Neurobiology of Learning Disorders

A Critical Review of the Neurobiology and Co-Morbidity of Learning Disorders Fernette Eide M.D. and Brock Eide M.D. M.A. Edmonds, Washington Slideshare.net/drseide drseide@neurolearning.com

Books, Intellectual Property: The Mislabeled Childand The Dyslexic AdvantageProfessional Advisory Board: SENG, Supportingthe Emotional Needs of Gifted

• Prevalence of Learning Disabilities 5-20% U.S. Children• Prevalence of ADHD is 10% of U.S. Children Shaywitz, 1998; CDC Vital and Health Statistics Dec 2010, 10:247; Larson et al., 2011.

NINDS: Learning disabilities are disorders that affect theability to understand or use spoken or written language,do mathematical calculations, coordinate movements,or direct attentionAACAP: Learning Disorders occur when the child oradolescents reading, math, or writing skills aresubstantially below that expected for age, schooling,and level of intelligence.IDEA 2004 : “…Must not require the use of a severediscrepancy between intellectual ability andachievement for determining whether a child has aspecific learning disability…”

46% of children with ADHD have a learning disabilityLarson, et al., Pediatrics, 2011

• Higher rates of depression and anxiety among children and adolescents with LD • LD & Anxiety – 9-20% of students with LD • LD and Depression – 13% of 7 year olds, 7% of 10 year olds • In Los Angeles Suicide Prevention Center Study, 50% suicides of children younger than 15 years had LDCasey et al, Dev Beh Paed 1992; Sideris, Int Rev Res MR 2006; Maughan et al,J Abnl Child Psych, 2003; Peck, Youth Suicide 1985; Emerson, 2003

Previous LD 28% 53% of outpatient No LDpsychiatry clinic have 47% Learning Disabilities (n=399) Unrecognized LD 25%Sundheim and Voeller, 2004 - Colorado

Reading Disability 5-17.5% Math Disability 5-8% Writing Disability 5-20% U.S. Department of Education: 2.8 million children with specific LD 21-23% Adult U.S. can read a little, but not enough to fill out an application or read a food labelShaywitz, 1998; Geary, 2004; Tomblin et al., 1997 ; Mayes and Calhoun, 2006;Smits and Engelman, 1997; ASHA, 2008

• Genetics of Learning Disabilities and ADHD• Neuropsychological Overlaps - LD & ADHD• Neurobiological Bases of Reading, Math, Writing Disorders, and ADHD• Unresolved Issues and Individual Factors Influencing Phenotype

RD, MD, ADHD are highly Probandwise Concordance heritable MZ DZ But - molecular genetics RD 66% 35% (candidate genes, DNA polymorphisms) suggest RD, ADHD 68% 24% MD, and ADHD are affected by multiple genes with small 40% 24% MD effect sizesWillcutt et al., J Dev Behav Pediatr 2010

90 90 34 6 60 60 23 4Scores 30 30 11 2 0 0 0 0 Phonemic Deletion Orthographic Coding Stroop Color Verbal Working Memory (word sounds) (spelling) Willcutt, Dev Neuropsych 2005

12 12 18 20 14 15 8 8 11Scores 10 7 4 4 5 4 0 0 0 0 WISC Coding WISC Symbol Search Wisconsin Card Sort Test CPT Commission Willcutt, Dev Neuropsych 2005

Phonology - sounds within wordsOrthography - spelling or word appearanceSemantics - word meaning Dehaene, 2009; Berl et al., 2010Articulatory loop - saying words to remember

ConLeft Temporo-parietal CortexLeft Inferior Frontal Gyrus DysRight Fronto-temporal Reading Rhyming LettersAnterior Cingulate Temple et al, PNAS 2003

Phoneme Working Memory Control Control Dyslexia Dyslexia Decreased Processing of Decreased Activation in Dyslexia Rapid Sounds in Dyslexia Good Readers Poor ReadersReading, Listening (especially over backgroundnoise), Note-taking, Foreign languageGaab et al., 2007; Beneventi et al., 2010; Auditory Brainstem ResponsesChandrasekaran et al., 2009 Poorer Speech in Noise with Dyslexia

Con Control Dyslexia Dyslexia Decreased Response to Motion With Dyslexia Slower Visual Blink in Dyslexics DyslexiaSpacing Dyslexics need larger font Size and increased s p a c i n g Control Letter size Eden et al, 1996; Hari and Renvall, 2001; Martelli et a., 2009; Zorzi et al, 2012

Dyslexia – Slower response times, Less ‘Automatic’ Learning Dyslexia ControlDyslexia – less Supplementary Motor Cortex – S1-2; more Cb S4-5 Writing, Working Memory Overload Robertson, 2007; Meghini et al., 2006

Development of Number Sense and Number Line Aster and Shalev, 2007; Dehaene et al., 2004

Butterworth, 2011

9 B IPS, prefrontal, Controls > Dyscalculia + 5 superior parietalDyscalculics have Lower R IPS ___Lower Performance Number Perception Number Quantity, Spatial Working Memory Problem Representation, Math Facts Retrieval Price et al., 2007; Ashkenazi et al., 2012

Incorrect vs. Correct High Math IncorrectDLPFC Low Math Incorrect fMRIPoor Math Subjects Show Weaker Response When Incorrect Ansari et al., Learning Indiv Diff 2011

“Neglect of written expression is a shortcoming in researchon learning disabilities.” - Mayes et al. Penn State • 50% of children in a university-based psychiatric clinic had dysgraphia or writing disability (ADHD, ODD, autism, anxiety, depression; n = 905) • WIAT-II / III more sensitive than WJ • Writing is complex - phonology, word meaning and retrieval, spelling, sentence organization, handwriting, executive function - planning sequencing, prioritizing, working memory, sustained attention, self-monitoring Mayes et al Percept Motor 2005

Poor Writers More Visual MonitoringIrregularly formed letters,Erratic spacing, pseudochorea Richards et al., 2011

“I am, myself, a very poor visualizer and find that I can seldom call to mindeven a single letter of the alphabet in purely retinal terms. I must trace theletter by running my mental eye over its contour in order that the image of itshall leave any distinctness at all. ” - William James Spelling Spelling requires more left hemispheric Activation than reading Under-recognized as a specific learning disability Often in the context of dyslexia / ‘stealth dyslexia’ Reading Handwriting and spelling errors found in 89% of suicide notes by adolescents Overlap Purcell et al Neuroimage, 2011 McBride and Siegel, J LD 1997

Complex Differences in Brain fMRI Activation Dyslexics vs. Controls on Spelling Tasks Multiple Different Brain Regions Orthographic task - 20 areas in controls, 11 in dyslexics; 6 areas in dyslexics not in controls Orthographic: bead – feal Morphological: build - builder Richards et al., J Neurolinguistics 2006; J Writing Res 2009

• Learning Problems associated with ADD and ADHD recognized under IDEA in 1991 (OSER Joint Policy Memo)

“Clearly a single abnormality of any one region does not cause ADHD. ” Selective Attention, Motivation / Novelty /Reward, Executive Function, Behavioral Inhibition, Working Memory, Attention Shifting Bush, Neuropharmacology 2010

ADHD – Weaker Fronto-Striato-Parieto-Cerebellar Activation Rubia et al Neuropharm 2009

Money Reward CPT ADHD Higher Activation with Reward; partially Normalized with Methyphenidate MPH Helped Omissions More than CommissionsLuman et al J Abn Child Psych 2012; Rubia et al Neuropharm 2009

ADHD Off Meds - Low Incentive: Lowerdeactivation Default NetworkADHD Off Meds - High Incentive:Increases deactivation Default NetworkADHD On Meds: Low Incentive:Deactivation like ControlADHD On Meds: High Incentive:No ChangeControls Deactivate Default Networkfor Inhibitory Control Task + IncentiveLiddle et al J Child Psych Psychiat 2011

Core Features of RD, MD, WD, ADHD•Broad vs. Narrow, Disease vs. Trait, Assessmentsand Screening, Medical vs Educational DefinitionsEffect of Individual Factors Such as IQ orDevelopmental Variation on Phenotype•Neurodiversity –Strengths as Well as Weaknesses

“It is more important to know what sort of person has adisease than to know what sort of disease a person has.” - Hippocrates• Developmental and IQ Effects on ADHD and Dyslexia• Strengths Associated with ADHD and Dyslexia

