Skip to main content
PMC home page
Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2003 Feb 28;358(1430):405–413. doi: 10.1098/rstb.2002.1210

Investigating individual differences in brain abnormalities in autism.

C H Salmond 1, M de Haan 1, K J Friston 1, D G Gadian 1, F Vargha-Khadem 1
PMCID: PMC1693120  PMID: 12639337

Abstract

Autism is a psychiatric syndrome characterized by impairments in three domains: social interaction, communication, and restricted and repetitive behaviours and interests. Recent findings implicate the amygdala in the neurobiology of autism. In this paper, we report the results of a series of novel experimental investigations focusing on the structure and function of the amygdala in a group of children with autism. The first section attempts to determine if abnormality of the amygdala can be identified in an individual using magnetic resonance imaging in vivo. Using single-case voxel-based morphometric analyses, abnormality in the amygdala was detected in half the children with autism. Abnormalities in other regions were also found. In the second section, emotional modulation of the startle response was investigated in the group of autistic children. Surprisingly, there were no significant differences between the patterns of emotional modulation of the startle response in the autistic group compared with the controls.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aylward E. H., Minshew N. J., Goldstein G., Honeycutt N. A., Augustine A. M., Yates K. O., Barta P. E., Pearlson G. D. MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults. Neurology. 1999 Dec 10;53(9):2145–2150. doi: 10.1212/wnl.53.9.2145. [DOI] [PubMed] [Google Scholar]
  2. Bachevalier J. Medial temporal lobe structures and autism: a review of clinical and experimental findings. Neuropsychologia. 1994 Jun;32(6):627–648. doi: 10.1016/0028-3932(94)90025-6. [DOI] [PubMed] [Google Scholar]
  3. Bailey A., Luthert P., Dean A., Harding B., Janota I., Montgomery M., Rutter M., Lantos P. A clinicopathological study of autism. Brain. 1998 May;121(Pt 5):889–905. doi: 10.1093/brain/121.5.889. [DOI] [PubMed] [Google Scholar]
  4. Balaban M. T. Affective influences on startle in five-month-old infants: reactions to facial expressions of emotions. Child Dev. 1995 Feb;66(1):28–36. doi: 10.1111/j.1467-8624.1995.tb00853.x. [DOI] [PubMed] [Google Scholar]
  5. Barbas H., Blatt G. J. Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey. Hippocampus. 1995;5(6):511–533. doi: 10.1002/hipo.450050604. [DOI] [PubMed] [Google Scholar]
  6. Barbas H., Gustafson E. L., Greengard P. Comparison of the immunocytochemical localization of DARPP-32 and I-1 in the amygdala and hippocampus of the rhesus monkey. J Comp Neurol. 1993 Aug 1;334(1):1–18. doi: 10.1002/cne.903340102. [DOI] [PubMed] [Google Scholar]
  7. Baron-Cohen S., Ring H. A., Bullmore E. T., Wheelwright S., Ashwin C., Williams S. C. The amygdala theory of autism. Neurosci Biobehav Rev. 2000 May;24(3):355–364. doi: 10.1016/s0149-7634(00)00011-7. [DOI] [PubMed] [Google Scholar]
  8. Baron-Cohen S., Ring H. A., Wheelwright S., Bullmore E. T., Brammer M. J., Simmons A., Williams S. C. Social intelligence in the normal and autistic brain: an fMRI study. Eur J Neurosci. 1999 Jun;11(6):1891–1898. doi: 10.1046/j.1460-9568.1999.00621.x. [DOI] [PubMed] [Google Scholar]
  9. Bauman M. L. Microscopic neuroanatomic abnormalities in autism. Pediatrics. 1991 May;87(5 Pt 2):791–796. [PubMed] [Google Scholar]
