2 -  Audiogenic seizures
The core syndrome of Kanner autism is only rarely
complicated by seizure disorder, although seizures
are part of the progressive course of many childhood
disintegrative disorders.  Like visible brain damage,
seizures represent the most serious aspect of any
impairment of brain function.  Thus investigation of
factors that lead to seizure activity can perhaps be
useful in trying to understand somewhat less serious
aspects of autism like abnormal reactions to the
auditory environment.

Recent research on audiogenic seizures may possibly
be relevant to auditory hyperreactivity (or
hyperacusis) in autistic children.  It could also be
relevant to auditory hallucinations in schizophrenia
and alcoholism.  Auditory hallucinations may in fact
result from sub-clinical seizure activity within the
auditory system.  In the past, autism was thought to be
the earliest and most severe manifestation of
schizophrenia [1-3].  The difference in the auditory
disorders manifest in autism and schizophrenia might
be related to differing degrees of damage and loss of
inhibitory function as described in articles on
audiogenic seizures in laboratory animals [4-9].

A genetically epilepsy-prone strain of laboratory rats
(GEPR) was discovered to have a natural
susceptibility to seizures provoked by auditory
stimulation such as the jangling of a set of keys.  This
genetic trait can in no way be thought of as an animal
model of a syndrome like autism, but the trait may be
the result of factors such as impairment of inhibitory
transmitter synthesis or decreased sensitivity of
post-synaptic receptors to stimulation by inhibitory
transmitters.  The same factors may be involved in the
auditory problems of children with autism.  It should
also be noted that audiogenic seizures have also
been induced in rats subjected to anoxia or injected
with hallucinogenic drugs.

Drugs that decrease susceptibility to audiogenic
seizures are alcohol, barbiturates and other
anti-convulsants.  Anoxia and drugs that increase
seizure susceptibility appear to be those that interfere
with inhibitory neurotransmitter functions.  Drugs that
decrease seizure susceptibility are those that facilitate
inhibitory neurotransmitter functions.  Such drugs and
the autoradiographic techniques for cerebral blood
flow, glucose uptake, and immuno-fluorescence
visualization of neuro-transmitters have been used to
investigate the nature of audiogenic seizures.
Nehlig et al. (1995) investigated cerebral blood flow
changes during audiogenic seizures in a genetically
prone strain of rats, and concluded that the inferior
colliculi have a central role in triggering these seizures
[10].  This is one more paper reporting the highest
baseline rate of cerebral blood flow in the inferior
colliculi.  In addition, the greatest increase in blood
flow during seizures was in the inferior colliculi and
other nuclei of the brainstem auditory pathway.

Kawai et al. (1995) produced susceptibility to
audiogenic seizures in laboratory rats by subjecting
them to cardiac arrest for five to seven minutes,
followed by resuscitation [4].  That function within the
inferior colliculus would be impaired was implied from
its well-known vulnerability to brief periods of anoxia.  
On the other hand, they found that placing lesions in
the inferior colliculi could prevent susceptibility to
seizures, and microscopic investigation of the brains
of the seizure-prone rats suggested loss of
gamma-aminobutyric acid (GABA) receptors in
neurons of the inferior colliculus.

GABA appears to act as an inhibitory transmitter,
opposing the excitatory function of glutamate [8].  
These and many other transmitters are in the process
of being discovered.
  1. Creak M (1938) Psychoses in children.  Proceedings of the Royal Society of
    Medicine 31:519-528.
  2. Bender L (1955) Twenty years of clinical research on schizophrenic children,
    with special reference to those under six years of age.  In Caplan G, ed.
    Emotional Problems of Early Childhood.  Basic Books, New York, pp 503-515.
  3. Faretra G. (1979) Lauretta Bender on autism: a review. Child Psychiatry Hum
    Dev. 1979 Winter;10(2):118-29.
  4. Kawai K, Penix LP, Kawahara N, Ruetzler CA, Klatzo I (1995) Development of
    susceptibility to audiogenic seizures following cardiac arrest cerebral
    ischemia in rats. Journal of Cerebral Blood Flow and Metabolism 15:248-258.
  5. Faingold CL, Riaz A (1995) Ethanol withdrawal induces increased firing in
    inferior colliculus neurons associated with audiogenic seizure susceptibility.  
    Experimental Neurology 132:91-98.
  6. Faingold CL. (1999) Neuronal networks in the genetically epilepsy-prone rat.
    Advances in Neurology. 1999;79:311-21.
  7. Yang L, Long C, Faingold CL (2001) Audiogenic seizure susceptibility is
    induced by termination of continuous infusion of gamma-aminobutyric acid or
    an N-methyl-D-aspartic acid Antagonist into the inferior colliculus. Exp Neurol.
    2001 Sep;171(1):147-52.
  8. Faingold CL. (2002) Role of GABA abnormalities in the inferior colliculus
    pathophysiology - audiogenic seizures. Hear Res. 2002 Jun;168(1-2):223-37.
  9. Garcia-Cairasco N (2002). A critical review on the participation of inferior
    colliculus in acoustic-motor and acoustic-limbic networks involved in the
    expression of acute and kindled audiogenic seizures. Hear Res. 2002 Jun;168
    (1-2):208-22.
  10. Nehlig A, Vergnes M, Hirsch E, Boyet S, Koziel V, Marescaux C (1995)
    Mapping of cerebral blood flow changes during audiogenic seizures in Wistar
    rats: effect of kindling. Journal of Cerebral Blood flow and Metabolism 15:259-
    269.
Full References
top
  1. Creak M (1938) Psychoses in
    children.
  2. Bender L (1955) Twenty years
    of clinical research on
    schizophrenic children, with
    special reference to those
    under six years of age.
  3. Faretra G. (1979) Lauretta
    Bender on autism: a review.
  4. Kawai K et al.(1995)
    Development of susceptibility
    to audiogenic seizures
    following cardiac arrest
    cerebral ischemia in rats.
  5. Faingold CL, Riaz A (1995)
    Ethanol withdrawal induces
    increased firing in inferior
    colliculus neurons
    associated with audiogenic
    seizure susceptibility.
  6. Faingold CL. (1999) Neuronal
    networks in the genetically
    epilepsy-prone rat.
  7. Yang L, et al. (2001)
    Audiogenic seizure
    susceptibility is induced by
    termination of continuous
    infusion of gamma-
    aminobutyric acid or an N-
    methyl-D-aspartic acid
    Antagonist into the inferior
    colliculus.
  8. Faingold CL. (2002) Role of
    GABA abnormalities in the
    inferior colliculus
    pathophysiology - audiogenic
    seizures.
  9. Garcia-Cairasco N (2002). A
    critical review on the
    participation of inferior
    colliculus in acoustic-motor
    and acoustic-limbic networks
    involved in the expression of
    acute and kindled audiogenic
    seizures.
  10. Nehlig A et al. (1995)
    Mapping of cerebral blood
    flow changes during
    audiogenic seizures in Wistar
    rats: effect of kindling.
References