Neurological Histopathology and Biological Changes in Autism |
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Cerebellum. The Purkinje cells contain round, darkly stained cytoplasmic inclusions (Luxol fast blue and cresyl violet; bar represents 10 mm.) |
Changes seen in AutismIn general
there is nothing to see under standard haematoxylin and eosin staining of
brain tissue. Complex assessment is
necessary to show alterations that are reliable and research has required
many samples in order to separate them from the controls. Electron microscropy findings are not good
either and not much has been done except in specific cases. Often the findings cannot be repeated
because the numbers of deaths is low in this group, and the death is often
due to some other cause that may have an effect on the histopathology e.g.
seizures. The use of PET, SPECT and MRI scanning in
children gives an opportunity to look at the metabolism of the brain and the
relative levels of usage of different parts.
Currently this is inadequately taken advantage of: probably because of
the sheer difficulty of organisation.
However, major groups claim specific changes.
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Overall
changes
The
changes in growth of the brain and brain parts has
been argued over for many years. The use
of MRI has given a chance but of course, by the time the child is realised to
have autism it is past the age that the scanning might be most useful to give
insight in this respect. As a result,
many of the results that we see are in slightly older children and compared
with controls. The finding of slightly
enlarged brains is fairly regular.
As
quoted from Pardo and Eberhart:
“One consistent finding in ASD is altered brain
growth, which has been extensively documented by Courchesne
et al. The clinical onset of autism appears to be preceded by two phases of
brain growth abnormalities: a reduced head size at birth, then a sudden and
excessive increase between 1–2 months and 6–14 months of age (2,3 4).
Furthermore, these reports and other recent neuroimaging studies have shown
that an abnormal pattern of brain overgrowth also occurs in areas of the
frontal lobe, cerebellum and limbic structures
between 2 and 4 years of age, a pattern
that is followed by abnormal slowness in brain growth”(54, 55, 57, 192)
Diagram 1: This comes from Pardo and
Eberhart and is an excellent insight into the mechanism by which the ASD
may appear. They realise that there may be many
individual factors and that they may take place at many separate points in the
development of the brain and at different times.
Hardan AY, Girgis RR, Adams J, Gilbert AR, Keshavan MS, Minshew NJ. Abnormal brain size effect on the thalamus in autism Psychiatry Res. 2006 Oct 30;147(2-3):145-51. (Findings from this larger study than previously are consistent with the previous report of an abnormal brain size effect on the thalamus in autism and support the possibility of abnormal connections between cortical and subcortical structures in this disorder. There was no correlation with clinical condition)
Courchesne E, Pierce K, Schumann CM, Redcay E,
Buckwalter JA, Kennedy DP, Morgan J.
Mapping early brain development in autism. Neuron.
2007 Oct 25;56(2):399-413. (this
is a complex description of the increased brain size in childhood, and how it
appears to come about in various periods.
A good review that seems to admit that there may be many formats to the
illness as the stimulation or inhibition of the various brain development
periods may all be important and effected differently)
Schumann CM, Hamstra J, Goodlin-Jones BL,
Lotspeich LJ, Kwon H, Buonocore MH, Lammers CR, Reiss AL, Amaral DG.
The amygdala is enlarged in children but not adolescents with autism; the
hippocampus is enlarged at all ages. J Neurosci. 2004
Jul 14;24(28):6392-401
Casanova
MF. The neuropathology of autism. Brain Pathol. 2007 Oct;17(4):422-33. Review. (tries to say that
much of the pathology that has been put forward has not been found to be
reliable). Changes in the size of the
brain, particularly the parietal lobes are larger in autism. Modified changes in astrocytes, and brain monocytes
(suggesting irritation). Decreased and modified synaptic interactions between neurones, some
of which are only visible under electron microscropes.
Hazlett
HC, Poe
M, Gerig
G, Smith
RG, Provenzale
J, Ross
A, Gilmore
J, Piven
J. Magnetic resonance imaging and head circumference study of brain size in
autism: birth through age 2 years .Arch Gen Psychiatry. 2005 Dec;62(12):1366-76 (Generalized enlargement of gray and
white matter cerebral volumes, but not cerebellar volumes, are present at 2
years of age in autism. Indirect evidence suggests that this increased rate of
brain growth in autism may have its onset postnatally in the latter part of the
first year of life.)
Courchesne E. Brain development in autism: early overgrowth followed by premature arrest of growth. Ment Retard Dev Disabil Res Rev. 2004;10(2):106-11. (growth of the brain in various periods and how this may be altered in autism)
Courchesne E, Redcay E, Kennedy DP. The autistic brain: birth through adulthood. Curr Opin Neurol. 2004 Aug;17(4):489-96.
DiCicco-Bloom E, Lord C, Zwaigenbaum L, Courchesne E, Dager SR, Schmitz C, Schultz RT, Crawley J, Young LJ. The developmental neurobiology of autism spectrum disorder. J Neurosci. 2006 Jun 28;26(26):6897-906. Review.
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005 Jan;57(1):67-81. Erratum in: Ann Neurol. 2005 Feb;57(2):304. (To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1.)
Pardo
CA, Vargas
DL, Zimmerman
AW. Immunity, neuroglia and neuroinflammation in autism. Int Rev
Psychiatry. 2005 Dec;17(6):485-95
Structural neuroimaging in autism. Hrdlicka M.
Neuro Endocrinol Lett. 2008 Jun;29(3):281-6. Review.
Research applications of magnetic
resonance spectroscopy to investigate psychiatric disorders.
Dager SR,
Neuroanatomy of autism.
Amaral DG, Schumann CM, Nordahl CW. Trends Neurosci. 2008 Mar;31(3):137-45. Postmortem and structural magnetic resonance imaging
studies have highlighted the frontal lobes, amygdala and cerebellum as
pathological in autism. However, there is no clear and
consistent pathology that has emerged for autism. Moreover, recent
studies emphasize that the time course of brain development rather than the
final product is most disturbed in autism. We suggest that the heterogeneity of
both the core and co-morbid features predicts a heterogeneous pattern of
neuropathology in autism.
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Decrease
in Purkinje cells in the cerebellum: similarly in all ages. Changes in the inferior olive were seen with
unusually large neurons in younger brains and neurones smaller than expected in
the older brains. Increased
packing of neuronal cells in the entorhinal cortex.
Curtailment
of maturation of the forebrain limbic system (most consistently the amygdala
the hypocampal formation and entorhinal cortex), abnormalities in the
cerebellar circuits, and and an unusual pattern of change of post natal brain
size. Also age-related
neuronal size and number in the Broca diagonal band. Great argument as to
reliable changes. They commonly
try to work out the point in the development of the brain at which the damage
would have taken place to produce the changes seen in individual brain
samples. Neuropathological studies in
autistic brains have shown small neuronal size and increased cell packing
density in a variety of limbic system structures including the hippocampus, a
change consistent with curtailment of normal development.