  10. Bauman M., Kemper T. L. Histoanatomic observations of the brain in early infantile autism. Neurology. 1985 Jun;35(6):866–874. doi: 10.1212/wnl.35.6.866. [DOI] [PubMed] [Google Scholar]
  11. Bradley M. M., Cuthbert B. N., Lang P. J. Pictures as prepulse: attention and emotion in startle modification. Psychophysiology. 1993 Sep;30(5):541–545. doi: 10.1111/j.1469-8986.1993.tb02079.x. [DOI] [PubMed] [Google Scholar]
  12. Carper R. A., Courchesne E. Inverse correlation between frontal lobe and cerebellum sizes in children with autism. Brain. 2000 Apr;123(Pt 4):836–844. doi: 10.1093/brain/123.4.836. [DOI] [PubMed] [Google Scholar]
  13. De Bellis M. D., Casey B. J., Dahl R. E., Birmaher B., Williamson D. E., Thomas K. M., Axelson D. A., Frustaci K., Boring A. M., Hall J. A pilot study of amygdala volumes in pediatric generalized anxiety disorder. Biol Psychiatry. 2000 Jul 1;48(1):51–57. doi: 10.1016/s0006-3223(00)00835-0. [DOI] [PubMed] [Google Scholar]
  14. Gadian D. G., Aicardi J., Watkins K. E., Porter D. A., Mishkin M., Vargha-Khadem F. Developmental amnesia associated with early hypoxic-ischaemic injury. Brain. 2000 Mar;123(Pt 3):499–507. doi: 10.1093/brain/123.3.499. [DOI] [PubMed] [Google Scholar]
  15. Heath R. G., Dempesy C. W., Fontana C. J., Myers W. A. Cerebellar stimulation: effects on septal region, hippocampus, and amygdala of cats and rats. Biol Psychiatry. 1978 Oct;13(5):501–529. [PubMed] [Google Scholar]
  16. Heath R. G., Harper J. W. Ascending projections of the cerebellar fastigial nucleus to the hippocampus, amygdala, and other temporal lobe sites: evoked potential and histological studies in monkeys and cats. Exp Neurol. 1974 Nov;45(2):268–287. doi: 10.1016/0014-4886(74)90118-6. [DOI] [PubMed] [Google Scholar]
  17. Hobson R. P., Ouston J., Lee A. What's in a face? The case of autism. Br J Psychol. 1988 Nov;79(Pt 4):441–453. doi: 10.1111/j.2044-8295.1988.tb02745.x. [DOI] [PubMed] [Google Scholar]
  18. Howard M. A., Cowell P. E., Boucher J., Broks P., Mayes A., Farrant A., Roberts N. Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism. Neuroreport. 2000 Sep 11;11(13):2931–2935. doi: 10.1097/00001756-200009110-00020. [DOI] [PubMed] [Google Scholar]
  19. Howlin P., Asgharian A. The diagnosis of autism and Asperger syndrome: findings from a survey of 770 families. Dev Med Child Neurol. 1999 Dec;41(12):834–839. doi: 10.1017/s0012162299001656. [DOI] [PubMed] [Google Scholar]
  20. Lang P. J., Bradley M. M., Cuthbert B. N. Emotion, attention, and the startle reflex. Psychol Rev. 1990 Jul;97(3):377–395. [PubMed] [Google Scholar]
  21. Middleton F. A., Strick P. L. Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. Science. 1994 Oct 21;266(5184):458–461. doi: 10.1126/science.7939688. [DOI] [PubMed] [Google Scholar]
  22. Nagahama Y., Fukuyama H., Yamauchi H., Matsuzaki S., Konishi J., Shibasaki H., Kimura J. Cerebral activation during performance of a card sorting test. Brain. 1996 Oct;119(Pt 5):1667–1675. doi: 10.1093/brain/119.5.1667. [DOI] [PubMed] [Google Scholar]
  23. Otsuka H., Harada M., Mori K., Hisaoka S., Nishitani H. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1H-MR spectroscopy study. Neuroradiology. 1999 Jul;41(7):517–519. doi: 10.1007/s002340050795. [DOI] [PubMed] [Google Scholar]
  24. Pierce K., Müller R. A., Ambrose J., Allen G., Courchesne E. Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI. Brain. 2001 Oct;124(Pt 10):2059–2073. doi: 10.1093/brain/124.10.2059. [DOI] [PubMed] [Google Scholar]
