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4 Passport control

5 a bit carried away.

6 appreciated the advice

7 forgot to talk to the manager, next thing I know my fmri

8 thankfully, when aroused

9 things back to normal

10 Inattentive impaired children and adolescents: how helpful are working memory paradigms? Professor Alasdair Vance and team Academic Child Psychiatry Department of Paediatrics University of Melbourne Royal Children s Hospital

11 Outline of presentation 1. Inattentive and impaired : definition 2. Our research approach 3. Key current findings 4. Future directions Prof. A. Vance

12 1. ADHD: definition DSM-IV: a clinically significant behavioural pattern inattention and/or hyperactivity/impulsiveness associated with impairment in one or more areas of functioning Questionnaires: >/= 1.5 SD above the mean for age, gender and IQ Prof. A. Vance

13 2. Our research approach Constrain measurement error * clinical phenotyping: pure versus comorbid disorders categorical and dimensional definition participants developmental stage, gender, IQ * cognitive neuroscience: optimal brain behaviour relationships * functional neuroimaging: task selection; within subject and between subject analysis Prof. A. Vance

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15 2. Our research approach - pure ADHD inattentive dimension -defined structured clinical interview and parent/teacher gold standard questionnaires -pre-pubertal children or post-pubertal adolescents -visuospatial not verbal domain -non-human primate derived tests -defined fmri task components, block/event design -FSL (GLM) versus SPM Prof. A. Vance

16 ADHD, combined type group: definition DSM-IV CRITERIA -inattention dimension and hyperactivity-impulsivity dimension -evident in at least two settings -onset before seven years of age -impairment in social, academic, occupational functioning -FSIQ > 80 -excluded: comorbid conduct disorder, major depressive disorder, learning disorders, speech/language disorders, developmental coordination disorder, tic disorders Prof. A. Vance

17 3. Our current findings mental rotation task 10s/1s ISI block design Prof. A. Vance

18 Prof. A. Vance

19 Silk, Vance et al, B J Psych 2005 N=14, CBCL inattention subscale T score: (10.72)

20 Dysthymic disorder definition: DSM-IV criteria -1 year or more (most of the day, for more days than not), <2 months absence in a given year -depressed and/or irritable mood predominant -2 or more of the following: feelings of hopelessness, low self-esteem appetite change, in/hyper somnia, anergia (fatigue), decreased concentration or decisiveness -FSIQ > 80 -excluded: comorbid ADHD-CT, conduct disorder, major depressive disorder, learning disorders, speech/language disorders, developmental coordination disorder, tic disorders Prof. A. Vance

21 Control>DD DD Control 5 Dysthymic disorder z-score 1

22 Control>DD DD Control Control 5 z-score 1 Control group: significant activation Region BA x y z Bilateral Parietal Lobe R Interior Parietal Lobule R Superior Parietal Lobule R Precuneus R Interior Parietal Lobule R Precuneus R Precuneus L Precuneus R Cuneus L Inferior Parietal Lobule L Precuneus Bilateral Frontal Lobe R Middle Frontal Gyrus R Middle Frontal Gyrus R Middle Frontal Gyrus R Inferior Frontal Gyrus R Middle Frontal Gyrus R Middle Frontal Gyrus R Middle Frontal Gyrus R Middle Frontal Gyrus R Middle Frontal Gyrus R Inferior Frontal Gyrus R Inferior Frontal Gyrus L Cingulate Gyrus L Middle Frontal Gyrus L Precentral Gyrus L Middle Frontal Gyrus L Middle Frontal Gyrus L Middle Frontal Gyrus L Inferior Frontal Gyrus Bilateral Limbic Lobe R Cingulate Gyrus L Cingulate Gyrus Left Occipital L Cuneus L Cuneus *No associated Brodmann area

23 Control>DD Control > Dysthymic disorder DD Control 5 z-score 1 N=14, CBCL inattention subscale T score: (9.75)

24 Prof. A. Vance

25 Region of activation BA C (mm) Z Control Group greater than ADHD-CT Group Parieto-Occipital R Precuneus R Cuneus Posterior Parietal R Inf. Parietal Frontal/Subcortical R Caudate Nucleus, Body Vance et al, Mol Psych 2007 N=24, CBCL inattention subscale T score: (9.43)

26 Control>Dysthymic disorder Dysthymic disorder Control 5 Dysthymic disorder z-score 1

27 Control>Dysthymic disorder Dysthymic disorder Control 5 Control z-score 1

28 Control > Dysthymic disorder Control>Dysthymic disorder Dysthymic disorder Control 5 z-score 1 N=16, CBCL inattention subscale T score: (9.44)

29 OCD: definition DSM-IV criteria -obsessions: intrusive, repetitive, involuntary, recognized as silly, senseless, purposeless by a given child and/or their parents, associated with increased physiological arousal, anxiety, distress -compulsions: intrusive, repetitive, involuntary ritualized actions that are designed to minimize the increased physiological arousal, anxiety, distress associated with the above obsessions -FSIQ > 80 -excluded: comorbid ADHD-CT, conduct disorder, major depressive disorder, learning disorders, speech/language disorders, developmental coordination disorder, tic disorders Prof. A. Vance

30 Region of activation BA C (mm) size Control group greater than OCD group Right Precuneus Left Precuneus Right DLPFC Left DLPFC Left lateral globus pallidus N=16, CBCL inattention subscale T score: (9.23)

31 3. Our current findings General Summary ADHD DD OCD Parietal/Precuneus A /C A/C A /C Basal ganglia A /C C A /C Prefrontal cortex A A /C A /C Prof. A. Vance

32 3. Our current findings Specific Summary ADHD Parietal/Precuneus R>L DD Parietal/Precuneus R>L OCD Precuneus R=L ADHD Caudate nucleus R>L DD Caudate/Putamen R (C only) OCD Globus pallidus L>R ADHD Sup/Inf FG R=L (A only) DD Mid/Inf FG R OCD DLPFC R=L Prof. A. Vance

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34 4. Future clinical directions - biomarker for clinical inattention - biomarker-developmental stage independent - target for medication and/or specific psychological treatment - target for monitoring of the above treatment - ADHD: parietal lobe main risk factor site? - OCD: global pallidus main risk factor site? - DD: insula main risk factor site? NB: methodological problems of parsing neural network components

35 4. Future research directions -interpretation: the problem of epiphenomena -comorbidity -developmental stage; age; gender -more specific cognitive neuroscience constructs. VSWM capacitance versus strategy. VSM encoding versus retrieval -more specific fmri tasks. Parietal BG PFC -multiple neuroimaging modalities. Oculomotor MRS DTI - target phenotypes for mol gen studies Prof. A. Vance

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