1. Brain Development in ADHD The NIMH Study

2. Processing Steps in Pictures MRIClassificationExtraction of Surfaces Cortical Thickness Blurred Thickness Map Longitudinal analyses using linear mixed model regression (Pinheiro and Bates 2000) Adjustment for multiple comparisons using false discovery rate at 0.05 (Genovese et al 2002)

3. a. b. Unadjusted thickness difference (mm) Global difference = 0.09 mm; p=.02 Significant group differences- t values (adjusted for IQ & mean cortical thickness) Regional Cortical Thickness: ADHD vs NV

4. -5 -3 (ii) Worse v. better outcome(i) Worse outcome v. NV(iii) Better outcome v NV t statistics Baseline Cortical Thinning Differs in AD/HD Subjects with Differing Clinical Outcomes Similar pattern if use DSM-IV definitions of persistent/remitted AD/HD Linear regression: thickness of L medial prefrontal cluster (R2=0.08, p<0.001), baseline teacher hyperactivity ratings (R2=0.04, p=0.03) associated with final C-GAS scores

5. Cortical Thinning in Adults with ADHD Volume Decrease Volume Increase B. Adults with ADHD have volume differences in brain regions involved in attention and executive control. These data are largely consistent with studies of children. Seidman et al. (2006) A. Cortical thinning in ADHD in a distinct cortical network supporting attention in the right hemisphere involving the parietal lobule, documenting that ADHD in adults is associated with thinner cortex in the cortical networks that modulate attention and executive function. Makris et al. (2007) - similar to pediatric

6. Shaw et al. 2006: Children with ADHD had global thinning of the cortex (mean reduction, -0.09 mm; p=.02)

7. T=-4 T=-2.1 fMRI Activation Peaks in ADHD Studies (relative to controls) Superimposed on Regions of Significant Cortical Thinning in NIMH Sample (Shaw et al. 2005) Rubia (1999) – ADHD<NV – motor task Durston (2003) – ADHD>NV go/no-go Rubia (1999)– ADHD<NV go/no-go (R side) Bush (1998)- ADHD<NV counting stroop Ernst (2003)- ADHD>NV affective decision making Booth (2005)- ADHD<NV go/no-go Schulz (2004) ADHD>NV go/no-go Schweitzer (2004)- ADHD<NV PASAT

8. T=-4 T=-2.1 fMRI Activation Peaks in ADHD Studies (relative to controls) Superimposed on Regions of Significant Cortical Thinning in NIMH Sample (Shaw et al. 2005) Rubia (1999) – ADHD<NV – motor task Durston (2003) – ADHD>NV go/no-go Rubia (1999)– ADHD<NV go/no-go (R side) Bush (1998)- ADHD<NV counting stroop Ernst (2003)- ADHD>NV affective decision making Booth (2005)- ADHD<NV go/no-go Schulz (2004) ADHD>NV go/no-go Schweitzer (2004)- ADHD<NV PASAT