Brain and Autism
 |
The Autistic Spectrum |
|
  A Johns Hopkins study has found new evidence that the brains of some people with autism
show clear signs of inflammation, suggesting that the disease may be associated with activation of the brain’s immune
system. “These findings reinforce the theory that immune response in the brain is involved in autism, although it is
not yet clear whether the inflammation is a consequence of disease or a cause of it, or both,” said Carlos Pardo-Villamizar,
M.D., assistant professor of neurology and pathology at Johns Hopkins and senior author of a report on the study published
early on-line in the journal Annals of Neurology on Nov. 15. Whatever the cause of the inflammation, it may provide a good target for developing new treatments,
adds Pardo. Autism is a disorder of the developing brain that appears in early childhood. According to the American
Neurological Association, it is estimated to afflict between two and five of every 1,000 children and is four times more likely
to strike boys than girls. Children with autism have difficulties in social interaction and communication and may show repetitive
behaviors and have unusual attachments to objects or routines. Autism has a strong genetic component in some families, although other causes likely play a role,
possibly including birth complications, diet, toxins or infections, says Pardo. “Scientists have found hints that the immune system may be involved in autism, but not all studies
have confirmed this,” said Pardo. “We wanted a more definitive answer, so rather than looking at the overall immune
system, we focused on immune responses inside the relatively sealed environment of the nervous system.” Led by first author Diana L. Vargas, M.D., a postdoctoral fellow working in Pardo’s laboratory,
the researchers examined tissue from three different regions of the brain in 11 people with autism, ages 5 to 44 years, who
had died of accidents or injuries. They also measured levels of two immune system proteins, called cytokines and chemokines,
found in the cerebrospinal fluid - the clear substance that surrounds, bathes and nourishes the brain and spinal cord - in
six living patients with autism, ages 5 to 12 years. Compared with normal control brains, the brains of people with autism showed evidence of an ongoing
inflammatory process in different regions of the brain and produced by cells known as microglia and astroglia, says Pardo.
Cytokine and chemokine levels in the cerebrospinal fluid also were abnormally elevated in patients with autism. “These findings suggest that the inflammation is localized to specific regions within the brain
and not caused by immune system abnormalities from outside the brain,” says Pardo. Pardo and colleagues are now studying how the genetic background of patients and families may influence
immune system reactions in the brain associated with autism. Other authors are Andrew Zimmerman, Caterina Nascimbene, and Chitra Krishnan. The study was funded
by the Cure Autism Now Foundation, the Autism Research Foundation, the National Institutes of Health, Dr. Barry and Renee
Gordon and an anonymous donor. On the Web: http://www3.interscience.wiley.com/cgi-bin/jhome/76507645 Editor's Note: The original news release can be found here. ********************************** Dustin Hoffman's portrayal in the
movie Rain Man may have turned public focus to autism but scientists have been scrutinizing it for years. Following decades
of research, significant advances have confirmed that biology is behind this brain disorder that is marked by deficits in
the higher order cognitive abilities involved in social, communication and problem-solving behavior. New findings on the genetic
and anatomical roots of autism are helping researchers piece together how the disorder evolves, which could lead to new treatments.
Kids burst off swings like
pop-corn popping. They argue over who jumped the farthest. Another child details to a play-mate his adoration for a fish-shaped
Beanie Baby. A group of youngsters conduct a game of jail tag under a jungle gym. All of this is normal behavior. But a completely different scenario emerges for children with the
brain disorder autism. Aloof, detached and withdrawn, many autistic children find everyday
social interactions are beyond their reach. All find them difficult. They have trouble showing or detecting emotion.
Some do not even speak. Others talk too much and seem odd because they go on and on about one topic, such as highways, and
report inane facts like the lengths of dinosaurs' necks. Cognitive abilities are impaired in most autistic children. Their
problem-solving is hindered and at times their attention seems unusually narrow and focused. They tend to have no common sense.
Many of their activities are repetitive and others seem to have no purpose - such as jumping while twiddling their fingers.
