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Neuropsychological studies of 
Autism Spectrum Disorders 
Uta Frith 
31st Annual Meeting of the Neuropsychology 
Association of Japan 
27th September Kanazawa
Infantile Autism Kanner 1943 
Inability to relate affectively to others 
Insistence on sameness 
Islets of ability 
2 Uta Frith Kanazawa September 2007
A little bit of history 
100 years ago 
autism not recognised at all 
70 years ago 
autistic children first described in the Netherlands, in the US, 
in Austria… 
50 years ago 
psychosocial origin presumed - not brain abnormality 
Now 
progress towards identifying brain abnormality, genetic risk 
factors and other putative causes 
3 Uta Frith Kanazawa September 2007
Everyone agrees on 
a biological basis for autism 
Autism is a biologically based condition 
With a strong genetic component 
With its effect on brain development 
There is some brain abnormality 
But 
We do not yet have biological markers 
4 Uta Frith Kanazawa September 2007
Everyone agrees on 
three key behavioural signs 
Difficulties in Social interaction 
Difficulties in Communication 
Restricted Patterns of Behaviour 
Not everyone agrees on how to explain these 
- at the cognitive level - at the brain level 
There are different cognitive theories 
These have led to new knowledge 
5 Uta Frith Kanazawa September 2007
No single theory is sufficient 
Three cognitive theories are needed 
- at least - 
To explain social and communication problems 
– E.g. Mind blindness 
To explain everyday coping problems 
– E.g. Executive dysfunction 
To explain cognitive strengths 
– E.g. Weak central coherence 
6 Uta Frith Kanazawa September 2007
Deficits in Social Cognition are a Core 
Feature of Autism 
One hypothesis explains many of the problems in 
communication and social interaction that are 
obvious from the second year of life 
Poor mentalizing ability 
A missing capacity due to specific brain abnormality 
• Affecting the intuitive ability to “read minds” 
• Leaving intact other social capacities 
7 Uta Frith Kanazawa September 2007
Baron-Cohen, Leslie and Frith, 1985: Sally-Anne test 
8 Uta Frith Kanazawa September 2007
9 Uta Frith Kanazawa September 2007
Sally (mistakenly) thinks her marble is in the basket 
Autistic children typically fail this test 
10 Uta Frith Kanazawa September 2007
Able autistic people can learn to read 
other minds but subtle problems persist 
Klin, 2000; Abell et al. 2000; Castelli et al. 2002 
Example: Heider & Simmer effect 
We are often compelled to attribute mental states to 
animated shapes 
Two triangles interacting together 
vs 
Two triangles just floating 
11 Uta Frith Kanazawa September 2007
Revealing components of the brain’s 
mentalising system 
compared with 
Brain activity 
while watching 
interacting 
triangles 
12 Uta Frith Kanazawa September 2007 
Brain activity 
while watching 
randomly 
moving triangles 
Comparison shows extra activity 
when we see interactions and mentalise 
Where?
QuickTime™ and a 
Animation decompressor 
are needed to see this picture. 
13 Uta FCritho mKaena ozauwt aa Snedp tepmlabye r- 2 i0t0’s7 nice out here.
QuickTime™ and a 
Animation decompressor 
are needed to see this picture. 
14 Uta Frith Kanazawa September Animation that does not invite me2n00ta7 lising drifting…floating…
Mentalising system 
Superior temporal sulcus 
15 Uta Frith Kanazawa September 2007 
Castelli et al., 2000 
Medial 
prefrontal 
cortex 
Basal temporal, periamygdaloid 
Basal temporal
Mentalising system in the autistic brain 
Reduced activation 
Weak connectivity between components 
16 Uta Frith Kanazawa September 2007
Brain activity associated with mentalizing in normal and autistic Ss 
2.5 
2 
1.5 
1 
0.5 
0 
-0.5 
R. extra-striate R. basal temporal R. STS R. medial prefrontal 
17 Uta Frith Kanazawa September 2007 
medial 
STS prefrontal 
Inferior 
V3 LO temporal 
10 autistic 
10 control 
Castelli et al 2002 
TP/ 
amygdala 
In autism reduced connectivity between V3 and anterior regions
What about reading own mind? 
Many people with autism say 
• they cannot describe their own feelings 
Why? 
• Do they not have the feelings? 
• Are they not aware of the feelings? 
• Are they not aware of having feelings? 
18 Uta Frith Kanazawa September 2007
Monitoring own feelings 
How does the picture make you feel? 
Pleasant - Neutral - Very unpleasant 
19 Uta Frith Kanazawa September 2007 
QuickTime™ and a 
TIFF (Uncompressed) decompressor 
are needed to see this picture.
