PowerPoint Presentation · 2012-09-18 · MARJOLEIN VERLY Conclusions STEFAN SUNAERT, MD, PHD PAUL DE COCK, MD, PHD LIEVEN LAGAE, MD, PHD NATHALIE ROMMEL, PHD INGE ZINK, PHD 18/09/2012

18-9-2012

1

Neuroanatomical and Functional

Substrates of language in Autism

Spectrum Disorder

JUDITH VERHOEVEN, MD, PHD

MARJOLEIN VERLY

S T E FA N S U N A E R T, M D , P H D

PA U L D E C O C K , M D , P H D

L I E V E N L A G A E , M D , P H D

N AT H A L I E R O M M E L , P H D

I N G E Z I N K , P H D

Autism Spectrum Disorders

Outline of the presentation

18/09/2012

1. Introduction

2. Aims

1. Specific studies

2. Conclusions and future prospects

Imaging in ASD

Introduction 18/09/2012 Imaging in ASD

Speech & language problems have high prevalence in

children (5%)

Primary speech & language disorders

SLI

Speech & language problems as part of a more global

developmental problem

ASD

Introduction Autism Spectrum Disorders

18/09/2012 Imaging in ASD

Social

Interaction Communication

Restricted repetitive behaviours & interests

Environment (Vaccines, Herpes

encephalitis)


Immune dysregulation

Genes

Pre- and perinatal risk

factors

Introduction:

ASD Today

Brain

Development &

Functioning

(Infection, Foetal alcohol syndrome, Valproate)

(SHANK3, Neurexin, Neuroligin)

Neurotransmittors

(Serotonin, GABA, Dopamine)

(Auto-Antibodies)


Introduction:

ASD The Future

Noisy brain

Messy Cables

Brain overgrowth Large heads

Disconnectivity Hypothesis

Neuronal disorganisation

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COGNITION

NEUROBIOLOGY

ASD phenotype


MOLECULAR &

CELLULAR

BIOLOGY

PHENOTYPE

Heterogeneous

GENOTYPE

Genetic heterogeneity

Study with

advanced

neuroimaging

Delineate a more

homogeneous

subgroup

More

homogeneous

neurobiology?

18/09/2012

Imaging in ASD

Phenotypical transition over time

Phenotypical Spectrum?

SL

I Mixed receptive-expressive profile

Pragmatic skill intact

Normal development

PL

I Adequate syntax & phonology

Pragmatic skills deficient

Normal development

AS

D-L

I Mixed receptive-expressive profile


Global developmental problems

AS

D Language

delay, no structural language deficit


Global developmental problems


18/09/2012

1. Introduction

2. Methods & Aims

3. Specific studies


Find more direct evidence for ASD being a

disorder of brain connectivity

Imaging in ASD


18/09/2012

1. Introduction

2. Methods & Aims

3. Specific studies


Investigate the overlaps between ASD and SLI

Imaging in ASD

18/09/2012

Imaging in ASD

COGNITIVE

LEVEL

Well characterized homogeneous subgroup

CELF-IV-NL, WISC-III, SRS, SCQ

Language, Intelligence, Autism scores

Neuropsychological testing

1u30 min

LANGUAGE

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Imaging in ASD

NEUROBIOLOGICAL

LEVEL

Imaging of the brain

Conventional images, DTI, fMRI

MRI scan

45 min

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18/09/2012

Imaging in ASD

13

NEUROBIOLOGICAL

LEVEL

• Conventional neuro-imaging

White

Matter

NEUROBIOLOGICAL

LEVEL

• Conventional neuro-imaging

• Diffusion Tensor Imaging

• Functional Magnetic Resonance Imaging


Gray

Matter


18/09/2012

1. Introduction

2. Aims

1. Specific studies


Imaging in ASD

Structural connectivity in ASD vs SLI

18/09/2012

Imaging in ASD

Structural connectivity


Hypothesis


If ASD & SLI share a common etiology

the same linguistic profile and

underlying connectivity deficits in the

language processing areas will be

found



Auditory cortex

Expressive language area

(Broca)

Receptive language area

(Wernicke)

Superior longitudinal fasciculus

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4

19 ASD-LI (13.8

1.6y)

21 CO (14.4

1.5y)

DSM IV diagnosis

(autism/PDD-NOS)

SCQ ≥ 15

SRS ≥60

Important language delay/impairment

R- handed

Intelligence > 80

Natively Dutch speaking

19 ASD-LI (13.8

1.6y)

21 CO (14.4

1.5y)

DSM IV diagnosis

(autism/PDD-NOS)

