Autism and the Limbic System

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Autism and the Limbic System
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Description

• Autism pathological self-absorbtion and
  preoccupation with self to exclusion of the
  outside world
• PDD gross and sustained impairment of social
  interation and communication
• - restricted and stereotyped patterns of
  behaviour, interests, and activities
• abnormalities manifested before age 3 in social
  development, language acquisition and play

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Limbic System

limbic system image 1 of 216
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Limbic System Circuits (MacLean, 1970)

• 1. Amygdala and hippocampus
• -affects behaviours related to
  self-preservation
• 2. Cingulate gyrus and septum
• - relate to sexual enjoyment
• 3.Hypothalamus and anterior thalamus
• -believed to be important for cooperative
  social behaviour

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Neuroimaging and CBF (cerebral blood flow)

• Perfusion patterns of CBF suggest possible
  locations for abnormalities of brain function,
  thus underlying cognitive dysfunction and
  abnormal behavioural patterns in autistic
  individuals
• Target areas showing abnormalities in CBF are the
  temporal cortex, anterior cingulate gyrus, and
  the hippocampus

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Neuropathological Post Mortem Studies

• Abnormal density and distribution of
• neurotransmitter receptor sites in the
  hippocampus
• Decreased dendritic complexities suggest a
  curtailment of maturation in this area
• Statistically significant reduction in density of
  BZ binding sites
• Decreased numbers of GABAergic Purkinje cells and
  altered cerebellar nuclei suggest defeceit in
  GABAergic system
• Suggests a decrease in inhibitory functions thus
  leading to repetitive behaviours

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MRI Studies

• Evidence of smaller area dentata in autistic
  patients
• Disproportionately large hemispheric white matter
  volumes in temporal region
• Smaller amygdala volume (up to 13.5 smaller than
  normals!)
• Suggests hypoplasia (undergrowth) in this area

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PET Scans

• Abnormalities of dopaminergic and serotonergic
  systems seen in the mesolimbocortical system -gt
  output to the amygdala, setpum, and hippocampus
• Hyperserotoninermia -gt increased arousal and
  increased self-stim behaviours

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Animal Models Infant Rhesus monkeys

• Effects of neonatal temporal lobe lesions
• AH lesion (amygdalo-hipoocamectomy) on left side
  at 1 week, right side at 3 weeks
• -tested socioemotional responsiveness _at_2 6 mos
• Results _at_ 2 months transient changes in less
  exploratory behaviour, less manipulation of
  objects in enviro, and gt passivity not longer
  apparent at 6 mos
• Resuts _at_ 6 months withdrew more often from
  social attempts by unoperated controls, socially
  inept and avoided contact, increased
  irritibility, locomotor stereotypes, and
  self-directed activities

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Animal Models Adult Rhesus Monkeys

• Short lasting increase in passivity
• Decrease in aggression and social proximity
• Fall of status in social hierarchy
• Monkeys operated on in adulthood retained at
  least some aspects of socioemotional repertoire
  they acquired during maturation
• Neonatally operated monkeys never acquired this
  repertoire

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References

• Bachavalier, J., Malkova, L., Mishkin, M.
  (2001). Effects of neonatal temporal lobe
  lesions on socioemotinal beahvior in infant
  rhesus monkeys (Macaca mulatta). Behavioral
  Neuroscience, 115(3), 545-559.
• Blatt, G., Fitzgerald, C. M., Guptill, J.T.,
  Booker, A. B., Kemper, T. L., Bauman, M. L.
  (2001). Density and distribution of hippocampal
  neurotransmitter receptors in autism An
  autoradiographic study. Journal of Autism and
  Developmental Disorders, 31, 537-544.
• Daenen, E. W. P. M., Wolterink, G., Gerris, M. A.
  F. M., Van Ree, J. M. (2002). The effects of
  neonatal lesions in the amygdala or ventral
  hippocampus on social behaviour later in life.
  Behavioural Brain Research, 136, 571-582.
• Koves, K., Kausz, M., Reser, D., Horvath, K.
  (2002). What may be the anatomical basis that
  secretin can improve the mental functions in
  autism? Regulatory Peptides, 109, 167-172.
• Nakagawa, Y. What is autism and what kind of
  learning environment is necessary for people with
  autism to enhance social interaction abilities.
  http//www.nakayoshi.org/t560-1.html.

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References Cont
Ohnishi, T., Matsuda, H., Hashimoto, T.,
Kunihiro, Y., Nishikawa, M., Uema, T.,
Sasaki, M. (2000). Abnormal regional cerebral
blood flow in childhood autism. Brain, 123,
1838-1844. Saitoh, O., Karns, C.M., Courchesne,
E. (2001). Development of the hippocampal
Formation from 2 to 42 years. Brain, 124,
1317-1342. Wolterink, G., Daenen, L.W.P.M.,
Dubbledam, S., Gerrits, M.A.F.M., Kruse, K.G.,
Van Der Heijden, J.A.M., Van Lee, J.M. (2001).
Early amygdala damage in the rat as a model
for neurodevelopmental psychopathological
disorders. European Neuropsychopharmacology,
11, 51-59. Winslow, J.T., Hearn, E.F.,
Ferguson, J., Young, L.J., Matzuk, M.M., Insel,
T.R. (2000). vocalization, adult
aggression, and fear behavior of an oxytocin null
mutant mouse. Hormones and Behavior, 37,
145-155. Young, L.J. (2001). Oxytocin and
vasopressin as candidate genes for pyschiatric
disorders Lessons from animal models.
American Journal of Medical Genetics
(Neuropsychiatric Genetics), 105, 53-54.