A good review: 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. taking
over from Bauman
ML, Kemper TL. The neuropathology
of the autism spectrum disorders: what have we learned? Novartis Found Symp.
2003;251:112-22; discussion 122-8, 281-97
Darby
JK. Neurpathologic
aspects of psychosis in children.
J autism Child Schizophr 1976;6:350-3 (he found no reliable
changes in 33 autistic brains).
Amaral
DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends
Neurosci. 2008 Mar;31(3):137-45. (he says that it is
a heterogenous group with a heterogenous causes of death and so it is not
surprising that we cant get specific changes)
Casanova
MF. The neuropathology of autism. Brain Pathol. 2007 Oct;17(4):422-33. Review. (tries to say that
much of the pathology that has been put forward has not been found to be
reliable). Changes in the size of the
brain, particularly the parietal lobes are larger in autism. Modified changes in astrocytes, and brain monocytes
(suggesting irritation). Decreased and modified synaptic interactions between neurones, some
of which are only visible under electron microscropes.
Rodier PM, Ingram JL, Tisdale B, Nelson S, Romano J. Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei J Comp Neurol. 1996 Jun 24;370(2):247-61.The human data suggest that the initiating lesion includes the motor cranial nerve nuclei. To test this hypothesis, we first examined motor nuclei in the brainstem of a human autistic case. The autopsy brain exhibited near-complete absence of the facial nucleus and superior olive along with shortening of the brainstem between the trapezoid body and the inferior olive. They also tried giving some rats in utero some valproate to see if the effect was the same: it wasn’t)
Chen
X, Liu H, Shim AH, Focia PJ, He X. Structural basis for synaptic adhesion
mediated by neuroligin-neurexin interactions. Nat Struct Mol Biol. 2007 Dec 16;
[Epub ahead of print] . They explain why the neuroligin genetic
mutations (as accused in autism) are likely to be associated with specific
changes in the ability of neurones to interact.
Tabuchi
K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM, Südhof TC. A neuroligin-3 mutation implicated in autism increases inhibitory
synaptic transmission in mice. Science. 2007
Oct 5;318(5847):71-6.
Garber K. Neuroscience.
Autism's cause may reside in abnormalities at the synapse. Science.
2007 Jul 13;317(5835):190 (editorial) – this shows how the
evidence with neuroligins has been appearing over the last 3 years.
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005 Jan;57(1):67-81. Erratum in: Ann Neurol. 2005 Feb;57(2):304. (Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues.)
Coleman PD, Romano J, Lapham L, Simon W. Cell
counts in cerebral cortex of an autistic patient. J Autism Dev Disord.
1985 Sep;15(3):245-55.Numbers of neurons and glia were counted
in the cerebral cortex of one well-documented case of autism and two age- and
sex-matched controls. Areas in which cell counts were made were primary
auditory cortex, Broca's speech area, and auditory association cortex. No
consistent differences in cell density were found between the brains of the
autistic patient and the control patients.”
All they could say was that the glia:neuronal
ratio was smaller in the autistic brain than in the two controls. Statistically this would not be
adequate.
Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, Ritvo A. Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. Am J Psychiatry. 1986 Jul;143(7):862-6. (this involved counts of the cell numbers and has been repeated)
Martchek M, Thevarkunnel S, Bauman M, Blatt G, Kemper T. Lack of evidence of neuropathology in the locus coeruleus in autism. Acta Neuropathol. 2006 May;111(5):497-9. Epub 2006 Apr 5.
A Bailey,
P Luthert, A Dean, B
Harding, I Janota, M Montgomery, M Rutter and P Lantos A clinicopathological study of autism Brain, Vol 121, Issue 5 889-905 (They are less happy with the reliable
findings that might be suggested elsewhere and wonder if the changes that they
found also in the Purkinje cells of the cerebellum are indeed much to do with
the clinical aspects of the condition, which they put towards involvement of the cerebral cortex but with little to be
seen under microscoscopy)
van Kooten IA, Palmen SJ, von Cappeln P, Steinbusch HW, Korr H, Heinsen H, Hof PR, van Engeland H, Schmitz C. Neurons in the fusiform gyrus are fewer and smaller in autism. Brain. 2008 Apr;131(Pt 4):987-99. Epub 2008 Mar 10.
Whitney ER, Kemper TL, Bauman ML, Rosene DL, Blatt GJ. Cerebellar Purkinje Cells are Reduced in a Subpopulation of Autistic Brains: A Stereological Experiment Using Calbindin-D28k. Cerebellum. 2008 Jun 28. [Epub ahead of print] (it is difficult to interpret this because of the lack of cerebellar syndromes that seem to be appear with autism, however it may be of value for interpretation of histopathology)
Neurons in the fusiform gyrus are fewer and smaller in
autism.
van Kooten IA, Palmen SJ, von Cappeln P, Steinbusch HW, Korr
H, Heinsen H, Hof PR, van Engeland H, Schmitz C.
Brain.
2008 Apr;131(Pt
4):987-99. We investigated the FG (analysing separately layers II, III, IV, V
and VI), in seven post-mortem brains from patients with autism and 10 controls
for volume, neuron density, total neuron number and mean perikaryal volume with
high-precision design-based stereology. To determine whether these results were
specific for the FG, the same analyses were also performed in the primary
visual cortex and in the cortical grey matter as a whole. Compared to controls,
patients with autism showed significant reductions in neuron densities in layer
III, total neuron numbers in layers III, V and VI, and mean perikaryal volumes
of neurons in layers V and VI in the FG.
This was tried against controls.
Cerebellar Purkinje cells are reduced in a subpopulation
of autistic brains: a stereological experiment using calbindin-D28k.
Whitney ER, Kemper TL, Bauman ML, Rosene DL, Blatt GJ.
Cerebellum. 2008;7(3):406-16
Morphological features of the medial superior olive in
autism.
The neuropathology of autism: where do we stand?
Big heads, small details and autism.
White S, O'Reilly H,
Cerebellar vermal volumes and
behavioral correlates in children with autism spectrum disorder.
Webb SJ, Sparks BF,
Elevated immune response in the brain
of autistic patients.
Li X, Chauhan A, Sheikh AM,
Patil S, Chauhan V, Li XM, Ji L, Brown T, Malik M. J Neuroimmunol. 2009 Feb 15;207(1-2):111-6. Results showed that proinflammatory
cytokines (TNF-alpha, IL-6 and GM-CSF), Th1 cytokine (IFN-gamma) and chemokine
(IL-8) were significantly increased in the brains of ASD patients compared with
the controls. However the Th2 cytokines (IL-4, IL-5 and IL-10) showed no
significant difference. The Th1/Th2 ratio was also significantly increased in
ASD patients. Conclusion: ASD patients displayed an increased innate and
adaptive immune response through the Th1 pathway,
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Electron microcroscopy
There
appears to be little data of reliable changes in autism that cannot be
predicted from standard methods of histopathology (if there are, please contact me!)