SCQ ≥ 15

SRS ≥60

Important language delay/impairment

R- handed

Intelligence > 80

Natively Dutch speaking

13 SLI (10.1

0.4y)

12 CO (10.2

0.3y)

Former longitudinal study SLI

Language delay with need for therapy < 4.4y

At least one test <p3 at start

At least one test <p10 at

re-evaluation




Methods

Phenotypical level

Neurobiological level DTI

of the major

language

tract

Standardized

linguistic

testing

Receptive

Score

Zscore - 5.75 (4.80) - 1.06 (0.57) 0.022*

p value <0.001* 0.029*


ASD-LI

study group

SLI

study group Between group

comparison

Expressive

Score

Z-score - 2.16 (1.68) - 1.36 (0.62) 0.649

p value <0.001* 0.001*


Language profile

Receptive language

Expressive language

Phenotypically

comparable

Mixed Expressive-Receptive


Methods

Superior longitudinal fasciculus SLF



-LI



Explore overlaps between ASD & SLI

Phenotypical level

Language profile SLI Language profile ASD-LI

SLF affected

Neurobiological level

SLF not affected

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Functional connectivity in ASD

18/09/2012

Imaging in ASD

Functional connectivity


Verb generation task (Benson et al 1999) localises cortical regions involved in language function

Off

10 scans

Off

10 scans

Off

10 scans

Off

10 scans

Off

10 scans

On

10 scans

On

10 scans

On

10 scans

On

10 scans

#@éé= ?

)[ =+%

[ &*.; WATCH

What can

you do with

it?

Car Chair Flower Baby

Method: active fMRI

OFF

ON


Method: active fMRI

MTG-right

IFG-left

MTG-left

Cb-right

SMA

Premotor-

left

DLPF

IFG-right

8 seeds

Controls

ASD-LI

conjunction


Close your eyes

Clear your mind

Method: resting state fMRI



Low frequency BOLD fluctuations


Reflects the brain activity in

rest

Functionally connected

networks show coordinated

fluctuations


Looking at low frequency fluctuations in the BOLD

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Functional connectivity of the language network

Results

BR

OC

A

BR

OC

A

WERNICKE

Controls ASD-LI

WERNICKE


Functional connectivity of the language network

Results

Controls

ASD-LI

Difference

map


A relative functional dissociation of cerebral and cerebellar

language regions in ASD-LI

Furthermore we found a negative correlation between the

severity of the autism and the cerebro-cerebellar

connectivity, indicating the specificity of our finding for ASD.

Conclusion


A detachment of the cortical language system from his

normal cerebellar control might alter normal language

development and functioning

in ASD-LI

Conclusion


Hypothesis

Role of arcuate fascicle in ASD

Interhemispheric asymmetry of the

SLF is related to the language

problems in ASD

Method


CO+: 72% (18/25)

ASD+: 41% (7/17)

CO-: 28% (7/25)

ASD-: 59% (10/17)

Bilateral presence AF Unilateral presence AF

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Results

ASD+ ASD-


Bilateral AF Unilateral AF

Language not affected

Phenotypical level

Language affected

Results



Results

CO+ CO-



Language score

Phenotypical level

Language score <

Results



Conclusion



Language score

Phenotypical level

Language score

Language score Language score

ASD

CO

+ -

ASD-LI >

<

A bilateral presence of the arcuate fascicle is a positive

prognostic marker for language in autism.


18/09/2012

1. Introduction

2. Aims & Methods

1. Specific studies

2. Conclusions

Imaging in ASD

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Autism Spectrum Disorders ?


General Conclusions


Homogeneous subgroup Disappearance of

variable WM

findings

Phenotypic

Heterogeneity

1. DTI in ASD vs ASD-LI


General Conclusions

2. DTI in ASD-LI vs SLI

Phenotypical level Neurobiological level

SLI

ASD-LI

Language profile Language tract


General Conclusions

3. Connectivity ASD-LI

SLF not

affected

Cerebellar

control

affected


General Conclusions

4. Asymmetry of AF

ASD language >

CO language >

18/09/2012

Imaging in ASD

Judith Verhoeven

Marjolein Verly

Professor S. Sunaert

Professor P. De Cock

Professor L. Lagae

Professor N. Rommel

Professor I. Zink

Thank you

Documents

PowerPoint Presentation · 2012-09-18 · MARJOLEIN VERLY Conclusions STEFAN SUNAERT, MD, PHD PAUL DE COCK, MD, PHD LIEVEN LAGAE, MD, PHD NATHALIE ROMMEL, PHD INGE ZINK, PHD 18/09/2012