Toward Understanding Girls with Autism: A Scientist & Father s Perspective

Transcription

1 Toward Understanding Girls with Autism: A Scientist & Father s Perspective Kevin Pelphrey Carbonell Family Professor and Director Autism and Neurodevelopmental Disorders Institute October 12, 2016 S L I D E 1

2 How do we understanding intentions? Pelphrey et al. (2003) Journal of Neuroscience S L I D E 2

3 S L I D E 3

4 S L I D E 4

5 Pretend SIT$ON$TABLE$ Picture schedules EARPLUGS)) Pixar Props HEADPHONES) Prizes! Mr. Monkey s Brain HELMET&ON& Yale Child Study Center Child Neuroscience Lab S L I D E 5

6 Neural Signatures of Autism State markers: dysfunction in children with ASD relative to siblings and typical children. Trait markers: shared dysfunction in siblings and children with ASD Compensatory mechanisms: enhanced activity unique to siblings S L I D E 6

7 R R State: ASD < TD & ASD < US Trait: US < TD & ASD < TD Compensatory: US > TD & US > ASD R Kaiser et al. (2010) Proceedings of the National Academy of Sciences S L I D E 7

8 Can we see autism s signature in the individual brain? S L I D E 8

9 Classification Analysis Discovery Replication? In each ROI: Trained classifier on Discovery cohort brain responses Predict the diagnostic categories of the Replication cohort Significance assessment Permutation testing 1001 permutations FDR control for multiple comparisons S L I D E 9

10 A weak response to biological motion is a marker of autism in boys (but not girls!) Björnsdotter et al., JAMA: Psychiatry, 2016 S L I D E 10

11 Autism Center of Excellence: Girls Network 250 Boys with ASD 250 TD boys 250 Girls with ASD 250 TD girls Unaffected siblings: ½ boys and ½ girls: 400 Total N = 1400 S L I D E 11

12 Sex differences in brain response to coherent versus scrambled biological motion ASD > ASD Caudate Paracingulate Amygdala Left VIIb Cerebellar view Right Crus I psts/ffg ITG/FFG Frontal pole Right temporo-occipital view Left temporo-occipital view Left frontal view Putamen ASD > TD Paracingulate TD > TD dmpfc Precuneus Left thalamus Left amygdala vmpfc Medial view Precuneus vmpfc Medial view : female; : male; dmpfc: dorsomedial prefrontal cortex; FFG: fusiform gyrus; ITG: inferior temporal gyrus; psts: posterior superior temporal sulcus vmpfc: ventromedial prefrontal cortex S L I D E 12

13 Girls Boys S L I D E 13

14 How do we translate basic science into real-world tools aimed at target engagement? S L I D E 14

15 Experimental Therapeutics Identify social and cognitive functions and their neural and genetic substrates. Link individual differences in neural and genetic substrates to autism symptoms. Translate basic science into treatment protocols aimed at target engagement. Test efficacy in blinded randomized controlled trials. Roll out of evidence based treatments. S L I D E 15

16 Schork (2015) Nature S L I D E 16

17 If you have met one person with autism S L I D E 17

18 Pivotal Response Training (PRT) S L I D E 18

19 Change in Behavior: Social Responsiveness Scale (SRS) Yang et al. (in press) Nature: Translational Psychiatry S L I D E 19

20 Change in brain, driving change in behavior p r = -.80**** Yang et al. (in press) Nature: Translational Psychiatry S L I D E 20

21 Cluster 1 Cluster 2 Neuro-prediction of treatment response R y = -50 mm y = -52 mm Cluster 3 Cluster 4 y = 18 mm y = -4 mm weights Increase in severity Yang et al. (in press) Nature: Translational Psychiatry Actual change in severity Decrease in severity r =.85, p <.0001 Predicted change in severity S L I D E 21

22 Can we boost brain responses before treatment? Art by Charlotte Pretzsch S L I D E 22

23 Intranasal Oxytocin Social Judgments Oxytocin Placebo x = 0 y = 5 x = -58 z = 0 Gordon et al. (2013) Proceedings of the National Academy of Sciences S L I D E 23

24 S L I D E 24

25 S L I D E 25

26 Neural Prediction of VR Treatment Response in Young Adults VR Platform Real-Time Interaction Individual-Driven Avatars Real Life Context & Environments Voice Modulation Face Emotion Capture Training Objectives Recognizing Others Starting a conversation Casual conversation Personal Response Job interview, developing a friendship, dating Self-Assertion Work dilemmas, confronting a friend S L I D E 26

27 Treatment outcomes Verbal and Non-verbal Emotion Recognition, WAIS-IV & WMS-IV(ACS)-Social Perception (SP) subtests Social Responsiveness Scale (SRS) Friendship network metrics Neuroimaging S L I D E 27

28 Brain Activation to Biological Motion Predicts Success in Virtual Reality Social Cognition Training for Adults! IFG Insula SMG STS Changes in Emotion Recognition (post minus pre) r =.77, p <.001 Pretreatment BIO > SCR, % Signal Change N = 17, threshold: Z > 3.6 (voxel), p <.05 (cluster) S L I D E 28

29 Acknowledgments The Carbonell Family NIMH NICHD NINDS Simons Foundation Autism Speaks Hilibrand Foundation John Merck Scholars Fund Autism Science Foundation I thank the participants and their families for participating in our research. I thank my colleagues who make this work successful and fun. kevinpelphrey@gwu.edu S L I D E 29