The Magnocellular Theory of Dyslexia

1. ECVP, 5/9/12 D R T The Magnocellular Theory of Dyslexia John Stein, Magdalen College, Oxford 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

2. Contrary to the phonological theory of dyslexia, reading is primarily a visual process! Visual processing

3. 5% of all primary school children complain of visual problems that impede their reading • 1392 unselected 8-10 yr old children • 10 primary schools • All social classes • 5.4% reported ‘always’ to one or more of these questions: Do letters blur; appear to move around (wobble); do they distort (look funny); do they change places; go double; glare; give you headaches? • 32% endorsed ‘sometimes’

4. Retinal Ganglion cells 10% are large magnocellular cells (50x p- cells in dendritic area) – respond to transients for timing visual events: fast responses, high contrast, flicker & motion sensitivity; control focus of visual attention & eye movements Most retinal ganglion cells are parvocellular (small): for colour, fine detail, high contrast (less vulnerable)

5. Visual magnocellular system directs visual attention & eye movements.

6. The magnocellular system stabilises visual perception Unwanted image motion, ‘retinal slip’ Feedback to eye muscle control system Detected by M- system Visual stability Identify letter order Locks eyes on target Orthographic skill Phonological skill

7. The visual magnocellular system is mildly impaired in many dyslexics • Impaired spatial frequency doubling (retina) • 30% smaller LGN magnocells post mortem • Lower sensitivity to flicker (V1) • Lower high frequency contrast sensitivity (V1) • Reduced and delayed evoked brain waves (V1-5?) • Impaired jitter compensation (V1-5) • Reduced RDK visual motion sensitivity (V5) • Reduced activation of V5 (FMRI) • Impaired focusing of visual attention (dorsal stream) • Reduced pop out in visual search (dorsal stream) • Impaired eye movement control • Visual crowding • Mini left neglect - clock drawing • Reduced waterfall illusion • Improved by transient system training • Improved by yellow or blue filters 90% of studies have confirmed m- deficit

8. ‘Magno’ tests v ‘phonological’ tests Joel Talcott

9. Although they do not mediate colour vision, magnocells are most sensitive to yellow. Due to pupillary dilatation yellow filters increase m- responses. Also remove –ve blue input (Stockman et al). So in some children yellow improves magnocellular function, hence visual motion sensitivity and binocular control, hence they improve reading

10. Yellow filters can improve reading Nicki Ray

12. Also blue filters can improve reading Nicki Ray

13. Blue filters probably work via brain clock in the hypothalamus hypothalamus Blue light Diurnal rhythms M-system Joe Taylor

14. Blue light at night reduces melatonin secretion by 27% Clare Visser

15. Impaired auditory magnocells in dyslexia? • Now generally agreed that dyslexics have abnormal auditory processing in the brainstem • Large ‘magnocellular’ neurones in the auditory brainstem signal changes in sound frequency and amplitude • Dyslexics have smaller magnocellular neurones in left medial geniculate nucleus (MGN) • Auditory m-cells express CAT 301 • They have lower AM & FM sensitivity • Dyslexics’ poor phonology may result from impaired development of auditory magnocells

16. Cerebellum- head ganglion of magnocellular system- head movement, balancing on one leg Control Dyslexic Catherine Stoodley

17. Magnocellular Neurones • Very vulnerable. Impaired m- cell and dorsal stream development has been found in prematurity, foetal alcohol syndrome, developmental dyslexia, dyspraxia, dysphasia, ADHD, ASD, Williams syndrome, schizophrenia, depression • M- cell high dynamic sensitivity requires high membrane flexibility provided by local environment of essential fatty acids, particularly omega 3s, found in fish oils • Hence vulnerable to omega-3 deficiency • A general 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 derive from same lineage; express same surface antigens, eg CAT 301 • Found throughout the whole brain: visual, auditory, skin, muscle proprioceptors, cerebral cortex, hippocampus, cerebellum, brainstem

18. Against? • A simple theory is easy to attack! • Consensus that dyslexics do have low level visual and auditory processing deficits • But 10% of studies have failed to show that visual problem is selectively magnocellular (mostly small numbers) • No ‘magnocellular test’ is entirely selective (Skottun) • The visual dorsal stream is not fed exclusively by the retino-geniculate magno system • Noise exclusion? What generates the noise? • Does a general magnocellular system of neurones exist? Immuno-histological evidence. Visual –auditory correlations • Different tests measure different aspects; weak correlations between them • Nevertheless 90% of studies concur

19. What causes this general magnocellular impairment? Compelling neurobiological evidence Genetic Immune System Nutrition

20. Genetic linkage/association • Are particular chromosomal markers/sites associated with poor reading? • Analyse the DNA of father, mother and their dyslexic and normally reading children • >400 Oxford; 100 Boulder (US) families • EU consortium; 1000 families, 2000 cases, 2000 controls, 50,000 markers per case

21. C6p MHC system: KIAA 0319 gene controls neuronal migration during early brain development in utero. Underexpression in dyslexics may explain migration errors, ectopias and impaired development of magnocellular neurones Silvia Paracchini

22. Dyslexia and the Immune System • High incidence of asthma, eczema, autoimmunity in dyslexics and their families • Development of magnocellular neurones is known to be regulated by the MHC cell recognition immune system (CAT 301) • Linkage of poor reading to surface recognition genes (KIAA 0319) on MHC system on C 6p • BSXB ‘autoimmune’ mice exhibit mismigrations and ectopias very similar to those seen in dyslexics • Evidence for antimagno antibodies in serum of mothers with dyslexic children (Angela Vincent)

23. Cod Liver Oil Queue, 1949

24. Fish Diet • Sea food was the main diet of early homanids until the invention of agriculture and then the processed food industry • Omega 3, docosahexanoic acid (DHA), allowed 10 fold expansion of brain size and 100 fold increase in connections compared with chimpanzees

25. Communication (speech, reading, social interactions) depends upon being able to accurately sequence speech sounds, letters and facial expressions This requires accurate sequential focussing of visual & auditory attention Main sequencing system – the ‘dorsal parieto-frontal attentional system’ is dominated by input from magnocellular neurones Impaired development of magnocellular neurones is found in most neurodevelopmental conditions Magnocellular neurones need omega 3 fish oils (DHA and EPA) to function properly But fish is expensive and 3/4s of population eat no fish at all DHA and EPA supplementscan improve attention, speech, reading and social interactions The Brain and Fish Oils

26. Omega 3 EPA supplements helped dyspraxic children to improve their concentration and their reading (RCT – Richardson & Montgomery)

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

28. D R T The magnocellular theory of dyslexia links genetics, immunology, neuropathology, psychophysics, reading, nutrition and effective treatments. What more can you ask? Visit The Dyslexia Research Trust (www.dyslexic.org.uk)