Chubykin
AA, Liu X, Comoletti D, Tsigelny I, Taylor P, Südhof TC. Dissection of
synapse induction by neuroligins: effect of a neuroligin mutation associated
with autism. J Biol Chem. 2005 Jun 10;280(23):22365-74. (contains
the electron microscope viewpoint of the synapse in these genetic mutants)
Casanova
MF. The neuropathology of autism. Brain Pathol. 2007 Oct;17(4):422-33. Review. (tries to say that
much of the pathology that has been put forward has not been found to be
reliable). Changes in the size of the
brain, particularly the parietal lobes are larger in autism. Modified changes in astrocytes, and brain monocytes
(suggesting irritation). Decreased and modified synaptic interactions between neurones, some
of which are only visible under electron microscropes.
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Neurobiology and Brain Biochemistry (take into account diagram 1)
Currently inadequately followed but clearly a
mechanism to follow the progressive pathology that takes place in the brain of
the autistic child and the physiology of the brain in a steady long term
condition.
Pardo CA, Eberhart
CG. The neurobiology of autism. Brain Pathol. 2007 Oct;17(4):434-47. Review. (they
are trying their best to associate the time of onset of the illness with the
disease that is seen. From that they try
to show why they see different pathology in different cases)
Chubykin
AA, Liu X, Comoletti D, Tsigelny I, Taylor P, Südhof TC. Dissection of
synapse induction by neuroligins: effect of a neuroligin mutation associated with
autism. J Biol Chem. 2005 Jun 10;280(23):22365-74. (contains
the electron microscope viewpoint of the synapse in these genetic mutants)
Kleinhans NM, Schweinsburg BC, Cohen DN, Müller RA, Courchesne E. N-acetyl aspartate in autism spectrum disorders: regional effects and relationship to fMRI activation. Brain Res. 2007 Aug 8;1162:85-97. Epub 2007 May 21 (this is an attempt to show changes in the regional effects of the transmitter: and they claim success, which would justify treatment being expected to make effect e.g. memantine)
McDougle
CJ, Erickson
CA, Stigler
KA, Posey
DJ. Neurochemistry in the pathophysiology of autism.
J Clin Psychiatry. 2005;66
Suppl 10:9-18. Does not actually say
what the changes are in the abstract.
Pardo CA, Eberhart CG. The neurobiology of autism. Brain Pathol. 2007 Oct;17(4):434-47. Review. Explains how things are moving much more rapidly and that further neurochemicals may be involved.
Minshew NJ, Williams DL. The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch Neurol. 2007 Jul;64(7):945-50. Review
Friedman SD, Shaw DW, Artru AA, Dawson G, Petropoulos H, Dager SR. Gray and white matter brain chemistry in young children with autism. Arch Gen Psychiatry. 2006 Jul;63(7):786-94.
Altered cerebellar feedback projections
in Asperger syndrome.
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MRI
Magnetic resonance imaging and positron emission
tomography. The data has built up and gradually it has
become clearer of the size of the brain, the different periods during which
changes from controls appear to take place.
It is quite clear that the higher technology later in the era has
managed to show much more specific changes that are relatively predictable in
ASD children. The problem must always be
as to whether the changes seen are secondary to chemistry (or some other factor
causing damage) or involved with the primary illness. What can be said is that many mental
illnesses cannot be shown to have MRI changes at all whereas the finding of
these alterations in ASD is itself significant.
Acosta MT, Pearl PL. Imaging data in autism: from structure to malfunction. Semin Pediatr Neurol. 2004 Sep;11(3):205-13. Review. (view of autism as a neurobiological disorder corresponding with different stages and events in brain development. Alterations in volume of the total brain and specifically the cerebellum, frontal lobe, and limbic system have been identified.)
Garber HJ, Ritvo ER, Chiu LC, Griswold VJ, Kashanian A, Freeman BJ, Oldendorf WH. A magnetic resonance imaging study of autism: normal fourth ventricle size and absence of pathology. Am J Psychiatry. 1989 Apr;146(4):532-4. (showed no difference between the autistics and the controls)
Bloss CS, Courchesne E. MRI neuroanatomy in young girls with autism: a preliminary study. J Am Acad Child Adolesc Psychiatry. 2007 Apr;46(4):515-23. (Girls with autism exhibited nearly every size-related abnormality exhibited by boys with autism. Furthermore, additional sites of abnormality were observed in girls, including enlargement in temporal white and grey matter volumes and reduction in cerebellar grey matter volume. Significant correlations were observed between age and white matter volumes (e.g., cerebral white matter rs = 0.950) for the girls with autism, whereas no significant age-structure size relationships were observed for the boys with autism.)
Wassink
TH, Hazlett
HC, Epping
EA, Arndt
S, Dager
SR, Schellenberg
GD, Dawson
G, Piven
J. Cerebral cortical gray matter overgrowth and functional variation of the
serotonin transporter gene in autism .Arch Gen Psychiatry. 2007 Jun;64(6):709-17
(They found that 5-HTTLPR genotype influenced gray matter volumes of the cerebral cortex (F(2,23) = 7.29, P = .004) and of 3 lobe-based subregions in the UNC sample of 29 children (frontal lobe gray matter: F(2,23) = 6.36, P = .01). The 5-HTTLPR short allele appeared to be additively associated with increasing gray matter volumes, an observation affirmed by tests of linear genotype effects (cortical gray matter: F(1,24) = 14.11, P = .001; frontal lobe gray matter: F(1,24) = 13.20, P = .001). Genotype did not influence cerebellar volumes. This was not measured with respect to platelet serotonin but the results seem reasonable. Checking the change using histopathology?: a very difficult process and ethically difficult also). The significance of the gene for serotonin transport see serotonin.
Akshoomoff N, Lord C, Lincoln AJ, Courchesne RY, Carper RA, Townsend J, Courchesne E. Outcome classification of preschool children with autism spectrum disorders using MRI brain measures. J Am Acad Child Adolesc Psychiatry. 2004 Mar;43(3):349-57 (indicate that variability in cerebellar and cerebral size is correlated with diagnostic and functional outcome in very young children with ASD, but they did not try this with older children, which it is unlikely to be of value to indicate)
Gaffrey MS, Kleinhans NM, Haist F, Akshoomoff N, Campbell A, Courchesne E, Müller RA. Atypical [corrected] participation of visual cortex during word processing in autism: an fMRI study of semantic decision. Neuropsychologia. 2007 Apr 9;45(8):1672-84. Epub 2007 Jan 16. (functional MRI (fMRI) scanning was carried out while the patient was actually performing an action involving being shown something and responding. The autistic patients showed unreliable, and poor response but it was different amongst the patients. The authors decided that it was difficult to interpret)
Belmonte MK, Mazziotta JC, Minshew NJ, Evans AC, Courchesne E, Dager SR, Bookheimer SY, Aylward EH, Amaral DG, Cantor RM, Chugani DC, Dale AM, Davatzikos C, Gerig G, Herbert MR, Lainhart JE, Murphy DG, Piven J, Reiss AL, Schultz RT, Zeffiro TA, Levi-Pearl S, Lajonchere C, Colamarino SA. Offering to share: how to put heads together in autism neuroimaging. J Autism Dev Disord. 2008 Jan;38(1):2-13. Epub 2007 Mar 9.
