John Stein, University Laboratory of Physiology, Oxford, UK

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The Brain Basis of Dyslexia

• John Stein, University Laboratory of Physiology,
  Oxford, UK

• Why reading is difficult visual and auditory
  requirements
• Dyslexia diagnosis and incidence, overlap with
  other neurodevelopmental conditions
• Impaired visual magnocellular development ?
  unstable binocular control ? visual confusion
• Impaired auditory development ? phonological
  confusion
• Impaired motor development ? speech impediments,
  clumsiness, poor handwriting
• Heredity dyslexia genes on Chromosomes
  1,2,6,15,18
• Environment immune system, nutrition fish oils

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Reading is difficult because it requires 1.
Rapid visual identification of letters, even in
experienced good readers 2. Rapid sequencing of
their order 3. Rapid translation into the sounds
they stand for 4. Background knowledge of
splitting words down into constituent phonemes
(phonology)
3
Reading is difficult!

• 20 of UK and US adults cannot find the word
  plumber in the yellow pages
• Difficulty learning to read is one of the
  greatest causes of individual and family misery
• Loss of self-confidence, depression, alcoholism,
  drug addiction, suicide
• Anti- social behaviour, aggression, crime
• 3/4 of prisoners in gaol are illiterate ½
  dyslexic
• Commonest cause of disability in University
  students

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Developmental dyslexia
0037 Valerius Maximus 1897 Berlin
Dyslexia 1898 Pringle Morgan Word
blindness 1930s Samuel Orton -
strephosymbolia 1950s McDonald Critchley Parietal
lobe 1960s Social explanation - Middle class
children are dyslexic,working class children are
thick!
1980s Linguistic theory - phonological
deficit 1990s Development of the brain is
different planum temporale, ectopias, problems
with all kinds of timing and sequencing
2000s Magnocellular theory impaired development
of visual, auditory and motor magno-neurones
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Percy F (Dr Pringle Morgan, 1896)

• Percy F has always been a bright and intelligent
  boy, quick at games and in no way inferior to
  others. His great difficulty is his inability to
  learn to read. This inability is so remarkable
  and so pronounced that I have no doubt that it is
  due to some congenital defect. In spite of
  laborious and persistent training, at the age of
  13 he still cannot even spell his own name, often
  writing Precy for Percy

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What is Developmental Dyslexia?
Reading and spelling significantly below that
expected from age and IQ
Symptoms 1. Reading/IQ discrepancy 2. 80
males 3. Poor phonology 4. Speech impairments
(lisps, spoonerisms, mispronuciations 5.
Unstable vision, visual confusion 6. Poor
spelling 7. Mixed handedness, left/right
confusions 8. Sequencing problems 9. Clumsiness
incoordination soft cerebellar signs
History 11. Family History of language, literacy
and psychiatric problems. 12. Difficult
birth 13. Delayed milestones (crawling, walking,
speech) 14. Developmental dyspraxia, dysphasia
hyperactivity 15. Otitis media _at_ age 1-3 16.
Asthma, eczema, hayfever
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Brain Differences in Dyslexia Ectopias (brain
warts) outgrowths through surface, particularly
in left language areas Symmetrical planum
temporale Thinner axons in left
hemisphere Smaller visual magnocells Less
activity in visual motion areas, left angular
gyrus, Wernickes and Brocas areas when
reading Delayed visual evoked potentials
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Your Brain

• 100 billion (1011) nerve cells (neurones)
• 10,000 contacts (synapses) between neurones
• ? 1 million billion (1 quadrillion 1015)
  connections
• More possible combinations of connections than
  there are particles in the Universe
• Your brain is the most complex organised entity
  in the whole Universe
• Reading is the most complex skill that most of us
  learn

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The Brains Reading System

• Input from eyes via relay in LGN to primary
  visual cortex at the back of the brain
• Further visual processing moving forwards in
  secondary visual cortical areas
• Links with auditory processing in angular gyrus
  to form lexicon (representation of visual and
  auditory form of words and their meaning)
• Projection forwards to speech areas, for internal
  speech as well as reading out loud

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Overlap (comorbidity) between developmental
dyslexia, dysphasia, dyspraxia, ADHD, autism
abnormal magnocellular neurones?

