鈥淲HEN Michael first started school at the age of 5 his writing was appalling.
You could hardly read a thing he wrote,鈥� says his mother. 鈥淗e went from being a
happy child to being very unhappy, miserable, tearful, because he just couldn鈥檛
understand why all those children around him could pick up this business of
reading and writing.鈥�
Michael鈥檚 teachers simply thought he was taking a little longer than the
other children鈥攖hat he鈥檇 catch up. It was three years before anyone
realised that he was dyslexic. Now, at the age of 18, Michael has the reading
age of a 12-year-old and the spelling ability of a 10-year-old.
快猫短视频s want to know what causes this strange condition, and why it only
becomes apparent when a child reaches the classroom. Dyslexia shows up as a
poorer reading and writing ability than expected from the child鈥檚 intelligence.
But because there is so much natural variability in how fast children learn to
read and write, the condition is often not properly diagnosed. Some people still
consider dyslexia an excuse for not learning or being taught well, and there are
many children like Michael who have been unfairly labelled as slow learners.
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People with dyslexia have no difficulty understanding the meaning of words,
recognising individual letter shapes, and seeing anything other than text. This
has led many scientists to say that dyslexia is caused by a specific problem
with the language centres in the brain. But momentum is gathering for a
completely different explanation.
John Stein of Oxford University, who specialises in vision, is the real
champion of this new theory. He says that the condition arises from an inability
to sense the most rapid changes in the world around us, particularly in what we
see and hear. This would mean there鈥檚 much more to the condition than a problem
with language and the more obvious reading and writing difficulties. 鈥淢y strong
belief is that dyslexia is a widespread neurological problem,鈥� says Stein.
Stein thinks that during fetal development, something damages or attacks
vulnerable young nerve cells as they grow and try to connect inside the brain.
But curiously, this is a very selective attack, targeting only those nerves that
relay information about fast-changing events. The most controversial part of his
theory is that the attack may come from the mother鈥檚 own body鈥攆rom her
immune system.
If he is right, this could explain a whole host of other lesser known
problems that researchers and people who work with dyslexic children have
associated with the condition. Many say that children with dyslexia can be
clumsy, with poor balance and coordination. There is other research and
anecdotal reports that children with dyslexia can have problems with memory, so
that remembering a list of instructions, or the days of the week and the months
of the year, can be tricky. But these are subtle mistakes that young children
often make, so they are easily overlooked and hard to quantify, particularly in
an otherwise intelligent and able child.
It is Stein鈥檚 discovery that there are specific defects in the way dyslexics
perceive the visual world that lies at the heart of his new theory. Although
vision may seem at first to be an obvious place to look for the cause of a
reading problem, calling dyslexia a visual defect has been surprisingly
controversial. People with dyslexia are certainly not blind, they seem to have
normal visual acuity and don鈥檛 notice problems with their view of anything other
than text. So Stein鈥檚 theory is stirring up a hornet鈥檚 nest among psychologists.
鈥淭o have Stein come along and say vision is part of dyslexia is very unpopular,鈥�
says Martin Turner, chief psychologist at Britain鈥檚 Dyslexia Institute.
Stein and his colleague Joel Talcott have been asking people to watch two
computer screens displaying what look like snowstorms of tiny dots moving around
at random鈥攕imilar to the 鈥渨hite noise鈥� on a poorly tuned TV set. At the
push of a button, Talcott makes some dots on one screen move in the same
direction. The challenge is to see how many dots must move together for the
viewer to notice. In a series of studies they have shown that people with
dyslexia are less likely to spot the change; they need more dots to be
synchronised before they notice the movement.
This seemingly simple observation turns out to be a good way of telling how
severe the dyslexia is. 鈥淭hey go hand in hand,鈥� says Stein. The poorer the
ability to detect a change in motion, the worse the reading and spelling. This
has convinced him that the visual system has an important part to play in
dyslexia.
Stein suggests that the defect lies in a set of very large nerve cells known
as magnocells. These cells form a pathway from the retina to the area where
information about images from the left and right eyes first combines鈥攖he
lateral geniculate nucleus 鈥攁nd onwards to the visual cortex. Their large
size and thick insulating coats of the fatty substance myelin enable them to
carry electrical impulses鈥攖he essential messages of the nervous
system鈥攆aster than other nerves. Their speed is crucial to their role of
telling the visual cortex about rapid changes or movement.
Other researchers agree that there鈥檚 something strange about this
magnocellular pathway or 鈥淢-pathway鈥�. In particular, Margaret Livingstone and
Albert Galaburda from Harvard Medical School in Boston have used arrays of scalp
electrodes to track the electrical signals in the brain. They found that the
M-pathway of dyslexics is slower to send impulses from the retina to the visual
cortex by about 50 milliseconds, potentially double the normal transmission
time鈥攁 significant delay given that the difference between the timing of
the bat required to hit a six at cricket and missing the ball altogether is only
a few milliseconds.
