LANGUAGE, READING, & GENES
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Transcript of LANGUAGE, READING, & GENES
LANGUAGE, READING, & GENES
Timothy C. Bates
http://www.psy.ed.ac.uk/people/tbates/courses/y2
Three lectures: two main parts Patient Case Studies and Language
Box and arrow models of cognition
Genetics and cognition: Testing cognitive models using genetics Genes involved in reading: biological and
psychological explanations
Outline of part 1
How should we make models of the mind?
How can we test those models? How do we get new data to test those
models?
Where is the mind?
Where is your thinking happening? It is not obvious that your brain is important
Forward step Egyptians knew that head injury affected the mind
Backward step Aristotle (350BC)
Had a lot of the theory right, but the location… Thought mind was in the heart Head just a heat radiator
The Brain in 1836
1836: George Combe (1788-1858) 1 of 13 children to an Edinburgh Brewer. His trust founded the Edinburgh Psychology
Department with a private grant in 1906
Reported that if an injury exposed the brain, physically touching the exposed area could cause rather precise alterations in mental function Anticipates intracranial stimulation and EEG in the 1940s
Also, reported a visible swelling (increase in blood flow) during mental activity Anticipates the basis of fMRI by 150 years!
How shall we represent what is happening in the brain?
Richard Feynman:The power of a diagram
(c) J. Eric Slone www.FeynmanOnline.com
How shall we represent what is happening in the brain?
Brain as informationprocessor
Patients, boxes, and arrows
Paul Broca (1861) Patient with Brain damage: “Tan”
Dysfluent, severe problems with repetition and naming, less severe problems with auditory comprehension
Preserved memory, attention and object recognition.
Ergo: Language is localized within the brain Cognition is not unitary, but has separable
parts
Paul Broca Fractionates Cognition
CognitionOther
CognitionLanguage
X
Carl Wernicke (1874)
Broca's patient had poor language output Mildly impaired comprehension Severe fluency deficit.
By contrast, Wernicke reported a patient with comprehension difficulties: “jargon aphasia” Preserved fluency Very poor comprehension
From Broca to Wernicke
CognitionOther
CognitionLanguage
OtherCognition
Language Comprehension
Language Production
X X
Carl Wernicke’s Model: Arrows
“Schema of the Psychic Reflex” (1874)
a: Acoustic Centre: storage of “auditory word images”
b: Motor Speech Imagery
a b
Cognitive Boxes & Arrows
Lichtheim (1885) German-Jewish Physician
"The reflex arc consists in an afferent branch aA, which transmits the acoustic impressions to A; and an efferent branch Mm, which conducts the impulses from M to the organs of speech; and is completed by the commissure binding together A and M. When intelligence of the imitated sounds is superimposed, a connection is established between the auditory centre A, and the part where concepts are elaborated, B."
AM
B
am
Bastien 1888: More fractionation
Bastien (UK) reported brain damage data with preserved writing, spoken input and output, and poor reading.
OtherCognition
SpokenComprehension
SpokenProduction
WrittenComprehension
WrittenProduction
X
Bramwell’s Patient (1897)
26yr old Scottish woman. Shortly after giving birth, she had a
stroke. She was left “deaf” to speech. But said… "Is it not strange that I can hear the
clock ticking and cannot hear you speak? Now let me think what that means".
Bramwell: Auditory Agnosia“word meaning deafness”
Relevant facts She can understand print, so …
She retains knowledge of word meanings. She can hear and understand
environmental sounds, so … She is not deaf.
Why then can't she understand speech?
What we know
She can understand print: Must not have lost all
knowledge of word meanings.
She can understand environmental sounds So she is not deaf
So why can't she understand speech?
Printed words
Spoken word
Non-speech sound
Semantics
The diagrammatic notation
Boxes A system of knowledge System for processing
perceptual or cognitive information
Arrows A pathway of
communication between two systems
Printed words
Spoken word
Non-speech sound
Semantics
Claims of this diagram: 1
Single system of semantic knowledge Not one system for
each input modality Auditory stimuli have
different pathways to the semantic system spoken words non-speech sounds
Printed words
Spoken word
Non-speech sound
Semantics
Claims of this diagram: 2
Words use different pathways to the semantic system spoken words written words
Interaction is at the semantic level, not before non-speech sounds,
spoken words and written words cannot interact until they have reached the semantic level.
Printed words
Spoken word
Non-speech sound
Semantics
Building out: Auditory analysis
Both speech and non-speech sounds share early mechanisms of hearing.
