The Current Status of the Magnocellular Theory of Dyslexia

John Stein, Magdalen John Stein, Magdalen College, College,

Oxford University, UKOxford University, UK

Supported by The Dyslexia Research Trust (www.dyslexic.org.uk), Dyers & Colourists, Esmee Fairbairn, Garfield Weston and Wellcome

Trusts, BBC Children in Need

DDRR

TT

1/3rd of English Children Leave School Unable to Read

Backward Reading

• Many children are poor readers simply because of low intelligence (‘garden variety’) or v. poor teaching

• Developmental dyslexia is reading significantly below that expected from child’s age and intelligence, despite good health, teaching and family support

• Dyslexia is more than reading - a neurological syndrome, involving slower processing, inattention, poor sequencing in all domains, poor short term memory

• ? caused by impaired development of ‘magnocellular’ timing neurones

Many possible levels of analysis

Genetics

Neuroanatomy

Neurophysiology

Psychophysiology

Cognition – phonology & orthography

Behaviour–reading & spelling

Definitions of Dyslexia

• Highly contentious: descriptive or aetiological?• Phonological definition purely descriptive and

tautologous – cf high blood sugar• Aetiological definitions – informed by

understanding cause eg insulin lack• Dyslexia – many possible levels; none map

perfectly onto each other• Magnocellular hypothesis is a unifying aetiological

theory linking genetics, physiology, cognition

Magnocellular Neurones

• Impaired m- cell development has been found in prematurity, foetal alcohol syndrome, developmental dyslexia, dyspraxia, dysphasia, ADHD, ASD, Williams, schizophrenia, depression, violent personalities

• High dynamic sensitivity requires high membrane flexibility provided by local environment of essential fatty acids, particularly omega 3s, found in fish oils

• Hence very vulnerable to omega-3 deficiency

• A system of large neurones specialised for temporal processing – tracking changes in light, sound, position etc. for direction of attention

• Large, fast conduction, fast transmission, high anisotropy

• All express same surface antigen, CAT 301

• Found throughout the whole brain: visual, auditory, skin, muscle proprioceptors, cerebral cortex, hippocampus, cerebellum, brainstem

Chromosome sites we have linked to reading skill

C6p ?KIAA 0319 gene - cell~cell recognition and immune control (MHC system)

Also DCD gene

Finnish pedigree

DYX1 gene

ROBO 3 gene

KIAA 0319 is strongly expressed

in dorsal visual

magno- cellular

pathway

C6 KIAA 0319 controls neuronal migration during early brain development in utero. Downregulation in

dyslexics may explain ectopias and other mismigrations of magnocellular neurones

2nd trimester ectopias in dyslexic brain. Seen also in auto immune mice

Abnormal magnocells in dyslexic brain

Dyslexia and the Immune System

• All magnocells (visual, auditory, motor) express common surface antigen – CAT 301

• Development of magnocellular neurones is known to be regulated by the MHC cell recognition immune system on chromosome 6p

• Linkage of poor reading to surface recognition gene KIAA 319 on Chromosome 6p close to MHC genes

• 50% of BSXB ‘autoimmune’ mice exhibit ectopias that are similar to those seen in dyslexic brains

• Our evidence that serum of mothers with dyslexic children contains antimagno antibodies

• Dyslexia is associated with autoimmune anomalies – allergies, eczema, asthma, lupus

Autoimmune conditions in dyslexics and controls

migraineuveitis

asthma

eczema

allergies

0

5

10

15

20

25

30

1 2 3 4 5

% a

ffect

ed Dyslexic

Control

High incidence of immune anomalies in dyslexics

Reading is primarily a visual process

Visual processing

Pathways through the visual system• Parvocellular

– High Spatial, Low Temporal frequencies

– Colour sensitive

• Magnocellular– Low Spatial, High

Temporal Frequencies– Insensitive to

isoluminant changes in colour

• Magnocellular deficit theory of dyslexia:•Deficit in the magnocellular system•Parvocellular system undamaged

Visual magnocellular system dominates dorsal visuomotor pathway -directs visual attention &

eye movements.

The visual magnocellular system is impaired in poor readers

• 30% smaller LGN magnocells post mortem

• Reduced and delayed evoked brain waves

• Unstable eye control• Reduced visual motion sensitivity• Lower sensitivity to flicker• Lower sensitivity to low spatial, high

temporal frequency contrast gratings

• Reduced activation of cortical visual motion areas (FMRI)

• Lower stereoacuity • Poor visual sequential attention -

slower visual search

• All these claims are controversial -3 problems:

• Definition of magno- system; strictly only definable anatomically in periphery

• Selectivity of stimuli• Mild deficit requires highly

sensitive test to reveal it• Nevertheless in the last 10 years

90% of new research papers have supported magnocellular deficit

• Brent Skottun has written 15 papers criticising others work!

Abnormal magnocells in dyslexic brain (but only 5 brains!)

DTI - Fewer large axons in left angular gyrus in dyslexics. Successful remediation increases their size

Delayed Brain Potentials Evoked by Moving Visual Stimulus (10 hz component)

Control

Dyslexic

Phase

Amplitude

Spectral Analysis(FFT) of steady state EEG

***

Dyslexics have lower sensitivity to ‘jitter’, hence unstable vision

0.00 2.00 4.00 6.00 8.00 10.00 12.00

60.00

80.00

100.00

120.00

Reading (s score)Eye discrepancy

Spelling (s score)Eye discrepancy

Vergence instability impairs reading; the greater the wobble, the worse is children’s reading

r = - 0.43

Weak magnocellular system causes unstable vision - oscillopsia

“The letters go all blurry”

“The letters move over each other, so I can’t 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”

“d’s and b’s sort of get the wrong way round”

“The page goes all glary and hurts my eyes”

“I keep on losing my place”

Although they do not mediate colour vision magnocells are most sensitive to yellow light. So in many children yellow filters can improve magnocellular function, hence visual motion sensitivity

and binocular control, hence improve reading

magnocells

Yellow filters can improve reading

Increase in literacy in 3 months

0

1

2

3

4

5

6

7

8

reading spelling

month

s

yellow

placebo

B - Dull Shifting Y - Highly Labile

Blue light

M-system

headachehypothalamus

Diurnal rhythms

Blue makes the letters keep still!

Blue filters improve reading even more

Increase in literacy

0

2

4

6

8

10

12

14

reading spelling

month

s

blue

placebo

Blue or yellow filters can improve magno function hence binocular control

Convergence

beforebefore

afterafter

0

5

10

15

20

25

30

cms

• Also blue can improve migraine headaches

• Many dyslexics suffer severe migraine

• Yellow often make them worse!

Improvement

B - Dull Shifting Y - Highly Labile

Blue light

M-system

headachehypothalamus

Diurnal rhythms

Reduction of melatonin secretion by blue light at night confirms it affects suprachiasmatic clock

0

20

40

60

80

100

120

neutral blue

%

The colour choice of 297 reading disabled 9 year olds

no colour preference49%

blue 25%

yellow 26%

1

2

3

Reading age increase in 3 months

0

1

2

3

4

5

6

7

8

nil grey normal,readingrecovery

(phonology)

yellow occlusion search blue omega 3sRA

in

cr.

(mo

nth

s)Elucidating the role of the visual system in reading has enabled us to develop

techniques for helping most of the dyslexics we see

*

* *

****

Many, but not all, dyslexics

have phonological

problems; these may be caused

by mild auditory magnocellular impairments

2nd and 3rd formants ascend in frequency for ‘b’;

but descend for ‘d’.

Subtle auditory impairments may reduce sensitivity to these changes in sound frequency

FM sensitivity determines phonological skill

Impaired auditory magnocells in dyslexia?

• Large neurones staining for CAT 301 in the auditory brainstem signal changes in sound frequency and amplitude

• Dyslexics have smaller magnocellular neurones in medial geniculate N.

• Lower AM & FM sensitivity, correlate with phonological deficit

• Reduced brainstem auditory evoked potentials correlate with reading deficit

• Thus dyslexics’ poor phonology may result from impaired development of auditory magnocells

Auditory and visual magnocellular sensitivity determines over half of differences in children’s reading ability

Thus the most important determinant of overall reading ability appears to be low level magnocellular sensitivity. Encouraging because this can be improved by training

Sensorimotor Basis of Dyslexia

Low visual magnocellular sensitivity - orthographic weakness

Low auditory magnocellular sensitivity - phonological problems

Lower motor magnocellular sensitivity – in coordination, poor balance

Lower kinaesthetic magnocellular sensitivity

Fish oils

C18 melanocortin receptor 5

Omega-3s protect neuronal function - 50% of the membrane enclosing this magnocellular nerve cell consists of a long chain omega 3 fatty acid (DHA); improves neuronal function because very flexible

Modern Western diet is a disaster!

• Too much: salt, sugar, saturated fat, omega 6s (from corn and soya bean oil)

• Too little: minerals, fibre, vitamins A & D, omega 3s from fish

• Far too much omega 6 - ratio of omega 6/omega 3 should be 1/1; currently it is 7/1!

Not very romantic!

Fatty acid deficiency in dyslexia and young

offenders?• Many children with

neurodevelopmental probems and young offenders have clinical signs of omega 3 deficiency:

• Low blood and brain n-3 FAs

• Omega 3 FA (fish oil) supplements can v. significantly improve m- function, attention, reading and violent offences

Durham RCT - Omega 3 EPA & DHA supplements helped dyspraxic children to improve their concentration

and their reading (Richardson & Montgomery)

Increase in Reading age in 3 months

0

1

2

3

4

5

6

7

8

9

10

n-3 placebo

RA

incr

ease

n-3

placebo

Omega–3, vitamins & mineral supplements reduced offences in Young Offenders by 1/3rd (Gesch et al.)

1133 offences: ITT- Active vs Placebo: -26.3 % (p ‹ 0.03)

0

0.2

0.4

0.6

0.8

1

1.2

1.4

Before Supplementation During Supplementation

Rat

io o

f R

ate

of D

isci

plin

ary

Inci

dent

s S

uppl

emen

tatio

n/B

asel

ine

Active

Placebo

Error bars at 2SE to indicate the 95% confidence interval

Supplementation for at least 2 weeks: -34.0% Violent offences only: -37.0%

Conclusions Conclusions

• Most dyslexics have impaired magnocellular function

• may result from:GeneticGenetic vulnerability

AntibodyAntibody attack Fatty Fatty acid acid (fish oil)(fish oil) deficiency

• This knowledge is exciting because these weaknesses cancan be remedied: auditory and phonological training, eye exercises, coloured filters, fish oil supplements

John SteinJohn Stein

Visit The Dyslexia Research Trust

(www.dyslexic.org.uk)

Wobbles, warbles & fish!

DDRR

TT