Livingstone and Galaburda have also looked at postmortem brain tissue from
people with dyslexia, and found that the M-pathway neurons look abnormal under
the microscope. Many are in the wrong place and they are often smaller than
usual.
Further evidence comes from Guinevere Eden, who worked with Stein at Oxford
before moving to the US National Institutes of Health. In 1996, she reported
that people with dyslexia have less brain activity than usual in the part of the
visual cortex that detects motion, known as V5 (Nature vol 382, p 66).
Last year, Jonathan Demb and David Heeger from Stanford University in California
confirmed and extended these findings, showing that there are also defects in
the primary visual cortex, area V1, the first cortical region to receive visual
information. Both V1 and V5 depend heavily on M-pathway neurons for their
input.
Although text isn鈥檛 usually moving, reading is not as smooth a process as it
seems and defects in the M-pathway could easily cause difficulties with reading
and writing. In a series of quick eye movements punctuated by brief pauses, the
retina fixes a sequence of images of the page. The brain lines up each image
next to the previous, slightly different one, to gain a smooth impression.
Normally, the M-pathway controls these eye movements. Stein has found that many
dyslexics, however, find it difficult to hold their eyes steady between eye
movements. This is only to be expected, he says, if the M-pathway is failing to
send adequate stabilising information to the brain. If the eyes are not steady,
they will send images that are moving slightly, which could explain, says Stein,
why dyslexics often complain that words seem to blur and dance around on the
page.
What is not so clear is how a visual defect can go completely unnoticed
except when reading or writing. However, Stein points out that a dyslexic
person鈥檚 perception of colour, shape and texture is normal. Colour and shape are
mostly conveyed to the visual cortex by a set of smaller neurons, known as the
parvocellular pathway or 鈥淧-pathway鈥�. The combined activity of the M-pathway and
the P-pathway create the visual scene, and subtle defects in perceiving any one
aspect of the visual scene are usually compensated for. Reading and writing,
says Stein, require a kind of attention to small, uniformly sized symbols that
other visual scenes, such as a view of the countryside or high street, do
not.
The separation of visual scenes into these two processing pathways may
explain why some people with dyslexia find it helps to place coloured sheets of
acetate over text or to wear colour-tinted lenses when trying to read. These,
says Stein, reduce the contrast of black letters on the white page, and shift
the visual burden from the M-pathway to the P-pathway.
But vision is clearly not the whole story. Although most dyslexics have
perfectly normal speech, many will have been slow to learn, muddling words to
produce, say, 鈥減ar cark鈥� instead of 鈥渃ar park鈥�, or 鈥渜uebebar鈥� instead of
鈥渂arbeque鈥�. Many also confuse sounds such as 鈥渟鈥�, 鈥渟h鈥�, 鈥渢h鈥�, 鈥渇鈥� and 鈥渧鈥� when
trying to read aloud, and may have trouble telling that 鈥減it鈥� and 鈥渂it鈥�, for
example, have the same endings but different beginnings.
This difficulty in analysing the smallest units of speech, or phonemes, is
characteristic of dyslexia, and a reason why many linguists believe that
dyslexia is a specific language defect. 鈥淭he extent to which you are a good oral
language user when you enter school is highly related to literacy skills later,鈥�
says cognitive neuroscientist Paula Tallal, of Rutgers University in Newark. She
agrees that there may be broader abnormalities in the nervous system of
dyslexics, but questions the relevance of the altered visual perception.
Tallal has shown that dyslexics have a problem with a variety of sounds. In
particular, they fail to hear two pure tones as separate if they are presented
too close together鈥攔ather like a rapid version of the 鈥渄ing-dong鈥� of an
electronic door bell. Most people notice the change if the gap between tones is
about 40 milliseconds or more, but people with dyslexia find this too rapid to
detect. Sounds such as 鈥渂a鈥� and 鈥渄a鈥�, which are also hard for dyslexics to
discriminate, involve similarly rapid changes in sound frequency.
Sound and vision
Stein and his group say that these auditory and visual problems are linked.
The threshold for sound detection suggests that there might be a delay in the
sound-processing pathways, similar to the visual delay in the M-pathway. In a
paper published last year in Current Biology (vol 8, p 791) Stein鈥檚
colleague Caroline Witton reported that people who have trouble detecting
rapidly changing visual signals also have problems detecting fast sound changes.
The severity of these defects also correlates with people鈥檚 ability to read and
spell.
Stein suggests that there may be the equivalent of an M-pathway in the
auditory system, which might also be damaged in dyslexia. In support of this,
Galaburda and colleagues have discovered that there are large neurons in the
sound-processing area of the brain, the medial geniculate nucleus, which are
less numerous and smaller than normal in people with dyslexia.