• Dyslexia - reading and spelling difficulties,
  unsteady eyes, visual and auditory inattention,
  incoordination
• Dysphasia (specific language impairment) speech
  impediments (mispronounciation, lisps,
  stuttering) auditory inattention, incoordination
• Dyspraxia incoordination, poor motor planning/
  execution, inattention
• ADHD -hyperactivity/impulsivity, inattention,
  incoordination
• Autism - inattention, incoordination, absent
  social communication skills
• All caused by impaired development of magnocells?

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The main problem for many dyslexics is visual
instability letters words appear to move
around and wobble. This is because their eyes
wobble when they try to read
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The Visual Problem of Reading
When reading the eyes are on the move most of the
time. Words can only be identified during very
brief fixations lasting 1/3rd sec.
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The visual magnocellular system controls reading
eye movements
10 of retinal ganglion cells are magnocellular
(large) they respond rapidly to time visual
events accurately they detect visual motion,
direct attention, control eye movements and
enable steady eye fixation
80 are parvocells (small) for colour, fine
detail, slower responses.
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The visual magnocellular system is impaired in
dyslexics

• Smaller LGN magnocells post mortem
• Delayed motion evoked brain waves
• Lower sensitivity to visual motion

• Reduced activation of V5/MT
• Lower contrast sensitivity
• Slower direction of visual attention
• Unstable binocular control

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Homophone test of orthographic skill
Which of rane and rain is the proper
spelling? This task demands accurate memory of
the words visual form - orthography. It cant
be solved by sounding out the letters because
both spellings sound the same. This homophone
test is the best predictor of reading skill in 10
year-old children Visual magnocellular motion
sensitivity predicts homophone/orthographic
performance. Over 1/5th of the differences
between peoples orthographic reading ability can
be explained just by their visual motion
sensitivity. Visual magnocellular sensitivity
affects how well children can develop visual
orthographic skill.
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Why should weak visual magnocellular function
impede reading?

• Many researchers believe that the only cause of
  dyslexia is poor phonological skill
• True but why cant dyslexics acquire good
  phonological skill?
• Because they have visual and auditory processing
  problems
• Letters tend to blur and jump around, and the
  letter sounds mix up.

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The visual magnocellular system stabilises the
eyes
Retinal motion, slip
Steady eye fixation
Feedback to eye control
Visual stability
Identify letter order
Orthographic skill
18
Visual Reading ProblemsChildrens quotes reveal
their unstable vision - oscillopsia
The letters go all blurry The letters move
over each other, so I cant tell which is
which The letters seem to float all over the
page The letters move in and out of the
page The letters split and go double The c
moved over the r, so it looked like another
c The p joined up with the c ds and bs sort
of get the wrong way round The page goes all
glary and hurts my eyes I keep on losing my
place
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DYSLEXICS IMPAIRED VISUOMOTOR FUNCTION

• Unsteady binocular fixation (wobbly eyes), hence
  unstable visual perception
• Jerky pursuit eye movements
• Restricted jerky vergence control

• Slower mental rotation
• Inaccurate dot localisation
• Lose place following vertical lines
• Slower visual search - less pop out

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Fixation Exercises
Double blind, randomised controlled trial
Reading increased 6 months in 3 months, ie 2
months/month Without special help these dyslexics
would probably only have gained 9 months in 18 ms
(ie ½ m/month) Best phonic remediation
programmes achieve 1 month per month also much
more expensive than a patch
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Vergence control