How can we add a shared component for speech and non-speech sound?
Printed words
Spoken word
Non-speech sound
Semantics
Auditory processing?
Rules for Arrows
We will need two arrows from auditory processing…
1 for speech 1 for non-speech
Is that OK?
Printed words
All sounds
Semantics
Auditory processing
The diagrammatic notation
Boxes A system of knowledge system for processing
perceptual or cognitive information
Arrows
A pathway of communication between two systems
Printed words
All sounds
Semantics
Auditory processing For
speechFor non-speech
One box per process
If we want to be able to dissociate non-speech from speech, we will need more boxes: More separate processes:
Printed words
All sounds
Semantics
Early Auditory processing
For speech
For non-
speech? ?
Three things, then, might explain Bramwell’s patient
• We need to:• Eliminate meaning for
spoken words• But…• Preserve meaning and
hearing for environmental sounds & printed words
• Preserve speech
Printed words
All sounds
Semantics
Early Auditory processing
Non-speech
Speech sounds
x
x
x
“turbid”Bramwell’s patient & the lexicon
•There are spoken words you can recognize as being “real” though you cannot define them.•So…
•A store of spoken-forms (words we can recognize) must be separate from a store of word meanings (semantics)
for non-speechsound
Bramwell’s patient & the lexicon
•Path from Auditory Processing to Input Lexicon?
•Phonological Input Lexicon itself?
•Path from Input Lexicon to Semantic System?
non-speechsound
?
?
?
A new fact from Bramwell
"I asked her … the question:`Do you like to come to Edinburgh?'
She did not understand it. I then communicated that I wished her to
repeat what I had said: She did so without hesitation.
I then asked her to write down the words she had just said.
She did so without the words having to be repeated a second time, and she then undoubtedly understood the question.”
Which of three lesions preserves spelling?
How can she write down “You” and “Edinburgh”? not “Yoo”
or“Edinburra” How does she
know how these are spelled?
Bramwell’s patient & the lexicon
•Path from Auditory Processing to Input Lexicon?
•Phonological Input Lexicon itself?
•Path from Input Lexicon to Semantic System?
non-speechsound
?
?
?
The necessary lesion
for non-speechsounds
Lexicon
Non-verbal acoustic Lexicon?
•Is there a complementary non-verbal acoustic lexicon?
•We need another patient…
•Wait 100 years.
Albert et al (1972)
Comprehension of spoken words tested “Point to the X” (shown a range of pictures)
100% correct. Comprehension of sounds
Played a tape recording of sounds made objects “Point to object whose sound you are hearing”
10% correct.
Lexicon
Final Model
here, here or here
Revision
What do boxes do? When do we know we need a new black
box? What can arrows do? List the tests given by Bramwell
Build the diagram from the tests Next: Association, Dissociation, Double
dissociation
A case of associated deficits
A patient comes in who cannot: Tell left-right from right
“Show me your left hand” (cannot do correctly) Calculate (dyscalculia)
“What is 100 - 7?” (cannot answer accurately) Express thoughts in writing (dysgraphia)
“Write a sentence” (cannot write) Distinguish Fingers (finger agnosia)
“Touch your nose with your index finger”
Is this association evidence for a left-right-writing-number-finger module?
Printed and spoken, and pictorial information
Telling left from right, and writing, and calculating and
telling one finger from another
Moving and talking and writing and moving fingers and hands
Gerstmann’s Syndrome (1924) Spatial location, finger knowledge,
calculation, and writing are associated. Association is evidence for shared
processes or shared anatomy It does not, however, support the
hypothesis that the processes are the same: it merely does not rule it out.
Tim Shallice (1988) From Neuropsychology to Mental Structure
What can we tell if one task is OK, and one is imperfect? This is called Dissociation
Prima-facie evidence that two tasks differ…
But… what if one task is just harder than another?
% c
orre
ct
Amount of Damage
Double Dissociation
Subject A: Significantly better at task 1 than task 2
Subject B: Significantly better at task 2 than task 1
Plausible inference: there are two modules: One is important for task 1 (but not task 2) One is important for task 2 (but not task 1).
Summary
Association: Compatible with shared function but also with shared
location, blood supply, biochemistry. Not much help for finding new boxes and arrows
Dissociation: Compatible with separate functions Also with compatible differential dependency on a single
function (differential task difficulty) Double Dissociation:
Supports modeling tasks as functionally distinct: two boxes
III: Genetic Neuropsychology Building on Cognitive neuropsychology
by incorporating genetics Examine genetic & environmental
influences on cognition Model separate paths to cognition in
genetic and environmental terms. Test & build new models using genetics
Bates (2008a)
Purpose of Genetic Neuropsychology Describe the functional architecture of
the mind using genetic dissociations Deduce information about how these
processes are implemented neurally Do the genes that build phoneme
extractors also build speech processing systems?
How do neurons extract phonemes?
Dyslexia
Dyslexia = “difficulty with words” (Berlin, 1884)
Prevalence Affect up to 17.5% of children despite adequate
intelligence, education, and social environment (Shaywitz & Shaywitz, 2005).
Onset The disorder begins in childhood, continuing into
adulthood (Bates, Castles, Coltheart, Gillespie et al., 2004)
Important negative social impact (Maughan, etal, 1996).
Dyslexia is familial
Hallgren, 1950 Thomas, 1905 Qu: What does familial mean? Qu: Why might reading look familial?
Genes, shared environments Twins allow us to compare these two
MZ twins = Identical genes and Identical family DZ twins = 50% genes and Identical family Different families = random genes, random
families
Heritability: Twins Reared Together Components of Individual Differences
Random or Unique Environment effect E = 1 - rmz
Heritable effect (Additive genetic effect) A = 2 * (rmz - rdz)
Shared or Common Environment C = (rmz - A)
Concepts of Genetic Modeling
A
“Reading”
Reading as the sum of genes, family, and unique effects
A = Additive genetic = 2* (rMZ-rDZ)C = Common (family) environment = A- rMZ
E = Unique effects and noise = 1-rMZ
C E
Basic Behavior Genetics
Most of the familial similarity is due to shared genes Heritability of around 0.7
DeFries, Fulker, & LaBuda, 1987; Bates et al., 2006; Gayan & Olson, 2003.
Family environment effects prior to school starting
Baker et al, 1997
Few family effects after school begins Olson etal (2002); Bates et al 2006
Dual Route Cascaded Model (DRC) (Coltheart et al. 2003)
Two tasks in reading aloud:
Access to your store of words Activate known words from
a store “lexicon” What happens if you look up
“GOP” ? Decoding new words
What sounds (phonemes) correspond to the letters?
How do you say: GOP ? How do you say: YACHT ?
Abstract letter units
Orthographic lexicon
Letter-sound conversion
Phonological lexicon
Phoneme units
Genetic Model of Reading (Bates et al 2007)
NonwordReading
Ag
Irregular Reading
.77
Eg
.33
.49.26
.38
.44
Airr Anon
EnonEirr
Summary of Genetic modeling Because variance in reading is heritable,
normal twins can inform us about the genetic neuropsychology of reading
Association Genes that influence all types of reading
Double dissociation Genes for lexical (whole word) processing
(and not for graphemes) Genes for sub-lexical (grapheme)
processing (and not for whole words)
Dual-route models and genes The next step is to move to gene
identification Identifying risk early in development
Understanding the connections and disconnections that might lead to reading difficulties
Deoxyribonucleic acid (DNA) James Watson, Francis Crick Maurice Wilkens, Rosalind Franklin
February 21, 1953
James Watson
Born 6th April 1928-
Francis Crick: 8/6/1916 – 28/7/2004
Genes
Origins What genes influence reading? How do they influence development? Are the genes used in other abilities, like
language, or face recognition? Treatment
What period is neural growth influenced? Early recognition, if neural growth can be
affected?
(p34-p36)
(p11-p16)
(p12-q13)
DYX8
DYX3
DYX5
(p21.3-p22)
(q13-q16)
(p15)
(q15-q21)
(p11)
(q27.3)
DYX2
DYX4DYX7
DYX1DYX6
DYX9
q12
Linkage: 11 Dyslexia Susceptibility Loci
DYX1C1 Dyslexia susceptibility 1 candidate 1
1. DCDC2 Doublecortin domain2. KIAA0319
ROBO1 Roundabout
Eleven Genes for reading
1p34-36 (Grigorenko et al., 2001; Rabin et al.,
1993; Tzenova et al., 2004 ; Bates et al, 2007)
2p15-16 (Chapman et al., 2004; Fagerheim, 1999;
Francks et al., 2002; Kaminen et al., 2003; Petryshen, et al., 2002 ; Bates et
al, 2007) 2q22.3
(Raskind et al. 2005 ; Bates et al, 2007),
3p12-q13 (Nopola-Hemmi et al., 2001; Taipale et
al., 2003 ; Bates et al, 2007)
6p23-21.3 (Cardon et al., 1994; Fisher et al., 1999;
Gayan et al., 1999; Grigorenko et al., 1997; Kaplan et al., 2002a; Chapman et al., 2004; Turic et al., 2003; Luciano, et al. 2007),
6q11.2 (Petryshen et al., 2001 ; Bates et al, 2007)
7q32 (Kaminen et al., 2003 ; Bates et al, 2007)
11p15.5 (Hsiung, Kaplan, Petryshen, Lu, & Field, 2004)
15q21.1 (Grigorenko et al., 1997; Morris et al., 2000;
Nopola-Hemmi et al., 2000; Nothen et al., 1999; Schulte-Körne et al., 1998 ; Bates et al, 2007)
18p21 (Chapman et al., 2004; Fisher et al., 2002;
Marlow et al., 2003; Bates et al, 2007)
Xq27.3 (de Kovel et al., 2004; Fisher et al., 2002 ; Bates
et al, 2007)
+DYX1C1 and DCDC2
Paracchini and Monaco (2007)
Building a brain that can read Guiding the growth of Neurons Neuronal Proliferation/connectivity
DCDC2 (Cope et al. 2005; Bates et al 2007)
KIAA0319 (Cope et al. 2005, Luciano et al 2007)
DYX1C1 (Bates et al 2007)
Nerves Crossing the midline ROBO1 (Hanula-Jouppi, 2005)
+KIAA0319; DCDC2; DYX1C1
All Linked to neuronal migration: (LoTurco 2007; Wang et al, 2006; Schumacher, 2006)
+Genes for Normal Reading
3839 twins, siblings and parents (768 families) 47.1% male; 98% Caucasian (~82% Anglo-Celtic)
Components of Reading Examination (CORE) Six reading and spelling tests of regular, irregular (e.g.,
yacht) and non-word (e.g., torlep) stimuli (Bates et al, 2004)
Significant associations of normal reading to DCDC2, DYX1C1, and KIAA0319
+DYX1C1 SNPs
marker position NONWORD IRREGULAR Prin Comp
rs685935 53.558203 . 0.0638 .
rs8043049 53.56508 . . .
rs6493791 53.568018 . . .
rs17819126 53.577202 0.0003 0.0086 0.007
rs3743204 53.577602 0.0089 . .
rs3743205 53.577822 . . .
rs8040756 53.585891 . . .
Mutation (GLY-SER)
+Genes for Reading
The models from cognitive neuropsychology are reflected in the genetic transmission of difference in ability to acquire whole word and sounding-out forms of reading
These modules appear to depend on early developmental cortical and subcortical neuronal migration
Dyslexia and normal reading associated with genes for neuronal migration in the cortex (DCDC2, DYX1C1, and KIAA0319) and across the midline of the brain (ROBO1)
Summary: Cognitive Neuropsychology Cognitive Neuropsychology uses deficits
to tell us about the structure of the mind Broca, Wernicke, Bramwell
Represent this structure using boxes and arrows Lichtheim
Summary: Box and arrow rules Boxes represent a store of information or
a process acting on information Arrows communicate information, but do
not transform it. Only needed in our models, because
patient data suggests that information can go to different places independently
Rules for claiming that two processes are different Association ✗ Dissociation ✓ Double Dissociation
A model of language
Bramwell’s patient Her symptoms His questions The boxes and arrows we must draw to
capture the abilities and disabilities that Bramwell identified
Genetic model
Boxes and arrows for Dyslexia Dual route model (Coltheart 2003)
Study similarities of Twins Genes show biological basis of different
modules Study DNA
Molecular biology describes the neuronal basis of language and its evolution.
Advanced Material
Double Dissociation
Subject A: Significantly better at task 1 than task 2
Subject B: Significantly better at task 2 than task 1
Plausible inference: there are two modules: One is important for task 1 (but not task 2) One is important for task 2 (but not task 1).
What other possibilities exist?
Assumptions of Double dissociation People are fundamentally the same
If people could differ in their basic mental architecture, then we might see a double dissociation where there was in fact only one module, but it was optimized for task 1 in person A, and task 2 in person B
Limitations and Problems
The box and functions are the level of analysis The algorithm of the box can often be deduced The actual circuits inside cannot be
Relies on cases of functional dissociation Things that do not dissociate in nature cannot be
distinguished with cognitive neuropsychology. Transcranial Magnetic Stimulation changes this
Lack of tools for replication and falsification Replication depends on (often rare) cases Wrong or false clinical observations of dissociation
not readily removed from the literature