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Autonomic Function in ASD: Physiology to Treatment Azadeh Kushki Holland Bloorview Kids Rehabilitation Hospital Institute of Biomaterials and Biomedical.

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Presentation on theme: "Autonomic Function in ASD: Physiology to Treatment Azadeh Kushki Holland Bloorview Kids Rehabilitation Hospital Institute of Biomaterials and Biomedical."— Presentation transcript:

1 Autonomic Function in ASD: Physiology to Treatment Azadeh Kushki Holland Bloorview Kids Rehabilitation Hospital Institute of Biomaterials and Biomedical Engineering University of Toronto

2 The Autonomic Nervous System (ANS) Platform Technology-based Intervention ANSBehaviourBrain

3 ANS parasympathetic innervation sympathetic innervation

4 ANS Markers Non-invasive, wearable sensing Long-term, in-situ measurements in naturalistic settings Associated with symptom domains in ASD

5 ANS Dysregulation in ASD Connections to brain structures affected in ASD (Anagnostou & Taylor 2011) –Amygdala, insula, anterior cingulate, thalamus, brainstem Linked to behaviour & function affected in ASD (Porges 2007) –Cognitive, affective, and behavioural regulation Atypicalities reported in disorders with overlapping phenotypes –ADHD (Borger et al. 1999; Crowell et al. 2006), anxiety (Thayer et al. 1996; Hofmann et al. 1995) Source:

6 ANS Dysregulation in ASD Emerging evidence to support ANS hyper-arousal (Cheshire 2012; Ming et al. 2005; Kushki et al. 2013; Bal et al. 2010; Porges et al. 2012; Neuhaus et al. 2013; Anderson & Colombo 2009; Puura et al. 2012) Preliminary findings on associations with behaviour –Social communication function (Neuhaus et al. 2013; Partiquin et al. 2013) –Emotion processing/anxiety (Kushki et al. 2013, Jansen et al.; Smeekens et al. 2013; Jansen et al. 2003) Inconsistent findings in literature (Cheshire 2012; Benevides & Lane 2013) –Variability in sample, methods, and measures –Nature of ANS function not well understood Many gaps remain

7 Measurements Source: Benarroch, 2014 Skin conductance Heart rate Heart rate variability

8 Methods Tasks & Sample X O Anxiety Attention Inhibition Social Cognition Baseline Green Red Blue Purple Orange TD (n=34)ASD (n=40) Age (years) FSIQ Sex (m:f)19:1533:7

9 *p<0.5, **p< Analysis: repeated measures linear regression, controlling for age, IQ, and sex ANS Function Results: Heart Rate Basal elevation, atypical response to anxiety * **

10 ANS Activity Results: HRV Atypical response to social cognition task * *p<0.5, **p< Analysis: repeated measures linear regression, controlling for age, IQ, and sex

11 ANS Activity Results: Skin Conductance Decreased levels, atypical response to anxiety ** *p<0.5, **p< Analysis: repeated measures linear regression, controlling for age, IQ, and sex *

12 The Autonomic Nervous System (ANS) Platform Technology-based Intervention ANSBehaviourBrain Sympathetic hyper-arousal

13 Hyper-arousal ASD Anxiety ASD x anxiety Shared neurobiology High comorbidity Phenotypic overlap Hyperarousal

14 Social Communication Questionnaire (SCQ) *p<0.5 Analysis: repeated measures linear regression, controlling for age, IQ, and sex *

15 Child Behaviour Checklist (CBCL) Anxiety/Depression Scale * *p<0.5 Analysis: repeated measures linear regression, controlling for age, IQ, and sex

16 Group Demographics Low anx (n=20)High anx (n=17) Age (years) FSIQ Sex (m:f)14:516:1 Low SCQ (n=10)High SCQ (n=27) Age (years) FSIQ Sex (m:f)8:223:4

17 Anxiety x ASD *p=0.03 Analysis: linear regression, controlling for age, IQ, and sex CBCL SCQ

18 The Autonomic Nervous System (ANS) Platform Technology-based Intervention ANSBehaviourBrain Sympathetic hyper-arousal ASD/Anxiety

19 Neuroanatomical Correlates Central Autonomic Control Cingulate cortex Insular cortex Amygdala Paraventricular nucleus Periaqueductal gray Hypothalamus Parabrachial nucleus Nucleus of the solidary tract Nucleus ambiguus Ventrolateral medulla Behavioural arousal Introception Emotion Stress response Homeostasis Integration of autonomic function with arousal & pain modulation Tonic control of blood pressure Respiration rhythm Autonomic reflexes

20 Methods Low anx (n=60) High anx (n=27) p-value Age (years) * Sex (m:f)52:820:7n.s. FSIQ n.s. SCQ n.s.

21 Child Behaviour Checklist (CBCL) Anxiety/Depression Subscale p=0.06 p=0.09

22 The Autonomic Nervous System (ANS) Platform Technology-based Intervention ANSBehaviourBrain Sympathetic hyper-arousal ASD/Anxiety Preliminary associations

23 Work in Progress Fetal heart rate Infants & toddlers Children & youth Anxiety control group Nonlinear analysis Development

24 The Autonomic Nervous System (ANS) Platform Technology-based Intervention ANSBehaviourBrain Sympathetic hyper-arousal ASD/Anxiety Preliminary associations

25 Translation Example An “app” for management of physiological arousal Augment existing treatments or used as stand-along device The Anxiety Meter

26 Anxiety Meter 1.0

27 The Anxiety Meter System Overview ECG sensor Smart phone

28 Methods Technical development Interface design Usability testing User-Centered Design

29 Arousal Detection Variability –Personalized time-varying baseline –Error-corrective learning –97% detection accuracy Specificity of ANS markers –Automatic classification schemes –Classification accuracy >80% Technical Challenges

30 Usability Testing Effectiveness, efficiency, satisfaction Usability issues detected: attention –New interface design Anxiety Meter 2.0

31 Anxiety Meter Work in Progress Device development ( ) Usability study #1 (Oct. 2014) Usability study #2 (Dec. 2014) Clinical Trial #1 (Jan. 2015)

32 Anxiety Meter Provisional patent filed Partnerships established OBI Entrepreneurship Fellow recruited Commercialization Update

33 Acknowledgements Participants and families Holland Bloorview staff –Stephanie Chow –Tabitha Chiu –Ajmal Khan –Krissy Doyle-Thomas –Susan Day Fragiadakis –Leanne Ristic –Naomi Peleg –Tom Nantais –Danielle D’Alessandro –Seth Sobel Collaborators –Evdokia Anagnostou –Jessica Brian –Jason Lerch –Daniel Cassel –Annie Dupius –Paul Arnold

34 From disability to possibility

35 Social Communication Questionnaire p=0.06 p=0.05


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