Being aware of having the feelings 
Monitoring inner feeling compared to picture colour 
Mentalizing system active 
Being aware of the feelings 
Introspecting on feeling evoked by unpleasant picture compared to 
feeling evoked by nice picture 
Anterior Insula active 
Actually having the feelings 
Looking at unpleasant picture compared to nice picture 
Amygdala - orbitofrontal system active 
20 Uta Frith Kanazawa September 2007
Monitoring feelings - Mentalizing system active 
Reduced activation in autism 
21 Uta Frith Kanazawa September 2007 
Difference 
between 
Controls and 
ASD
22 Uta Frith Kanazawa September 2007 
MentS 
MentS 
MentS AntIns 
Amygdala 
Sel f 
Aware of having feelings 
Aware of feeling 
Just feeling
The non-social difficulties 
Executive functions 
• A range of higher-order control processes 
• Needed to act flexibly in novel or complex situations 
Poor executive control is associated with poor frontal 
lobe function and explains a range of problem 
behaviours in people with ASD 
23 Uta Frith Kanazawa September 2007
Examples of executive function tests 
performed poorly by people with ASD 
Wisconsin Card sorting Tower of London 
Think about different dimensions for sorting 
Don’t perseverate 
24 Uta Frith Kanazawa September 2007 
Plan several steps ahead 
Don’t forget the rules
What symptoms can be explained by 
executive function failure? 
Not being able to 
• inhibit no-longer-useful behaviour (perseveration) 
• respond flexibly in the face of change 
• plan ahead 
• monitor behaviour to check when goal is reached 
• hold in mind several things at once 
25 Uta Frith Kanazawa September 2007
How to cope with 
poor executive control? 
• Give clear structure 
• Give constant prompts and reminders 
• Give outside support 
• Specific techniques 
– For routinising behaviour 
– For coping with novelty 
• Coping with anxiety 
Most intervention programmes are geared to 
alleviate executive function problems 
26 Uta Frith Kanazawa September 2007
Cognitive strengths 
also need to be explained 
Weak central coherence Theory (WCC) 
attempts to explain 
• Fascination with small details 
• Superior perceptual discrimination 
• Savant skills 
27 Uta Frith Kanazawa September 2007
Explaining the non-social features 
Weak central coherence 
• WCC an information processing style 
– tendency to process details at the expense of global meaning 
– opposite to strong central coherence where global precedes local 
• More likely in relatives of individuals with autism 
• Advantages when analytic skills are required 
• Disadvantages when overall meaning is crucial 
28 Uta Frith Kanazawa September 2007
Embedded Figures Test 
29 Uta Frith Kanazawa September 2007
Cognitive strengths in autism 
(A) Block Design subtest of the Wechsler intelligence test, (B) locating embedded figures, (C) 
copying impossible figures. (D) identifying target size in Ebbinghaus illusion. 
(E and F) Finding the odd-man-out in cluttered displays whether the target is defined by a single 
feature as in (E) or by a conjunction of features as in (F). 
(G) tolerating higher levels of noise in determining the orientation of luminance-defined sine-wave 
gratings. 
30 Uta Frith Kanazawa September 2007
Weak central coherence 
can produce problems in everyday life 
A fragmentary world 
• Inability to use context to make sense 
of situation 
• Diminished top-down influences on 
perception 
Example: walk - don’t walk 
different actions can be required even with identical 
signal depending on context 
31 Uta Frith Kanazawa September 2007 
QuickTime™ and a 
TIFF (Uncompressed) decompressor 
are needed to see this picture.
A common denominator for social and 
non-social symptoms of ASD? 
• No shared social world 
• No shared physical world 
• The cognitive system lacks some basic preferences 
• Information is processed without prior expectations 
– As if anything is possible 
• Perception does not use prediction 
no TOP and no TOP-DOWN MODULATION 
32 Uta Frith Kanazawa September 2007
What is this? 
33 Uta Frith Kanazawa September 2007
34 Uta Frith Kanazawa September 2007
The same picture again: Obviously it is a cow ! 
35 Uta Frith Kanazawa September 2007
Bottom-up vs Top-down in the Brain 
Two kinds of neural systems 
driving neurons: bottom-up input 
controlling neurons: top-down expectations 
In autism 
The two systems don’t connect well together 
Hence poor top-down modulation 
36 Uta Frith Kanazawa September 2007 
TIFF (UQnucicokmTpimrees™sed a)n dde caompressor are needed to see this picture. 
What is meant by TOP-DOWN?
What happens in the brain during top-down modulation? 
