Mani Pavuluri MD PhD Professor and Director Pediatric Brain Research and Intervention Center Berger-Colbeth Endowed Chair in Child Psychiatry

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1 Mani Pavuluri MD PhD Professor and Director Pediatric Brain Research and Intervention Center Berger-Colbeth Endowed Chair in Child Psychiatry

2 Focus of the Talk fmri Activity Studies fmri Treatment Studies fmri Connectivity Studies A Dimensional Model in Child Psychiatry

3 Reason to Investigate: Neurocognitive Function in PBD Pavuluri et al, 2006, Am J Psych

4 Longitudinal Study: Neurocognitive Problems Don t Go Away Pavuluri et al, 2009, JACAAP

5 fmri Activity Studies - Mapping the Real Estate in PBD Pavuluri and Sweeney, 2008 JAACAP

6 fmri Activity Studies

7 Fronto-limbic Affective Circuit TASK FINDING HC VPFC PBD DLPFC STG PBD-HC V1/V2 V1/V2 Amygdala OPERATION Euthymic unmedicated sample Pavuluri et al, 2006 Biol Psych

8 Face Response Circuit TASK FINDING DLPFC OFC Insula STS V1/V2 MTG OPERATION Euthymic unmedicated sample Pavuluri et al, 2006 Biol Psych

9 Pavuluri et al, 2009 JAACAP Occipito-Limbic Circuit (Reactive Circuit) TASK FINDING OPERATION Euthymic unmedicated sample

10 Pavuluri et al, 2008 Psych Neuroimage Interfacing Circuit TASK FINDING PBD HC PBD - HC OPERATION Euthymic unmedicated sample

11 Cognitive Circuit TASK FINDING LAMOTRIGINE IMPROVES FRONTO-STRIATAL ACTIVITY GO TRIAL STOP TRIAL OPERATION Unmedicated Sample at Baseline Pavuluri et al, 2010 J Clin Psych

12 fmri Treatment Studies

13 Lamotrigine Increases VLPFC Activity and Decreases Amygdala Activity TASK Keep in mind? Keep in working memory store ANGRY FACE CONDITION BASELINE ANGRY FACE CONDITION AT FOLLOW-UP VS. BASELINE (Based on task used in Passarotti et al., 2010) Passarotti et al, 2011 Psychopharmacology

14 DBRCT of Divalproex vs. Risperidone: Differential Activity During Affective Working Memory Paradigm Left VLPFC Left Ventral Striatum Pavuluri et al, 2010, ACNP

15 Pavuluri et al, in press Risperidone and Divalproex: Treatment Effects Risperidone: Responders vs. Non-responders Divalproex: Responders vs. Non-responders Amygdala Medial PFC Color matching Paradigm

16 fmri Connectivity Studies

17 Affective Working Memory Paradigm Passarotti et al, 2011 PBD Conference Affect Evaluation and Regulation Network Direct Comparison Between Groups (Two Sample t-test)

18 Passarotti et al, submitted Affect Evaluation and Regulation Network Between-Group Differences in activation in the Affect Evaluation and Regulation Network. Red indicates greater brain region engagement in PBD than in HC, blue indicates the opposite Group differences in ACC, VLPFC, amygdala and PHG Temporal correlation fit of BOLD fmri signal change to face emotion in PBD and in HC

19 Wegbreit et al, 2011 PBD Conference Functional Connectivity PBD and HC Over the Duration of Trial EVALUATIVE AFFECTIVE CIRCUIT REACTIVE AFFECTIVE CIRCUIT

20 Treatment Effects in Real-Time Divalproex Pre and Post Treatment Evaluative Affective Circuit Wegbreit et al, 2011 PBD Conference

21 Treatment Effects in Real-Time Risperidone Pre and Post Treatment Evaluative Affective Circuit Wegbreit et al, 2011 PBD Conference

22 Evaluative Affective Circuit Recruited During Response Inhibition Risperidone engaged left insula Divalproex engaged subgenual cingulate cortex Wegbreit et al, 2011, PBD conference

23 Risperidone and Divalproex: Reactive Affective Circuitry During Response Inhibition Amygdala is engaged poorly even after treatment Wegbreit et al, 2011, PBD conference

24 Amygdala Activity is More Engaged in Responders vs. Non-Responders Amygdala in Fronto-limbic Circuit Wegbreit et al, in progress

25 Pioneering Work in the Field - Reflecting Pediatric BRAIN Center Alessandra Passarotti PhD Ezra Wegbreit PhD Lisa Lu PhD Binu Vargese MA Richard Whitley MA James Ellis BA Jacklynn Fitzgerald BA Jon O Neil BA Allison Lowes BA Meredith Wong BA Stephanie Monroe BA Bryn Levitan BA Nicole Witowski BA Nathan Carley BA Noah Yulish BA Gail Schuck BA Jean Madigan BA MRI Methodology Minjie Wu PhD Joe Zhou PhD Deb Little PhD Genomics and Neurochemistry Jeff Bishop Pharm D Christian Gossett BA Clinical Sonali Nanayakkara MD Julie Carbray DNSc Amy West PhD Sally Weinstein PhD Collaborators John Sweeney PhD Mike Stevens PhD

26 A Dimensional Model in Child Psychiatry

27 Developmental Affective Neuroscience: Framework for Studying Dimensions of Wellness and Illness Pavuluri et al, submitted

28 The Pediatric Brain Research And Intervention Center Phone: (312) www/psych.uic.edu/brain-center The Pediatric Brain Research and Intervention Center Institute for Juvenile Research University of Illinois at Chicago Department of Psychiatry 1747 West Roosevelt Road Chicago, Illinois 60608

29 A Big Thanks to Our Team! Pediatric BRAIN Center Alessandra Passarotti PhD Ezra Wegbreit PhD Lisa Lu PhD Binu Vargese MA Richard Whitley MA James Ellis BA Jacklynn Fitzgerald BA Jon O Neil BA Allison Lowes BA Meredith Wong BA Stephanie Monroe BA Bryn Levitan BA Nicole Witowski BA Nathan Carley BA Noah Yulish BA Gail Schuck BA Jean Madigan BA MRI Methodology Minjie Wu PhD Joe Zhou PhD Deb Little PhD Genomics and Neurochemistry Jeff Bishop Pharm D Christian Gossett BA Ghan Shyam Pandey PhD Yogesh Dwivedi PhD Clinical Sonali Nanayakkara MD Julie Carbray DNSc Amy West PhD Sally Weinstein PhD Collaborators John Sweeney PhD Mike Stevens PhD

30 Also incredibly thankful to NIH/NIMH 1R01MH081019A 1R01MH A1 RC1MH HHSN C DANA Foundation NARSAD Foundation AFSP Marshall Reynolds Foundation Blue Harbor Foundation Berger-Colbeth Endowment

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