What neuroimaging can teach us about ESSENCE

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1 What neuroimaging can teach us about ESSENCE Nouchine Hadjikhani, MD, PhD Martinos Center for Biomedical Imaging Massachusetts General Hospital Harvard Medical School MIT-Division of Science and Technology Gillberg Centrum

2 ESSENCE: Early Symptomatic Merci pour votre attention! Syndromes Eliciting Neurodevelopmental Clinical Examinations

3 ESSENCE: attention-deficit/hyperactivity disorder (ADHD) developmental coordination disorder (DCD) Intellectual Merci Developmental pour votre Disorder attention! (IDD) Specific Language Impairment (SLI) Tourette syndrome Early inset bipolar disorder Behavior phenotype syndromes Neurological and seizure disorders presenting with behavioral/cognitive problems autism spectrum disorder (ASD)

Imaging studies in ASD: caveats ASD is a NEURODEVELOPMENTAL disorder: there is an evolution over time ASD is a spectrum disorder: one needs to define

4 Imaging studies in ASD: caveats ASD is a NEURODEVELOPMENTAL disorder: there is an evolution over time ASD is a spectrum disorder: one needs to define which color one is examining Brain imaging studies are typically restricted to individuals with normal IQ, for obvious practical reasons

5 What is autism? A neurodevelopmental disorder Four to ten times more frequent in boys Affects 1:68 children, 1:42 boys (CDC 2014) Defined as the presence of social and communication impairment as well as repetitive/restricted behaviors (DSM 5)

6 ESSENCE: Early before age 5 There is a clear developmental aspect in ASD, and brain as well as behavior undergo lots of changes

7 White matter differences Diffusion tensor Imaging (DTI) is a measure of white matter integrity Fractional Anisotropy (FA) is an index of myelinisation/maturation 16 children and adolescents (10-20 years old) and 14 adults (21-43 years old) with high functioning (IQ>80) ASD and age-, IQ- and gender matched controls Bakthiari et al, NeuroImage Clinical 2012

8 White matter differences young (<20y) ASD vs. controls adult ASD vs. controls No Difference! Bakthiari et al, NeuroImage Clinical 2012

9 White matter correlation with age ASD: r=0.41, p=0.03; NT: r=0.02, p=ns ASD: r=0.38, p=0.04; NT: r= 0.04, p=ns Age range: Bakthiari et al, NeuroImage Clinical 2012

10 Cortical thickness differences

11 Cortical thickness differences IPL - inferior parietal lobule Somato-sensory and motor cortex STS - superior temporal sulcus IFC - inferior frontal cortex Hadjikhani et al. Cerebral Cortex 2006

12 Cortical thickness differences correlation with symptoms, here with ADI-R IFG opercularis lh (MNS): r=-0.57, p<0.05 IPL rh (MNS) : r=-0.67, p<0.01 STS rh (MNS) : r=0.40, p<0.1 Hadjikhani et al. Cerebral Cortex 2006

13 Early Symptomatic Syndromes Eliciting ESSENCE Merci pour votre attention! Neurodevelopmental Clinical Examinations Questions: Do we observe the same trajectories in other ESSENCE DISORDERS? Are cortical thickness changes present already early, or are they the consequence of brain plasticity?

14 functional imaging in ESSENCE two examples One of extreme differences One of surprising similarity

15 Pointing with the eyes brain imaging of joint attention deficits in ASD Joint attention deficits are a hallmark of autism Joint attention is very important in language acquisition

presence of a danger, whereas direct gaze is more ambiguous How do

16 Making theory of mind inferences by integrating social cues in faces is essential In a fearful face, averted gaze signal the presence of a danger, whereas direct gaze is more ambiguous How do participants with HFA perceive fearful faces gazing towards an unseen danger?

17 IPS FEF TPJ STG N=22 dacc FFA IFG OFC N=22 Zurcher et al, PLoS One 2013

18 CONTROLS: More activation for averted gaze in fearful face ASD: Almost similar activation for both conditions more activation in the SC for direct gaze pulvinar Superior colliculus Zurcher et al, PLoS One 2013

19 Empathy in autism Impaired social understanding in ASD Seemingly reduced reactions to others emotions often interpreted as lack of empathic concern

20 Empathy generally tested for social expressions

21 Prkachin & Mercer (1989) and Botvinick et al. (2005)

22 Empathy Cognitive EQ: perspective taking/theory of mind. Ex: I can tell if someone is masking their true emotion; I am good at predicting how someone will feel Social EQ: Ex: I find it hard to know what to do in a social situation; I often find it difficult to judge if something is rude or polite Emotional EQ:I get upset if I see people suffering on news programs; I tend to get emotionally involved with a friend s problems

23 Affective empathy - sharing Emotional contagion pain matrix Pain perception Emotional arousal Hypothal, AMY, hippo, OFC Cognitive empathy Mental state attribution mpfc, STS NT Perspective taking DLPFC NT Empathic behavior prosocial concern

24 36 adolescents and adults with ASD (33 ; 23.5 ± 8.7 (mean age ± SD)) Empathy 31 controls, matched for age, gender and IQ Lateral prefrontal cortex Hadjikhani et al, Translational Psychiatry 2014

25 NT & ASD: Affective empathy - sharing Emotional contagion pain matrix Pain perception Emotional arousal Hypothal, AMY, hippo, OFC

26 NT & ASD: Affective empathy - sharing Emotional contagion pain matrix NT: Cognitive empathy Pain perception Emotional arousal Hypothal, AMY, hippo, OFC NT Mental state attribution mpfc, STS NT Perspective taking DLPFC NT Empathic behavior prosocial concern

mpfc, STS NT Perspective taking DLPFC NT

Cognitive empathy Mental state attribution mpfc

27 NT & ASD: Affective empathy - sharing Emotional contagion pain matrix NT: Cognitive empathy Pain perception Emotional arousal Hypothal, AMY, hippo, OFC NT Mental state attribution mpfc, STS NT Perspective taking DLPFC NT Empathic behavior prosocial concern ASD: Cognitive empathy Mental state attribution mpfc ASD Personal distress ASD Empathic behavior Perspective taking DLPFC

28 Cognitive process X? Cognitive process Y? NT? NT? NT? Cognitive process Y? ESSENCE? ESSENCE??

function can be extremely different (joint attention), or

29 Within ESSENCE, ASD shows clear developmental trajectory Brain anatomy is different and changes over time Brain function can be extremely different (joint attention), or surprisingly similar (empathy for pain) Conclusions

30 Conclusions Future brain imaging research will help us understand the similarity and the differences between the different ESSENCE conditions

31 Göteborg Christopher Gillberg Eva Billstedt Nanna Gillberg Adam Helles Harvard Medical School - MGH Jasmine Boshyan Bruce Fischl Paulami Naik Josh Snyder Noreen Ward Brest Eric Lemonnier Boston University Robert Joseph Helen Tager-Flusberg Thank you to EPFL Reyhaneh Baktiari Cristina Granziera Loyse Hippolyte Juliana Iranpour Amandine Lassalle Anthony Lissot Karine Métrailler Ophélie Rogier Britt Russo Carole Schwab Nicole Zürcher Wietske Van den Zwaag Nouchine Hadjikhani

The Excitatory/Inhibitory imbalance hypothesis in autism evidence from neuroimaging

The Excitatory/Inhibitory imbalance hypothesis in autism evidence from neuroimaging Nouchine Hadjikhani, MD, PhD Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital Harvard