37 Uta Frith Kanazawa September 2007
Vuilleumier (2001) 
“Attend to vertical (horizontal) location” 
Geoff Bird, Caroline Catmur, 
Giorgia Silani, Uta Frith and 
Chris Frith (2003) 
Before picture flashes up 
38 Uta Frith Kanazawa September 2007 
When expecting to 
see faces or houses 
in one of two 
locations, then 
activity in the is 
enhanced in the 
brain regions that 
process faces or 
houses: 
Parahippocampal 
Place area 
Fusiform Face area
39 Uta Frith Kanazawa September 2007 
(a) Attentional modulation of response 
in fusiform gyrus at x = - 42, y = - 80, z = - 12 
0 
0.4 
0.35 
0.3 
0.25 
0.2 
0.15 
0.1 
0.05 
Control Autistic 
Group 
% Signal Change 
(b) Attentional modulation of response 
in parahippocampal gyrus at x = - 26, y = - 46, z = - 12 
0 
1.6 
1.4 
0.8 
0.6 
0.4 
0.2 
1 
1.2 
Control Autistic 
Group 
% Signal Change 
Evidence for lack of top-down 
modulation 
The difference in the response when 
attended and unattended 
Less modulation in Fusiform Face Area 
And 
in Parahippocampal Place Area 
in autism 
in autism
Evidence for lack of top-down modulation 
in mentalizing 
In autism 
• Visual areas detect mentalizing stimuli and 
process them in detail 
• but higher-level processes fail to interpret them 
40 Uta Frith Kanazawa September 2007
A speculation about brain reorganisation 
in autism 
Cognitive deficits may reflect disconnections 
between driving and controlling neurons 
Disconnections may be a consequence of lack of 
appropriate pruning of re-entrant (backward) 
connections during the early years of life 
(Chris Frith, 2003) 
41 Uta Frith Kanazawa September 2007
Causes of TOPMOD failure 
• Brain re-organisation may fail in first two years of life 
– Probably under genetic control 
• To test this we would need to study actual progress of 
brain reorganization in development 
• Ideally using longitudinal high-field scanning 
An exciting programme for the future 
42 Uta Frith Kanazawa September 2007
Even more speculation… “The absent self” 
• High-order control system in the brain = self 
• Provocative idea: In autism - this self is absent or weak 
• The individual lacks awareness of this self and cannot 
reflect on own feelings 
• Analogy of absent chief executive of a big organisation 
– staff are working well and problems arise only in certain situations, 
e.g. when priorities have to be set. 
• Can be strength: basic level sensory processes may 
flourish and may dominate behaviour 
• Can be weakness: Basic level processes may overwhelm 
perception 
• Thus individual may suffer the fate of a feather in the storm 
of sensations 
43 Uta Frith Kanazawa September 2007
Thanks to my colleagues and collaborators 
Francesca Happé, Chris Frith, 
Fulvia Castelli, Elisabeth Hill, Geoff Bird, Rachel 
Brindley, Giorgia Silani, Tania Singer 
and Sarah White 
Thanks to the MRC for funding this research 
44 Uta Frith Kanazawa September 2007

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U.Frith Neuropsychology of autism. Talk given at Kanazawa+notes 2007

  • 1. Neuropsychological studies of Autism Spectrum Disorders Uta Frith 31st Annual Meeting of the Neuropsychology Association of Japan 27th September Kanazawa
  • 2. Infantile Autism Kanner 1943 Inability to relate affectively to others Insistence on sameness Islets of ability 2 Uta Frith Kanazawa September 2007
  • 3. A little bit of history 100 years ago autism not recognised at all 70 years ago autistic children first described in the Netherlands, in the US, in Austria… 50 years ago psychosocial origin presumed - not brain abnormality Now progress towards identifying brain abnormality, genetic risk factors and other putative causes 3 Uta Frith Kanazawa September 2007
  • 4. Everyone agrees on a biological basis for autism Autism is a biologically based condition With a strong genetic component With its effect on brain development There is some brain abnormality But We do not yet have biological markers 4 Uta Frith Kanazawa September 2007
  • 5. Everyone agrees on three key behavioural signs Difficulties in Social interaction Difficulties in Communication Restricted Patterns of Behaviour Not everyone agrees on how to explain these - at the cognitive level - at the brain level There are different cognitive theories These have led to new knowledge 5 Uta Frith Kanazawa September 2007
  • 6. No single theory is sufficient Three cognitive theories are needed - at least - To explain social and communication problems – E.g. Mind blindness To explain everyday coping problems – E.g. Executive dysfunction To explain cognitive strengths – E.g. Weak central coherence 6 Uta Frith Kanazawa September 2007
  • 7. Deficits in Social Cognition are a Core Feature of Autism One hypothesis explains many of the problems in communication and social interaction that are obvious from the second year of life Poor mentalizing ability A missing capacity due to specific brain abnormality • Affecting the intuitive ability to “read minds” • Leaving intact other social capacities 7 Uta Frith Kanazawa September 2007
  • 8. Baron-Cohen, Leslie and Frith, 1985: Sally-Anne test 8 Uta Frith Kanazawa September 2007
  • 9. 9 Uta Frith Kanazawa September 2007
  • 10. Sally (mistakenly) thinks her marble is in the basket Autistic children typically fail this test 10 Uta Frith Kanazawa September 2007
  • 11. Able autistic people can learn to read other minds but subtle problems persist Klin, 2000; Abell et al. 2000; Castelli et al. 2002 Example: Heider & Simmer effect We are often compelled to attribute mental states to animated shapes Two triangles interacting together vs Two triangles just floating 11 Uta Frith Kanazawa September 2007
  • 12. Revealing components of the brain’s mentalising system compared with Brain activity while watching interacting triangles 12 Uta Frith Kanazawa September 2007 Brain activity while watching randomly moving triangles Comparison shows extra activity when we see interactions and mentalise Where?