For years, faulty parenting was to blame. Now accumulating science
shows that the disorder is born of biology. New genetic and anatomical data are leading to: Approximately one in 500 Americans has some form of autism, perhaps
540,000 people, according to the Autism Society of America. Several decades ago, their parents were told that a terrible experience
of rejection or not enough mother-child bonding made their child turn inward and shut off the outside world. Research starting
in the 1960s, however, unearthed important evidence that suggested autism had a biological root and was not a result of inadequate
parenting. In the 1980s, autopsy and neuroimaging studies directly demonstrated that abnormalities existed in the brains of
those with autism. Since that time, research is indicating that people with autism are
born with altered genes. For example, in families with one autistic member, researchers found evidence that suggests versions
of a gene may be linked to the disorder. This gene produces a specific protein that normally works to reabsorb the chemical
serotonin into nerve cells for reuse. The linkage has not been found, however, in families with more than one autistic member.
In another example, a new study implicates a second gene. This gene may relate to a receiving area, known as a receptor, for
the chemical gamma-amino butyric acid. Currently researchers are trying to confirm these and other genetic findings, and understand
how they may relate to the disorder. In addition, a number of other large-scale studies are underway. Researchers suspect that several different groups of altered genes
cause autism by interfering with the brain's chemical message systems that guide brain development and later serve as chemical
messengers, or neurotransmitters, between nerve cells in the mature brain. Additional genetic insights may explain research that indicates multiple
brain regions are involved in autism. For example, examinations of autistic patients indicate that there are abnormalities
in cerebellar brain regions implicated in motor, sensory, language, cognitive and attention functions. In another example,
researchers found from autopsy studies that the overall brain size of a subset of autistic patients appeared extremely large,
which suggests that the projections and wiring of cells in the outermost brain layer known as the cerebral cortex are involved
in causing this disorder. These and many additional lines of research are helping scientists
get closer to characterizing the brain and cognitive abnormalities of autism. For more information please contact Leah Ariniello, Science Writer,
Society for Neuroscience, 11 Dupont Circle, NW, Suite 500, Washington DC, 20036. http://apu.sfn.org/content/Publications/BrainBriefings/autism.html ************************************************
In contrast to people who do not have autism, people with autism
remember letters of the alphabet in a part of the brain that ordinarily processes shapes, according to a study from a collaborative
program of the National Institute of Child Health and Human Development of the National Institutes of Health. The study was conducted by researchers in the NICHD Collaborative
Program of Excellence in Autism (CPEA) at the University of Pittsburgh and Carnegie Mellon University. It supports a theory
by CPEA scientists that autism results from a failure of the various parts of the brain to work together. In autism, the theory
holds, these distinct brain areas tend to work independently of each other. The theory accounts for observations that while
many people with autism excel at tasks involving details, they have difficulty with more complex information. The study and the theory are the work of Marcel Just, Ph.D., Professor
of Psychology at Carnegie Mellon University in Pittsburgh, Pennsylvania and Nancy Minshew, M.D., Professor of Psychiatry and
Neurology at the University of Pittsburgh School of Medicine and their colleagues. The study is scheduled for on-line publication
November 29 in the journal Neuroimage, at Science Direct. "This finding provides more evidence to support a promising theory
of autism," said Duane Alexander, M.D., Director of the NICHD. "If confirmed, this theory suggests that therapies emphasizing
problem solving skills and other tasks that activate multiple brain areas at the same time might benefit people with autism." People with autism typically have difficulty communicating and interacting
socially with others. The old saying "unable to see the forest for the trees" applies to people with autism, describing how
many of them excel at matters of detail, yet struggle to comprehend the larger picture. For example, some children with autism
may become champions at spelling bees, but have difficulty understanding the meaning of a sentence or a story. "The language pattern in autism is a microcosm for the disorder,"
Dr. Just said. "People with autism are good at a lower level of analysis but have a deficit at the higher level." In the current study, the researchers used a brain imaging technique
known as functional magnetic resonance imaging (fMRI) to measure the brain activity of 14 individuals with high functioning
autism while they performed a simple memory task involving letters of the alphabet. Specifically, the study volunteers were
shown a sequence of letters. After each letter, they were asked to name the letter that preceded it. In some cases, they were
asked to name the letter that appeared two letters previously. The autism volunteers' brain activation patterns were compared
to a control group of people who did not have autism, but were of a similar age and I.Q. level. Both groups successfully completed the task. However, the fMRI scans
revealed different brain activation patterns between the two groups. Compared to the control group, the volunteers with autism
showed more activation in the right hemisphere, or half, of the brain, and less activation in the left hemisphere. The left
hemisphere takes the lead in processing letters, words and sentences, whereas the right hemisphere plays a larger role in
processing shapes and visual information. Dr. Just said that the brain could interpret letters either spatially,
as geometric shapes, or linguistically, by the names of the letters. The imaging data indicated that the volunteers with autism
remembered letters as shapes, while the control group remembered them by their names. The brain activation patterns of the two groups also differed in
other ways. While performing the task, the group with autism showed less activation in the anterior, or front, parts of the
brain, and more activation in the posterior, or rear parts of the brain. Dr. Just explained that the brain's anterior portions
carry out higher-level thinking and reasoning while the posterior portion is more involved with perceiving details. Compared to the control group, the different brain areas of the people
with autism were less likely to work in synchrony (at the same time) while recalling the letters. Such synchronization between
brain areas takes place during many kinds of higher-level thinking and analysis that prove difficult for many people with
autism. These current findings provide evidence in support of the theory
developed by these researchers. Called the theory of underconnectivity in autism, it maintains that autism results from a
failure of the brain's neurological wiring — the fibers of nervous system tissue that interconnect the individual parts
of the brain. Deprived of effective connections, the different brain areas must work independently, sometimes performing at
a higher level individually than they do in people who do not have autism. This may allow some people with autism to excel
at spelling and other detail-oriented tasks but make it difficult for them to comprehend more complex material. The researchers published their theory in the July issue of Brain,
in conjunction with the results of another fMRI study of volunteers with autism. In that study, volunteers were asked a question
about a simple sentence that they had just read. When the people with autism performed the task, their brains showed less
synchronization than did the brains of the control group. Moreover, the brains of the group with autism had less activation
in an anterior part of the brain that integrates the words of a sentence, and more activation in a posterior brain area that
comprehends individual words. Many behavioral therapies to treat autism stress rote learning, Dr.
Minshew explained. Such strategies are helpful, particularly early in a child's development. However, if the theory of underconnectivity
proves valid, therapies that stimulate brain areas to work in synchrony might also offer some benefit. Such therapies might
stress problem solving skills and creative thinking, and attempt to foster flexibility in thinking. Dr. Just noted that more evidence to support the theory might come
from the group's on-going studies of other cognitive abilities. The researchers are attempting to determine if underconnectivity
is a general feature of the brain in autism, and are using brain imaging studies to examine the brain's white matter in people
with autism. White matter is the part of the brain that consists of the larger neurological connections spanning different
parts of the brain. Source: http://autism.about.com/od/autisminprint/i/brainprocessing_2.htm *********************************
MGH study details brain changes in autism,
language disorder Physician Referral Service: 1-800-388-4644 Source: http://www.massgeneral.org/news/releases/032204herbert.html *************************************************
Unlike normally developing and mentally retarded children, autistic 3- and 4-year-olds
do not react to a picture of their mother but do react when they see a picture of a familiar toy, a University of Washington
psychologist has found. Geraldine Dawson will report her result Thursday in Minneapolis at the annual meeting of the Society
for Research in Child Development. Her finding suggests that an impairment in face recognition may turn out to be one of the
earliest indicators of abnormal brain development in autism. Dawson, who directs the UW Autism Center, said human brains seem to be wired to be interested in faces
and there appears to be a specialized system for face recognition. "We know that even newborn babies are drawn to face-like stimuli. This inborn interest in faces is
the start of social development," she said. "This new study tells us something very fundamental about abnormalities in autism.
It may be an important clue to actual brain circuits that are not functioning properly. Since all of the children in the study
reacted similarly to toys and only the children with autism had problems with face recognition, it tell us autism is not a
global problem. Rather, it indicates an abnormality in those brain circuits responsible for social function. It highlights
that autism is a disorder of the social brain." Dawson said the idea that face recognition may be hard-wired, or something
people are born with, is controversial. "Just as with language, the brain comes with a readiness to recognize faces. But it also requires
experience. With autism there may be some other reason why children don't pay attention to faces. They may not find it rewarding,
and then that part of their brain does not develop further." The region of the brain that appears to be specifically devoted to face recognition is the right fusiform
gyrus, located in the temporal lobe, according to Dawson. To learn how the brain operates, Dawson used a device called a geodesic net that looks like a hairnet
and fits over the head. It records electrical brain impulses from 64 places on a child's scalp. Similar devices for adults
record data from 128 locations. Dawson's study involved 34 children with autism, 21 normally developing children and 17 with
mental retardation but no autism. Some autistic children also are mentally retarded. Each of the children was shown two sets of images - faces and objects - about 50 times. First they
were shown digitized photos of their mother or a stranger. Then they were shown digitized photos of a favorite or an unfamiliar
toy. The net measured brain activity half a second after each image was shown and picked up the specific brain signal to that
stimulus. Earlier research has shown that normally developing children as young as 6 months old show different
brain activity when they see their mother and when they see a stranger. Dawson's research revealed a similar pattern among
normal and mentally retarded 3- and 4-year-old children, but the autistic children failed to recognize their mother. However,
all three groups exhibited similar reactions when they saw images of a favorite toy versus an unfamiliar one. She believes
the ability to recognize faces may turn out to be a key tool in identifying children with autism. Previous research by Dawson
has shown that a child's failure to look at faces at age 1 is the best predictor of autism. "Today we can reliably identify autism in children at age 2, but it is difficult to identify babies
with autism," she said. "What usually catches parents' attention around 12 months is that their child is not picking up language.
Parents are also especially sensitive to picking up autism symptoms in a younger sibling. Siblings of children with autism
have 1-in-20 odds of having autism." Dawson, whose research was funded by the National Institute of Child Health and Human Development,
next plans to replicate the mother-stranger picture study with 18-month-old autistic toddlers to see if this identification
process operates at an earlier age. Also being reported at the Minneapolis meeting is related research by Dawson and UW doctoral
student James McPartland that shows adults and adolescents with autism have abnormal reactions to faces. The Autism Center
is part of the UW's Center on Human Development and Disability. Dawson and an interdisciplinary team are attempting to find
the neurobiological and genetic causes of autism and design interventions to help autistic children.
Autism and related disorders are among the most common developmental disabilities, occurring in one
in 500 people. Autism is characterized by an impaired ability to communicate or relate socially with others. People with the
disorder typically have a limited range of activities and interests. ******************************************* Binstock's Anterior Insular Cortex Hypothesis for Linkage Between Gut
and Brain.
Binstock (http://www.jorsm.com/~binstock/insular.htm) has developed a hypothesis to explain the gut-brain relationships for autistic children.
The anterior insular cortex (aIC) links visceral sensation from the gastrointestinal
tract with the amygdala and the hypothalamus (1-6). The anterior insular cortex also participates in oral phenomena, object
recognition, and naming (5) along with "apraxia of speech" (7,8). Twenty-five stroke patients with articulatory deficits all had a lesion within "a discrete
region of the left precentral gyrus of the insula", whereas this area was "completely spared" in 19 stroke patients without
these deficits (7). Autism-spectrum children with atypical oral habits and/or disorders of naming and of
language (9-10) also tend to have a typical gastrointestinal symptoms (11-12). There is also a growing volume of anecdotal
data that a small subgroup of autism-spectrum children experiences improved sound production and language use in response
to treatments whose focus and effects are gastrointestinal. These treatments include gluten-free and casein-free diets, anti-Candida
therapies, anti-viral therapies, and antibiotic therapies (13-19,31,32) suggesting that the underlying neuronal circuitry
is intact. Binstock suggests that the aIC and associated nuclei could become disrupted by at least
two mechanisms: (I) intraneuronal migration of a neurotropic virus and/or (II) chronic hyperstimulation of the gastrointestinal
tract. Gesser and colleagues have documented (I) the translocation of HSV from the gastrointestinal
tract into the mesenteric nervous system (rats and humans), and (II) the migration of mesenteric HSV as far as theamygdaloid
nuclei in rats (20-23). In this theory, viruses could migrate from the gastrointestinal tract through neural pathways into
the central nervous system. Given a high rate of stimulation of neuron pathways reporting gastrointestinalconditions
to limbic regions and cortex, neurotransmitter or intracellular-messenger use in excess of their production or recirculation
could occur, thereby inducing a change of function of neurons within the aIC. This hypothesis provides a basis for helping autistic children through treating their
gastrointestinal disturbances. References:
Neurobiology of Disease 1Department of Psychiatry and Behavioral Sciences, Center for Neuroscience and the M.I.N.D. (Medical
Investigation of Neurodevelopmental Disorders) Institute, University of California Davis, Sacramento, California 95817, 2Stanford
Psychiatry Neuroimaging Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine,
Stanford, California 94305, 3Department of Radiology, University of California Davis School of Medicine, University
of California Davis Imaging Research Center, Sacramento, California 95817, 4Department of Anesthesia and Pain Medicine,
University of California Davis School of Medicine, Sacramento, California 95817, and 5California National Primate
Research Center, University of California Davis, Davis, California, 95616
Key words: Asperger; amygdaloid complex; development; mental retardation; MRI; neuroanatomy The neuropathology of autism has not yet been clearly established. Among the brain regions that have
been implicated are the cerebellum, brainstem nuclei, amygdala, hippocampal formation, and various cortical
areas. Bauman and Kemper (1985 Structural magnetic resonance imaging (MRI) studies of the amygdala have provided inconsistent results
(for review, see Cody et al., 2002 Although individuals diagnosed with mental retardation make up Diagnostic assessments were conducted either at the M.I.N.D. Institute Clinic of the University of California
Davis Medical Center or at Stanford University in the Division of Child and Adolescent Psychiatry and
Child Development. Clinicians (B.L.G.-J. and L.J.L.) experienced in the diagnosis of autism spectrum disorders
were formally trained to administer the Autism Diagnostic Interview-Revised (ADI-R) (Lord et al., 1994 An IQ exam was also administered to all participants; the particular test used was based on their verbal
ability. Higher-functioning children and typically developing controls were given either the Wechsler
Intelligence Scale for Children (Wechsler, 1991 Participants who met criteria for autism with a full-scale IQ of >70 were included in the high-functioning
autism group. Participants with a diagnosis of autism and a full-scale IQ of <70 were included in
the low-functioning autism group. A diagnosis of Asperger syndrome was given to study participants who
met the criteria for high-functioning autism, as determined by the ADOS-G, met DSM-IV criteria for Asperger syndrome,
and had developed phrase language before 36 months of age. A more detailed description of the clinical
protocol used in this study has been published previously (Lotspeich et al., 2004 Typically developing control participants had a full-scale IQ of >70 and did not have a family member
with an autism spectrum disorder. Participants were excluded from the study if they had a diagnosis
of fragile X, seizure disorder, tuberous sclerosis, obsessive-compulsive disorder, bipolar disorder, or any other
major neurological illness. All volunteers with an IQ of <70 who had not been tested previously for fragile
X were tested before MRI (Kimball Genetics, Denver, CO); none of the participants in the study tested
positively for fragile X. Neuroimaging Because volume measurement accuracy is related to the linearity of magnetic field gradients in each
of the MRI systems, an intersite comparison and calibration were conducted before imaging study participants.
Images were collected from three healthy adult volunteers (one male and two females) at each of the three MRI
sites for in vivo validation of volume measurement accuracy. Images were acquired with the same pulse
sequence and analyzed at the Stanford Psychiatry Neuroimaging Laboratory using BrainImage 5.x software
(developed by A. L. Reiss in 2002). Total brain and segmented tissue volumes were compared between the three
systems. The percentage difference between MRI systems for each participant was averaged across participants
to arrive at a mean percentage difference for each volumetric measure. The a priori requirement for
combining volume measurements across sites was a difference of no more than 5%. A 1.2% difference for
total cerebral tissue and a 1.8% difference for cerebral gray matter were found. Lotspeich et al. (2004 The protocol for scanning each participant included a three-dimensional coronal spoiled gradient recalled
echo (SPGR) series (repetition time, 35 msec; echo time, 6 msec; field of view, 24 cm; matrix, 256 x 256; section thickness, 1.5 mm; number of slices, 124; total scan time, 14 min and
24 sec) that was used for the volumetric assessment of the amygdala. In addition, a two-dimensional (2D) sagittal
T1 spin echo, a 2D proton density/T2 interleaved double echo, and a diffusion tensor sequence were collected on
all participants for other analyses. A parent or guardian for each participant signed consent before the child entered the MRI scanner and
was present throughout the duration of the scan in an adjacent waiting room. Those study participants
requiring anesthesia (isoflurane) to undergo MRI (19 LFA, 13 HFA, and 7 ASP) were imaged at University of
California Davis Hospital. All remaining participants were scanned at either the University of California
Davis Research Imaging Center (6 HFA, 9 ASP, and 18 CON) or at Stanford University (8 HFA, 9 ASP, and
9 CON). After reviewing the images, 13 participants were excluded from the study (1 LFA, 6 HFA, 1 ASP, and 5 CON)
because of excessive movement, distorted images resulting from orthodontics, or additional diagnostic information
that precluded the series from being used. Within each diagnostic group, excluded participants did not
differ from included participants with respect to age, IQ, or symptom severity. Volumetric analysis of the amygdala
The initial tracing process involved defining the borders in coronal sections starting with the most
caudal level in which the amygdala was visible. Outlines were also checked in horizontal (axial) and
sagittal views (Fig. 1) that were simultaneously available to the rater while tracing the amygdala. The following guidelines
detail the procedures used for systematic outlining of the amygdala. Caudal third of the amygdala. At its caudal extent (Fig. 2a), the amygdala is bordered dorsally by the substantia innominata, laterally by the putamen,
and ventrally by the temporal horn of the lateral ventricle. The medial surface of the amygdala abuts
the optic tract. The outline (Fig. 2a) at this level started at the dorsolateral extent of the optic tract and extended laterally to
the junction of the amygdala and putamen. The outline continued ventrally along the lateral border of the amygdala
until the lateral ventricle was reached. The outline was then extended medially along the dorsal surface
of the ventricle to the ventrolateral extent of the optic tract and completed along the optic tract to
the starting point. The lateral border of the amygdala with the putamen is not always clear in the coronal views.
Therefore, the border was first drawn in the coronal views and further edited in the horizontal view
during the revision process (see below) (Fig. 1b).
The starting point of the outline at this level is the dorsomedial extent of the amygdala. If the medial
extent of the optic tract extends more laterally than the medial surface of the brain formed by the
temporal lobe, then this remains the starting point as described for the caudal section. However, if the surface
of the brain extends farther laterally than the optic tract, then the starting point becomes the dorsolateral
extent of the medial surface. The outline of the amygdala then extends from this point laterally until
it meets the fibers of the anterior commissure. The outline follows the white matter along the lateral surface
of the amygdala to the ventricle (or dorsal surface of the hippocampus) and is then drawn medially along the alveus
to the medial surface of the brain. The outline was completed along the medial surface of the amygdala.