Redcay E, Courchesne E. When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biol Psychiatry. 2005 Jul 1;58(1):1-9.
Courchesne E, Pierce K. Brain overgrowth in autism during a critical time in development: implications for frontal pyramidal neuron and interneuron development and connectivity. Int J Dev Neurosci. 2005 Apr-May;23(2-3):153-70. Review.
Courchesne E. Brain development in autism: early overgrowth followed by premature arrest of growth. Ment Retard Dev Disabil Res Rev. 2004;10(2):106-11. Review
Müller RA, Kleinhans N, Pierce K, Kemmotsu N, Courchesne E. Functional MRI of motor sequence acquisition: effects of learning stage and performance Brain Res Cogn Brain Res. 2002 Aug;14(2):277-93 (superior parietal and occipital regions are most intensely involved in visually driven explicit digit sequence learning during early stages and low performance, whereas later stages of acquisition and higher levels of performance are characterized by stronger recruitment of prefrontal and mediotemporal regions.)
Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003 Jul 16;290(3):337-44.
Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD, Chisum HJ, Moses P, Pierce K, Lord C, Lincoln AJ, Pizzo S, Schreibman L, Haas RH, Akshoomoff NA, Courchesne RY. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology. 2001 Jul 24;57(2):245-54. (Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism)
Hazlett HC, Poe M, Gerig G, Smith RG, Provenzale J, Ross A, Gilmore J, Piven J. Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch Gen Psychiatry. 2005 Dec;62(12):1366-76. (Generalized enlargement of gray and white matter cerebral volumes, but not cerebellar volumes, are present at 2 years of age in autism)
Hazlett HC, Poe MD, Gerig G, Smith RG, Piven J. Cortical gray and white brain tissue volume in adolescents and adults with autism. Biol Psychiatry. 2006 Jan 1;59(1):1-6. Epub 2005 Sep 1. (These findings give evidence for left-lateralized gray tissue enlargement in adolescents and adults with autism, and demonstrate a regional pattern of cortical lobe volumes underlying this effect.)
Zilbovicius M, Meresse I, Chabane N, Brunelle F, Samson Y, Boddaert N. Autism, the superior temporal sulcus and social perception. Trends Neurosci. 2006 Jul;29(7):359-66. Epub 2006 Jun 27. Review (this goes over the scanning factors that suggest the involvement of the sulcus)
Boddaert N, Chabane N, Gervais H, Good CD, Bourgeois M, Plumet MH, Barthélémy C, Mouren MC, Artiges E, Samson Y, Brunelle F, Frackowiak RS, Zilbovicius M. Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study.
Neuroimage. 2004 Sep;23(1):364-9.
Gervais H, Belin P, Boddaert N, Leboyer M, Coez A, Sfaello I, Barthélémy C, Brunelle F, Samson Y, Zilbovicius M. Abnormal cortical voice processing in autism. Nat Neurosci. 2004 Aug;7(8):801-2. Epub 2004 Jul 18. (this is done using functional magnetic resonance and trying to see which parts of the brain are active when specific action of the brain takes place)
Boddaert N, Zilbovicius M. Functional neuroimaging and childhood
autism. Pediatr Radiol.
2002 Jan;32(1):1-7. Epub 2001 Nov 13.
(Functional brain imaging, such as positron emission tomography (PET), single
photon emission computed tomography (SPECT) and functional MRI (fMRI) have
added a new perspective to the study of normal and pathological brain
functions. In autism, functional studies have been performed at rest or during
activation. However, first-generation functional imaging devices were not sensitive
enough to detect any consistent dysfunction. Recently, with improved
technology, two independent groups have reported bilateral hypoperfusion of the
temporal lobes in autistic children. In addition, activation studies, using
perceptive and cognitive paradigms, have shown an abnormal pattern of cortical
activation in autistic patients. These results suggest that different
connections between particular cortical regions could exist in autism. They are admitting that we simply don’t know
much just yet but their finding must fit in somehow with other groups)
Boger-Megiddo I, Shaw DW, Friedman SD, Sparks BF, Artru AA, Giedd JN, Dawson G, Dager SR. Corpus callosum morphometrics in young children with autism spectrum disorder. J Autism Dev Disord. 2006 Aug;36(6):733-9. (they could show decreased inter-hemipheric connections by a decreased in size of the cc)
Munson J, Dawson G, Abbott R, Faja S, Webb SJ, Friedman SD, Shaw D, Artru A, Dager SR. Amygdalar volume and behavioral development in autism. Arch Gen Psychiatry. 2006 Jun;63(6):686-93 (Larger right amygdalar volume was associated with more severe social and communication impairments at ages 3 and 4 years. Larger right amygdalar volume also was predictive of poorer social and communication abilities at age 6 years)
Dager
SR, Wang L, Friedman SD, Shaw DW, Constantino JN, Artru AA, Dawson G,
Csernansky JG. Shape
mapping of the hippocampus in young children with autism spectrum disorder.
AJNR Am J Neuroradiol. 2007 Apr;28(4):672-7. (using
3D MRI images they could show that
children with ASD exhibited an alteration of hippocampal shape
consistent with inward deformation of the subiculum. This pattern of hippocampal-shape
deformations in the children with ASD was accentuated in the more severely
affected subgroup of children with AD and was associated with deficits on
neuropsychologic tests of medial temporal lobe but not prefrontal function.)
Hrdlicka M. Structural neuroimaging in autism. (Review) Neuro Endocrinol Lett. 2008 Jun 25;29(3). This attempts to go over all the MRI scanning that has taken place and indicate when and how the changes appear to take place.
Gabis L, Huang W, Azizian A, Devincent C, Tudorica A, Kesner-Baruch Y, Roche P, Pomeroy J. 1H-Magnetic Resonance Spectroscopy Markers of Cognitive and Language Ability in Clinical Subtypes of Autism Spectrum Disorders. J Child Neurol. 2008 May 16. (significantly lower N-acetyl-aspartate/creatine ratios bilaterally in the hippocampus-amygdala but not cerebellum, whereas myo-inositol/creatine was significantly increased in all measured regions)
Cleavinger HB, Bigler ED, Johnson JL, Lu J, McMahon W, Lainhart JE. Quantitative magnetic resonance image analysis of the cerebellum in macrocephalic and normocephalic children and adults with autism. J Int Neuropsychol Soc. 2008 May;14(3):401-13. (They found that there was little difference between that found in the autistic and control sample: so it was difficult)
McAlonan GM, Suckling J, Wong N, Cheung V, Lienenkaemper N, Cheung C, Chua SE. Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome. J Child Psychol Psychiatry. 2008 Jul 29 (ahead of print). (Children with high-functioning autism (HFA) had significantly smaller grey matter volumes in subcortical, posterior cingulate and precuneus regions than the Asperger's group. Compared to controls, children with HFA had smaller grey matter volumes in predominantly fronto-pallidal regions, while children with Asperger's had less grey matter in mainly bilateral caudate and left thalamus. In addition we found a significant negative correlation between the size of a grey matter cluster around BA44 language area and the age of acquisition of phrase speech in the children with HFA.)