  • 13. QuickTime™ and a Animation decompressor are needed to see this picture. 13 Uta FCritho mKaena ozauwt aa Snedp tepmlabye r- 2 i0t0’s7 nice out here.
  • 14. QuickTime™ and a Animation decompressor are needed to see this picture. 14 Uta Frith Kanazawa September Animation that does not invite me2n00ta7 lising drifting…floating…
  • 15. Mentalising system Superior temporal sulcus 15 Uta Frith Kanazawa September 2007 Castelli et al., 2000 Medial prefrontal cortex Basal temporal, periamygdaloid Basal temporal
  • 16. Mentalising system in the autistic brain Reduced activation Weak connectivity between components 16 Uta Frith Kanazawa September 2007
  • 17. Brain activity associated with mentalizing in normal and autistic Ss 2.5 2 1.5 1 0.5 0 -0.5 R. extra-striate R. basal temporal R. STS R. medial prefrontal 17 Uta Frith Kanazawa September 2007 medial STS prefrontal Inferior V3 LO temporal 10 autistic 10 control Castelli et al 2002 TP/ amygdala In autism reduced connectivity between V3 and anterior regions
  • 18. What about reading own mind? Many people with autism say • they cannot describe their own feelings Why? • Do they not have the feelings? • Are they not aware of the feelings? • Are they not aware of having feelings? 18 Uta Frith Kanazawa September 2007
  • 19. Monitoring own feelings How does the picture make you feel? Pleasant - Neutral - Very unpleasant 19 Uta Frith Kanazawa September 2007 QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.
  • 20. Being aware of having the feelings Monitoring inner feeling compared to picture colour Mentalizing system active Being aware of the feelings Introspecting on feeling evoked by unpleasant picture compared to feeling evoked by nice picture Anterior Insula active Actually having the feelings Looking at unpleasant picture compared to nice picture Amygdala - orbitofrontal system active 20 Uta Frith Kanazawa September 2007
  • 21. Monitoring feelings - Mentalizing system active Reduced activation in autism 21 Uta Frith Kanazawa September 2007 Difference between Controls and ASD
  • 22. 22 Uta Frith Kanazawa September 2007 MentS MentS MentS AntIns Amygdala Sel f Aware of having feelings Aware of feeling Just feeling
  • 23. The non-social difficulties Executive functions • A range of higher-order control processes • Needed to act flexibly in novel or complex situations Poor executive control is associated with poor frontal lobe function and explains a range of problem behaviours in people with ASD 23 Uta Frith Kanazawa September 2007
  • 24. Examples of executive function tests performed poorly by people with ASD Wisconsin Card sorting Tower of London Think about different dimensions for sorting Don’t perseverate 24 Uta Frith Kanazawa September 2007 Plan several steps ahead Don’t forget the rules
  • 25. What symptoms can be explained by executive function failure? Not being able to • inhibit no-longer-useful behaviour (perseveration) • respond flexibly in the face of change • plan ahead • monitor behaviour to check when goal is reached • hold in mind several things at once 25 Uta Frith Kanazawa September 2007
  • 26. How to cope with poor executive control? • Give clear structure • Give constant prompts and reminders • Give outside support • Specific techniques – For routinising behaviour – For coping with novelty • Coping with anxiety Most intervention programmes are geared to alleviate executive function problems 26 Uta Frith Kanazawa September 2007
  • 27. Cognitive strengths also need to be explained Weak central coherence Theory (WCC) attempts to explain • Fascination with small details • Superior perceptual discrimination • Savant skills 27 Uta Frith Kanazawa September 2007
  • 28. Explaining the non-social features Weak central coherence • WCC an information processing style – tendency to process details at the expense of global meaning – opposite to strong central coherence where global precedes local • More likely in relatives of individuals with autism • Advantages when analytic skills are required • Disadvantages when overall meaning is crucial 28 Uta Frith Kanazawa September 2007
  • 29. Embedded Figures Test 29 Uta Frith Kanazawa September 2007
  • 30. Cognitive strengths in autism (A) Block Design subtest of the Wechsler intelligence test, (B) locating embedded figures, (C) copying impossible figures. (D) identifying target size in Ebbinghaus illusion. (E and F) Finding the odd-man-out in cluttered displays whether the target is defined by a single feature as in (E) or by a conjunction of features as in (F). (G) tolerating higher levels of noise in determining the orientation of luminance-defined sine-wave gratings. 30 Uta Frith Kanazawa September 2007
  • 31. Weak central coherence can produce problems in everyday life A fragmentary world • Inability to use context to make sense of situation • Diminished top-down influences on perception Example: walk - don’t walk different actions can be required even with identical signal depending on context 31 Uta Frith Kanazawa September 2007 QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.
