I am unable to attend the IACC meeting to be held July 16.  Please provide my comments
below, plus the attached research proposal to members of the IACC for the July 16 meeting.  
Thanks.

Eileen Nicole Simon
conradsimon.org
11 Hayes Avenue, Lexington MA 02420-3521
(781) 862-5326 or (617) 512-0424 (cell)
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Attached to this email is a research proposal I put together as an assignment for a course I
took five years ago in Cognitive Neuroscience.  I continue to believe that auditory system
dysfunction should be investigated as a factor in developmental language disorder, and that
the auditory system is susceptible to injury by all of autism’s many etiologies.

The inferior colliculi are among the brainstem structures fully myelinated and functional
before birth [1, 2].  Myelination of the temporal and frontal language areas follows a
consistent schedule during the first three years after birth, which correlates with the normal
stages of language development [3].  Growth of axons toward developing targets in the
cerebral cortex depends upon orderly neurotransmission from brainstem structures [4].  
Impairment however slight, within structures like the inferior colliculi cannot be dismissed as
“minimal.”

Landau et al. (1955) and Sokoloff et al. (1977) found that blood flow and aerobic metabolism
are higher in the inferior colliculi than in any other area of the brain [5, 6].  In research on
glucose uptake in the brain Sokoloff et al. commented:

    “The highest values were clearly in the structures involved in auditory functions with
    the inferior colliculus the most metabolically active structure in the brain.” [6, p912]

In research with monkeys on asphyxia at birth, Ranck and Windle (1959) discovered the
inferior colliculi to be most prominently affected [7].  Faro and Windle (1969) observed
disrupted maturation throughout the brains of monkeys kept alive for many months or years
[8].  The areas of the brain affected in monkeys can be compared to the finding of defects of
neurogenesis and neuronal migration observed in the brains of people with autism [9, 10].

The inferior colliculi have been found to stand out brightly in fMRI scans [11, 12].  This is due
to the “blood oxygenation level dependent” (BOLD) signal, the result of high blood flow in
these small midbrain structures [12].

The inferior colliculi are susceptible to injury from toxic substances [13-16].  This has always
been reported as a surprise finding.  As Morgan et al. (2004) commented:

    “Although the posterior colliculus is not typically examined in standard brain survey
    sections, a fortuitous section in one animal indicated severe necrosis.” [16, p136]

I could be wrong, but until evidence to the contrary can be provided, perinatal damage of the
inferior colliculi should be a focus of research, and added to the IACC strategic plan.

The obstetric protocol of clamping the umbilical cord immediately at birth should be
changed.  Until the mid 1980s obstetric textbooks taught that the cord should not be clamped
until the newborn infant is breathing.  Most infants appear to withstand early termination of
placental respiration, but I believe those who don’t may account for the increased prevalence
of autism.

References
  1. Yakovlev PI and Lecours A-R. The myelogenetic cycles of regional maturation of the
    brain.  In A. Minkowski (Ed.), Regional Development of the Brain in Early Life (pp. 3-
    70).  Oxford: Blackwell Scientific Publications, 1967.
  2. Moore JK, Perazzo LM, Braun A. Time course of axonal myelination in the human
    brainstem auditory pathway. Hear Res. 1995 Jul;87(1-2):21-31. Erratum in: Hear Res
    1995 Nov;91(1-2):208-9.
  3. Pujol J, Soriano-Mas C, Ortiz H, Sebastian-Galles N, Losilla JM, Deus J. Myelination of
    language-related areas in the developing brain. Neurology. 2006 Feb 14;66(3):339-43.
  4. Friauf E, Lohmann C. Development of auditory brainstem circuitry. Activity-dependent
    and activity-independent processes. Cell Tissue Res. 1999 Aug;297(2):187-95.
  5. Landau WM, Freygang WH, Rowland LP, Sokoloff L, Kety SS. The local circulation of
    the living brain; values in the unanesthetized and anesthetized cat. Trans Am Neurol
    Assoc. 1955-1956;(80th Meeting):125-9.
  6. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD,
    Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the
    measurement of local cerebral glucose utilization: theory, procedure, and normal
    values in the conscious and anesthetized albino rat. J Neurochem. 1977 May;28(5):
    897-916.
  7. Ranck JB, Windle WF. Brain damage in the monkey, Macaca mulatta, by asphyxia
    neonatorum. Exp Neurol. 1959 Jun;1(2):130-54.
  8. Faro MD, Windle WF. Transneuronal degeneration in brains of monkeys asphyxiated
    at birth. Exp Neurol. 1969 May;24(1):38-53.
  9. Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Marchi E, Ma SY, Chauhan A,
    Chauhan V, Bobrowicz TW, de Leon M, Louis LA, Cohen IL, London E, Brown WT,
    Wisniewski T. The neuropathology of autism: defects of neurogenesis and neuronal
    migration, and dysplastic changes. Acta Neuropathol. 2010 Jun;119(6):755-70.
  10. Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review
    and future directions. Int J Dev Neurosci. 2005 Apr-May;23(2-3):183-7.
  11. Budd TW, Hall DA, Goncalves MS, Akeroyd MA, Foster JR, Palmer AR, Head K,
    Summerfield AQ. Binaural specialisation in human auditory cortex: an fMRI
    investigation of interaural correlation sensitivity. Neuroimage. 2003 Nov;20(3):1783-94.
  12. Baumann S, Griffiths TD, Rees A, Hunter D, Sun L, Thiele A. Characterisation of the
    BOLD response time course at different levels of the auditory pathway in non-human
    primates. Neuroimage. 2010 Apr 15;50(3):1099-108.
  13. Squier MV, Thompson J, Rajgopalan B. Case report: neuropathology of methyl
    bromide intoxication. Neuropathol Appl Neurobiol. 1992 Dec;18(6):579-84.
  14. Cavanagh JB, Nolan CC. The neurotoxicity of alpha-chlorohydrin in rats and mice: II.
    Lesion topography and factors in selective vulnerability in acute energy deprivation
    syndromes. Neuropathol Appl Neurobiol. 1993 Dec;19(6):471-9.
  15. Husain K, Whitworth C, Hazelrigg S, Rybak L. Carboplatin-induced oxidative injury in
    rat inferior colliculus.  Int J Toxicol. 2003 Sep-Oct;22(5):335-42.
  16. Morgan DL, Little PB, Herr DW, Moser VC, Collins B, Herbert R, Johnson GA, Maronpot
    RR, Harry GJ, Sills RC. Neurotoxicity of carbonyl sulfide in F344 rats following
    inhalation exposure for up to 12 weeks. Toxicol Appl Pharmacol. 2004 Oct 15;200(2):
    131-45.
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Conrad Simon Memorial Research Initiative
To seek understanding of brain system impairments in autism.
http://conradsimon.org/