Viewpoint on the Brain Disorder in Autism

Viewpoint on the Brain Disorder in Autism

  (based on a review of research papers in the medical literature)

Viewpoint on the brain disorder(2003) (View in 2000)

The auditory system The inferior colliculus Hemoglobin & the brain

Concepts of autism Autism spectrum Social responsibility

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Conrad Simon Memorial Research Initiative
Posted:  December 14, 2003
© Copyright 2003
Eileen Nicole Simon
Introduction | I. Brain damage at birth | II. Auditory system | III. Language
IV.  Childhood handicaps | V. Brainstem Damage | VI.  References | Summaries
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Topics (section links):

Introduction

I. BRAIN DAMAGE AT BIRTH
1 - Asphyxia at Birth
2 - Hypoxic Birth
3 - Asphyxia Versus Hypoxia
4 - Human Conditions
5 - Stages of Asphyxia
6 - The Umbilical Cord Lifeline
7 - Developmental Delay
8 - Poor Manual Dexterity
9 - Progressive Degeneration
10 - Autism and Complications at Birth
11 - Mercury, and Other Toxic Factors

II. THE AUDITORY SYSTEM
12 - Metabolic Rank Order
13 - The Auditory System
14 - Auditory Dysfunction

III. LANGUAGE
15 - Language by Ear
16 - Verbal Auditory Agnosia
17 - Echolalic Speech
18 - Echolalic Speech is Pragmatic

IV. CHILDHOOD HANDICAPS
19 - Auditory and Motor Handicaps
20 - Increased Incidence of Autism
21 - Fetal to Postnatal Adaptation
22 - Forgotten History
23 - Worth Remembering
24 - Hemoglobin
25 - Infant Anemia
26 - Autism in Twins
27 - Male-Female Differences

V. BRAINSTEM DAMAGE
28 - Variable Vulnerability
29 - Patterns of Damage
30 - Wernicke's Encephalopathy
31 - Suffocation at the Molecular Level
32 - Thiamine Deficiency
33 - Brain-Gut Relationship

VI. REFERENCES
34 - Bibliography
35 - Autism and Complications at Birth
36 - Umbilical Cord Clamping

Summaries

[Site Links]


Overview (Summaries):

The inferior colliculus has the highest blood flow and highest rate of aerobic metabolism of any structure in the brain. Protective mechanisms lead to sparing of this midbrain auditory nucleus under adverse conditions like hypoxia. Neuropathology caused by chronic hypoxia or circulatory insufficiency involves the cerebral cortex and brainstem nuclei that are less metabolically active. Brain damage in survivors of resuscitation following circulatory arrest, drowning, or suffocation includes the inferior colliculus. The inferior colliculus is also damaged by poisons that disable enzymes of aerobic metabolism.

Asphyxia at birth selectively damages the inferior colliculus. The inferior colliculus appears to be important for recognition of distinctive features of speech; speech understanding is lost in adults with damage of the inferior colliculi. Inability to distinguish syllable and word boundaries in rapid streams of speech should be considered as the cause of the language disorder of children with autism, and that this is the result of damage to the inferior colliculi at birth.


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Main Points:

  1. The brainstem auditory pathway is susceptible to damage by all of the known medical conditions associated with autism, because it is the most metabolically active system of the brain.

  2. Protective mechanisms prevent auditory system damage except in catastrophic circumstances like circulatory arrest, suffocation, or poisons that disrupt aerobic metabolism.

  3. Partial oxygen insufficiency during late gestation or birth is one cause of cerebral palsy, whose victims in some cases learn language on time and demonstrate good to excellent cognitive and social skills.

  4. Total oxygen deprivation during late gestation or birth selectively damages the inferior colliculi in the midbrain auditory pathway, and is proposed here as a possible cause of the language and auditory attention problems of children with autism.

  5. Damage to the inferior colliculi has been noted in previously normal adults who have lost the ability to understand spoken language [Meyer et al. 1996, Johkura et al. 1998, Masuda et al. 2000].

  6. Verbal auditory agnosia (VAA), an inability to distinguish syllable and word boundaries in rapid streams of speech, has been identified as an underlying problem in some children with autism [Rapin 1997].

  7. Inhibitory neurons in the inferior colliculus appear to stop transmission of ongoing sounds, providing a means for detecting sound onset which may also be involved in detection of syllable and word boundaries.

  8. Difficulty learning a foreign language, without accent, past the first decade of life may indicate that verbal auditory agnosia (VAA) is a normal affliction of aging, and most severe in the elderly who lose the ability to engage in conversation in noisy environments.

  9. Most young children learn language by ear and in a foreign language environment as easily learn a second language.

  10. Abnormalities of the amygdala, hippocampus, mammillary bodies, cerebellum, and inferior olives have been observed in the brain of individuals with autism; all are part of a subcortical pattern of damage caused by asphyxia and toxic substances.

  11. Protective mechanisms may prevent visible damage in the inferior colliculi and allow more noticeable abnormalities in the rank-order of subcortical nuclei that are somewhat less metabolically active.

  12. The subcortical pattern of damage may imply impairment of function within the inferior colliculi even in the absence of visible involvement.

  13. Progressive involvement of the cerebral cortex was observed in monkeys subjected to asphyxia at birth, and indicates a mechanism that could explain failure of frontal lobe maturation in children with autism.

  14. Complications at birth are recognized as common in children with autism but their possible significance underestimated.

  15. Immediate clamping of the umbilical cord has become a standard practice within the past 20 years, but an infant who does not breathe right away will suffer at least a brief but potentially catastrophic period of oxygen deprivation.

  16. In research on asphyxia at birth in monkeys, asphyxia was produced by preventing breathing and clamping the umbilical cord; visible damage of the inferior colliculi occurred in some monkeys subjected to as little as six minutes of asphyxia.

  17. Immediate clamping of the umbilical cord ought to be considered as one possible reason for the increased incidence (or prevalence) of autism evident within the last two decades.
The inferior colliculus is important for understanding speech
Meyer B, Kral T, Zentner J. (1996) Pure word deafness after resection of a tectal plate glioma with preservation of wave V of brain stem auditory evoked potentials. Journal of Neurology, Neurosurgery and Psychiatry. 61:423-424.

Johkura K, Matsumoto S, Hasegawa O, Kuroiwa Y. (1998) Defective auditory recognition after small hemorrhage in the inferior colliculi. Journal of the Neurological Sciences. 161:91-96.

Masuda S, Takeuchi K, Tsuruoka H, Ukai K, Sakakura Y. (2000) Word deafness after resection of a pineal body tumor in the presence of normal wave latencies of the auditory brain stem response. The Annals of otology, rhinology, and laryngology. 2000 Dec;109(12 Pt 1):1107-1112.


Verbal auditory agnosia
Rapin I (1997) Autism. New England Journal of Medicine 337:97-104.

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SUMMARIES

I. BRAIN DAMAGE AT BIRTH

1 - Asphyxia at Birth
Experiments with monkeys on asphyxia at birth were undertaken in the 1950s to investigate ways to prevent cerebral palsy. The outcome was not cerebral palsy, and damage to the brain was confined to the brainstem. The inferior colliculus in the midbrain auditory pathway was always most severely involved. The inferior colliculus had been found in earlier experiments on cerebral circulation to have the highest rate of blood flow in the brain.

2 - Hypoxic Birth
In the initial experiments asphyxia was inflicted by covering the newborn monkey's head and clamping the umbilical cord, producing a sudden catastrophic cutoff of respiratory gas exchange. Cerebral palsy was found in later experiments to result from partial blocking of umbilical blood flow late in gestation. Circulatory insufficiency induced in this way led to widespread damage throughout the brain. Hypoxia is a state of partial oxygen insufficiency. Asphyxia occurs when oxygen delivery is completely blocked and if not fatal results in a predictable pattern of brainstem damage.

3 - Asphyxia Versus Hypoxia
Asphyxia is different from hypoxia. Protective mechanisms go into effect to preserve oxygen delivery to the inferior colliculus during a period of hypoxia. High blood flow to the inferior colliculus supports a high rate of aerobic metabolism, generating high levels of carbon dioxide. Hemoglobin delivers oxygen in exchange for carbon dioxide, an immediate adjustment that ensures continuing support of aerobic metabolism in this nucleus of the auditory system. The rest of the brain then becomes deprived of oxygen, and over time widespread damage occurs.

4 - Human Conditions
Asphyxia causes a sudden and catastrophic cessation of aerobic metabolism that is often fatal. Damage to the inferior colliculus is evident in children and adults who survive for at least several days following resuscitation. In the 1960s damage involving only the brainstem was thought to underlie what was then referred to as "minimal cerebral dysfunction."

5 - Stages of Asphyxia
Monitoring what happens during the stages of asphyxia indicates that the heart, brain, and other organs incur compromise earlier than the time required for visible damage to be evident.

6 - The Umbilical Cord Lifeline
Clamping of the umbilical cord at birth is a human invention and a dangerous procedure if performed on an infant who is not yet breathing. Respiration is the most immediate and essential need of all life forms dependent upon oxygen. Placental respiration must be maintained until an infant's lungs and heart have completed the transition from pre- to postnatal adaptation.

7 - Developmental Delay
Monkeys subjected to asphyxia at birth exhibited muscle weakness and delay in developing motor control; they never overcame poor manual dexterity. The asphyxiated monkeys were not deaf, despite the conspicuous damage to the inferior colliculus, but they did not orient to sounds as normal monkeys did.

8 - Poor Manual Dexterity
Monkeys subjected to asphyxia at birth remained deficient in manual dexterity. Large and laboriously produced handwriting is characteristic of children with developmental delay and children with "high functioning" autism.

9 - Progressive Degeneration
Widespread degeneration was evident in the brains of monkeys who survived several months or years following asphyxia at birth. Anomalies of the same brain areas (cerebellum, amygdala, corpus callosum, etc.) are evident in the brains of individuals who were autistic in childhood.

10 - Autism and Complications at Birth
Many children with autism suffered complications at birth. Oxygen insufficiency is the greatest danger during a difficult birth. Problems during labor and delivery are frequently attributed to pre-existing genetic factors, but monkeys subjected to experimental asphyxia had no pre-existing problems.

11 - Mercury, and Other Toxic Factors
In the experiments with monkeys the effects of high levels of bilirubin (jaundice) were investigated. Bilirubin did not enter brain tissue except in monkeys that had been subjected to asphyxia. Mercury preservatives in vaccines and other substances may also only cross a blood-brain barrier compromised by asphyxia or hypoxia. Does the hepatitis-B vaccine need to be given in the newborn nursery?
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II. THE AUDITORY SYSTEM

12 - Metabolic Rank Order
Methods to measure cerebral circulation were extended to measure aerobic metabolism. The same brainstem nuclei with highest blood flow were found by several measures to have highest aerobic metabolism. The inferior colliculus is at the top of the rank order by every measure.

13 - The Auditory System
The inferior colliculus evolved to provide auditory alerting for visual attention. The auditory system is always active, even during sleep. The auditory and visual colliculi of the midbrain tectum may be the locus of consciousness in the brain.

14 - Auditory Dysfunction
Children with autism are often over-sensitive to loud sounds and noisy environments (hyperacusis). Auditory evoked potential testing indicates delay of signal transmission in some children with autism. Auditory dysfunction raises the possibility of auditory system impairment by asphyxia at birth. Asphyxia of duration too brief to produce visible damage may still lead to impairment of neurotransmitter systems in the inferior colliculus.


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III. LANGUAGE

15 - Language by Ear
Most children learn language by ear. Language learning begins before the language circuits of the temporal and frontal lobes are fully myelinated and mature. Children normally learn language through recognition of stressed syllables, which leads to the well recognized stage of language development known as "telegraphic speech" (baby talk).

16 - Verbal Auditory Agnosia
"Agnosia" is a failure of recognition in the apparent absence of sensory deficit. Agnosia for speech sounds has been reported in some children with autism, and has been termed "verbal auditory agnosia." At least three cases of verbal auditory agnosia have been reported in adults following damage of the inferior colliculus.

17 - Echolalic Speech
Some children with autism begin to use parroted phrase fragments (echolalic speech) at the time most children are at the "telegraphic speech" stage of development. The child who hears syllable boundaries is able to detect small units of meaning (morphemic units), to recognize their recurrence in the speech of those around him, and eventually to rearrange their use in new contexts. Use of phrase fragments indicates failure to detect syllable boundaries, and again raises the issue of auditory dysfunction in autism.

18 - Echolalic Speech is Pragmatic
Kanner (in 1946) referred to the echolalic speech of autistic children as "irrelevant and metaphorical speech." The irrelevant nature of echolalic speech is because of its use out of context; its partial fit to context makes it seem metaphorical. Phrase fragments are not as easily rearranged as morphemic units to fit context. "You don't want to go swimming?" was not a question, but one autistic child's emphatic statement that she didn't want to go in the water; this statement also provides an example of "pronoun reversal."
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IV. CHILDHOOD HANDICAPS

19 - Auditory and Motor Handicaps
Motor handicaps associated with the brainstem pattern of damage were transient and overcome except for manual dexterity in monkeys subjected to asphyxia at birth. More serious permanent disorders of movement indicate impairment of function in the basal ganglia or cerebral cortex. Most children with autism show signs of both, thus signs of damage caused by both asphyxia and hypoxia. Asphyxia is more likely to occur as the final insult of a difficult hypoxic birth. Signs of auditory dysfunction in children with autism would seem to indicate catastrophic impairment of aerobic metabolism by asphyxia at birth or by any of the other medical conditions associated with autism.