  25. Rosen J. B., Hamerman E., Sitcoske M., Glowa J. R., Schulkin J. Hyperexcitability: exaggerated fear-potentiated startle produced by partial amygdala kindling. Behav Neurosci. 1996 Feb;110(1):43–50. doi: 10.1037//0735-7044.110.1.43. [DOI] [PubMed] [Google Scholar]
  26. Salmond C. H., Ashburner J., Vargha-Khadem F., Connelly A., Gadian D. G., Friston K. J. Distributional assumptions in voxel-based morphometry. Neuroimage. 2002 Oct;17(2):1027–1030. [PubMed] [Google Scholar]
  27. Salmond C. H., Ashburner J., Vargha-Khadem F., Gadian D. G., Friston K. J. Detecting bilateral abnormalities with voxel-based morphometry. Hum Brain Mapp. 2000 Nov;11(3):223–232. doi: 10.1002/1097-0193(200011)11:3<223::AID-HBM80>3.0.CO;2-F. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sasaki K., Jinnai K., Gemba H., Hashimoto S., Mizuno N. Projection of the cerebellar dentate nucleus onto the frontal association cortex in monkeys. Exp Brain Res. 1979 Sep;37(1):193–198. doi: 10.1007/BF01474266. [DOI] [PubMed] [Google Scholar]
  29. Schmahmann J. D., Pandya D. N. Anatomic organization of the basilar pontine projections from prefrontal cortices in rhesus monkey. J Neurosci. 1997 Jan 1;17(1):438–458. doi: 10.1523/JNEUROSCI.17-01-00438.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schmidt L. A., Fox N. A. Fear-potentiated startle responses in temperamentally different human infants. Dev Psychobiol. 1998 Mar;32(2):113–120. doi: 10.1002/(sici)1098-2302(199803)32:2<113::aid-dev4>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  31. Stuss D. T., Benson D. F., Kaplan E. F., Weir W. S., Naeser M. A., Lieberman I., Ferrill D. The involvement of orbitofrontal cerebrum in cognitive tasks. Neuropsychologia. 1983;21(3):235–248. doi: 10.1016/0028-3932(83)90040-4. [DOI] [PubMed] [Google Scholar]
  32. Stuss D. T., Levine B., Alexander M. P., Hong J., Palumbo C., Hamer L., Murphy K. J., Izukawa D. Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes. Neuropsychologia. 2000;38(4):388–402. doi: 10.1016/s0028-3932(99)00093-7. [DOI] [PubMed] [Google Scholar]
  33. Sugawara M., Sadeghpour M., De Traversay J., Ornitz E. M. Prestimulation-induced modulation of the P300 component of event related potentials accompanying startle in children. Electroencephalogr Clin Neurophysiol. 1994 Mar;90(3):201–213. doi: 10.1016/0013-4694(94)90092-2. [DOI] [PubMed] [Google Scholar]
  34. Teunisse J. P., de Gelder B. Impaired categorical perception of facial expressions in high-functioning adolescents with autism. Child Neuropsychol. 2001 Mar;7(1):1–14. doi: 10.1076/chin.7.1.1.3150. [DOI] [PubMed] [Google Scholar]
  35. Thomas K. M., Drevets W. C., Dahl R. E., Ryan N. D., Birmaher B., Eccard C. H., Axelson D., Whalen P. J., Casey B. J. Amygdala response to fearful faces in anxious and depressed children. Arch Gen Psychiatry. 2001 Nov;58(11):1057–1063. doi: 10.1001/archpsyc.58.11.1057. [DOI] [PubMed] [Google Scholar]
  36. Van Paesschen W., Connelly A., Johnson C. L., Duncan J. S. The amygdala and intractable temporal lobe epilepsy: a quantitative magnetic resonance imaging study. Neurology. 1996 Oct;47(4):1021–1031. doi: 10.1212/wnl.47.4.1021. [DOI] [PubMed] [Google Scholar]
  37. Van Paesschen W., Connelly A., King M. D., Jackson G. D., Duncan J. S. The spectrum of hippocampal sclerosis: a quantitative magnetic resonance imaging study. Ann Neurol. 1997 Jan;41(1):41–51. doi: 10.1002/ana.410410109. [DOI] [PubMed] [Google Scholar]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES