Feb. 2002

On Demand Accelerated Performance Newsletter


ACCELERATED PERFORMANCE

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Accelerated neurodevelopment allows us the ability to
maximize and use our intellectual, physical, and emotional strengths
simultaneously.
When accelerating brain power, daily tasks such as working, studying,
and sports become easier to do and manage. The brain is functioning at
optimal levels and is able to make quick attentional shifts on demand.
This is the state of mind that peak performers call "the zone" and is
accessible at will.
On Demand Accelerated Performance will be
offering programs and assessments on how you can achieve top performance
from your brain and mind. If interested please contact us.


NEWS BRIEFS

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Possible Migraine Origin Found
Y.E. Knight and P.J. Goadsby
Neuroscience, 2001, 106:4:793-800


Migraine is likely to be due to episodic brain dysfunction in pathways
involved in the control of pain and other sensory modalities, such as
light and sound. To investigate the influence of the PAG on pain
transmission from intracranial structures, we examined spinal trigeminal
neuronal activity in response to PAG stimulation in a model of
trigeminovascular nociception in the cat. Evoked trigeminal neuronal
activity in the spinal cord was reversibly inhibited by stimulation of
the PAG. The effect was robust with a mean reduction in evoked activity
of -61±21%. This effect could be seen both ipsilateral and contralateral
to the side of PAG stimulation and was well localized to the
ventrolateral PAG.


These data demonstrate that a role of the PAG is to inhibit afferent
trigeminal nociceptive traffic. Considered with neurosurgical and human
functional imaging studies, these data support the notion that brainstem
dysfunction might lead to disinhibition of trigeminal afferents and be
important in the pain process of migraines.


For more information click the link below.
http://journals.bmn.com/journals/list/latest?uid=NSC.bmn03220_03064522_v0106i04_01003037&rendertype=abstract&node=TOC%40%40NSC%40106%4004%40106_04



CHRONIC MIGRAINE
RESEARCHERS REPORT HYPOTHALAMIC INVOLVEMENT
Journal of Neurology, Neurosurgery, & Psychiatry.
December 2001

Researchers report findings of hypothalamic involvement in
chronic migraine (CM). The investigators measured melatonin,
prolactin, growth hormone and cortisol nocturnal secretion.
They noted three ways in which their findings may change
clinicians' approach to CM. (1) Melatonin supplementation
may potentially help CM patients; (2) The hypercortisolemia
found in CM can explain why some patients develop
hypertension; (3) Lower prolactin levels suggest a
hyperdopaminergic state, favoring the use of neuroleptics in
this condition.

http://healthy.net/asp/templates/news.asp?Id=3988


Brain-Behavior Relationships:
Lessons from Studies of the Frontal Lobes
Stuss DT, Levine B.
The Rotman Research Institute, Baycrest Center for Geriatric Care,
Departments of Psychology and Medicine (Neurology, Rehabilitation
Science), University of Toronto, Toronto, Ontario


Clinical neuropsychologists have adopted numerous (and sometimes
conflicting) approaches to the assessment of brain-behavior
relationships. We review the historical development of these approaches
and we advocate an approach to clinical neuropsychology that is informed
by recent findings from cognitive neuroscience. Clinical assessment of
executive and emotional processes associated with the frontal lobes of
the human brain has yet to incorporate the numerous experimental
neuroscience findings on this topic. We review both standard and newer
techniques for assessment of frontal lobe functions, including control
operations involved in language, memory, attention, emotions,
self-regulation, and social functioning. Clinical and experimental
research has converged to indicate the fractionation of frontal
subprocesses and the initial mapping of these subprocesses to discrete
frontal regions. One anatomical distinction consistent in the literature
is that between dorsal and ventral functions, which can be considered
cognitive and affective, respectively. The frontal lobes, in particular
the frontal poles, are involved in uniquely human capacities, including
self-awareness and mental time travel.


The North American Millers' Association Announces the Latest for
Preventing Birth Defects
WASHINGTON, Jan 9, 2002 (U.S. Newswire via COMTEX)

The North American Millers' Association (NAMA) issued a public service
announcement about the benefits of bread and pasta for women of
childbearing age.

Since January 1998, all enriched flour, rice, pasta, cornmeal and other
cereal grain products in the United States have been fortified with
folic acid to help reduce the incidence of neural tube defects (NTDs) in
infants.

These foods were chosen for fortification with folic acid because they
are staple products for most of the U.S. population, and because they
have a long history of being successful vehicles for improving nutrition
to reduce the risk of nutrient deficiency diseases.

Folic acid is in many healthful foods. A bowl fortified breakfast
cereal, enriched pasta or bread, a bowl of lentil soup, a large spinach
salad, or a tall glass of orange juice will put a woman well on her way
to the recommended daily allowance of 0.4 mg. The tricky part is that
NTDs occur in an embryo before a woman may realize she's pregnant.

Since more than half of pregnancies are unplanned, FDA has taken steps
to fortify food so that all women of childbearing age get a daily dose
of folic acid. Without it, most women 19 to 50 get only 0.2 mg of folic
acid each day, according to U.S. Department of Agriculture estimates.

On December 3 a study was released by the Journal of Nutrition that
shows the benefits of fortifying grain products with folic acid are even
greater than expected. Researchers at Tufts University investigated the
effects of folic acid fortification in adults.

Their results show that the introduction of folic acid in common foods
significantly improved folate levels by more than expected in most
middle aged and elderly Americans, regardless of whether they took
additional vitamin supplements or not.

Signs of folic acid deficiency may include headaches, forgetfulness,
loss of appetite, diarrhea, weight loss, weakness, sore tongue, heart
palpitations, and irritability.

For background information on folic acid fortification visit

http://www.babybag.com/articles/wh-folic.htm or
http://www.wheatfoods.org

The study released by the Journal of Nutrition can be found at
http://www.nutrition.org

http://www.namamillers.org


RESEARCH AND ADVANCEMENTS

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Researchers Develop Alzheimer's Test
Healthy News

LOS ANGELES (AP) - Researchers at the University of California at Los
Angeles said Wednesday they have created the first test that records the
onset of Alzheimer's disease.

The test, which identifies lesions associated with Alzheimer's in a
person's brain, could improve early diagnosis and lead to more effective
treatment, said Dr. Stephen Bartels, president of the American
Association of Geriatric Psychiatry.

"This is a huge step forward in getting a jump on the disease before it
progresses to cause brain impairment," Bartels said of the test,
reported in the January issue of the American Journal of Geriatric
Psychiatry.

Alzheimer's, a degenerative brain disease that causes memory loss,
disorientation, depression and decay of bodily functions, affects an
estimated 4 million Americans.

The disease often begins with memory lapses and advances to dementia.
People with advanced cases require constant care and lose the ability to
recognize even their loved ones. Among the disease's victims is former
President Reagan.

The UCLA discovery means patients will be able to undergo a noninvasive
test that includes a PET scan and the injection of a chemical tracer,
which identifies the brain lesions linked to the disease.

"Find these tiny lesions, and you will likely find the disease," said
Dr. Jorge Barrio, who led the UCLA research team.

The accuracy of current diagnostic tests can be as low as 55 percent
compared with autopsy results, he added.

Positron emission tomography, or PET, uses radiation to measure
biochemical reactions like those between the tracer and brain lesions,
while CT and MRI scans produce anatomical images.

"We think the research is very exciting, but at the same time we're
cautious," said Michelle Plauche, director of health education for the
Los Angeles chapter of the Alzheimer's Association.

"This technology is most useful when an individual is under the care of
their physician, when there's some indication this test may be useful or
if the doctor is having trouble determining the cause of a patient's
memory loss," she said.

Plauche said she hopes the research will prompt insurance companies to
cover the $1,500 average cost of a PET scan.

The research was funded by the Department of Energy, the Charles A. Dana
Foundation, the Alzheimer's Association and The Institute for the Study
of Aging Inc.


Mechanisms of cerebral cortical patterning in mice and humans

Nature 413, 519-523 (2001). | Article | PubMed |
1. Division of Neurogenetics, Beth Israel Deaconess Medical Center, and
Department of Neurology, Harvard Medical School, Boston, Massachusetts
02115, USA
2. Department of Pathology, Division of Neuropathology, Children's
Hospital and Brigham & Women's Hospital, Boston, Massachusetts 02115,
USA

All the higher mental and cognitive functions unique to humans depend on
the neocortex (`new' cortex, referring to its relatively recent
appearance in evolution), which is divided into discrete areas that
subserve distinct functions, such as language, movement and sensation.
With a few notable exceptions, all neocortical areas have six layers of
neurons and a remarkably similar thickness and overall cell density,
despite subtle differences in their cellular architecture. Furthermore,
all neocortical areas are formed over roughly the same time period
during development and provide little hint at early developmental stages
of the rich functional diversity that becomes apparent as development
comes to an end. How these areas are formed has long fascinated
developmental neuroscientists, because the formation of new cortical
areas, with the attendant appearance of new cortical functions, is what
must have driven the evolution of mammalian behavior.

There are two general viewpoints about how cortical areas form which can
be seen as defining the ends of a mechanistic spectrum. One school of
thought suggests that cortical organization reflects the afferent input
receivedÑfor example, visual cortex is visual because that is where
information from the eyes ends up1, 2. There is now a large body of
literature supporting the importance of destination and electrical
activity of afferent inputs in shaping cortical pattern and refining the
cellular architecture of cortical areas. This literature has been
reviewed recently3 and will not be further discussed here.

The other school of thought suggests that a significant amount of
patterning information exists in the cortex before and independent from
the arrival of afferent inputs. Indeed, early experimental evidence for
such `intrinsic' patterning of the cortex preceded by decades our more
recent insights into how these differences might be determined. Both
limbic cortex, the evolutionarily `older' neighbor of neocortex4, 5, and
neocortical regions6, 7 have a molecular `memory' of their origin when
deprived of normal afferent input in transplant or explant settings
during cortical neurogenesis. More recently, a striking amount of
intrinsic cortical patterning has been shown in two different mouse
mutants that lack thalamocortical connections, the major afferent input
into the cortex8, 9. These and other studies suggest that intrinsic
cortical specification occurs by the time neurons are being generated by
the dividing progenitor cells of the cortex, which lie next to the
ventricles in a layer known as the ventricular zone (VZ). The
possibility that positional information could be encoded by the cortical
VZ progenitor cells themselves, then maintained by postmitotic cortical
neurons, developed from the observation that most postmitotic neurons
enter the cortex from the cortical VZ through a restricted radial
migration along radially oriented glial guide fibers10.

There is now considerable evidence supporting the cortical VZ as a
repository of positional information that is critical for cortical areal
patterning. The mechanisms involved in patterning the cortical VZ are
the subject of this review. Although much of our insight into these
mechanisms has relied on studies in mice, humans are subject to a wide
variety of naturally occurring mutations that have identified cortical
patterning genes through a `forward genetics' approach. We therefore
attempt to integrate mouse and human studies into a hierarchy of events
that pattern the cortical VZ.

Early morphological changes in the forebrain. To define the anatomical
context in which the developing cortex is patterned, we first summarize
the dramatic topological transformations that accompany the earliest
stages of corticogenesis (Fig. 1). After the initial induction of neural
tissue11, the cortex is formed at the rostralmost portion of the neural
tube and is quickly subdivided into two halvesÑthe left and right
telencephalic vesicles (the future cerebral hemispheres). This
subdivision depends on the dorsal midline roof plate, where low levels
of proliferation and high levels of apoptosis result in its fixation and
invagination relative to the rapidly expanding hemispheres12 (Fig. 1).
During this period, each hemisphere forms a distinct bulge in its
ventral region, the ganglionic eminence (the future basal ganglia),
which morphologically distinguishes ventral from dorsal telencephalon.
As these events proceed, the cortex becomes exposed to several potential
sources of secreted signaling molecules, often called `organizers',
which include, first, the anterior neural ridge in the rostral midline,
second, the roof plate in the dorsal midline, third, the cortical hem,
which lies between the dorsal midline roof and the cortical VZ, and
fourth, other potential sources of signaling molecules, such as the
surface ectoderm (the future skin) and mesenchymal elements that lie
between the skin and brain, including the future meningeal cells that
surround the adult brain (Fig. 2a).

Cortical VZ as a source of projection neurons
Direct studies of cell lineage are consistent with the idea that
cortical VZ progenitor cells help to establish cortical patterning (Fig.
3). These studies show that cortical VZ progenitors can form large
columnar `clones' of neurons (Fig. 3a), most of which become
glutamatergic projection neurons of the cortex13-17. Because projection
neurons form the efferent output of the cortex and define areal-specific
connectivity, these cell-lineage studies provide the cortical VZ with
the potential to directly affect area-specific development. A defect
that resembles these large columnar clones can be seen in certain human
cortical dysplasias (`abnormal development'; Fig. 3b). Human cortical
dysplasias can involve large expanses of the cortex, but more often
involve only small cortical regions. The shape of these
dysplasiasÑpresumably clonal in origin, though this is not provenÑis
occasionally strikingly reminiscent of the large clones seen in cell
lineage studies, with a broadening `tornado' outline and an apparent
origin in or near the VZ (Fig. 3a and b). These highly epileptic lesions
commonly express glutamatergic markers, but often lack GABAergic
markers, which is consistent with a clonal origin from cortical VZ
progenitor cells18-20.

In contrast to the columnar clones of cortical VZ progenitors, other
cortical neurons are derived from clones that disperse widely across the
cortex14, 15, 21-23 (Fig. 3c). Remarkably, many if not all of these
widespread clones are not generated by cortical VZ progenitors at all,
but instead by progenitor cells in subcortical sites, including the
ganglionic eminence24, 25. Subcortically derived neurons migrate long
distances to reach the cortex and seem to represent the bulk of cortical
GABAergic interneurons (roughly 75% in mice)16, 26 as well as some
glutamatergic neurons4, 24, 25, 27 (see Fishell review in this issue).
Another potential source of cortical neurons that come from outside the
cortical VZ is the roof plate region28. Whether these non-cortical
VZ-derived neurons are important for area-specific patterning or are
selectively deficient in any human cortical disorders remains unknown,
although cortical GABAergic neuronal dysfunction may be central to the
pathogenesis of both schizophrenia and bipolar disorder29, 30.

Induction of the telencephalon
The cell-lineage studies show that the cortical VZ has the potential to
directly affect cortical areal development, but how does the cortical VZ
get formed in the first place? Perhaps the earliest definitive step in
cortical VZ induction is mediated by an organizer at the rostralmost end
of the developing embryo known as the anterior neural ridge31 (ANR; Fig.
2a). Removal of the ANR from explants results in a failure to express
Foxg1 (previously Bf1), a transcription factor that selectively marks
future cortical VZ progenitors before the telencephalon is
morphologically distinguishable31, 32 and that is required for normal
telencephalic and cortical morphogenesis33. The ability of the ANR to
induce Foxg1 expression in explants can be mimicked by the exogenous
application of an ANR-derived signaling molecule, fibroblast growth
factor 8 (Fgf8). Because some cortical tissue remains in mice without
Foxg1 function33, 34, the ANR-Fgf8-Foxg1 pathway may be complemented by
other pathways that help induce the cortex.

Induction of the midline roof plate
A step in forebrain development that seems distinct from telencephalic
induction is the formation of the dorsal midline roof plate, as
illustrated by a mouse and human malformation known as holoprosencephaly
(HPE). HPE, the most common congenital brain malformation in humans, is
defined by the failure to separate the forebrain into two hemispheres,
resulting in a single forebrain `holosphere' and a continuous cerebral
cortex across the midline35 (Fig. 4). The cerebral cortex is always
smaller than normal but present36, whereas the lack of forebrain
division and continuity of cortex across the dorsal midline indicate a
failure in dorsal midline development. The pathogenesis of HPE therefore
involves a fundamental defect of the roof plate, and the genes
implicated in HPE are likely to belong to signaling pathways that induce
and/or maintain roof plate function or confer competence in roof plate
neuroepithelium to respond to such signals. At least 12 genetic loci
have been implicated in human HPE37, and the genes corresponding to four
of these loci are now known.

One of the genes implicated in human37 and mouse38 HPE is Sonic hedgehog
(SHH, the HPE3 locus), a well-known secreted signaling molecule that
acts as a primary inducer of ventral neural structures and fates in
several organisms35, 39. In the mouse forebrain, Shh is expressed in
ventral domains within neural tissue (the hypothalamic region and
ventral telencephalon) and in prechordal mesoderm, a group of mesodermal
cells that underlie the ventral forebrain35, 39 (Fig. 2a). In mice,
total loss of Shh function results in HPE38, whereas selective loss of
Shh from its ventral telencephalic domain does not cause HPE40. This
suggests that the HPE phenotype and roof plate induction rely on Shh
that is produced in prechordal mesoderm and/or the hypothalamic region.

In addition to SHH, heterozygous germline mutations in three other genes
have been implicated in human HPE, all of which encode transcription
factors: the SIX3 homeobox gene (HPE2)41, 42, the ZIC2 zinc-finger gene
(HPE5)43, 44 and the TGIF homeobox gene (HPE4)45, 46. Presumably these
transcription factor genes form some kind of genetic pathway along with
SHH, but exactly how they interrelate is still unknown. In mice, Six3 is
expressed first in rostralmost neural and non-neural tissue, then later
within the ventral forebrain47, thus coinciding with SHH-expressing
regions as well as the ANR. Six3 may therefore be important for anterior
and/or ventral organizer function, but the Six3 null phenotype in mice
has not yet been reported.

In contrast to Shh and Six3, Zic2 is predominantly expressed in the
dorsal neural tube in and around the roof plate48. This distinctive
dorsal pattern of Zic2 expression is consistent with the lack of
significant craniofacial defects in humans43, 44 and mice49 with HPE due
to ZIC2 mutations, and suggests that Zic2 is involved in the induction
and/or maintenance of the roof plate. TGIF has been genetically linked
to SHH on the basis of coexisting TGIF and SHH mutations within some HPE
families45. In mice, TGIF has also been implicated in a transforming
growth factor- (TGF) signaling pathway50-52 that leads to HPE when
disrupted46, but the site of action of TGIF and its relationship to the
SHH pathway remain to be determined.

In summary, a failure in roof plate development represents a central
defect in HPE, but exactly how the growing number of HPE genes
interrelate and lead to roof plate dysfunction remains unclear. Some HPE
genes (SHH and SIX3) are expressed in or around the ANR and prechordal
mesoderm (Fig. 2a), suggesting that these anterior and ventral
organizers are somehow linked to dorsal roof plate development. On the
other hand, ZIC2 is expressed in the roof plate itself and seems to be
essential for normal roof plate development.

Specification of the dorsal telencephalon
After its initial induction by extrinsic signals, the telencephalon
becomes specified into dorsal (pallial) and ventral (subpallial)
regions, and certain basic helix-loop-helix (bHLH) transcription factors
regulate this process53. The bHLH proteins Neurogenin1 (Ngn1) and Ngn2
are selectively expressed by dorsal telencephalic progenitors, and Ngn2
or Ngn1;Ngn2 mutant cortices show a loss of dorsal markers and a gain of
ventral markers, including the ventral bHLH gene Mash1. Misexpression of
Mash1 in the cortical VZ is sufficient to drive ventral marker
expression, suggesting that Ngn1 and Ngn2 promote cortical development
by suppressing Mash1-dependent ventral fates53. Like the Neurogenins,
mouse Gli3 is expressed throughout the dorsal telencephalon, and the
Gli3 null cortex lacks certain dorsal cortical (hippocampal) markers and
gains expression of ventral markers54. Mutations in the GLI3 gene have
been discovered in some human diseases, but it is uncertain if these
mutations cause abnormal cortical development. The Ngn1/2 and Gli3
studies suggest that dorsal specification of the cortical VZ involves
the suppression of ventral fates. The defects in Ngn1/2 and Gli3 mutants
are not identical, however, and Ngn2 expression does not appear to be
affected in Gli3-/- embryos54. Gli3 and Ngn2 may therefore act in
parallel pathways rather than in series to regulate dorsal specification
of the cortical VZ.

Selection of a cortical VZ fate
Following dorsal telencephalic specification, the dorsal telencephalon
must be further subdivided into dorsal midline epithelial fates (choroid
plexus epithelium and cortical hem) and the cortical VZ, a process in
which the LIM homeobox gene Lhx2 has a specific role. Lhx2 is
selectively expressed in the cortical VZ but not in dorsal midline
epithelia, and mice lacking Lhx2 show a near-total loss of the cortical
VZ and a massive excess of dorsal midline fates28, 55. Residual cortical
VZ progenitors in Lhx2 mutants (as defined by expression of the mutant
Lhx2 allele28) continue to express Foxg1 and Ngn2, thus indicating a
normal dorsal telencephalic progenitor identity, but fail to express
several cortical VZ markers28, 55. This suggests that Lhx2 is not
essential for the specification of telencephalic or dorsal identity, but
acts instead to `select' a cortical VZ fate from already-specified
dorsal telencephalic progenitors28. This Lhx2 selector function may be
conserved evolutionarily, because the Drosophila orthologue of Lhx2
(apterous) is a well-known selector gene that acts in a similar fashion
within the dorsal wing compartment56-58.

Regional specification of the cortical VZ
Once the cortical VZ fate is selected, regional specification of the
cortical VZ must occur. This critical step in cortical VZ patterning
remains poorly understood, but some studies suggest that localized
signaling molecules may be central to this process. For example,
sensorimotor VZ progenitors can be reprogrammed to induce limbic
cortex-specific markers (LAMP)5 and connectivity59, 60 when transplanted
at appropriate times into putative limbic areas, suggesting the
importance of location within the cortical VZ for regional
specification. The reprogramming for limbic marker expression can be
recapitulated in vitro by treating actively cycling sensorimotor
progenitors with TGF, a ligand for the erbB receptors, which are
differentially expressed by cortical VZ progenitor cells61. Finally, the
highest expression levels of TGF in the normal brain occur in the
subpallium, and the cortical regions closest to the subpallium are the
ones that express LAMP61. Taken together, these findings lead to a model
in which regional specification of the cortical VZ depends on the
localized production of instructive signaling molecules as well as the
location and receptor repertoire of individual progenitor cells in the
cortical VZ61.

Expansion of the cortical VZ
In addition to their potential roles in regional specification,
signaling molecules seem to regulate the expansion of the cortical VZ.
One source of these signals is the dorsal midline roof plate28 (Fig. 2).
Selective ablation of roof plate cells results in a cortical VZ that is
signficantly reduced in size. Because cortical tissue is not directly
ablated in these experiments28, the roof plate seems to provide signals
that act on the cortex at a distance. The role for roof plate signals in
cortical expansion would be consistent with the holoprosencephaly
phenotype, in which the roof plate deficit is associated with a cortex
that is present, but always small. Roof plate-derived signals are likely
to include secreted proteins known as the bone morphogenetic proteins
(Bmps; Fig. 2), based on their central roles in roof plate-mediated
signaling during spinal cord development62. Multiple Bmp genes are
induced in and around the forebrain roof plate before the telencephalon
can be recognized morphologically (E8.5)12, and the disproportionately
small telencephalon in mice lacking Bmp5 and Bmp7 (ref. 63) provides
genetic evidence that Bmp signals regulate expansion. In addition to
regulating cortical VZ expansion, roof plate-derived Bmps may also
regulate cortical VZ patterning, because roof plate signals, which
probably include Bmp4 and Bmp2, regulate the graded expression of Lhx2
in the cortical VZ28.

Signals from the cortical hem, which is located next to the dorsal
midline roof (Fig. 2b), are also directly implicated in local cortical
VZ expansion12, 64, 65. Like Bmps, the Wnts represent a large family of
secreted proteins that mediate signaling functions in a number of
embryonic systems. Mouse Wnt genes are activated in and around the
cortical hem after the cortical VZ has been induced (E11.5)64, and loss
of hem-specific Wnt3a function in mice causes defective proliferation of
progenitors in the hippocampal VZ, the region of the cortical VZ
immediately adjacent to the cortical hem65. This Wnt3a null defect
appears to be phenocopied by loss-of-function mutations to mouse Lef1, a
transcriptional mediator of Wnt signaling that is expressed by
hippocampal VZ progenitors66, suggesting that a cortical hem-Wnt3a-Lef1
pathway is critical for hippocampal VZ proliferation. These studies
support the notion that Wnt signals have a primary role in stimulating
proliferation throughout the mouse nervous system65, 67.

Regulating the relative sizes of cortical areas
Recent studies on the Emx2 and Pax6 homeobox genes demonstrated how
patterning of the cortical VZ can affect cortical areal development.
Specifically, these two transcriptional regulators expressed in the
cortical VZ regulate the relative sizes of cortical areas. Emx2 and Pax6
are expressed in graded and opposing fashions within the cortical VZ:
the Emx2 gradient is high posteriorÐlow anterior, whereas the Pax6
gradient is low posteriorÐhigh anterior68. Loss of Emx2 function in mice
results in marked size reductions to posterior cortical areas (including
hippocampus and visual neocortical areas), whereas anterior neocortical
regions (including motor areas) are either shifted or expanded68, 69.
Correspondingly, loss of Pax6 function (Small eye mice) results in a
decreased anterior neocortical size68. Importantly, these defects
correspond well to the normal expression gradients of Emx2 and Pax6,
suggesting that the Emx2 and Pax6 countergradients within the cortical
VZ provide an intrinsic code that directly regulates cortical area size.

The human EMX2 and PAX6 genes have also been implicated in human
cortical malformations and may reflect the essential functions of Emx2
and Pax6 defined in mice. Human EMX2 mutations are associated with a
rare cortical malformation known as schizencephaly (`split brain'),
which is characterized by a full-thickness defect or cleft in the
cerebral wall (Fig. 5). Heterozygous germline mutations in EMX2 have now
been described in several sporadic cases and in affected siblings70-72.
In general, EMX2 mutations are found in severe cases of schizencephaly
in which much of the cerebral cortex is absent. When less of the cortex
is affected, the location of the clefts is neither stereotyped70, 72 nor
predisposed to occur in the posterior cortical regions most dependent on
Emx2 function in mice68, 69. It is possible, however, that
haploinsufficiency together with incomplete penetrance could account for
the differences among humans carrying the same EMX2 mutation72 and
between humans and mice with EMX2 mutations.

Humans with PAX6 mutations possess a complex brain malformation that
compares favorably with the Pax6 mutant phenotype in mice73, 74. In
addition to eye defects, human PAX6 heterozygotes have subtle
alterations in forebrain size and shape74. More severe defects in the
olfactory system and cerebral cortex are present in a compound
heterozygote carrying two different PAX6 mutant alleles75, which
supports a gene dosage effect for human PAX6 mutations. However, it
remains unknown if patients with PAX6 mutations might have shifts or
changes in cortical areal size that would correspond to the essential
patterning function of Pax6 in mice.

From cortical VZ to cortical areas
Ultimately, the initial blueprint laid out by organizers and intrinsic
transcriptional regulators of the cortical VZ must be converted into the
topographically organized and functionally diverse areas of the mature
cortex. Although the Emx2 and Pax6 studies suggest that this conversion
must occur, they do not reveal its underlying mechanisms. One
possibility would be to transfer either the transcription factors
themselves or their expression profiles in cortical VZ progenitors
directly to their neuronal progeny. Although Emx2 and Pax6 may not be
expressed by cortical neurons, other transcription factors such as Emx1
and Lhx2 in rodents76, 77 and primates78 show similar patterns of
expression in the cortical VZ and in cortical neurons, which is
consistent with such a mechanism. The unique combinations of
transcription factors in either progenitors or neurons could then direct
the differential expression of target genes that allow area-specific
differentiation and connectivity. Molecules that regulate axon guidance,
such as those that mediate cellÐcell interactions, are among the most
likely of these transcriptional targets, because they are directly
involved in axon target selection in multiple systems79. Importantly,
several genes encoding cellÐcell interaction proteins, such as
cadherins78, 80-82, immunoglobulin superfamily members83, 84 and the
ephrin/Eph receptors82, 85, 86 are expressed in specific patterns across
the cortex, many of which are graded and/or correspond to functional
areas and their boundaries. The ephrin/Eph receptor system in particular
seems to have a general role in the formation of topographic maps in the
brain82, 85, 87, including in the somatosensory cortex82, 88. It is
particularly tempting to speculate that the cellÐcell interaction
molecules that show graded expression in the cortex might be directly
regulated by transcription factors that also show a graded pattern in
the cortex or cortical VZ.

The hierarchy of events in cortical patterning
These studies provide insight into the sequence of events that specify
the cortical VZ and ultimately pattern the cerebral cortex (Fig. 6). The
initial pathways responsible for induction of the telencephalon
(ANR-Fgf8-Foxg1) and the dorsal midline roof plate (HPE genes) are
separable. Following induction of the telencephalon, dorsal
telencephalic tissue is specified (Neurogenins and Gli3), and a cortical
VZ fate is selected from other dorsal fates (Lhx2). The cortical VZ then
becomes regionally specified by the influence of localized signaling
molecules. Signaling molecules, including those from the dorsal midline
region (roof plate and cortical hem), then act on the cortical VZ to
regulate its expansion, with the relative sizes of cortical VZ fields
and ultimately cortical areas being determined by gradients of intrinsic
transcriptional regulators (Emx2 and Pax6). Regional patterning
information encoded in the cortical VZ is then transferred into the
overlying cortex, and afferent input into the intrinsically patterned
cortex acts to sculpt mature area-specific features.

This hierarchical model of cortical patterning requires much further
elaboration and elucidation. During early induction, it is unclear if
telencephalic and roof plate induction are linked, how anterior and
ventrally derived signals lead to roof plate induction, and whether the
cortical neuroepithelium is selectively induced. The roof plate is
likely to have other roles in addition to regulating cortical VZ
expansion, which may include induction of the cortical hem and regional
specification of the cortical VZ, based on its known functions in the
spinal cord. During cortical VZ specification, dorsal specification may
occur in parallel or in series with cortical VZ selection, and may also
be directly linked to Pax6-mediated cortical VZ expansion, because the
proper spatial localization of Neurogenins depends on an interplay
between the Pax6 and Gsh2 homeobox genes89-91. The involvement of
particular molecules in specification versus proliferation and cell
death can be a difficult problem for developmental biologists, but will
need to be further clarified. Finally, the later stages of this process
involving the conversion of cortical VZ pattern into the overlying
cortex, the differential expression of axon guidance molecules, and the
potential role of non-cortical VZ-derived neurons in providing some
aspects of area specificity remain almost completely unexplored.

Abnormal cortical patterning in other human disorders
Just as the human HPE genes provide a `forward genetics' approach to
define genes involved in patterning, there are other naturally occurring
human mutations that could provide similar clues. One such set of
diseases are the symmetric polymicrogyrias (Fig. 7). Several familial
forms of polymicrogyria (`too many small gyri') have now been
reported92, many of which show a regional distribution within the
cortex93 (bilateral frontal, bilateral perisylvian, biparietal and
bioccipital; Fig. 7). These genetic polymicrogyrias produce a cortex
that appears relatively normal overall, but shows regional
disorganization of cortical cellular architecture and lamination.
Patients with regional polymicrogyrias have clinical findings that tend
to correspond to the location of the most severe abnormalities. For
example, bilateral frontal polymicrogyria is associated with prominent
motor signs due to the involvement of motor cortex, but with only mild
to moderate mental retardation94. In contrast, perisylvian
polymicrogyria is most severe in cortical areas devoted to language and
control of the mouth, thus resulting in difficulties with swallowing,
articulation and language acquisition as well as frequent and severe
seizures. The regional nature of these defects suggests the involvement
of genes that are required for regional patterning of the cortex, but
this remains unproven until the responsible genes are identified.

Neural tube defects represent a large and heterogeneous group of
disorders that involve incomplete closure of the neural tube (and
therefore by definition, an improperly formed roof plate), and some
neural tube defects may represent primary defects of early induction and
patterning. Two human malformations potentially related to neural tube
defects are exencephaly (openings of the skull with protruding brain)
and anencephaly (complete absence of the brain), which seem to be
well-modeled by certain mouse mutants49, 64, 95. Microcephaly (`small
head') is relatively common and may frequently represent primary defects
in cortical VZ expansion. Mutations in human genes that regulate later
events in cortical patterning may not cause gross malformations of the
cortex, but instead more subtle cognitive and behavioral defects, such
as the speech and language deficits caused by mutation of the FOXP2
transcription factor gene98.

Summary
Recent evidence continues to implicate the cortical VZ as a critical
source of patterning information that ultimately leads to the formation
of functionally diverse cortical areas. Several intrinsic
transcriptional regulators have been shown to regulate distinct steps
during cortical VZ patterning. However, numerous extrinsic influences on
the cortical VZ and emerging cortex are also known. In addition to the
role of afferent cortical input, extrinsic influences include organizers
that pattern the cortical VZ via secreted signaling proteins and
progenitor cells outside the cortical VZ that produce migratory cortical
neurons. Taken together, these studies provide insight into the
hierarchy of events that lead from the induction of cortical
neuroepithelium to the formation of cortical areas. The discovery of
genes responsible for cortical malformations in humans has been a
valuable complement to the basic studies on cortical patterning in mice,
and the links between mice and humans should continue to provide
invaluable insight into the pathogenesis of human disease and the
mechanisms that pattern the mammalian cerebral cortex.

Received 18 August 2001; Accepted 21 September 2001.


KIDS NEWS

---

Preemies get into less trouble
New England Journal of Medicine

Very small premature babies born in the late 1970s turned out less
intelligent than other youngsters their age, a study found. But to
researchers' surprise, they got into less trouble as teens, perhaps
because they had doting parents.

As expected, the preemies in the study had learning difficulties and
persistent neurological problems while growing up. But they also
reported significantly less risky behavior as young adults than a
comparison group.

Differences between the groups were found when it came to the use of
alcohol, marijuana and other illegal drugs; conviction of a crime or
other contact with police; and, for girls, having sex and getting
pregnant by age 20.

"That was totally unexpected, because there's a lot of literature that
criminality is related to lower IQ," said Dr. Maureen Hack, who led the
study as director of the neonatal follow-up program at Rainbow Babies
and Children's Hospital in Cleveland. She said the researchers thought
the preemies would have had more behavior problems.

She said one possible explanation is that the preemies' parents saw
their children as particularly precious and watched over them more.

Dr. Henry Shapiro, chairman of the American Academy of Pediatrics'
section on developmental pediatrics, said there is no evidence that the
hypothesis is correct. But he said the study could help policymakers
better plan for the medical and educational needs of premature babies.

Infants of very low birth weight, 3.3 pounds or less, account for 1
percent of all U.S. births, or about 40,000 babies per year.

The babies in the study were born at 29 weeks and just over 21/2 pounds
on average.

They were born between 1977 and 1979, before neonatal intensive care
units and specialized technology were widely used to keep tiny preemies
alive. Today, lung treatments, breathing machines, intravenous feeding
and other technology enable some preemies as small as a pound to
survive, though with significant disabilities.

Hack said her findings would probably apply to many of today's premature
infants.

Past research on premature babies found higher rates of learning
disabilities such as attention deficit disorder and of neurological
problems such as cerebral palsy, blindness and deafness.

Earlier studies generally followed children until school age. This study
followed the preemies until age 20 and examined their physical growth,
behavior and mental health as well as intelligence.

The research was reported in Thursday's New England Journal of Medicine.
It was funded by the National Institute of Child Health and Human
Development.

The researchers examined 242 Cleveland-area preemies at age 8 and again
at 20, through IQ tests, neurological examinations and questionnaires
completed by both the children and their parents. The preemies were
compared with 233 area children with normal birth weights.

As expected, the preemies were slightly less likely to have graduated
from high school, had somewhat lower IQs, and had higher rates of
neurological problems and subnormal height; the preemie men were barely
half as likely as their counterparts to be attending college.

But except for cigarette smoking and sexual activity among the males,
the preemies got into less trouble as teens.

"Even those with learning problems, they show resilience" and feel
good about themselves, Hack said.

Hack just started a long-term study of babies born at less than 2 pounds
from 1992 through 1995 that will study levels of parental monitoring and
socializing. She wants to determine why they get into less trouble.


Eye disorder linked to ADHD in children
Apr 14, 2000 (Reuters Health) --
Reuters

An eye disorder appears to be linked to attention-deficit/hyperactivity
disorder (ADHD) in children, according to University of California, San
Diego researchers.
The eye problem, called convergence insufficiency, is a physical problem
of the eye that makes it difficult to keep both eyes focused on a near
target. The disorder affects less than 5% of children -- but the
research team found that it is three times more common in children with
ADHD than in other children.
"This is the first report on the potential connection of these two
disorders," Dr. David B. Granet said this week during the American
Academy of Pediatric Ophthalmology and Strabismus meeting in San Diego.
Granet and colleagues reviewed the records of 266 children identified as
having an inability to keep both eyes focused on a close target. The
investigators found that 26 children (9.8%) also had a diagnosis of
ADHD. "Twenty of these patients were on medication for ADHD when
diagnosed with convergence insufficiency," Granet told Reuters Health.
When the researchers reviewed their institution's records of 1,700
children diagnosed with ADHD, they discovered that about 176 also had
eye exams, Granet said. "Of these, almost 16% or 28 children also had
convergence insufficiency," he added.
This analysis shows that "children with ADHD had three times the
incidence of convergence insufficiency than what was expected in
children walking in off the street," Granet said.
Convergence insufficiency "makes it more difficult to concentrate on
reading, which is also one of the ways doctors diagnose ADHD," Granet
commented.
"Convergence insufficiency may not be well known outside the field of
eye care specialists," Granet told Reuters Health. "We don't know if
children are being misdiagnosed with ADHD when they truly have
convergence insufficiency or vice versa," he said. "We also don't know
if one causes the other or if medications used for ADHD cause
convergence insufficiency," he added.
"More study needs to be completed to confirm the connection and to
answer these questions," Granet said.
Granet also noted that convergence insufficiency responds to eye
exercises that can be done at home.


AUDITORY NEWS/UPDATES

---

Auditory evoked cortical potentials in children with severe language impairment
IngerTonnquist-Uhlen
Department of Audiology, Karolinska Hospital, Stockholm, Sweden

Development of normal speech and language functions is closely related
to normal hearing. However, most children with delayed or disturbed
speech development show normal tone thresholds and here the
investigation has to include higher levels in the auditory system. There
is evidence for a connection between language impairment and a central
auditory processing disorder, but the underlying mechanisms are not well
understood. There is also a need for objective diagnostic methods of
central auditory function.

In the present study, a computerized method of mapping the scalp
topography of long-latency (cortical) auditory evoked potentials (LAEP)
was used for assessment of the function in central auditory pathways .
Topographic mapping of the LAEP component N I, in adults and normal
children, showed reproducible and valid results. In adults, a focal
negativity, focus of NI (FNI), with a frontocentral position and
contralateral to the stimulated ear was observed. The N I maps in normal
children showed a pattern similar to that in adults,
but with some age-related changes. The Nl latencies declined
significantly with age in normal children and reached adult values at
the ages of 14-16 years.

The topography of the LAEP components N I, P2, N2 and the T complex was
investigated in 20 children with severe language impairment (LI). The
study also included auditory brainstem responses (ABR),
electroencephalography (EEG), quantitative EEG (qEEG) and magnetic
resonance imaging (MRI). Twenty normal children served as controls (C).

A similar topographic pattern was found in the LI and the C children,
but with a higher proportion of deviating and non-focal maps in the LI
group. The latencies of all components were significantly longer in the
LI than in the C children. The diagnostic value of LAEP topography,
latency and amplitude was estimated with a scoring system, whereby
significantly higher scores were found in the LI group than in the C
group. With all three parameters together the sensitivity was 65%, with
a specificity of 90%.

There was a high degree of pathological EEGs in the LI group. ABR
abnormalities were seen in some LI subjects. MRI was normal in all but
two LI children. There was no significant correlation between the
results of EEG,ABR, MRI and the total score of LAEP, but some
LI children showed a wide pathological pattern. In 17 of the 20 LI
subjects a pathological result was obtained in one or more of the
investigations.

In conclusion, our results may indicate that language impairment has a
dual pathophysiology, a specific auditory disorder (LAEP, ABR) and a
non-specific general cerebral disturbance (EEG, MRI). The highly varying
results among the present LI children, with specific and/or non-specific
deviations, may be due to heterogeneity of the group with different
aetiologies of their language impairment, or to a general developmental
disturbance with a varying distribution and penetrance. The scoring
system of LAEP proved to be the most sensitive method in separating the
LI children from the controls. This may be a promising model for
individual diagnostic criteria and for classification of language
impairment.

Startle Reflex Triggered by Vestibular Stimuli

The startle reflex is elicited by strong and sudden acoustic, vestibular
or trigeminal stimuli. The caudal pontine reticular nucleus, which
mediates acoustic startle via the reticulospinal tract, receives further
anatomical connections from vestibular and trigeminal nuclei, and can be
activated by vestibular and tactile stimuli. This suggests that this
pontine reticular structure could mediate vestibular and trigeminal
startle.
The vestibular nucleus, however, also projects to the spinal cord
directly via the vestibulospinal tracts, and therefore may mediate
vestibular startle via additional faster routes without a synaptic relay
in the hindbrain.
In the present study, the timing properties of the vestibular efferent
pathways mediating startle-like responses were examined in rats using
electrical stimulation techniques.
In awake rats, combining vestibular nucleus stimulation with either
acoustic stimulation or trigeminal nucleus stimulation enhanced the
whole-body startle-like responses and led to strong cross-modal
summation without collision effects.
We propose that the vestibulospinal tracts participate strongly in
mediating startle produced by activation of the vestibular nucleus. The
convergence of the vestibulospinal tracts with the reticulospinal tract
within the spinal cord therefore provides the neural basis of
cross-modal summation of startling stimuli.


VISION NEWS/UPDATES

---

What You See May Not Be There
Rotman Research Institute

Have you ever noticed that after staring out the side car window for a
long time, when the car comes to a stop that it looks like you are
actually moving backwards? Or after staring at an object in one color,
such as red, for a long time, that you then have a ghostly image of that
object in green? These are aftereffects that involve seeing something
that is not really there. How these aftereffects happen is of interest
in our research. Dr. O'Craven and her colleagues would like to know what
is going on in your brain when something appears to be moving but it is
not really moving.

One particular brain region in the visual area, known as "MT", responds
to motion. While scientists have studied the different ways in which MT
responds to motion, nobody knows what is going on in this region when
you "see" motion that isn't really there, as in the aftereffect
described above. By examining the brain's activity when there is real
motion in comparison to when there is an illusory aftereffect, we can
gain a better understanding of why we see things that aren't really
there.

For more information click the link below. http://www.rotman-baycrest.on.ca/content/news_events/news_events.html

Visual Processing: A Roving Eye
Rebecca Craven

As we view the world around us, our eyes frequently make ballistic
movements from one point of gaze to another. These 'saccades', which can
occur several times per second, are usually automatic and go unnoticed.
This is somewhat surprising. After all, when the image of a fast-moving
object sweeps across the static retina, we are normally aware of its
motion. So why is it that we fail to detect the comparable motion of
images as they sweep across the retina during saccades? This apparent
paradox has previously been explained by the intrasaccadic suppression
of visual sensitivity. But as Garc’a-PŽrez and Peli report in the
Journal of Neuroscience, it seems that we might have underestimated our
capacity for visual perception during saccades.
For more information please click on the link below.
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrn/journal/v2/n11/full/nrn1101-761a_fs.html


SPEECH AND LANUGAGE

---

19 Characteristics of children with language processing disorders

Language processing is the ability of the brain to attach meaning and to
attend to a given auditory sound. Processing ability allows a person to
listen to and comprehend speech in the presence of background noise.

Characteristics of children with language processing disorders:
1. These children have normal hearing, but can display behavior typical
of a child with a mild to moderate hearing loss.

2. Often these children may have been premature babies.

3. 85-90% of children that have processing problems, have had a history
of chronic middle ear infection. Of note is the fact that one month of
hearing loss is equal to three months of auditory listening skill
development.

4. These children have poor auditory attending skills.

5. They may not understand questions.

6. They often give a response so people will leave them alone. They know
what to say, but they don't know what it means.

7. They're IQ scores are usually average to above average.

8. They do poorly on the Coding Subtest of the WISC-R.

9. They have language delays, often affecting vocabulary development

10.They have difficulty understanding multiple meaning words. Eg.
range=stove =a parcel of land =price range/scores

11. Time concepts are difficult to understand. These children live for
the here and now! They do not think ahead!

12. They have difficulty following directions. This becomes more obvious
as the group size increases and the background noise increases.(gym,
assembly, open area classes)

13. They hesitate for a long time before responding.

14. They are disorganized...they misplace personal belongings, they are
slow/pokey, they have difficulty staying on task.

15. They are very, very, very distractible!

16. They have difficulty seeing the "whole picture"! They don't see
cause and effect to many things.

17. They may be viewed as a behavior problem in the classroom and at
home..."He's old enough and should know better".

18. They have difficulty in social interactions. They are unable to
'read' other's feelings,

19.They have difficulty maintaining friendships...they often seem "off
the wall". NOTE: Many of these characteristics are similar to children
who have attention deficit disorders. Therefore, an accurate diagnosis
is crucial to further recommendations and programming.


Putting Language Genes in Perspective
by Dorothy V.M. Bishop
Trends in Genetics.
Posted January 18, 2002 á Issue 118

A point mutation has recently been found in a gene from affected members
of a family with an autosomal dominant pattern of inheritance for
specific speech and language impairment. However, this does not mean we
have localized the "gene for language." The phenotype is complex, and
the affected gene, which is concerned with regulating activity of other
genes, is common to human and mouse. The discovery is nevertheless
important, because it will help us to identify target genes that play a
role in development of the neural circuitry involved in language.

Can we find a gene or genes that are crucial for language?

In the context of this question, language experts are excited by the
mounting evidence that some forms of developmental language impairment
are strongly heritable. Specific language impairment (SLI) is the
diagnosis given when language development goes awry in an otherwise
normally developing child. Typically, the child is slow in starting to
talk, and might still be producing only single word utterances at three
or four years of age, when most children would be speaking in phrases.
Although language progresses, it can lag well behind age level, with the
child producing simplified sentences and having limited vocabulary, so
that a five-year-old says "me go there," rather than "I went to the
park." The boundaries of SLI are fuzzy and prevalence rates depend on
the precise definition used, but a recent US survey suggested that as
many as 7% of six-year-olds met the criteria for SLI. In the 1990s, both
family studies and twin studies provided converging evidence for a
strong genetic component to the etiology of SLI. This appeared to raise
the prospect that, if we could find the gene or genes implicated in
causing SLI, we might discover the biological basis of Chomsky's innate
language faculty.

For more information please click the link below. http://news.bmn.com/hmsbeagle/118/notes/feature11

Children With Speech Language Impairment
J. Bruce Tomblin and Jennifer Pandich
Trends in Cognitive Sciences, 1999, 3:8:283-285

In the past decade, there has been an increasing interest among
linguists and psychologists in the language development of children with
developmental impairments such as Williams syndrome 1, Down syndrome,
and autism. Recently, children with specific language impairment (SLI)
have been the focus of papers by Gopnik, Joanisse and van der Lely.
These papers join others in examining the grammatical skills of these
children in the hope of gaining insights into the nature of their
language deficits, and to test theories concerning the cognitive bases
and the possible biological and genetic bases of language development. A
common issue within this work is the degree to which the development of
language or particular sub-components of language (such as syntax and
morphology) can be differentially affected relative to other aspects of
language Ð or to more basic cognitive systems. Thus, in the same way
that focal brain injury has been used for many years to provide a means
to study questions of localization and modularity in mature language
systems, investigators are now studying developmental language disorders
to inquire about these issues in language and cognitive development.

http://journals.bmn.com/journals/list/browse?uid=TICS.etd00110_13646613_v0003i08_00001353&rendertype=abstract


TRADITIONAL CHINESE MEDICINE

---

Abstinence of drugs through acupuncture
The Nervus Science Research Center

CHINA, Jan 17, 2002 (AsiaPort via COMTEX) -- Han Jisheng, the Professor
from The Nervus Science Research Center of Beijing University, has found
that by stimulating four acupuncture points on human body with
low-frequency electric impulse, the resuming rate of the ex-addicts was
reduced to 70%.

The four acupuncture points are the inner pass point, outer pass point,
laogong point and the hegu point.

According to the introduction of Professor Han, in his research, he
found that through the stimulation to the four traditional acupuncture
points, which could change the secretion inhibition resulted from the
long time drug using, and enable its secretion function recover to the
state of self-support and reach the goal of abstinence of drugs.


Auricular (Ear) therapy acupuncture for addiction

Soothing instrumental music tinkles, as a medical staffer inserts
hair-thin, steel needles into the ear of a recovering drug addict.
Nearby, several people wait their turn.

It is a scene commonly found in thousands of substance abuse treatment
centers across the United States and Europe. And now it is showing up in
Maine.

ACCESS, Maine Medical Center's treatment program for mentally ill adults
dealing with substance abuse, is running a yearlong study to see if
auricular acupuncture, when used as an adjunct to counseling and medical
care, helps to reduce cravings for alcohol and drugs and relieve
tension. Proponents say acupuncture is integral to a well-balanced
treatment program.

Every Monday, Wednesday and Friday, an acupuncturist spends 2 1/2 hours
at the Portland ACCESS office, offering a modified form of the ancient
Chinese therapy to a steady stream of clients, who also receive group
and individual counseling.

While some of the state's 99 licensed acupuncturists and naturopathic
doctors may serve recovering addicts in their private practices, experts
believe that the ACCESS study is the first orchestrated attempt to bring
free acupuncture services to that population in nearly a decade.

The state Office of Substance Abuse is funding the study through a
$51,000 grant, a move its director, Kim Johnson, said speaks to the
state's growing openness to new ideas and alternative treatments as drug
problems in certain parts of the state grow more acute.

The study, which began in September, "is really our first experiment
around how it works with that population," Johnson said. "If the
outcomes are really positive, we could look at extending it."

There have been other attempts in Maine to provide free acupuncture
services to recovering addicts in a group setting. In the mid-1990s, a
substance abuse program called Crossroads for Women offered services at
a residential facility in Windham for about a year. Then funding ran
out, said Johnson, formerly with Crossroads.

Also during that period, the Westbrook Community Hospital, now Mercy
Hospital's Recovery Center, unsuccessfully tried to start a pilot
program that would enable patients to use Medicaid to pay for
acupuncture.

In Maine and most other states, Medicaid still does not cover
acupuncture treatments. Neither does the state's largest insurance
company, Anthem Blue Cross Blue Shield of Maine, unless acupuncture is
specifically written into one's policy.

"We're not saying acupuncture is good or bad, but right now the medical
benefits are not supported by the science," said Bill Cohen, spokesman
for Anthem, which stopped offering general coverage for acupuncture in
October.

Some studies show that acupuncture benefits recovering addicts, while
others show it has no effect.

Uncertainty about the efficacy of acupuncture in treating substance
abuse may be why it has received little exposure and funding for that
use in Maine, Johnson said.

"When money is relatively short, it's harder to do things that are
experimental," she said. Johnson added that other states "have used
acupuncture a lot for opiate abuse, which has only recently become a
problem in Maine" - a reference to the rise in OxyContin abuse and
heroin use.

Other states with severe drug and alcohol problems, such as New York,
Connecticut and Florida, "were desperate and willing to try anything,"
said Sheldon Ganberg, the acupuncturist who helped develop both the
Westbrook Community Hospital and ACCESS projects.

In Maine, state lawmakers "just weren't desperate enough. They weren't
willing to give up the funds," said Ganberg, who moved his practice to
Port St. Lucie this year, partly out of frustration.

ACCESS' Dr. Paul Ranucci, though, is optimistic that if acupuncture is
shown to be effective in Maine, it may be more readily used to "enable
(patients) to make more use of therapy to address personal matters that
contribute to their substance abuse." As a result, he said, clients
could stay in treatment longer and eventually become less dependent on
community services.

In places such as New York City, acupuncture is often coupled with
therapy to help substance abuse patients, said Dr. Michael Smith of
Lincoln Hospital in the South Bronx, founder of the National Acupuncture
Detoxification Association.

"We've been doing this 25 years," Smith said. "Almost every addict in
the New York area has heard about this if they haven't tried it."

On a trip to Maine in the mid-1990s, Smith gave a presentation on
acupuncture to the psychology staff at Maine Med. Ranucci, who attended,
became determined to start a project that would use NADA protocol, which
pairs counseling with a five-point acupuncture system.

The points on the outer ear represent the sympathetic nervous system,
kidney, liver, lung and shenmen, or "spiritgate." Stimulation of the
points is believed by some to establish normal neurochemical balance in
the brain and to speed excretion of substances from the body.

Elizabeth Garnett, who was hired by ACCESS, is one of the handful of
acupuncturists in Maine who is trained by NADA. With each of the study's
25 participants, she inserts needles into the same points on the ear.
Then the patients sit silently on couches for about 45 minutes.
Afterward, Garnett uses adhesive to stick a vaccaria seed on the ear of
the patient who wants to be able to press on a particular point without
her help.

Garnett used to offer acupuncture to recovering addicts in her own
practice, but was unhappy that some clients failed to also seek
counseling. She said the study at ACCESS - which stands for Adult
Assertive Community Treatment - creates an ideal situation by providing
one location for participants to get both services.

"Acupuncture does a great job in terms of helping deal with cravings and
withdrawal symptoms, anxiety and issues that came up," she said. "But in
terms of behavioral changes and long-term changes that one has to make,
you really need to have the counseling piece, both individual and
group."



NEURODEVLOPMENT FEATURE HIGHLIGHT

---

The Feldenkrais Method:
A Dynamic Approach to Changing Motor Behavior
Originally Published:20011201.

The Feldenkrais Method was designed as an approach to changing and
improving motor behavior over time-or simply, motor development-whether
within a single session or over years of training. Interestingly, the
Feldenkrais Method has been in practice since the 1940s, long before
many theorists began to recognize and study the connections between
dynamic systems theory and human motor behavior.

Little experimental research has been published that examines the
effects of Feldenkrais on performance. Regardless, its use with
individuals and groups is increasing in a variety of settings including
private practices, health clubs, schools and universities, and hospitals
and clinics (FELDENKRAIS GUILD of North America, 1996). Practitioners
might work with an infant learning to stand up from the floor; an older
adult trying to get down to the floor without falling; athletic teams,
dance companies, or orchestras seeking to refine performance; or workers
wanting to avoid repetitive motion complaints.

We begin with an overview of the Feldenkrais Method, then draw parallels
and distinctions between Feldenkrais and dynamic systems theory.

For information on the Feldenkrais Method please clink the link below.
http://www.healthy.net/asp/templates/news.asp?Id=3891


NUTRITION NEWS

---

New Research Uncovers Nutrient's Role What Choline
Does for the Brain And The Body

Body and mind both benefit from a dietary supplement called choline. Or
so say health and nutrition stores and Web sites. They sell drinks,
bars, and capsules with claims that these will enhance physical
endurance and mental suppleness.

Soon, the grocery store may be studded with banner labels extolling
products as good, if not excellent, sources of choline. Eggs, red meat,
and a variety of fortified foods will probably be among the first to
sport such tags.

Approved in October, these labeling claims are the first authorized
under a new federal law. It permits food manufacturers to identify their
products as a rich source of any nutrient that has previously been
established to be necessary for good health.

Not permitted on those labels, however, is any statement of a specific
health benefit. As such, few people would understand the reason for
purchasing foods high in choline, a nutrient that remains well below the
radar screen of most grocery shoppers.

Medical researchers, however, are exploring the effects of choline in
various arenas. In fact, for several years there has been clear evidence
that lack of choline can harm an individual's liver.

But more recent experiments in animals suggest that the compound can
have more subtle benefits. A few scientists are, for example,
investigating hints that extra choline in the adult diet boosts
brainpower.

Generating far more excitement is evidence that supplemental choline
given to a pregnant female can offer her offspring a wealth of life-long
benefits. A growing number of rat studies indicate that choline
enrichment in the womb can alter brain development in ways that
facilitate learning later in life.

Prenatal choline may even guard the brain against toxic assaults and
disease, not to mention senility and other neurodegenerative changes,
notes Christina L. Williams, who heads the department of psychological
and brain sciences at Duke University in Durham, North Carolina.

This may explain why the National Institute on Aging has been a major
sponsor of studies investigating effects of prenatal choline enrichment.
"After all," quips neuropsychologist H. Scott Swartzwelder of the Durham
Veterans Affairs Medical Center, "aging begins at conception."

A chemical building block of every cell, choline plays an integral role
throughout the body and throughout life. It's an ingredient of the
membranes surrounding cells. It also transports a cholesterol carrier
out of the liver and helps rid the blood of homocysteine, an amino acid
that at high concentrations increases the risk of heart disease.
Furthermore, choline is a precursor to molecules that relay signals
between nerve cells, including those in the brain.

Though the liver synthesizes choline, it may not produce adequate
amounts, at least from the food that some people in the United States
eat. Recognizing that a shortage of choline in the diet causes liver
damage, the Institute of Medicine (IOM) in Washington, D.C., established
the first choline recommendations three years ago. This organization,
which develops daily intake guidelines for vitamins and other nutrients,
advocates eating about 0.5 grams per day.

Meeting the IOM's dietary-intake goals, however, can be a hit-or-miss
proposition since there is a dearth of data on how much choline most
foods contain. Steven H. Zeisel's laboratory at the University of North
Carolina in Chapel Hill has just begun a systematic assay to quantify
the choline in commonly eaten U.S. foods. Performed for the Agriculture
Department, the tests should yield data on 300 of the most popular items
by January 2002 and 2,700 more over the following year.

New studies show, too, that prenatal nutrition may influence how much of
the nutrient an individual requires. Moreover, the IOM's nutrition
guidelines were developed to prevent liver damage, whereas optimum
health may require more choline.

More than a decade ago, Williams and her husband, Warren H. Meck, also
at Duke, began their studies of choline's impacts on rat brains.

Meck, a neuroscientist, had been enriching the diets of adult rats with
choline in hopes that it might improve their performance in certain
memory tests. He knew that choline was a building block of
acetylcholine. A chemical that nerve cells use in signaling, it plays an
important role in memory.

Recalls Williams, "I asked if he had considered administering choline
early in development," when the brain structures central to memory were
forming. He hadn't.

So, Meck and Williams launched a study in which they gave pregnant
female rats water laced with choline. This supplementation roughly
quadrupled the animals' normal choline intake. For a few weeks after
birth, the pups received injections of additional choline.

The scientists then tested these offspring throughout their short lives
on their recall of locations in a maze where the researchers had hidden
food. The experiment measured whether the rats could remember-and not
revisit-sites they had already emptied as they sought out the remaining
food during the day.

"We found that the prenatally supplemented animals clearly outperformed
the others," Williams says. With repeated testing, scores improved for
many of the animals in both the supplemented group and an unsupplemented
group that served as a control. Yet even after 16 weeks of daily
testing, she notes, the supplemented rats continued to make fewer errors
than the others did.

One aspect of the results was even more startling; Williams notes. The
more difficult the tests of memory and learning became, the bigger the
apparent benefit of that prenatal enrichment. The best explanation is
that the choline-supplemented offspring could "hold more information,"
Williams told Science News. "We know of no other treatment that
increases memory size."

Her group and others have repeatedly confirmed the findings. "What's so
amazing," Williams contends, is that the aptitude for learning in
prenatally supplemented animals "is as good in old age as it was when
they were young. They show no decline." In contrast, animals not
supplemented prenatally with choline show signs of senility in old age.
It appears that, with supplementation, "we're building a better brain,"
she says.

Nuances in choline action are showing up. By narrowing the window of
prenatal supplementation, Williams and others have identified only two
small periods during which extra choline boosts a rat's intelligence.
The first is from days 12 to 17 in gestation. This correlates roughly
with the second half of a human pregnancy. The other window runs from
two to four weeks after birth-a period that corresponds loosely with
human infancy and toddlerhood.

Recently, scientists have begun delving into what underlies that first
malleable period. It coincides with the formation of a complex network
of choline-sensitive nerve cells that sends information to a region of
the brain known as the hippocampus, Williams notes. This area is active
in learning and memory.

Five years ago or so, Williams and other researchers asked Swartzwelder
to look for signs that early choline exposure somehow changes the brain.
Dubious that a week of prenatal enrichment could smarten animals, much
less trigger detectable physiological changes, he nonetheless agreed to
a pilot study.

The results changed his perspective.

In a hippocampal neuron, certain patterns of incoming chemical signals
can trigger a response called long-term potentiation. During this
response, newly arriving signals are more effective than under other
conditions. The process helps cement memories by "promoting the encoding
and consolidation of new information. It's the first step in learning,"
Swartzwelder explains.

Compared with hippocampal tissue from unsupplemented animals, brains
primed with prenatal choline showed long-term potentiation more readily,
Swartzwelder found. When he then turned to brains from animals whose
mothers had been choline-deficient, he found hippocampal circuits
unusually resistant to the effect.

It appeared that choline is "powerful stuff," Swartzwelder recalls. But
to make sure of his results, he repeated the analyses, using rats reared
and treated by a different group of researchers. Again, he saw the same
effect. Overall, the greater the prenatal exposure to choline, the
larger the effect on the brain.

That was two years ago. Now, Swartzwelder is focusing on glutamate, a
primary chemical messenger responsible for triggering long-term
potentiation. Brain cells have specialized protein complexes, called
NMDA receptors, that respond to glutamate. They don't promote long-term
potentiation unless they receive closely timed signals from other brain
cells.

Swartzwelder's team has now shown that NMDA receptors in the brains of
animals that received prenatal choline enrichment are unusually
responsive to signals. This finding suggests that these animals might
make memories more readily than others do.

Prenatal supplementation with choline can also protect the brain later
in life. That finding, to be published soon in the Journal of
Neuroscience, is "the wildest thing of all," Swartzwelder says.

His group and its collaborators find evidence that choline can influence
the effects of a toxic drug. Prenatal supplementation protects neurons
in the brains of adolescent rats from the cell death ordinarily
associated with high doses of a drug that blocks the NMDA receptors.

Last year, prenatal choline supplementation in another study prevented
memory defects following drug-triggered brain lesions. The researchers
used a drug that induces convulsive epileptic seizures in rodents.
Epileptic seizures not only damage the brain, but they also tend to
impair memory and learning.

Gregory L. Holmes of Harvard Medical School's Center for Research in
Pediatric Epilepsy in Boston and his colleagues administered the
neurotoxic drug to rodents-some of which had received prenatal choline
supplementation-and then monitored the animals' learning skills.

Using a standard test of spatial memory, the researchers daily released
each rat into a pool of milky water and waited for the animal to find a
stationary platform just beneath the surface. Animals that had not
experienced seizures oriented themselves more quickly every day. This
learning showed up in rats whether or not they had received prenatal
choline supplementation.

After the experienced rats developed epilepsy, however, the pattern
changed. When tested a week after seizures, prenatally supplemented
animals remembered where the platform was and in succeeding days
continued to improve their performance. But rats that had received no
prenatal choline supplementation acted as if they had no memory of where
the platform had been and showed less improvement in finding it during
the following days.

If studies of people confirm an effect of prenatal choline on the
brain's response to assaults after birth, Holmes' team wrote in the
November 15, 2000 Journal of Neuroscience, these findings "could lead to
nutrition-based preventive strategies." The authors liken the
possibility to the use of folate vitamins now routinely prescribed to
pregnant women to prevent neural tube defects in the fetus.

Jan Krzysztof Blusztajn of Boston University, a co-author on that paper,
has been probing biochemical differences that arise from prenatal
choline supplementation.

Three years ago, he showed that extra choline available during
hippocampal development permanently modifies that area's efficiency in
using the nutrient. When choline concentrations in the womb are low, the
brain becomes "very frugal" with this nutrient, Blusztajn says, whereas
the choline metabolism of animals that encounter an abundance in the
womb "becomes quite wasteful." Prenatal conditions probably determine
how much choline an adult requires.

His studies indicate that an overly frugal hippocampus may lead to
problems. Its parsimony may leave little choline free to perform
mentally demanding activities

With a low stockpile of choline, production of the neurotransmitter
acetylcholine may prove insufficient to carry sustained highthroughput
communications between memory neurons. They just poop out and learning
slows. However, Blusztajn reports that prenatally supplemented rats
"have some sort of cognitive reserve-which is probably also a
biochemical reserve. It lets them sustain longer [choline-fueled]
neurotransmission."

Evidence is emerging that choline supplementation in adulthood, too, may
sometimes improve memory. This result comes from a study of people who,
because of gastrointestinal problems, receive virtually all of their
nutrition intravenously. Manufacturers don't regularly fortify with
choline most nourishment that's administered intravenously.

"We now know that between 20% and 50% of patients receiving
[intravenous] nutrition long-term develop liver disease," notes Alan L.
Buchman of Northwestern University Medical School in Chicago. Some die;
others may survive with transplants. In the September-October Journal of
Parenteral and Enteral Nutrition his team reports on a pilot study of 15
volunteers with gastrointestinal problems who were receiving intravenous
nutrition. Signs of liver damage disappeared in those seven who had been
randomly assigned to receive supplemental choline for 24 weeks.

The researchers also administered IQ and other tests to 11 participants.
These initially scored below normal on verbal, memory and visual memory
tests. In the January-February Journal of Parenteral and Enteral
Nutrition, the scientists reported that those scores improved
"significantly" in the men and women receiving supplemental choline.
This suggests, they said, that severe choline deficiency in adulthood
may impair memory reversibly.

Zeisel is beginning several more human trials. In one, resembling the
animal experiments, 80 pregnant women will be given specially prepared
waffles and asked to eat one with each meal from about 15 weeks into
their pregnancy until a month after their baby is born. Some of the
women will get normal waffles, the rest will get ones fortified with
either one egg or its choline equivalent in the form of soy lecithin.

When the women's babies are 10 and 12 months old, psychologists will
test the infants' visual memory-the child's recall of where Mom's
picture last appeared.

Zeisel has also just launched the first detailed analysis of how much
choline people need for basic health. Eighty volunteers will be held,
Zeisel says, for 71 days in a university metabolic ward. Everything they
eat and excrete will be measured. The food-resembling heavily fortified
milk shakes-will initially carry a normal range of recommended
nutrients. Then, all the participants will be switched to a choline-free
version.

They'll remain on that diet until enzymes indicative of liver damage
begin appearing in their blood. At that point, Zeisel says, "we'll begin
adding back increasing amounts of choline until we discover how much it
takes to return each to normal."

Because the test will include men and women, blacks and whites, and
premenopausal and postmenopausal women, it should determine whether
particular groups differ in their needs.

Today, few people exhibit overt choline deficiency. Zeisel suspects,
however, that at least some teeter on the brink of insufficiency.
Because the best-known choline-rich foods tend to be animal products,
especially ones high in fat, he worries that vegans and those who have
successfully pared most fat from their diet may be vulnerable.

Don't be afraid of eating eggs despite their cholesterol, he chides.
Their yolks are among the richest known natural sources of choline. A
tall glass of skim milk offers as much choline as an egg does. And
coming soon, predicts Gregory Paul, director of nutrition for Central
Soya of Fort Wayne, Indiana, will be a host of foods-orange juice, baked
goods, and pasta-- fortified with choline-rich soy lecithin.

So, keep an eye out for those new choline labels, Williams says; they'll
help identify "what we call food for thought."



RECIPE OF THE MONTH (and other good things to eat)

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"Baked Bananas with Sweet, Sour, and Spicy Sauce."

The notion that a green banana is a good banana is a grave
mistake. Brown spots on the skin are not a sign of spoiling,
but a sign that the bananas are ready to be consumed.
Rather than just "consuming" them, however, consider turning
your ripe bananas into a delicious dessert or snack worthy
of a gourmet palette. Danish chef Oscar Umahro Cadogan has
created for you the recipe "Baked Bananas with Sweet, Sour,
and Spicy Sauce." Note that all of the ingredients are
natural and address the special diet considerations for:
dairy-free, gluten-free, low fat, vegan, vegetarian,
anti-cancer, cardiovascular disease, inflammatory bowel
diseases.

This dish is meant as a dessert, but it also makes a good snack
in-between meals. Do not make this dish with bananas that are not fully
ripe.


* 4 tbs brown rice vinegar
* 4 tsp finely grated ginger
* 1 tsp nigella seeds, also called black onion seeds, roasted and ground finely
* 12 green cardamom pods, roasted and the seeds ground finely
* 2 ripe bananas, still in the skins


Cooking Instructions
1) Combine brown rice vinegar, grated ginger, nigella seeds, and
green cardamom together in a bowl and stir.
2) Bake the bananas in the skins for 15 minutes in a 400¡ F (200¡ C) hot oven.
3) Arrange each banana on a plate and slice both bananas open
lengthwise while still in their skins. Pour the rice vinegar/ginger
mixture over the openings in the skins and serve the bananas immediately
while still hot.



BOOK NOTES

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"Herbal Medicine for Children"
by Janet Zand L.Ac., O.M.D.

Herbal medicine has a long and respected history. Many
familiar medications of modern times were developed from
ancient healing traditions that treated health problems with
specific plants. Today, science has isolated the medicinal
properties of a large number of botanicals, and their
healing components have been extracted and analyzed. In
"Herbal Medicine for Children" Janet Zand L.Ac., O.M.D.
traces this history and points out that almost all of the
current research validating herbal medicine has been done in
Germany, Japan, China, Taiwan, and Russia. She explains the
various ways herbs are compounded, presents a chart of
common herbs and their uses, and offers suggestions for how
to work with an herbalist for treating children and adults.

http://healthy.net/asp/templates/article.asp?ID=1187


MIND/BODY/SPIRIT

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Laughter Proving To Be The Best Medicine

When was the last time you laughed really hard - a hearty,
sidesplitting belly laugh that suddenly grabbed you and sent
you reeling out of control? Or you laughed so hard that you
forgot what triggered it, leaving you laughing without
reason? Modern science is beginning to confirm that this
kind of laughter is not only enjoyable, it's also health-
promoting, reports Dr. David Sobel in "Good Humor, Good
Health." Laughter is an invigorating tonic that heightens and
brightens mood, gently releasing us from tensions and social
constraints. Dr. Sobel brings us up to date on what the research
on humor shows and how we can use humor to stay healthy.

http://healthy.net/asp/templates/column.asp?PageType=Column&id=187

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Thank you for Visiting the On Demand NewsLetter...Please feel free to email this news letter to a friend.

Thank You,
The CrossRoads Team

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