u.frith neuropsychology of autism. talk given at kanazawa+notes 2007

Neuropsychological studies of Autism Spectrum Disorders

Uta Frith31st Annual Meeting of the Neuropsychology

Association of Japan27th September Kanazawa

2 Uta Frith Kanazawa September 2007

Inability to relate affectively to others Insistence on sameness

Islets of ability

Infantile Autism Kanner 1943


A little bit of history

100 years agoautism not recognised at all

70 years agoautistic children first described in the Netherlands, in the US, in Austria…

50 years agopsychosocial origin presumed - not brain abnormality

Nowprogress towards identifying brain abnormality, genetic risk factors and other putative causes


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

ButWe do not yet have biological markers


Difficulties in Social interactionDifficulties in Communication

Restricted Patterns of Behaviour

Everyone agrees on three key behavioural signs

There are different cognitive theoriesThese have led to new knowledge

Not everyone agrees on how to explain these- at the cognitive level - at the brain level


No single theory is sufficientThree 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


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


Baron-Cohen, Leslie and Frith, 1985: Sally-Anne test


Sally (mistakenly) thinks her marble is in the basket

Autistic children typically fail this test


Two triangles interacting togethervs

Two triangles just floating

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


Revealing components of the brain’smentalising system

compared with

Brain activity while watching interacting triangles

Brain activity while watching randomly moving triangles

Comparison shows extra activity when we see interactions and mentalise

Where?

13 Uta Frith Kanazawa September 2007Come out and play - it’s nice out here.

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14 Uta Frith Kanazawa September 2007drifting…floating…Animation that does not invite mentalising

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Superior temporal sulcusSuperior temporal sulcus

Basal temporal, periamygdaloid

Castelli et al., 2000

Medial Medial prefrontalprefrontal

cortexcortex

Basal temporal

Mentalising systemMentalising system


Mentalising system in the autistic brain

Reduced activation

Weak connectivity between components


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R. extra-striate R. basal temporal R. STS R. medial prefrontal

medialprefrontalSTS

InferiortemporalLOV3

Castelli et al 2002

Brain activity associated with mentalizing in normal and autistic Ss

10 autistic10 control

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?


Monitoring own feelingsHow does the picture make you feel?Pleasant - Neutral - Very unpleasant

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Monitoring inner feeling compared to picture colour

Mentalizing system active

Introspecting on feeling evoked by unpleasant picture compared to feeling evoked by nice pictureAnterior Insula active

Looking at unpleasant picture compared to nice picture Amygdala - orbitofrontal system active

Being aware of having the feelings

Actually having the feelings

Being aware of the feelings


Reduced activation in autism

Difference between Controls and ASD

Monitoring feelings - Mentalizing system active


MentS

MentS

AntInsMentS

Amygdala

Aware of having feelings

Aware of feeling

Just feeling

Self


The non-social difficultiesExecutive 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


Examples of executive function testsperformed poorly by people with ASD

Wisconsin Card sorting Tower of London

Think about different dimensions for sortingDon’t perseverate

Plan several steps aheadDon’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


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


Cognitive strengths also need to be explained

Weak central coherence Theory (WCC)

attempts to explain• Fascination with small details• Superior perceptual discrimination• Savant skills


Explaining the non-social featuresWeak 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


Embedded Figures Test


(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.

Cognitive strengths in autism


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 perceptionExample: walk - don’t walk different actions can be required even with identical

signal depending on context

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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


What is this?


The same picture again: Obviously it is a cow !


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

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What is meant by TOP-DOWN?


What happens in the brain during top-down modulation?


Vuilleumier (2001)

Geoff Bird, Caroline Catmur, Giorgia Silani, Uta Frith and Chris Frith (2003)

Before picture flashes up“Attend to vertical (horizontal) location”

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 areaFusiform Face area


(a) Attentional modulation of response

in fusiform gyrus at x = - 42, y = - 80, z = - 12

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Control Autistic

Group

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(b) Attentional modulation of response

in parahippocampal gyrus at x = - 26, y = - 46, z = - 12

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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 modulationin mentalizing

In autism• Visual areas detect mentalizing stimuli and

process them in detail • but higher-level processes fail to interpret them


A speculation about brain reorganisation in autism

Cognitive deficits may reflect disconnectionsbetween 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)


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


• 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

Even more speculation… “The absent self”


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

u.frith neuropsychology of autism. talk given at kanazawa+notes 2007

Science

autism21 uta frith kanazawa

floating11 uta frith

test10 uta frith kanazawa

brain developmentthere

brain levelthere

brain abnormalitybutwe

unpleasant picture

specific brain abnormality