Average IQHigh IQSuperior IQ Superior IQ Late Bloom Prefrontal CxAge Shaw et al. Nature 2006

Gifted ‘Overexcitabilities’ DSM IV ADHD• Active and energetic • Often ‘on the go• Love of movement • Runs about, climbs• Rapid speech • Talks excessively• Intense physical activity • Fidgets, squirms• Need for action • Often leaves seat• Heightened play of imagination • Difficulty playing quietly• Elaborate dreams • Distractible, forgetful, careless mistakes (daydreaming in DSM-III) Ackerman, Roeper Review 1997

Diffuse Attention Associated with Higher Creativity Among High IQ Harvard Study Latent Inhibition Carson et al J Personality Soc Psych 2003

80 CPT6040 High IQ Can Compensate for20 Omission and Commission Errors on CPT0 Vis O Vis Com Aud O Aud ComPark et al. Psychiatr Invest 2011 (n=266, p’s: 0.013, 0.009, < 0.001, 0.001)

High IQ Does Not Fully Compensate for Working Memory in ADHD 74% of High IQ-ADHD children had at least 1 S.D. Discrepancy Between VCI/PRI and Working Memory Index 40% had 2 S.D. DiscrepancyWISC III/IV Composite IQ Scores Brown et al. Open J Psych 2011 (n=117)

High IQ Does Not Fully Compensate for Processing Speed in ADHD 80% of High IQ-ADHD children had at least 1 S.D. Discrepancy Between VCI/PRI and Working Memory Index 42% had 2 S.D. DiscrepancyWISC III/IV Composite IQ Scores Brown et al. Open J Psych 2011 (n=117)

High IQ students with ADHD don’tshow developmental lag of lowIQ students with ADHD Control High IQ ADHD High IQ ADHD Low IQ show developmental lag (not shown)

High IQ Does Not FullyCompensate for WorkingMemoryHigh IQ Does Not FullyCompensate forProcessing SpeedHigh VCI and PRI can exist (n = 50; Eide et al., in prep)

High IQ May Compensate for Some, Not All Language TasksProblem with defining dyslexiaby reading comprehension:working memory, processingspeed, and non-contextualreading may be inaccurate (n = 50; Eide et al., in prep)

High IQ Does NotCompensate for Writing (n = 50; Eide et al., in prep)

10 yo SBLM 172 11yo VIQ 13716 yo SBLM 150

Weaker: Visual Search, Visual Sequencing, Central Attention Stronger: Spatial Contextual Learning, Peripheral Attention, 3D Maze 3,500 2,625 Dyslexia 1,750 Control 875 0 Response Time (msec) Shorter Response Times with Dyslexia No Significant Difference in AccuracySchneps et al., 2007; Attree et al., 2009; Karolyi et al., 2003

Problems SolvedConnect dots with 4 lines not lifting pen.Make B from A only moving 3 circles Everatt et al, Dyslexia1999

Dyslexics OutperformControls on Divergent Thinking Tasks Everatt et al, Dyslexia1999

Mother: “I asked my 11 year old Dyslexic son, ‘What do youthink of when I say the word "cat?“’ After about 5SECONDS I said, ‘I think of a fuzzy kitten.’ Eventually he said,‘Well, first I wondered are you talking about someonenamed Cat or are you talking about a tiger or a lion, ormaybe you mean a mama cat with her kittens or maybe acute little kitty, or maybe you mean a cat walk up in thesky.’ This is what he thought of in the 5 seconds while Ithought of a fuzzy kitten before I interrupted his train ofthought. Now imagine what these people are capable ofthinking about. They arent slow, they are just thinking of somany things while we with our simple minds are thinking ofone simple thing.”

Verb Generation - Control vs Dyslexic Specific Activation Different Networks Activated for Specific Tasks Dyslexia-Specific: parahippocampal gyrus, fusiform, lingual gyrus ? context word retrieval, imageryGenerate a Verb Associated with a NounExample: Boat...Sailing Baillieux et al., 2009

Fernette Eide M.D. and Brock Eide M.D. M.A. Edmonds, Washington Slideshare.net/drseide drseide@neurolearning.com DyslexicAdvantage.com Please complete your evaluation forms. Thank you!

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Neurobiology of Learning Disorders

by Drs. Brock and Fernette Eide on Oct 16, 2012

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