Midrostrocaudal third of the amygdala. At midrostrocaudal levels (Fig. 2c), the amygdala is outlined in much the same way as just described. In more rostral sections (Fig. 2d), the hippocampus decreases in size and the entorhinal cortex begins to form part of the medial
surface of the amygdala. At this point, a thin band of white matter separates the amygdala from the entorhinal
cortex. Outlining at this level was initiated at the dorsolateral extent of the medial surface of the brain
and continued laterally to the white matter of the temporal lobe. The outline then follows the white
matter along the lateral surface of the amygdala until it reaches the ventricle (or dorsal surface of the hippocampus).
The outline continues medially along the alveus of the hippocampus to the white matter tract that separates
the amygdala from the entorhinal cortex. The outline then follows the white matter tract to a point
on the medial surface of the brain that coincides with the semiannular sulcus. The outline is then completed along
the medial surface of the amygdala. Rostral third of the amygdala. In rostral sections (Fig. 2e), the dorsomedial surface of the amygdala forms a portion of the medial surface of the brain.
The amygdala is bordered laterally by white matter of the temporal lobe, ventrally by the temporal horn
of the lateral ventricle and by subamygdaloid white matter, and ventromedially by the entorhinal cortex. The outline
begins at the semiannular sulcus on the medial surface of the brain and continues laterally along the
dorsal surface of the amygdala. It is then extended ventrally along the white matter that lines the
lateral surface of the amygdala to the ventricle. The outline is then drawn medially along the white matter that
forms the ventral surface of the amygdala and dorsomedially along the white matter that separates the
amygdala from the entorhinal cortex until the semiannular sulcus is reached. However, the white matter
that separates the amygdala from the entorhinal cortex is not always clear. In this case, a diagonal line is
drawn from the most medial point of the subamygdaloid white matter that is visible to the semiannular sulcus.
At the rostral pole of the amygdala (Fig. 2f), the outlining rules are very similar to what has just been described above. However, the
gray-matter-white-matter boundaries are more difficult to delineate. Therefore, it was necessary to confirm the
rostral boundary of the amygdala by reviewing the outlines in sagittal images (see below) (Fig. 1c). Editing the amygdala in horizontal and sagittal views. The outline was then reviewed systematically
in the horizontal and sagittal planes (Fig. 1b,c, arrows). Two areas consistently needed revision. These included (1) the dorsolateral border of the amygdala
with the putamen and (2) the rostral extent of the amygdala. The horizontal plane provided a more reliable
view of the border between the amygdala and putamen. In cases in which the putamen had been included
in the original outline of the amygdala, the boundary between the structures was straightened by providing
a best-fit line along the white matter separating the amygdala from the putamen (Fig. 1b, arrows). This line was determined by connecting the white-matter tracts on the medial and lateral
portions of the rostral pole of the putamen. As noted above, the rostral pole of the amygdala was also difficult to define in coronal sections. Thus,
the rostral border was reviewed in sagittally oriented sections. The white matter that forms the ventral
border of the rostral amygdala (Fig. 1c, arrows) can be followed dorsally around the rostral limit of the amygdala and was used to
correct the rostral border of the amygdaloid complex. Finally, we again reviewed the amygdala in coronal sections to ensure that the outlines had not been
erroneously altered. Once the outlines were completed, we used Analyze software to calculate the volume
of the left and right amygdala. Volumetric analysis of the hippocampus In previous experimental studies from our laboratory, the hippocampal formation has included the dentate
gyrus, the CA fields of the hippocampus, the subiculum, presubiculum, and parasubiculum, and the entorhinal
cortex (Amaral, 1994 Two raters (C.M.S. and J.H.) who were blind to subject diagnosis manually traced the hippocampus after
establishing reliability of tracing methods on MRI scans from 30 subjects with an inter-rater correlation
of 0.96 for the left hippocampus and 0.97 for the right hippocampus. Each rater obtained an intrarater reliability
of >0.96. The hippocampus was initially defined in coronal sections starting with the most caudal level in which
it was visible (Fig. 3). Outlines were reviewed in the horizontal and sagittal views (Fig. 1) that were simultaneously available while tracing the hippocampus. The following guidelines detail the
procedures used for systematically outlining the hippocampus.