20 - Increased Incidence of Autism
The increased prevalence of autism is more likely due to increased incidence of asphyxia at birth than to increases in the medical conditions associated with autism. Textbooks on obstetrics in the late nineteenth and early twentieth centuries stressed the importance of leaving the umbilical cord intact until the newborn infant is breathing. The modern procedure of immediate umbilical cord clamping needs to be investigated as a possible cause of increased prevalence of auditory dysfunction in children.

21 - Fetal to Postnatal Adaptation
The alveoli of the lungs become functional by perfusion with blood at birth. Resuscitation by ventilation in the intensive care unit often requires use of blood volume expanders. Normal blood volume is best ensured by maintaining placental circulation through the umbilical cord.

22 - Forgotten History
Experimental asphyxiation of newborn monkeys would no longer be permissible. But the findings of past research projects remain important and merit re-examination.

23 - Worth Remembering
Comments made by Windle in 1969 are worth heeding still today, especially:
(a) To clamp the umbilical cord immediately is equivalent to subjecting the infant to a massive hemorrhage.
(b) It is no longer acceptable to assume that the human infant will escape harm from a short exposure to asphyxia at birth.
(c) Although improvement can be expected, we know that the brain of a "recovered" monkey is damaged whereas we only assume that the brain of a "recovered" human infant is normal.

24 - Hemoglobin
The release of oxygen from hemoglobin provides an explanation for why the effects of hypoxia are so different from those of asphyxia. The quickest adjustment to an environment of oxygen insufficiency is provided by the action of hemoglobin in delivering oxygen first to tissues producing the most carbon dioxide. The inferior colliculus is spared under hypoxic conditions, but first to sustain damage during any catastrophic interference with aerobic metabolism

25 - Postnatal Anemia
Clamping the umbilical cord at birth is equivalent to subjecting the infant to a massive hemorrhage; this loss of blood was shown over 60 years ago to lead to anemia in infancy. An anemic child is in a state of chronic hypoxia, which will impede normal growth of brain and other organs.

26 - Autism in Twins
Concordance of autism in identical twins is not 100 percent. Differences between concordant twin pairs are greater than similarities. Twins are more vulnerable to perinatal problems, which is also evident from the larger than would be expected number of non-identical twin pairs in which both are autistic.

27 - Male-Female Differences
Males have higher metabolic needs than females and are thus more vulnerable to any factor that interferes with aerobic energy production. Males outnumber females in most developmental disorders. Growth retardation was immediately evident in males but not females following neonatal asphyxia in laboratory rats.
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V. BRAINSTEM DAMAGE

28 - Variable Vulnerability
Protective mechanisms increase blood flow to the inferior colliculus in any circumstance that leads to impairment of aerobic metabolism. This has been revealed in several experiments with toxic chemicals. Total catastrophic disruption of aerobic metabolism damages the rank order of brainstem nuclei of high metabolic rate. Partial interference with aerobic metabolism spares the inferior colliculus and leads to damage of less metabolically active brain centers.

29 - Patterns of Damage
Circulatory insufficiency most often leads to damage of the cerebral cortex. Brainstem damage with or without involvement of cortical areas has been reported in people resuscitated after drowning, suffocation, or cardiac arrest. Brainstem damage has often been compared with that found in monkeys asphyxiated at birth and also in Wernicke's encephalopathy.

30 - Wernicke's Encephalopathy
Gayet (in 1875) and Wernicke (in 1881) described damage restricted to the brainstem in cases of airway damage, alcoholism, and ingestion of sulfuric acid. This pattern of damage is associated most often with alcoholism and thiamine (vitamin B1) deficiency.

31 - Suffocation at the Molecular Level
An increasing array of toxic substances has been found to interfere partially or catastrophically with aerobic metabolism. Brainstem nuclei are affected in varying degrees.

32 - Thiamine Deficiency
Thiamine (vitamin B1) is an essential cofactor for enzymes of aerobic metabolism. Deficiency of thiamine in the diet or because of malabsorption in gastrointestinal disorders leads to Wernicke's encephalopathy or variants of this pattern of damage.

33 - Brain-Gut Relationship
Autonomic functions such as intestinal peristalsis are controlled by brainstem centers. Damage to these autonomic centers can impair intestinal function. Intestinal dysfunction in turn leads to malabsorption and/or absorption of digestional fragments that should be excluded. Toxic fragments of digestion may be toxic to the brain and further compound the effects of earlier damage.


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