|Working papers||Viewpoint on the brain disorder(2003)||(View in 2000)|
|and notes:||The auditory system||The inferior colliculus||Hemoglobin & the brain|
|Concepts of autism||Autism spectrum||Social responsibility|
|Conrad Simon Memorial Research Initiative|
|Updated: December 20, 2006|
|Note: Until recently I used the nom de plume Nicole Simon for publication.|
Simon EN (2006)
Comment on "Asperger syndrome: Familial, pre- and perinatal factors" by Gillberg and Cederlund. J Autism Dev Disord. 2006 Feb;36(2):291-2. [letter].
This was a response to two articles by these authors that reported perinatal problems in children with Asperger syndrome. More than half the children described had not been talking in full sentences by the age of two. I pointed out that while many children with Asperger syndrome appear to have a superior command of language, they often make idiosyncratic use of phrases tangential, at best, to conversational context. Once again I urged consideration of auditory system impairment resulting from anoxia at birth as contributory to developmental language disorder across the autism spectrum.
Simon EN (2005)
Auditory agnosia caused by a tectal germinoma. Neurology, 2005 Jul 26;65(2):339 [letter].
This letter is online (with a reply from the authors) at http://www.neurology.org/cgi/eletters/63/12/2387; it was submitted in response to a case report, of a 14-year-old boy who lost the ability to understand spoken language because of neoplastic growth that invaded the auditory tectum. This is one of several reports that have appeared since 1991 in which injury of the inferior colliculi was revealed by use of MRI.
Simon EN (2004)
Autism as a birth defect. Birth Defects Res Part A Clin Mol Teratol, 2004 Jun;70(6):416 [letter].
Environmental factors associated with autism can produce variants of Wernicke's encephalopathy with involvement of oculomotor and facial nuclei, diminished Purkinje cells in the cerebellum, and brainstem nuclei like the inferior olives and relay nuclei of the auditory pathway. Impairment within the auditory system merits investigation as a primary site of injury potentially underlying the developmental language disorder of children with autism.
Simon EN (2004)
The lessons of MMR. Lancet, 2004 May 1;363(9419):1473-4 [letter].
This letter was sent in response to an excellent commentary by Lancet Editor Richard Horton, The Lessons of MMR (Lancet, 06 March 2004, pp747-749), in which he pointed out that one consequence of the MMR controversy had been a redirection of public attention to autism, a condition sadly neglected by medicine. The hope I expressed was that attention to this horrible disorder might continue in more productive ways. I could never join the parental chorus of fury over MMR – the end result going no further than "the brain," viewed as a homogeneous organ. How impairment of specific brain systems underlying (first and foremost) developmental language disorder should in my opinion be the focus of public-funded research.
Simon N. (2000)
Autism's home in the brain. Neurology. 2000 Jan 11;54(1):269-70. PMID: 10636173; UI: 20100128.
This letter was in response to four articles on autism in the March 23, 1999 issue of Neurology. The letter is accompanied by replies from the authors. Each of the four papers had proposed impairment of different systems in the brain. Comment on the four papers brought up for discussion whether the proposed impairments might all stem from perinatal disruption of aerobic metabolism by anoxia, infections, or exposure to toxic substances during gestation. Beyond knowing that neurological functions are impaired, the mechanism of damage must be sought, and include all known etiologies of autism.
Simon N. (1999)
Auditory dysfunction in autism: a submicroscopic form of Wernicke's encephalopathy? J Autism Dev Disord. 1999 Oct;29(5):426-7. PMID: 10587890; UI: 20055202.
Autistic behaviors have been observed in children with genetic disorders and infections that damage the brain. Some children exposed to alcohol during gestation have also been found deficient in reciprocal social interactions and with impaired language development. Alcohol affects brainstem nuclei and the cerebellum in a pattern of damage known as Wernicke's encephalopathy. Involvement of many of the same areas has been noted in brains from individuals with autism. The auditory system is prominently affected in Wernicke's encephalopathy and auditory dysfunction may underly the language disorder of autistic children. Impairment of metabolism in the brain areas affected by Wernicke's encephalopathy may be shared in common by all of the etiologies of autism.
Simon N. (1999)
The auditory system, brain maturation, and development in autistic children. J Autism Dev Disord. 1999 Feb;29(1):94-5. PMID: 10098000; UI: 99198073.