  • 32. A common denominator for social and non-social symptoms of ASD? • No shared social world • No shared physical world • The cognitive system lacks some basic preferences • Information is processed without prior expectations – As if anything is possible • Perception does not use prediction no TOP and no TOP-DOWN MODULATION 32 Uta Frith Kanazawa September 2007
  • 33. What is this? 33 Uta Frith Kanazawa September 2007
  • 34. 34 Uta Frith Kanazawa September 2007
  • 35. The same picture again: Obviously it is a cow ! 35 Uta Frith Kanazawa September 2007
  • 36. Bottom-up vs Top-down in the Brain Two kinds of neural systems driving neurons: bottom-up input controlling neurons: top-down expectations In autism The two systems don’t connect well together Hence poor top-down modulation 36 Uta Frith Kanazawa September 2007 TIFF (UQnucicokmTpimrees™sed a)n dde caompressor are needed to see this picture. What is meant by TOP-DOWN?
  • 37. What happens in the brain during top-down modulation? 37 Uta Frith Kanazawa September 2007
  • 38. Vuilleumier (2001) “Attend to vertical (horizontal) location” Geoff Bird, Caroline Catmur, Giorgia Silani, Uta Frith and Chris Frith (2003) Before picture flashes up 38 Uta Frith Kanazawa September 2007 When expecting to see faces or houses in one of two locations, then activity in the is enhanced in the brain regions that process faces or houses: Parahippocampal Place area Fusiform Face area
  • 39. 39 Uta Frith Kanazawa September 2007 (a) Attentional modulation of response in fusiform gyrus at x = - 42, y = - 80, z = - 12 0 0.4 0.35 0.3 0.25 0.2 0.15 0.1 0.05 Control Autistic Group % Signal Change (b) Attentional modulation of response in parahippocampal gyrus at x = - 26, y = - 46, z = - 12 0 1.6 1.4 0.8 0.6 0.4 0.2 1 1.2 Control Autistic Group % Signal Change Evidence for lack of top-down modulation The difference in the response when attended and unattended Less modulation in Fusiform Face Area And in Parahippocampal Place Area in autism in autism
  • 40. Evidence for lack of top-down modulation in mentalizing In autism • Visual areas detect mentalizing stimuli and process them in detail • but higher-level processes fail to interpret them 40 Uta Frith Kanazawa September 2007
  • 41. A speculation about brain reorganisation in autism Cognitive deficits may reflect disconnections between driving and controlling neurons Disconnections may be a consequence of lack of appropriate pruning of re-entrant (backward) connections during the early years of life (Chris Frith, 2003) 41 Uta Frith Kanazawa September 2007
  • 42. Causes of TOPMOD failure • Brain re-organisation may fail in first two years of life – Probably under genetic control • To test this we would need to study actual progress of brain reorganization in development • Ideally using longitudinal high-field scanning An exciting programme for the future 42 Uta Frith Kanazawa September 2007
  • 43. Even more speculation… “The absent self” • High-order control system in the brain = self • Provocative idea: In autism - this self is absent or weak • The individual lacks awareness of this self and cannot reflect on own feelings • Analogy of absent chief executive of a big organisation – staff are working well and problems arise only in certain situations, e.g. when priorities have to be set. • Can be strength: basic level sensory processes may flourish and may dominate behaviour • Can be weakness: Basic level processes may overwhelm perception • Thus individual may suffer the fate of a feather in the storm of sensations 43 Uta Frith Kanazawa September 2007
  • 44. Thanks to my colleagues and collaborators Francesca Happé, Chris Frith, Fulvia Castelli, Elisabeth Hill, Geoff Bird, Rachel Brindley, Giorgia Silani, Tania Singer and Sarah White Thanks to the MRC for funding this research 44 Uta Frith Kanazawa September 2007

Notas do Editor

  1. Neuropsychological studies of Autism Spectrum Disorders Notes for a talk given on 27th September, Kanazawa By Uta Frith
  2. When Leo Kanner, the Baltimore Child Psychiatrist, first described the condition he called ‘infantile autism’, he identified 3 core features: Inability to relate affectively to others Insistence on sameness Islets of ability
  3. Autism has a short history but there have been major advances. Only 70 years ago were there was barely a recognition of autism, although already some very first descriptions appeared. Now we know that there is a whole spectrum of autistic disorder, from mild to severe. We know it is a life-long disorder with a basis in the brain. So we are in a position to describe the nature of autism and begin to ask about the genetic causes of the condition.
  4. While only 50 years ago there was much speculation about a psychogenic cause of autism, now everyone agrees that there is a biological basis of autism and that there is brain abnormality. But, we do not yet have biological markers. We define autism spectrum disorders in terms of behavioural criteria.
  5. Everyone agrees on three key behavioural criteria, already identified by Kanner, But not everyone agrees on how to explain the behavioural signs. We need to consider explanations of behaviour at the cognitive level and at the brain level.
  6. No single cognitive theory is sufficient to explain the core behavioural features of autism. At present we have three theories which are needed to explain the social problems, the everyday coping problems, and the cognitive strengths (islets of ability). The three theories are: “Mindblindness”, “Executive Dysfunction”, “Weak Central Coherence”.
