D (2002). Structural MR image processing using the BRAINS2 toolbox. Computerized Medical Imaging and Graphics 26, 251264.
Miller MT, Ventura L (2001). Moebius syndrome/sequence: a summary of a Brazil study. Teratology 63, 260.
Nolte J (2002). Human Brain: An Introduction to its Functional Anatomy. Mosby: St Louis, MO.
Ornitz EM (1983). The functional neuroanatomy of infantile autism. International Journal of Neuroscience 19, 85124.
Pfaendner NH, Reuner G, Pietz J, Jost G, Rating D, Magnotta VA, Mohr A, Kress B, Sartor K, Hahnel S (2005). MR imaging-based volumetry in patients with early-treated phenylketonuria. American Journal of Neuroradiology 26, 16811685.
Pickett J, London E (2005). The neuropathology of autism: a review. Journal of Neuropathology and Experimental Neurology 64, 925935.
Piven J, Nehme E, Simon J, Barta P, Pearlson G, Folstein SE (1992). Magnetic resonance imaging in autism: measurement of the cerebellum, pons, and fourth ventricle. Biological Psychiatry 31, 491504.
Rodier PM (2002). Converging evidence for brain stem injury in autism. Development and Psychopathology 14, 537557.
Rodier PM, Ingram JL, Tisdale B, Nelson S, Romano J (1996). Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei. Journal of Comparative Neurology 370, 247261.
Sears LL, Finn PR, Steinmetz JE (1994). Abnormal classical eye-blink conditioning in autism. Journal of Autism and Developmental Disorders 24, 737751.
Skoyles JR (2002). Is autism due to cerebral–cerebellum disconnection? Medical Hypotheses 58, 332336.
Stromland K, Nordin V, Miller M, Akerstrom B, Gillberg C (1994). Autism in thalidomide embryopathy: a population study. Developmental Medicine and Child Neurology 36, 351356.
Talairach J, Tournoux P (1988). Co-Planar Stereotaxic Atlas of the Human Brain: Three-Dimensional Proportional System. Thieme Medical: New York.
Volkmar FR, Cohen DJ, Paul R, Klin A (2005). Handbook of Autism and Pervasive Developmental Disorders. John Wiley & Sons: Hoboken, NJ.
Wechsler D (1991). Wechsler Intelligence Scale for Children – Third Edition. Psychological Corporation: San Antonio, TX.
White T, Andreasen NC, Nopoulos P, Magnotta V (2003). Gyrification abnormalities in childhood- and adolescent-onset schizophrenia. Biological Psychiatry 54, 418426.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 1
Total number of PDF views: 21 *
Loading metrics...

Abstract views

Total abstract views: 176 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 19th November 2017. This data will be updated every 24 hours.