Brainstem auditory nuclei are the earliest to mature in the human fetal brain. There is evidence that neurochemical events in the developing auditory system may stimulate growth of higher cognitive centers in the cerebral cortex. Damage to brainstem auditory nuclei has been found in infants who died during the perinatal period. The suggestion is made that early impairment of the auditory system might also interfere with subsequent stages of development in autistic children. Echolalic autistic children do not reword what they have heard but recite whole phrases from memory to express their needs. Many of the etiological factors that lead to autism are known to affect the auditory system and may be responsible for this language decoding disorder.
Simon N. (1998)
Hemoglobin and the brain: a piece of the autism puzzle? J Autism Dev Disord. 1998 Dec;28(6):579-80. PMID: 9932245; UI: 99131037.
Multiple etiologies of autism spectrum disorders have been identified. It is proposed here that the "Bohr effect" of hemoglobin might explain why motor disabilities are more likely to result from conditions that partially disrupt metabolism in the brain, while impairment of brainstem sensory systems could be expected as the outcome following brief periods during which metabolic processes are totally blocked.
Simon N. (1997)
Autism and the inferior colliculus. J Autism Dev Disord. 1997 Aug;27(4):494-6. PMID: 9261672; UI: 97404978.
The inferior colliculus has the highest rate of metabolism of any structure in the brain. It is therefore vulnerable in some circumstances to the effects of genetic metabolic disorders, toxic substances, infections, nutritional deficiencies, and anoxia, many of which have been associated with autism as etiologic factors. It is suggested that dysfunction within this brainstem area should be explored for its potential relevance to etiology of the core syndrome of autism, and a few citations to the literature on cerebral metabolism are given.
Simon N. (1990)
Infantile autism and Wernicke's encephalopathy. Med Hypotheses. 1990 Jul;32(3):169-72. Review. PMID: 2204786; UI: 90377023.
In this paper I discuss evidence that brain damage in infantile autism may involve the same complex of brainstem nuclei that are damaged by alcohol abuse, thiamine deficiency, and asphyxia. These are metabolically the most active structures in the brain, which makes them vulnerable to many injurious factors. It is my belief that the high metabolic rate in the brainstem nuclei could support a control function for multiplexing of neural pathways, and that if this control is lost it may result in the defects of awareness and responsiveness seen in autistic children.
Simon N. (1978)
Kaspar Hauser's recovery and autopsy: a perspective on neurological and sociological requirements for language development. J Autism Child Schizophr. 1978 Jun;8(2):209-17. PMID: 353024; UI: 78218009.
Reprinted in S. Chess and A. Thomas (eds.) Annual Progress in Child Psychiatry and Child Development 1979, Vol. 12, Chapter 11, pp. 215-224, Brunner/Mazel: New York, 1979.
Also reprinted in J. Money and G. Williams (eds.) Traumatic Abuse and Neglect of Children at Home, Chapter 6, pp 56-62. Johns Hopkins Press: Baltimore, 1979.
The feral children literature has frequently been cited for relevance to understanding historical antecedents of autism. Kaspar Hauser, who appeared in Nuremberg, Germany in 1828, is one of these children, raised under conditions of extreme deprivation. His case history and gradual acquisition of language after age 17 years are summarized. There is strong evidence that he was the prince of Baden, abducted from his cradle in 1812. Findings of postmortem examination, conducted after his assassination, are discussed. Hauser's postadolescent recovery of language contradicts the notion of a "critical period" for language development.
Simon N, Volicer L. (1976)
Neonatal asphyxia in the rat: greater vulnerability of males and persistent effects on brain monoamine synthesis. J Neurochem. 1976 May;26(5):893-900. PMID: 946815; UI: 76192939.
In the rat, neonatal asphyxia produced by suffocation did not leave permanent visible lesions in the brain, nor did it result in permanent motor impairment, although a delay in the development of some reflexes was observed. A transient retardation of body and brain growth, which was more pronounced in males, was found. By 5-6 weeks of age, body and brain weights of asphyxiated rats were no longer significantly different from control animals. However, an increase in brain norepinephrine synthesis was found to persist after maturation. An alteration of serotonin metabolism was found after maturation only in asphyxiated males. The possibility that neonatal asphyxia in the rat is a model for abnormal development of monoamine metabolism, relevant to early childhood behavior disorders such as infantile autism or the syndrome of minimal brain dysfunction is discussed.
Simon N. (1975)
Echolalic speech in childhood autism. Consideration of possible underlying loci of brain damage. Arch Gen Psychiatry. 1975 Nov;32(11):1439-46. PMID: 812450; UI: 76087034.
Reprinted in S. Chess and A. Thomas (eds.) Annual Progress in Child Psychiatry and Child Development 1976, Vol. 9, Chapter 25, pp. 471-490, Brunner/Mazel: New York, 1977.
The speech of echolalic autistic children is (1) specifically lacking in appropriate use of expressive-intonational features, but (2) the echolalic child's clear articulation of words and phrases indicates that discrimination of phonemic features is intact. The impairment in aphasic disorders is just the reverse. Failure to attend to auditory stimuli and the characteristic language disorder are among the most consistent findings in autistic children; they could be related. Discrimination of differential stress emphasis is the way the normal young child extracts major morphemic word stems and syntactic features from environmental speech; this may be a primitive perceptual function of brain stem auditory centers. The brain stem auditory system is especially vulnerable to perinatal injury. Damage to this system is an example of the kind of lesion that might lead to behavioral handicaps without neurological signs.
Simon EN. (1975)|
Long-term Effects of Neonatal Asphyxia in the Rat. Doctoral Dissertation, Boston University, Boston MA, 1974, 193 pp. University Microfilms, Ann Arbor MI, Order No. 75-5520.
Neonatal asphyxia in the albino rat was chosen as a possible model for abnormal development of monoamine metabolism in the brain. This could, perhaps, have bearing on the etiology of childhood schizophrenia (or early infantile autism).
Recent research on the effects of asphyxia in the prenatal or perinatal period has revealed that in several species, including man, the resulting injury to the central nervous system may be confined to brainstem structures without involvement of the cerebral hemispheres. Research on monoamines in the central nervous system indicates that their normal metabolism depends upon integrity of some of the brainstem areas that are damaged by perinatal asphyxia.
Infant rats were asphyxiated within 24 hours after a natural birth in 12 cc. Capacity air-tight vials. Only about half of the asphyxiated animals survived the first 24 hours after this severe insult. The survivors appeared to be quite depressed during the first 24 hours after asphyxia; most did not gain a normal amount of weight during this period and many lost up to half a gram in the first day. Growth retardation persisted for the first two weeks of life; brain growth was also retarded, and males were more severely affected than females.
There were delays in development of the grasp reflex and reflex orientation to gravity on an inclined plane; however no spasticity or noticeable long-term neurological defect resulted. Histological examination at three to six weeks of age did not reveal necrosis or degeneration of any brain areas; only patchy gliosis and sparser distribution of nerve cells in some brain areas could be observed.
The conversion of radioactive tyrosine and tryptophan to dopamine, norepinephrine, and serotonin was measured in the brains of control and neonatally asphyxiated animals between five and six weeks of age. The precursor amino acids were administered by injection into the tail-vein, and the animals were sacrificed from 30 to 150 minutes after injection. The brains were assayed for radioactive and endogenous tyrosine, tryptophan, dopamine, norepinephrine, and serotonin; a preliminary separation of these five compounds was made on ion exchange columns, then each compound subsequently purified and measured individually.
The synthesis rate of norepinephrine from tyrosine in the brain was nearly doubled in the neonatally asphyxiated group. The synthesis rate of dopamine was not affected by neonatal asphyxia. The catabolic rate constant for serotonin was increased in asphyxiated males only, but the synthesis rate was not affected. There was less penetration of radioactive tryptophan, five minutes aftere intravenous injection, into the brains of both male and female asphyxiated animals, while the penetration of radioactive tyrosine was the same as in a control group.
An increase in the monoamine oxidase enzyme activity of the brain, measured in vitro, was found in both male and female asphyxiated animals, which may indicate a tendency for higher catabolism of all monoamines. Tyrosine hydroxylas activity is normally inhibited by excess norepinephrine in the enzyme environment, which is the major mechanism controlling synthesis rate. Rapid catabolism of norepinephrine by increased monoamine oxidase activity may therefore interfere with the normal regulation of catecholamine synthesis.
The effects of birth asphyxia on neurologic status and behavior appear not to be lon lasting, and histology reveals no gross structural changes; however, functional defects persist. Metabolism of neural units and the blood-brain barrier appear to be permanently altered. It is of possible significance that male animals were more vulnerable to neonatal asphyxia, as there is a 4:1 greater preponderance of males over females in the human population who develop early schizophrenic illness (or infantile autism).
|Viewpoint on the brain disorder in autism (2003) | (View in 2000)
The auditory system | The inferior colliculus | Hemoglobin & the brain
Concepts of autism | Autism spectrum disorders | Social responsibility
|Update: December 2007
(Conversion in progress)
Working paper (2000)
Working paper (2003)
The auditory system
The inferior colliculus
Hemoglobin & the brain
Concepts of autism
Neurology 2000 (discussion)
Pictures (Conrad and his brothers)
Death in a group home
© Copyright 1999-2007
Eileen Nicole Simon
Conrad Simon Memorial Research Initiative