Stein is now taking his arguments a step further. He believes that the defect
in processing rapid sensory information in dyslexia extends even beyond the
visual and auditory systems. With Caroline Rae of the MRC magnetic spectroscopy
unit in Oxford, he has shown that the chemical reactions of the body鈥檚 automatic
pilot, the cerebellum, are slightly different in people with dyslexia, which
could explain why some people with dyslexia are more clumsy and less coordinated
than normal. They are currently looking at the signals from the skin-sensing
pathways to see whether there might be an equivalent to the M-pathway and a
delay here too.
But given all the physiological evidence that dyslexia is a sensory deficit,
rather than a language disorder, Stein鈥檚 next step is to try to explain how the
defects in large M-pathway neurons arise in the first place. Perhaps only then
will he succeed in convincing his sceptics. To be in such a state of disarray,
he thinks something must have prevented the neurons from developing properly in
the fetal brain. The answer, he believes, lies with the way dyslexia runs in
families.
Stein has teamed up with geneticist Tony Monaco from the Wellcome Trust
Centre for Human Genetics in Oxford to try to identify which genes are
responsible for dyslexia. By studying families in which at least two members
have dyslexia, the team found that those members shared a group of genes that
are found on a particular part of chromosome number 6. The shared region is
suspiciously close to a group of genes called the MHC genes, which control the
human immune system. Their role is to code for the cell-surface proteins that
white blood cells use to recognise the difference between our own body and
invading viruses.
Monaco remains cautious about claiming that it is the MHC genes that cause
dyslexia, because there is no direct proof that the group of genes shared by
dyslexics is not just a neighbouring group. But even though the brain and the
immune system are held to be entirely separate, there are some indications of
how the immune system could influence M-pathway development.
One possibility was suggested last November by Carla Shatz from the
University of California, Berkeley, who has been studying the visual system in
cats. Normally, as the brain grows, new neurons grope around with long slender
protrusions, making contact with others nearby to discover whether they are in
their correct positions. Shatz identified an important molecule used by neurons
to decide when they have made the right contacts鈥攁nd it turns out to be an
MHC class I protein, produced by the MHC genes (Neuron, vol 21, p 505).
Furthermore, its partner molecule, called zeta, which recognises its shape and
binds to it, is also found on neurons. Shatz believes that the dual function of
MHC proteins is a well designed economy within the body.
Although she hasn鈥檛 yet found exactly which neurons use the MHC signals, she
did find that the parts of cats鈥� visual system with the most MHC gene activity
were in the areas that receive the greatest input from M-pathway
neurons鈥攖he lateral geniculate nucleus and the V1 region. She also found
the MHC genes were active in the medial geniculate nucleus, where auditory
processing takes place, as well as in the hippocampus, which is important for
memory formation.
The next question is to ask whether the same MHC genes help to wire up the
visual and auditory pathways of humans, and whether this activity is somehow
abnormal in dyslexics. 鈥淭he door is wide open to figure out what expresses class
I,鈥� says Shatz. 鈥淚t would be extremely cool for people to look at
诲测蝉濒别虫颈肠蝉.鈥�
But Stein prefers another idea. He thinks that during pregnancy the mother
may make antibodies against the fetal neurons, and that these antibodies cross
the placenta into the fetal circulation and end up in the baby鈥檚 brain. Here
they could stick to, and mask, the surface markers on the magnocells. Without
the right markers on the surface of the neurons, they may fail to grow and
connect properly, and may even die.
Early intervention
Stein has some preliminary evidence to support his antibody theory. Mothers
may continue producing antibodies against the fetus for years after giving
birth, and sometimes do have antibodies in their bloodstream which can recognise
the neurons of their own children. Stein and Angela Vincent from the Institute
for Molecular Medicine in Oxford, have been investigating whether, after
injecting antibodies from mothers of dyslexic children into pregnant mice, any
cross the placenta and fetal blood brain barrier.
Interestingly, many of the offspring developed coordination problems. But it
is far too early to say whether the maternal antibodies actually cause this
problem, still less what happens in humans. Livingstone thinks the idea that an
immune attack on the fetus might lead to dyslexia is speculating too far. 鈥淚t鈥檚
a real stretch,鈥� she says.
Whatever the underlying cause, Stein hopes that dyslexia will be seen as a
far broader syndrome than at present. His tests of visual perception could lead
to routine ways of identifying the more subtle differences between individuals
with dyslexia. 鈥淎rmed with this knowledge teachers will be able to remediate a
child鈥檚 particular weaknesses,鈥� he says. More importantly, he would like to see
dyslexia diagnosed more quickly and at an earlier age, perhaps using simple
tests like the moving dots. This would be a cause for rejoicing, says Turner.
鈥淚f you could introduce tests at, say, the age of three, then you could
intervene early and reduce the long-term suffering of many people.鈥�
