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The Current Status of the Magnocellular Theory of Dyslexia

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1 The Current Status of the Magnocellular Theory of Dyslexia
John Stein, Magdalen College, Oxford University, UK The Current Status of the Magnocellular Theory of Dyslexia Supported by The Dyslexia Research Trust (www.dyslexic.org.uk), Dyers & Colourists, Esmee Fairbairn, Garfield Weston and Wellcome Trusts, BBC Children in Need

2 1/3rd of English Children Leave School Unable to Read

3 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

4 Many possible levels of analysis
Genetics Neuroanatomy Neurophysiology Psychophysiology Cognition – phonology & orthography Behaviour–reading & spelling

5 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

6 Magnocellular Neurones
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 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

7 Chromosome sites we have linked to reading skill
C6p ?KIAA 0319 gene - cell~cell recognition and immune control (MHC system) Also DCD gene ROBO 3 gene Finnish pedigree DYX1 gene

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9 KIAA 0319 is strongly expressed in dorsal visual magno- cellular pathway

10 C6 KIAA 0319 controls neuronal migration during early brain development in utero. Downregulation in dyslexics may explain ectopias and other mismigrations of magnocellular neurones

11 2nd trimester ectopias in dyslexic brain. Seen also in auto immune mice

12 Abnormal magnocells in dyslexic brain

13 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

14 High incidence of immune anomalies in dyslexics

15 Reading is primarily a visual process
Visual processing

16 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

17 Visual magnocellular system dominates dorsal visuomotor pathway -directs visual attention & eye movements.

18 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!

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

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

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

22 (FFT) of steady state EEG
Spectral Analysis (FFT) of steady state EEG Phase Control Amplitude Dyslexic

23 * * *

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

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

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27 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”

28 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

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30 Yellow filters can improve reading

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32 headache hypothalamus Blue light Diurnal rhythms M-system

33 Blue makes the letters keep still!

34 Blue filters improve reading even more

35 Blue or yellow filters can improve magno function hence binocular control

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37 Also blue can improve migraine headaches
Improvement Also blue can improve migraine headaches Many dyslexics suffer severe migraine Yellow often make them worse!

38 headache hypothalamus Blue light Diurnal rhythms M-system

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

40 The colour choice of 297 reading disabled 9 year olds

41 Elucidating the role of the visual system in reading has enabled us to develop techniques for helping most of the dyslexics we see ** ** * * *

42 Many, but not all, dyslexics have phonological problems; these may be caused by mild auditory magnocellular impairments

43 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

44 FM sensitivity determines phonological skill

45 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

46 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

47 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

48 C18 melanocortin receptor 5
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

49 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!

50 Not very romantic!

51 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

52 Durham RCT - Omega 3 EPA & DHA supplements helped dyspraxic children to improve their concentration and their reading (Richardson & Montgomery)

53 Omega–3, vitamins & mineral supplements reduced offences in Young Offenders by 1/3rd (Gesch et al.)
1133 offences: ITT- Active vs Placebo: % (p ‹ 0.03) Supplementation for at least 2 weeks: % Violent offences only: %

54 Conclusions Most dyslexics have impaired magnocellular function
may result from: Genetic vulnerability Antibody attack Fatty acid (fish oil) deficiency This knowledge is exciting because these weaknesses can be remedied: auditory and phonological training, eye exercises, coloured filters, fish oil supplements

55 The Dyslexia Research Trust (www.dyslexic.org.uk)
Wobbles, warbles & fish! John Stein Visit The Dyslexia Research Trust (www.dyslexic.org.uk)


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