  7. I start with the “Mindlblindness Theory”. This theory explains many of the behavioural signs of autism in social interaction and communication. These signs are present from the second year of life and remain lifelong. They change in their behavioural manifestation over the course of development. Their different forms can be explained quite well by mindblindness, or poor mentalizing ability. Mentalising refers to our pervasive and automatic ability to attribute mental states to others, that is, to read other minds.
  8. This test, known as the Sally-Anne test, is a way of explaining what is meant by mentalising ability is. The test can be enacted with dolls or with real people. This makes no difference. This test was first published in 1985 (Baron-Cphen, Leslie & Frith) and these are the dolls that were used then. ”Here is Sally and here is Anne. Sally has a basket and Anne has a box. Sally has a marble. She puts it in her basket. She covers the basket with the cloth.”
  9. “Sally goes out to play. While Sally is out, Anne, naughty Anne, takes the marble out of Sally’s basket and puts it into her own box.”
  10. “Now Sally comes back and wants to play with her marble. Where will Sally look for the marble?” The correct answer is “in the basket”, because this is where Sally thinks the marble is. She could not know that Anne transferred the marble to the box, because she was not in the room at the time the transfer happened. Therefore Sally now has a false belief: she believes the marble is in the basket. Her belief explains what she will do next. The reality, where the marble actually is, does not explain what she will do next. A belief is a typical mental state. We use mental states, rather than reality, to explain what people are going to do. This is what we mean by mentalising, or mindreading. Five-year old normally developing children understand this perfectly, but not autistic children. Autistic children say that Sally will look for the marble where it really is (in the box).
  11. <number> Many experiments have investigated mentalising ability, e.g. the attribution of a false belief to another person, in autistic individuals. These experiments have shown that autistic children can over many years learn to mentalise after a fashion. This never becomes spontaneous or automatic. Autistic adults with normal or high intelligence (on the mild end of the spectrum of autistic disorders) can pass the Sally-Anne test with ease. Still they have problems in real life. For example they have difficulty in attributing mental states spontaneously to animated shapes in silent movies. Heider and Simmel in 1945 have shown that normal adults attribute mental states to animated shapes automatically. This is known as the Heider & Simmel effect. So, we are compelled to perceive a (carefully scripted) sequence of moving triangles as interacting with each other. This can be contrasted with randomly moving triangles. In this case we are not tempted to attribute mental states to them, but we perceive them as moving randomly.
  12. <number> It is possible to use functional Magnetic Resonance Imaging (fMRI) to reveal the brain’s mentalising system. This is done by contrasting two condition. In one condition, the person in the scanner watches interacting triangles. In the other condition the person watches randomly moving triangles. The comparison shows the extra activity in the areas of the brain when we see interacting triangles and spontaneously mentalise. This is known as the subtraction method of neuroimaging. It shows us where in the brain the activity occurs that is of interest to the experimenter.
  13. Here is an example of a carefully scripted sequence of triangles interacting with each other. We spontaneously attribute mental states to them (we mentalise). For example, here we see a scenario where the big triangle tries to get the little triangle to come outside to play. The little triangle seems to be afraid to go outside, but eventually is persuaded by the big triangle to go outside and play. Normal adults often perceive the meaning of the sequence as a mother trying to gently coax the child to go outside the house. People with autism find it very difficult to get this sort of meaning.
  14. <number> Here is an example of a sequence of randomly floating triangles. This movie does not invite mentalising. The triangles are not perceived as interacting. People with autistic spectrum disorder have no difficulty in seeing randomly floating triangles.
  15. <number> This slide shows where the extra brain activity occurs when we subtract brain activation found while watching interacting triangles from brain activation found while watching randomly moving triangles. This subtraction method reveals a brain system involving three main components shown on the slide: Medial prefrontal cortex, Superior temporal sulcus and periamygdaloid region. This is now known as the brain’s mentalising system. This system has been revealed in a number of different neuroimaging studies with different stimuli, for example, short stories, which in one condition do involve mentalising and in another condition do not involve mentalising. The components of this brain system are working in concert in normal people and are all highly active during mentalising.
  16. <number> In autism the mentalising system shows reduced activation and there is weak connectivity between its components.
  17. This slide shows activation in the mentalising system in both normal adults (light blue) and adults at the mild end of the autism spectrum (dark blue), while watching the interacting triangles across a number of different animations. In autistic adults activation is reduced in the main components of the mentalising system: the 3 columns on the right of the figure. In the visual processing areas of the brain (the leftmost column) activation was equally high in normal and autistic individuals. This shows that autistic people can visually distinguish the two types of animations very well and the visual regions respond with greater activity to the interacting triangles. However, autistic people cannot interpret the meaning of these visually very different animations.This interpretation depends on top-down input from the main components of the mentalising system. In the case of autism the connectivity between the visual regions the mentalising regions is weak.
  18. <number> Most studies on mentalising in autism concern reading other minds. What about reading own mind? We know from autobiographies that people with autism have difficulties describing their own inner mental states, and in particular their own feelings. Why is this? Do they not have the feelings? Are they not aware of the feelings? Or, are they not aware of having the feelings?