Redcay E, Courchesne E. Deviant Functional Magnetic Resonance Imaging Patterns of Brain Activity to Speech in 2-3-Year-Old Children with Autism Spectrum Disorder. Biol Psychiatry. 2008 Jul 29.(ahead of print) (at 2-3 years, children with ASD might be on a deviant developmental trajectory characterized by a greater recruitment of right hemisphere regions during speech perception.)
Gomot M, Belmonte MK, Bullmore ET, Bernard FA, Baron-Cohen S. Brain hyper-reactivity to auditory novel targets in children with high-functioning autism. Brain. 2008 Jul 31 The present study employed event-related fMRI during a novel auditory detection paradigm. Participants were twelve 10- to 15-year-old children with ASC and a group of 12 age-, IQ- and sex-matched typical controls. The ASC group responded faster to novel target stimuli. (fascinating in that it suggested that the autistic children, even at 12 years of age responded rapidly to novel incidents, as if they had not learned to interpret the incidents before action in the brain in some way. The authors suggest that this may have significance concerning why ‘avoid change’ was continuously found in ASD…and perhaps it is because novelty is a major factor in their brain).
Hrdlicka M. Structural neuroimaging in autism. Neuro Endocrinol Lett. 2008 Jun;29(3):281-6. (a review)
3D cerebral cortical morphometry in autism: increased folding in children and adolescents in frontal, parietal, and temporal lobes. Awate SP, Win L, Yushkevich P, Schultz RT, Gee JC. Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv. 2008;11(Pt 1):559-67. All they can show is that there is an increase in the localised folding of brain surfaces in autism, particularly in children rather than adolescents.
Autism diagnostics by 3D texture analysis of cerebral
white matter gyrifications.
Voxel-based morphometry study on brain
structure in children with high-functioning autism.
Voxels are 3-D
pictures of the brain using MRI. Using
voxel-based morphometry, we compared global and regional brain volumes in 17
high-functioning autistic children with 15 matched controls. We identified
significant reduction in left white matter volume and white/gray matter ratio
in autism. Regional brain volume reductions were detected for right anterior
cingulate, left superior parietal lobule white matter volumes, and right
parahippocampal gyrus gray matter volume, whereas enlargements in bilateral
supramarginal gyrus, right postcentral gyrus, right medial frontal gyrus, and
right posterior lobe of cerebellum gray matter in autism.
Three-dimensional mapping of the
lateral ventricles in autism.
Diffusion tensor
imaging of white matter in the superior temporal gyrus and temporal stem in
autism. Lee JE, Bigler ED, Alexander AL, Lazar M, DuBray MB,
Chung MK, Johnson M, Morgan J, Miller JN, McMahon WM, Lu J, Jeong EK, Lainhart
JE. Neurosci Lett. 2007 Sep 7;424(2):127-32. Recent MRI studies have indicated
that regions of the temporal lobe including the superior temporal gyrus (STG)
and the temporal stem (TS) appear to be abnormal in autism.
Quantitative
magnetic resonance image analysis of the cerebellum in macrocephalic and
normocephalic children and adults with autism. Cleavinger HB,
Bigler ED, Johnson JL, Lu J, McMahon W, Lainhart JE. J Int Neuropsychol Soc. 2008 May;14(3):401-13. Total cerebellum volumes and surface areas of
four lobular midsagittal groups were measured. Independent t-tests between
autism and control subjects matched for head size revealed no significant
differences. In autism, with and without
macrocephaly, cerebellar structures were found to be proportional to head size
and did not differ from typically developing subjects.
Gray and white matter imbalance--typical structural
abnormality underlying classic autism?
Diffusion tensor imaging of frontal
lobe in autism spectrum disorder.
Sundaram SK, Kumar A, Makki MI, Behen ME,
Chugani HT, Chugani DC. Cereb Cortex.
2008 Nov;18(11):2659-65. The apparent diffusion
coefficient (ADC) was significantly higher for whole frontal lobe (P = 0.011),
long (P < 0.001) and short range (P = 0.0126) association fibers in ASD
group. There was a trend toward statistical significance in the fractional
anisotropy (FA) of whole frontal lobe fibers (P = 0.11). FA was significantly
lower in ASD group for short range fibers (P = 0.0031) but not for long range
fibers (P = not significant [NS]). There was no between-group difference in the
number of frontal lobe fibers (short and long) (P = NS). The fiber length
distribution was significantly more positively skewed in the normal population
than in the ASD group (P < 0.001).
What they did find was that there was a difference between the two
groups, no matter how this could not agree with other researchers.
Eur Psychiatry. 2008 Jun;23(4):289-99.
Structural brain abnormalities have been described in autism but studies are
often small and contradictory. Autism
may result from abnormalities in specific brain regions and a global lack of
integration due to brain enlargement. Inconsistencies in the literature partly
relate to differences in the age and IQ of study populations. Some regions may
show abnormal growth trajectories. Not a
particularly specific article.
Aberrant functional connectivity in autism: evidence from
low-frequency BOLD signal fluctuations.
Noonan SK, Haist F, Müller
RA. Brain Res.
2009 Mar 25;1262:48-63. A number of recent studies have examined
functional connectivity in individuals with Autism Spectrum Disorders (ASD),
generally converging on the finding of reduced interregional coordination, or
underconnectivity. Underconnectivity has been reported between many brain
regions and across a range of cognitive tasks, and has been proposed to
underlie behavioral and cognitive impairments associated with ASD.
While functional connection MRI (fcMRI) patterns were found to be
largely similar across the two groups, including many common areas, effects for
the ASD group were generally more extensive. These findings, although
inconsistent with generalized underconnectivity in ASD, are compatible with a
model of aberrant connectivity in which the nature of connectivity disturbance
(i.e., increased or reduced) may vary by region.
Nau JY. Rev Med
Suisse.
2009 Mar 4;5(193):546. French.
Ke X, Tang T, Hong S, Hang
Y, Zou B, Li H, Zhou Z, Ruan Z, Lu Z, Tao G, Liu Y. Brain Res. 2009 Apr 10;1265:171-7.