• The eyes have to converge for near vision when
  reading
• The vergence eye movement control system is
  highly vulnerable (eg alcohol makes you see
  double!)
• Control of vergence eye movements is dominated
  by the visual magno system
• Dyslexics have very unstable vergence control

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Patching the left eye
Double blind, randomised controlled trial
Reading increased 3 yrs in 18 months, ie 2
months/month, 25 scale points Without special
help these dyslexics would probably only have
gained 9 months in 18 ms (ie ½ m/month) Phonic
remediation programmes usually achieve only 1
month per month improvement also much more
expensive
23
Yellow Filters

• Retinal magnocellular ganglion cells receive 45
  from red (LW) light receptors (cones) 45 from
  green (MW) and 10 inhibition from blue cones
• Deep yellow filters eliminate the inhibitory blue
  cone input
• Hence yellow enhances magnocellular sensitivity -
  visual motion, binocular control
• 1/3rd of dyslexics benefit from wearing yellow
  filters for 3 months their eye control improves
  and their reading progress can increase four fold

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Blue Filters

• c. 10 of dyslexics seem to have too weak blue
  input to magnocells
• These children often complain of glare and
  letters moving around
• Blue filters can improve their reading
  dramatically (8 months in 3 ms)

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Coloured Filters

• In summary we find that the vision of c.40 of
  dyslexics can be helped by giving them simple,
  cheap, yellow or blue filters for 3 months
• These correct imbalanced input to visual
  magnocellular neurones
• Other colours expensive systems do not help so
  much because they do not selectively affect the
  input to the visual magnocellular system

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Treatment

• Understanding the role of the visual
  magnocellular system in the acquisition of
  orthographic skill has led to significant
  improvements in treatment
• Coloured filters can help 40 of dyslexics to
  quadruple their reading progress
• Binocular exercises or monocular patching can
  help another 1/3rd to quadruple their reading
  progress

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Auditory/phonological errors due to poor
auditory discrimination?

• Whisk/wisp, deaf/death, effect/affect
• They came down on the food like a flock of
  vouchers
• The gossip spread like wild flies
• This strike will bring the country to a Stanstead
• Dry as a door nail dead as rust a cartoon of
  soup
• Ears (eves) dropping an endearment (endowment)
  policy
• Sort (saute) of potatoes customs and exile
• After a time I syphoned (deciphered) it
• Concord is so noisy too many decimals
• I torned and tussed all night
• Its just like flogging a brick wall

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Does auditory sensitivity determine phonological
ability?

• High auditory sensitivity to changes in sound
  frequency (FM) and amplitude (AM) is required to
  distinguish letter sounds
• Dyslexics have lower than normal sensitivity to
  frequency and amplitude modulated sounds

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Auditory sensitivity Phonology

• Nonsense words - tegwop, blint, plomt,
  peltip,visht can only be read if the letters
  can be translated into their sounds quickly and
  accurately
• Nonword reading tests phonological ability
• Individuals FM AM sensitivity predicts their
  ability to read these nonsense words

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• Sensory Basis of Reading Skills
• In summary nearly 2/3rds of the differences in
  childrens reading abilities can be explained by
  their non reading IQ, and how sensitive their
  visual and auditory magnocellular systems are
• Teaching quality and other sociocultural
  influences account for less than one third
• Nevertheless good teaching is crucially important!

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Motor Disorders in Dyslexia

• Cerebellum is brains autopilot for prediction
• Magnocellular Systems project to the cerebellum
• Cerebellar neurones stain for CAT 301 hence it
  is part of the magno system
• Cerebellum is underactive in Dyslexics
• Explains their balance and coordination problems,
  but not their reading difficulties
• Therefore expensive balance exercises unlikely to
  help dyslexics reading

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Genetic Studies

• In over 300 Oxford families we have analysed the
  DNA of father, mother and at least one dyslexic
  child
• To find out whether particular chromosomal sites
  are associated with poor reading
• Strong associations with C6 and C18 found
• We are now searching these sites to identify
  genes that may contribute to the differences in
  brain development found in poor readers.
• This will clarify why the development
  magnocellular neurones is impaired in dyslexia

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Dyslexia, Genetics and the Immune System

• Development of magnocellular neurones is
  regulated by the immune system recognising magno-
  surface antigen, CAT 301
• Linkage of poor reading to immune control genes
  on Chromosomes 6 18
• High incidence of immune anomalies in dyslexics
  allergies, asthma, eczema, lupus
• Evidence for antimagno antibodies in serum of
  some mothers with dyslexic children

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Dyslexic Mice!