  19. <number> We conducted an fMRI experiment where people with mild autism spectrum disorder and normal adults were asked to introspect on their own feelings while watching pictures. These pictures were taken from the International Affective Picture Scales. Some pictures arouse pleasant feelings, others unpleasant feelings. Our subjects were asked to indicate on a sliding scale how each picture made them feel. They were then shown the same pictures again. But this time they had to indicate, again on a sliding scale, how much colour was contained in each picture. This enabled us to find out the extra activity in the brain when people introspected on their inner feelings, and when they just evaluated the colour content of the stimuli. We could also compare brain activity when pleasant and unpleasant pictures were shown, regardless of the task.
  20. <number> Here are the different comparisons of brain activation that we made in this study. We compared what happened when people evaluated their inner feelings vs evaluating colour. Here the mentalising system was active. This system is involved in reading minds. Not only other minds, but also own minds. 2. We compared what happened when people evaluated their inner feelings in the presence of unpleasant vs pleasant picture. Here the Anterior Insula was active. This region is known to be active when people feel pain and bodily sensations. 2. We compared what happened when people were simply exposed to unpleasant vs pleasant pictures. This activated the Amygdala system of the brain. This is known to be active when people are aroused by strong negative emotions.
  21. <number> This slide shows the extra brain activation in the mentalising system of the brain (medial prefrontal cortex, superior temporal sulcus) when people introspected on their own feelings vs evaluating the colour content of the picture. In the circled areas there was a significant group difference: People with autism showed reduced activation in these regions compared to normal adults.
  22. <number> This slide shows in a schematic way how we might answer the three questions posed at the beginning of this study. Do autistic people not have feelings? No. Autistic people do have feelings. Their amygdala system was just as active as that of normal people when exposed to unpleasant pictures. 2. Are they not aware of the feelings? Yes and no. Autistic people are aware of the feelings to the extent that they are able to identify their own feelings. This shows individual differences. About half the people in the autism group were not good at identifying their own feelings. These people showed less activation in the Anterior Insula than the others in the group. Are they not aware of having the feelings? Yes. Autistic people are not aware of themselves as having feelings - at least not to the same extent as normal people. They cannot read their own minds. My interpretation is that perhaps there is no inner ‘self’ to read the feelings, as represented by the amygdala and anterior insula systems. Autism could mean an ‘absent self’.
  23. Autism is not only characterised by difficulties in social interaction and communication. There are non-social difficulties as well. The theory of executive dysfunction tries to explain these difficulties. Executive function is an umbrella term for a range of higher-order control processes which are needed to act flexibly in novel or complex situations. Poor executive control is associated with poor frontal lobe function. By analogy, autistic people suffer from poor frontal lobe function.
  24. This slide shows two popular neuropsychological tests, Wisconsin Card Sorting and Tower of London. Autistic people tend to perform poorly on these tests. They tend to perseverate on sorting when dimensions on the Wisconsin test are switched by the experimenter, and they tend to make poor plans on the Tower of London test.
  25. Laboratory tests of executive functions confirm the nature of the difficulties that autistic people experience in their everyday life. Examples are: Not being able to inhibit no-longer-useful behaviour (perseveration) Not being able to respond flexibly in the face of change Not being able to plan ahead Not being able to monitor behaviour to check when goal is reached Not being able to hold in mind several things at once All these difficulties are apparent when autistic people have to do their daily shopping in a supermarket, for example.
  26. The same advice that is used to rehabilitate patients with frontal lobe damage is also useful for autistic people. Most intervention programmes for autism are geared to alleviate executive function problems. Typically these programmes involve the following points: Give clear structure Give constant prompts and reminders Give outside support There are techniques for routinising behaviour, for coping with novelty and for coping with anxiety. These all benefit autistic people, even those at the mild end of the autism spectrum.
  27. A deficit account, such as the executive dysfunction account, cannot explain the cognitive strengths and islets of ability in autism. One theory that tries to explain these strengths (fascination with small details, superior perceptual discrimination, savant skills) is: Weak Central Coherence.
  28. Weak Central Coherence is an information processing style: a tendency to process details at the expense of global meaning This is the opposite to strong central coherence where global precedes local. Weak Central Coherence as a processing style is found also in relatives of individuals with autism, who are themselves not at all autistic. This style has advantages when analytic skills are required, but can have disadvantages when overall meaning is crucial
  29. The Embedded Figures Test is performed well by people with a Weak Central Coherence processing style. They find the small detail in the overall pattern very easily and quickly.
  30. These examples show tests where autistic individuals often show superior performance compared to IQ- matched controls. (A) Block Design subtest of the Wechsler intelligence test is often a cognitive strength in the profile of performance. (B) locating embedded figures is often a cognitive strength. (C) copying of impossible figures has been shown to be superior. (D) Ebbinghaus illusion: the surrounding elements can make the (identical) central targets appear quite different. Autistic observers are less susceptible to this illusion. However there is some controversy about this finding. (E and F) Autistic observers are faster and less error prone at finding the odd-man-out in cluttered displays whether the target is defined by a single feature as in (E) or by a conjunction of features as in (F). (G) Observers with ASD can tolerate higher levels of noise in determining the orientation of luminance-defined sine-wave gratings (Bertone et al. 2005).