Proceeding rostrally (Fig. 3b), the dorsomedial extent of the hippocampus forms a portion of the medial surface of the brain. The
pulvinar of the thalamus also appears along the dorsomedial surface. The ventral surface of the thalamus is separated
from the dorsal surface of the hippocampus by CSF on the medial surface of the brain. The dorsolateral
surface of the hippocampus is formed by the fornix. The lateral border is formed by the temporal horn
of the lateral ventricle. The ventral surface of the hippocampus is formed by white matter of the temporal lobe.
The outline at this level (Fig. 3b) began at the medial extent of the hippocampus, which is ventral to the thalamus. It was extended laterally
along the dorsal surface of the hippocampus until it reached the fornix. The outline continued ventrally
along the temporal horn of the lateral ventricle to the subhippocampal white matter and continued medially
along the white matter to the starting point. Midrostrocaudal third of the hippocampus. In the body of the hippocampus (Fig. 3c), the medial surface of the hippocampus forms the medial surface of the brain. At this level, white
matter (the alveus) makes up the dorsal surface of the hippocampus. A small section of the temporal horn
of the lateral ventricle may be visible along the dorsolateral surface of the hippocampus. The ventral
border is formed by subhippocampal white matter. The starting point of the outline at this level (Fig. 3c) is the medial extent of the hippocampus on the medial surface of the brain. The outline was
drawn laterally along the dorsal surface of the hippocampus, ventral to the alveus, to the temporal horn
of the lateral ventricle. The outline continued ventrally and then medially along the white matter of the temporal
lobe to the starting point. Proceeding rostrally (Fig. 3d), the hippocampus is outlined in much the same way as just described. The starting point for the
outline at this level (Fig. 3d) was the medial surface of the hippocampus. The outline was drawn dorsally along the medial surface
of the hippocampus to the alveus. The outline continued laterally along the dorsal surface of the hippocampus until
it reached either the temporal horn of the lateral ventricle or the white matter of the temporal lobe. The
outline was then drawn ventrally along the lateral ventricle or temporal lobe white matter to the subhippocampal
white matter. It was completed medially along the white matter to the medial surface of the brain.
Rostral third of the hippocampus. In rostral sections (Fig. 3e), the hippocampus forms part of the medial surface of the brain and is limited dorsally by the alveus,
laterally by the temporal horn of the lateral ventricle, and ventrally by white matter of the temporal
lobe. The outline (Fig. 3e) was started at the medial surface of the brain and extended laterally along the alveus to
the temporal horn of the lateral ventricle. The outline was continued ventrally along the lateral ventricle
to the subhippocampal white matter. The outline was completed by tracing medially along the subhippocampal
white matter to the medial surface of the brain. At its rostral extent (Fig. 3f), the hippocampus decreases in size and is mainly subiculum. The entorhinal cortex begins to form
part of the medial surface of the hippocampus. The two structures are separated by a band of fibers extending from
the subhippocampal white matter to the semiannular sulcus on the medial surface of the brain. The dorsal
surface of the hippocampus often appears to be fused with the ventral surface of the amygdala at this
level, but the two structures are separated by the alveus or by a thin portion of the lateral ventricle. The hippocampus
continues to be bordered laterally by the temporal horn of the lateral ventricle and ventrally by white matter
of the temporal lobe. The outline (Fig. 3f) began at the dorsomedial extent of the hippocampus. This point is found at the junction of the alveus
and the band of fibers extending from the subhippocampal white matter toward the semiannular sulcus. From this
point, the outline continued laterally along the alveus, then ventrally along the temporal horn of the
lateral ventricle, until the subhippocampal white matter was reached. The outline was completed medially
along the white matter, which separates the hippocampus from the entorhinal cortex, to the starting point. Once
the outlines were completed, we used the Analyze software package to calculate the volumes of the left
and right hippocampus. Total cerebral volume measurement | ||||||||||||||||||||||||||||||||||||
Top
Abstract
Introduction
70% of the population of children on the autistic spectrum (Fombonne, 2003