• All mothers develop antibodies to their foetus
• Some cross the placenta (eg rhesus
  incompatibility)
• A few cross into the brain and damage it (eg
  Rasmussens encephalitis)
• Mouse model of placental transmission (Angela
  Vincent, Oxford)
• Serum from mother with 2 dyslexic children
  injected into pregnant mice
• Coordination of pups impaired
• Cerebellar metabolism (MRS) abnormal
• Antibodies bound to mouse cerebellar Purkinje
  cells
• ie mothers antibodies can attack foetal brain
  magnocells
• But its not mums fault! Placenta is foetus
  tissue and vulnerable

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Why Fish Oils?

• Hugh Sinclair, Magdalen College, Oxford,
  persuaded wartime government to give cod liver
  oil to all pregnant mothers and children
• Highly unsaturated fatty acids (HUFAs) constitute
  20 of the weight of the brain
• HUFAs particularly important for magnocellular
  function
• Treatment with HUFAs can improve reading
• My brother is a well known fish chef in Britain,
  Rick Stein!

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Fatty Acid Deficiencies in Dyslexia?

• Some dyslexics have signs of HUFA deficiency dry
  bumpy skin, dry scurfy hair, brittle nails,
  excessive thirst, frequent urination
• Low blood and brain HUFAs
• Elevated levels of PLA2 enzyme
• Treatment with HUFAs can improve attention,
  coordination and reading

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Magnocellular Neurones

• A rapid reaction system of large neurones with
  fast transmission
• They time changes in intensity, frequency,
  position
• Found throughout the nervous system visual,
  auditory, skin, muscles, cerebellum
• They recognise each other because they have same
  surface antigen, CAT 301

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Magnocellular Neurones

• Development controlled by immunological (MHC)
  regulation site on chromosome 6
• Impaired development in developmental dyslexia,
  dyspraxia, dysphasia, ADHD, autism, prematurity,
  Williams syndrome
• Association of these conditions with
  autoimmunity asthma, eczema etc
• High dynamic sensitivity requires high membrane
  flexibility provided by highly unsaturated fatty
  acids (fish oils)
• Hence they are vulnerable to HUFA deficiency (we
  eat too little fish!)

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Fast magnocellular neurones are especially
vulnerable to lack of highly unsaturated fatty
acids (HUFAs omega - 3 fish oils) Their fast
ionic channels expand when they open so they
need flexible HUFAs in the surrounding membrane
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Conclusions

• Dyslexics reading, spelling, attentional and
  coordination problems may all result from
  impaired development of magnocellular neurones in
  the brain these are specialised for tracking
  transients, visual, auditory, motor
• Visual magnocellular weakness causes visual
  instability, hence letter position confusions ?
  fuzzy orthographic representations, leading to
  poor orthographic skill.
• Auditory magnocellular weakness impedes
  letter/sound translation ? low phonological skill

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Conclusions 2

• Weak magnocellular function may result
  from Genetic vulnerability Immunological
  attack HUFA deficiency
• However do not be downhearted! These weaknesses
  can be remedied eye exercises, coloured
  filters, phonological training, fish oil
  supplements
• BUT remember Einstein, Churchill were dyslexic!

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Neurones, Genes Fish, the Brain Basis of
Dyslexia

• John Stein, University Laboratory of Physiology,
  Oxford, UK

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