  31. An example of the bad effect of exreme Weak Central Coherence is from the movie Rainman. Rainman walks across the street. Suddenly the traffic lights change to red. He immediately stands still in the middle of the traffic, a very dangerous situation. Rainman interprets the red signal without concern for the overall meaning. Having already started to cross the road, he should not stop at the red signal. Instead Rainmain should hurry up to get across, or go back. This example also shows that Weak Central Coherence can be understood as a kind of Context-blindness. This is a disadvantage of this processing style. In the extreme case the result is a fragmentary world.
  32. We can now ask the question whether there is a common explanation for both the social and non-social features of autism. One common denominator is that autistic people do not live in a shared social world or shared physical world. What is the reason for this? Perhaps the cognitive system lacks some innate basic preferences. Perhaps information is processed without being guided by prior expectations. Perhaps perception does not use prediction. This hypothesis brings together the idea of an absent self and the idea that context has little effect on perception. The hypothesis suggests a lack of top-down modulation.
  33. This is an example to explain what I mean by top-down modulation. The first slide gives a picture that seems completely chaotic, without meaning. There is no prior expectation to guide our perception. Anybody who has not seen the following slide should say that they have no idea what this is a picture of. But, once you have seen the second slide, you will know what it is.
  34. Here we get an expectation of what it is that the first picture shows. It is a cow. We now can use this information (top-down modulation) to look again at the first picture.
  35. Top-down modulation has transformed our perception. Now it is completely clear what this picture is. A cow. We see better when we have an expectation of what to see. Is autistic perception always like our perception was when we saw the first picture? Due to a lack of top-down modulation?
  36. What is meant by top-down modulation? The opposite of Top-down is Bottom-up. Here the idea is proposed that there are two kinds of neurons: driving neurons (= bottom up) and controlling neurons (= top-down). The proposal is that in the autistic brain these two neural systems don’t connect well together.
  37. What happens in the brain during top-down modulation? A brain imaging experiment gives some clues. This experiment was first conducted by Vuilleumier (2001). Bird et al. repeated this experiment with autistic adults. Again these individuals were at the mild end of the autism spectrum.
  38. This slide shows the design of Vuilleumier’s fMRI experiment (2001), which was also used by Bird et al, 2003. People in the scanner are told in advance whether to attend to the horizontal or vertical location where pairs of faces and pairs of houses are shown for a split second. They have to say whether a pair is the same or different. The brain activation in the region that processes faces is enhanced, when faces are shown in the attended location. Vice versa, brain activation in the region that processes houses is enhanced when houses are shown in the attended location. This is an example of top-down modulation.
  39. The results of Bird et al.’s experiment were clear: autistic people showed much less enhanced activation in either the face or the house processing regions of the brain. This is evidence for a lack of top-down modulation. This lack of top-down modulation is particularly striking in the case of faces. This is interesting as people with autism often seem to find faces difficult to identify.
  40. In the fMRI experiment too there was evidence for a lack of top-down modulation. In the slide earlier on, we saw that the visual areas of the brain were activated in a normal way, but the components of the mentalising system which are more anterior in the brain, did not show increased activation in autism. Autistic people can distinguish visually the interacting and randomly moving stimuli, but they can’t interpret them.
  41. There is an interesting speculation (due to Chris Frith, 2003) about the reason that top-down neurons are not efficient and not well-connected with driving neurons in the autistic brain. The idea is that brain reorganisation early in development is faulty. Perhaps it is precisely the controlling, neurons which are not reorganised as they proliferate in development during the first two years of life. It has been suggested that there is a failure of pruning in the young autistic brain, resulting in bigger brains. This failure could be specific to controlling neurpns. Driving neurons, on the other hand, may not be so affected. Perhaps they need less reorganisation, as they are functioning already from birth. This combination could explain the superior perception of detail (efficient driving neurons) with an apparent inability to take into account higher level context and prior expectations (inefficient controlling neurons).
  42. The speculation about brain re-organisation in early life is only speculation. It still needs to be tested. This could be done by longitudinal studies and using high-field scanners. This is an exciting programme of research for the future.
  43. I am tempted to provide even more speculation: inefficient controlling neurons may lead not only to poor top-down control, but may also result in a poor idea of the self. The ‘absent self’ would explain why there are executive function problems, and why there are problems in reading own and other minds. There is no self to do the mind-reading. I use the analogy for the self as the chief executive of a big company. The staff of the company are working well by themselves and the chief executive only needs to intervene in certain situations, when problems arise and when priorities have to be set. This can be a strength: basic level sensory processes may flourish and may dominate behaviour. But this can also be a weakness: Basic level processes may overwhelm perception. We know from the study I presented earlier that autistic people have strong feelings, but do not realise that it is themselves who have the feelings. Thus the autistic individual may suffer the fate of a feather in the storm of sensations.
  44. Acknowledgements to my friends and colleagues and to the MRC for funding this research.