Twelve male children with HFA and ten matched typically
developing children underwent diffusion tensor imaging (DTI) as well
three-dimensional T1-weighted MRI for voxel-based morphometry (VBM). We found a
significant decrease of the white matter density in the right frontal lobe,
left parietal lobe and right anterior cingulate and a significant increase in
the right frontal lobe, left parietal lobe and left cingulate gyrus in the High
Functioning Autism group compared with the control group.
MRI findings in 77 children with
non-syndromic autistic disorder.
Boddaert N, Zilbovicius M,
Philipe A, Robel L, Bourgeois M, Barthélemy C, Seidenwurm D, Meresse I, Laurier
L, Desguerre I, Bahi-Buisson N, Brunelle F, Munnich A, Samson Y, Mouren MC,
Chabane N. PLoS One. 2009;4(2):e4415. MRIs were judged as
uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69
patients), abnormalities were reported. Three predominant abnormalities were
observed, including white matter signal abnormalities (19/69), major dilated
Virchow-Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all,
52% of the MRIs were interpreted as normal (36/69 patients). CONCLUSIONS: An
unexpectedly high rate of MRI abnormalities was found in the first large series
of clinical MRI investigations in non-syndromic autism. These results could
contribute to further etiopathogenetic research into autism.
Corpus callosum volume and
neurocognition in autism.
Keary CJ,
Conturo TE, Williams DL,
Smith CD, Gultepe E, Akbudak E, Minshew NJ. J Int Neuropsychol Soc. 2008 Nov;14(6):933-46.
The
hippocampo-fusiform (HF) and amygdalo-fusiform (AF) pathways had normal size
and shape but abnormal microstructure in the autism group. The right HF had
reduced across-fiber diffusivity (D-min) compared with controls, opposite to the
whole-brain effect of increased D-min. In contrast, left HF, right AF, and left
AF had increased D-min and increased along-fiber diffusivity (D-max), more
consistent with the whole-brain effect. There was a general loss of
lateralization compared with controls. The right HF D-min was markedly low in
the autism subgroup with lower
Abnormalities in MRI traits of corpus callosum in autism
subtype.
He Q, Karsch K, Duan Y. Conf Proc IEEE Eng Med Biol
Soc. 2008;2008:3900-3. they showed by 3D that the corpus collosum (which connects
the left with the right hemisphere), is smaller in ASD patients.
Casanova MF, El-Baz A, Mott
M, Mannheim G, Hassan H, Fahmi R, Giedd J, Rumsey JM, Switala AE, Farag A. J Autism Dev Disord. 2009
May;39(5):751-64. Autistic patients manifested a significant reduction in
the aperture for afferent/efferent cortical connections, i.e., gyral window.
Furthermore, the size of the gyral window directly correlated to the size of
the corpus callosum.
Bookheimer SY,
Wang AT, Scott A, Sigman M, Dapretto M. J Int Neuropsychol Soc. 2008 Nov;14(6):922-32
1H MR spectroscopy as a diagnostic tool
for cerebral creatine deficiency.
Dezortova M, Jiru F,
Petrasek J, Malinova V, Zeman J, Jirsa M, Hajek M. MAGMA. 2008 Sep;21(5):327-32. Total creatine (tCr) constitutes one of the most prominent
signals in human brain MR spectra. A significant decrease in the tCr signal
indicates a severe disorder of creatine metabolism. We describe the potential
of 1H MR spectroscopy in differential diagnosis of creatine transporter
(SLC6A8) deficiency syndrome. Metabolic
images of N-acetylaspartate, tCr and choline concentrations showed a very low
tCr signal in the male, which was approximately three times lower than in his
sister (male/female/controls: tCr=1.6/4.6/7.5 mM). Despite creatine
supplementation, no improvement in clinical status and tCr concentration in the
MR spectra of the male was observed and diagnosis of
SLC6A8 deficiency was proposed. Sequence analysis of the SLC6A8 gene revealed a
novel pathogenic frameshift mutation c.219delC; p.Asn74ThrfsX23, hemizygous in
the male and heterozygous in the female. CONCLUSIONS: The diagnosis of X-linked
mental retardation caused by the SLC6A8 deficiency can be independently
established by 1H MR spectroscopy.
An MRI and proton spectroscopy study of
the thalamus in children with autism.
Hardan AY, Minshew NJ,
Melhem NM, Srihari S, Jo B, Bansal R, Keshavan MS, Stanley JA. Psychiatry Res. 2008 Jul 15;163(2):97-105.
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Positron Emission Scanning (PET – positron emission tomography)
This is may be carried out by the injection of water that has an oxygen atom that has an atomic weight of 15 and hence is emitting positrons. Parts of the brain that are most being used will have more of this in that they will be provided with more blood and uptake of water. Using computer techniques to show a difference between different periods it is possible to show which parts of the brain are most active. Other labelled molecules can be used to show how they are being used similarly to very specific substrates (e.g. the labelled tryptophan to follow serotonin manufacture). Currently in autism this technique is under-assessed.
The picture shows a PET scan from Castelli et al. indicating the areas of the brain that are used to a greater degree during the testing that they carried out. The white lines are arrows pointing to the areas of the brain that showing excess activity.
Castelli F, Frith C, Happé F, Frith U. Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain. 2002 Aug;125(Pt 8):1839-49. (changes from control in the handling by the brain of random vs non-random shapes. They showed medial prefrontal and amygdaloid area deficits during these)
Guilloteau D, Chalon S. PET and SPECT exploration of central monoaminergic transporters for the development of new drugs and treatments in brain disorders. Curr Pharm Des. 2005;11(25):3237-45. (this is more of a suggestion of work that could be done rather than some that has already results to state): similarly Sundaram SK, Chugani HT, Chugani DC. Positron emission tomography methods with potential for increased understanding of mental retardation and developmental disabilities. Ment Retard Dev Disabil Res Rev. 2005;11(4):325-30
Hall
GB, Szechtman H, Nahmias C. Enhanced
salience and emotion recognition in Autism: a PET study. Am J
Psychiatry. 2003 Aug;160(8):1439-41 (they managed to show that
there was a change in the PET demonstrable activity in the brain of autistic
wrt controls when recognising or taking in emotional interaction. They admitted that this was difficult and
required further work. It had been done
as a test of limbic activity, which had been shown in other groups using PET).
Chandana SR, Behen ME, Juhász C, Muzik O, Rothermel RD, Mangner TJ, Chakraborty PK, Chugani HT, Chugani DC. Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism. Int J Dev Neurosci. 2005 Apr-May;23(2-3):171-82. (they had shown previously that there was variation and particular increase in serotonin production in specific areas of the brain. I this paper they show that this varies over time and that this will change in a predictive manner for the patient). See: Chugani DC, Muzik O, Behen M, Rothermel R, Janisse JJ, Lee J, Chugani HT Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children .Ann Neurol. 1999 Mar;45(3):287-95.Pfund Z, Chugani DC, Muzik O, Juhász C, Behen ME, Lee J, Chakraborty P, Mangner T, Chugani HT.Alpha[11C] methyl-L-typtophan positron emission tomography in patients with alternating hemiplegia of childhood. J Child Neurol. 2002 Apr;17(4):253-60.
DeVito
TJ, Drost DJ, Neufeld RW, Rajakumar N, Pavlosky W, Williamson P, Nicolson R.
Evidence for cortical dysfunction in autism: a proton magnetic resonance
spectroscopic imaging study. Biol Psychiatry. 2007 Feb 15;61(4):465-73
(showing a change in certain aminoacids)
Boddaert N, Barthélémy C, Poline JB, Samson Y, Brunelle F, Zilbovicius M. Autism: functional brain mapping of exceptional calendar capacity. Br J Psychiatry. 2005 Jul;187:83-6. (and attempt for PeT to show which parts of the brain are used by a single patient when carrying out a task for which they are known to be exceptionally brilliant).
Zilbovicius M, Boddaert N, Belin P, Poline JB, Remy P, Mangin JF, Thivard L, Barthélémy C, Samson Y. Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography.
Am J Psychiatry. 2000 Dec;157(12):1988-93.
Müller RA, Behen ME, Rothermel RD, Chugani DC, Muzik O, Mangner TJ, Chugani HT. Brain mapping of language and auditory perception in high-functioning autistic adults: a PET study. J Autism Dev Disord. 1999 Feb;29(1):19-31.
Müller
RA, Chugani DC, Behen ME, Rothermel RD, Muzik O, Chakraborty PK, Chugani HT. Impairment of dentato-thalamo-cortical
pathway in autistic men: language activation data from positron emission
tomography. Neurosci Lett. 1998 Mar 27;245(1):1-4.
Cortical surface thickness as a classifier: boosting for
autism classification.
Friedman SD, Shaw DW, Artru AA, Richards TL, Gardner J, Dawson G, Posse S, Dager SR. Regional brain chemical alterations in young children with autism spectrum disorder. Neurology. 2003 Jan 14;60(1):100-7. (clearly important findings in that they could look for small molecules in the brain. They studied using dual-echo proton echoplanar spectroscopic imaging (32 x 32 matrix-1 cm(3) voxels) to measure brain chemical concentrations and relaxation times. ASD subjects demonstrated reduced N-acetylaspartate (NAA) (-10%), creatine (Cre) (-8%), and myo-inositol (-13%) concentrations compared to Typical Development controls and prolonged NAA T(2r) relative to TD (7%) and Delayed Development (9%) groups. Compared to DD subjects, children with ASD also demonstrated prolonged T(2r) for choline (10%) and Cre (9%). Regional analyses demonstrated subtle patterns of chemical alterations in ASD compared to the TD and DD groups. All very interesting but they did not try to state the reason why these findings might be present)
Friedman
SD, Shaw DW, Artru AA, Dawson G, Petropoulos H, Dager SR. Gray and white matter brain chemistry in
young children with autism. Arch Gen Psychiatry. 2006
Jul;63(7):786-94. (The children with ASD demonstrated significantly
decreased levels of Choline containing compounds (Cho) (P = .04)
and mI (P = .008) and trend-level n-acetyl acetic
acid (NAA) (P = .09) in gray matter compared with
the delayed development group. For white matter, both children with ASD and
children with DD showed a similar pattern of NAA and mI level
decreases (for children with ASD vs children with TD: NAA, P = .03;
myo-inositol (mI), P = .04; for children with DD vs
children with TD, NAA, P = .03; mI, P = .07).
In several analyses, cerebral volume contributed significantly as
a covariate. The children with ASD
demonstrated decreased gray matter concentrations of Cho (P<.001),
creatine plus phosphocreatine (P = .02), NAA (P = .02),
and mI (P = .008) compared with children with
TD. This article has a good review of
the data by other authors so far.
Figure: A cross sectional with spectrtrographic image indicating
specific chemicals and hence can be measured during actions of the brain. (spectrum E shows
the different chemical peaks)
Petropoulos H, Friedman SD, Shaw DW, Artru AA, Dawson G, Dager SR. Gray matter abnormalities in autism spectrum disorder revealed by T2 relaxation. Neurology. 2006 Aug 22;67(4):632-6. (they look at the water content during different brain actions)
Silani G, Bird G, Brindley R, Singer T, Frith C, Frith U. Levels of emotional awareness and autism: an fMRI study. Soc Neurosci. 2008;3(2):97-112. (a strong relationship between questionnaire scores and brain activity was found in the anterior insula (AI), when participants were required to assess their feelings to unpleasant pictures. Regardless of self-reported degree of emotional awareness)
An MRI and proton spectroscopy study of
the thalamus in children with autism.
Regional cerebral blood flow in childhood autism: a SPET
study with SPM evaluation.
Investigating The Predictive
Value Of Whole-Brain Structural MR Scans In Autism: A Pattern Classification Approach.
Ecker C, Rocha-Rego V, Johnston P, Mourao-Miranda J, Marquand A, Daly EM,
Brammer MJ, Murphy C, Murphy DG; the AIMS Consortium. Neuroimage.
2009 Aug 13. Multivariate analysis aimed at numerous
sections of the brain was applied to gray matter scans correctly classified
adult ASD individuals at a specificity of 86.0% and a sensitivity of 88.0%.
68.0% of all cases were correctly classified using white matter anatomy. The
distance from the separating hyperplane (i.e. the test margin) was
significantly related to current symptom severity.
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(post mortem: this is a mechanism by which radio-labelled
compounds are interacted with sections of brain, and then a photographic plate
put next to them to see where in the section the labeling has stuck)
Guptill JT, Booker AB, Gibbs TT, Kemper TL, Bauman ML, Blatt GJ. [3H]-flunitrazepam-labeled benzodiazepine binding sites in the hippocampal formation in autism: a multiple concentration autoradiographic study. J Autism Dev Disord. 2007 May;37(5):911-20. (They took the reduction seen in the number of hippocampal benzodiazepine binding sites to suggest alterations in the modulation of GABA(A) receptors in the presence of gamma amino butyric acid (GABA) in the autistic brain, possibly resulting in altered inhibitory functioning of hippocampal circuitry.
Blatt
GJ, Fitzgerald
CM, Guptill
JT, Booker
AB, Kemper
TL, Bauman
ML. Density and distribution of hippocampal
neurotransmitter receptors in autism: an autoradiographic study. J Autism Dev Disord.2001 Dec;31(6):537-43
(they agreed with the results from Guptill above but they could not find any
differences with other binding sites: In contrast, the density and distribution of the other six receptors
studied (3[H]-80H-DPAT labeled 5-HT1A receptors, 3[H]-ketanserin labeled 5-HT2
receptors, 3[H]-pirenzepine labled M1 receptors, 3[H]-hemicholinium labeled
high affinity choline uptake sites, 3[H]-MK801 labeled NMDA receptors, and
3[H]-kainate labeled kainate receptors) in the hippocampus did not demonstrate
any statistically significant differences in binding.)
Electroencephalographs
Electrical
indication of the changes of the activity of the brain as measured using wires
into the scalp.
Reinhold JA, Molloy CA, Manning-Courtney P. Electroencephalogram
abnormalities in children with autism spectrum disorders. J Neurosci Nurs.
2005 Jun;37(3):136-8. (EEG studies were
conducted on a subgroup of children while following established practice
parameters for evaluating children for ASD. Abnormal EEG results were obtained
in 85 (27%) of the 316 children evaluatedfor ASD. Within the subset of abnormal
results, 64 children had autism, 10 had an ASD or milder presentation, 6 had
another developmental disorder, 3 had Rett syndrome, had Down syndrome, and 1
had Wolf-Hirshhorn syndrome. The ASD
patients are often assessed using EEG for possibility of epilepsy but it is
always difficult to interpret. This
study may at least give some kind of level as to what to expect in an ASD
patient)
Plioplys AV. Autism: electroencephalogram abnormalities and clinical improvement with valproic acid.Arch Pediatr Adolesc Med. 1994 Feb;148(2):220-2.
EEG mu rhythm and imitation impairments
in individuals with autism spectrum disorder.
Bernier
R, Dawson G, Webb S, Murias M. Brain Cogn. 2007 Aug;64(3):228-37.
Coben R, Clarke AR, Hudspeth W, Barry RJ. EEG power and coherence in autistic spectrum disorder. Clin Neurophysiol. 2008 May;119(5):1002-9. Epub 2008 Mar 10.( These results suggest dysfunctional integration of frontal and posterior brain regions in autistics along with a pattern of neural underconnectivity. It is the largest of the EEG studies but it also shows nothing specific and difficulty in interpretation for specific purposes. The references present in this also show how little work has been done previously in this direction)
EEG photic driving: right-hemisphere reactivity deficit
in childhood autism. A pilot study.
Lazarev VV, Pontes A,
deAzevedo LC. Int
J Psychophysiol. 2009 Feb;71(2):177-83. Intermittent photic stimulation at 11 fixed frequencies of
3-24 Hz revealed latent deficiency of the right hemisphere in the photic
driving reactivity, predominantly at the fast alpha and beta frequencies of
stimulation. The left-side prevalence was observed: 1) in the total number of
driving peaks evaluated for the first four harmonics in the EEG spectra of 14
cortical areas and 2) in the driving amplitude in the spectra of the 2
occipital areas. As compared to 21 normally developing boys matched on age who
did not show interhemispheric asymmetry
Giannotti F,
Cortesi F, Cerquiglini A, Miraglia D, Vagnoni C, Sebastiani T, Bernabei P. J Autism Dev Disord. 2008 Nov;38(10):1888-97.
Electrophysiological signatures: magnetoencephalographic
studies of the neural correlates of language impairment in autism spectrum
disorders. Roberts TP, Schmidt GL, Egeth M, Blaskey L, Rey MM, Edgar
JC, Levy SE. Int
J Psychophysiol. 2008 May;68(2):149-60.
Deficient brainstem encoding of pitch
in children with Autism Spectrum Disorders.
Dexmedetomidine for sedation during
electroencephalographic analysis in children with autism, pervasive
developmental disorders, and seizure disorders. Ray T, Tobias
JD. J Clin Anesth. 2008 Aug;20(5):364-8. The idea being to look for
problems with this in ASD children. MAIN RESULTS: 18 children received oral dexmedetomidine
(range, 2.9-4.4 microg/kg) before placement of an i.v.. Forty patients received
an i.v. loading dose of dexmedetomidine (2.1 +/- 0.8 microg/kg), which was
given in increments of 0.5 to one microg/kg every three to 5 minutes until a
sedation score of 3 to 4 was achieved. Effective sedation was eventually
achieved in all patients. An i.v. infusion of dexmedetomidine was started (1.5
+/- 0.2 microg kg(-1) hr(-1)) in all patients. During
performance of the EEG, adjustments in the infusion rate (increase or decrease)
or additional bolus doses were necessary in 25 patients. No significant
hemodynamic or respiratory effects were noted. CONCLUSIONS: Dexmedetomidine
provides effective sedation during EEG analysis in children with autism or PDD.
Magnée MJ, Oranje B, van
Engeland H, Kahn RS, Kemner C. Neuropsychologia. 2009 Jun;47(7):1728-32. Using a cross-sensory P50 suppression
paradigm, this study investigated low-level audiovisual interactions on
cortical EEG activation, which provides crucial information about functional
integrity of connections between brain areas involved in cross-sensory
processing in both disorders. These
results are in accordance with the notion that filtering deficits may be
secondary to earlier sensory dysfunction. Also, atypical cross-sensory
suppression was found.
Thompson L, Thompson M,
Reid A. Appl Psychophysiol
Biofeedback.
The role of epilepsy and epileptiform
EEGs in autism spectrum disorders.
Spence SJ,
Enticott PG, Bradshaw JL,
Iansek R, Tonge BJ, Rinehart NJ. Dev Med Child Neurol. 2009
Groen Y, Wijers AA, Mulder
LJ, Waggeveld B, Minderaa RB, Althaus M.
Clin
Neurophysiol. 2008 Nov;119(11):2476-93.
This can be used to some degree to show that specific parts of the brain is being used adequately but full interpretation is difficult without specific anatomical changes. This is often measured using PET.
Gendry Meresse I, Zilbovicius M, Boddaert N, Robel L, Philippe A, Sfaello I, Laurier L, Brunelle F, Samson Y, Mouren MC, Chabane N. Autism severity and temporal lobe functional abnormalities. Ann Neurol. 2005 Sep;58(3):466-9. (they looked for a relationship between the cerebral blood flow in different parts of the brain)
Boddaert N, Chabane N, Belin P, Bourgeois M, Royer V, Barthelemy C, Mouren-Simeoni MC, Philippe A, Brunelle F, Samson Y, Zilbovicius M. Perception of complex sounds in autism: abnormal auditory cortical processing in children. Am J Psychiatry. 2004 Nov;161(11):2117-20.
Zilbovicius
M, Garreau B, Samson Y, Remy P, Barthélémy C, Syrota A, Lelord G. Delayed maturation of the frontal cortex in
childhood autism. Am J Psychiatry. 1995 Feb;152(2):248-52.
Neurological
interaction between brain sites
The suggestion has been that different parts of the brain are poorly connected in autism.
All sorts of ideas put forward to explain the changes in brain size etc.
Reduced variability in motor behaviour: an indicator of
impaired cerebral connectivity?
A pathogenetic model of autism
involving Purkinje cell loss through anti-GAD antibodies.
The association between tick-borne
infections, Lyme borreliosis and autism spectrum disorders.
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