SHEN ET AL TABLE2.Associations of neuropsychological variables with ADHD symptoms and gray matter volumes of the signficant clusters ADHD Symptoms Gray Matter Volume Total Score Inattention Prefrontal Cluster Posterior occipital Cluster Measure 95%C 95%C1 95%C1 95%C 95%C1 Norking memory019*015.0240.09*0.05.0140.21*0.16025-0.04 0.08.0.01 -0.08*-0.12.-0.03 01001 n0y0.16*0.12.0.210.070.03.0120.180.13.0.22-0.04-0.09.0.005-0.07… -0.11-0.02 010*+0.05.0.150.05 oretedfo 0.001,0.10011*0.06.015-0.05-0.09.-0.002-0.05-0.09.-3.3e-4 0120.08,0170.080.03.013012*0.07,0.16-0.04-0.09,0.005-0.05 -010.-0.01 Gray mat ite and total ic p<0.05."p<0.01.p<0.00 additionally controlling for handedness and totalintracranial correlations were not confounded by one another(Table 2) volume. There was no significant correlation between ADHI and discounting rate was positively associated with working ADHD-200 clinical sample.Using a mask of the significant memory errors(r=0.13,df1952,p<0.00L,95%C1-0.08,0.17) ci) variability (r=0.09.df=1835, simificant clusters by comparing patients with control Neuroanatomical Correlates of Inattention in subjects;2)which ADHD patient subtype had the lowest gray a Population-Based Cohort control subjects:and3)whether medication had any remedial =3:3.357 voxels:peak t=-4.29.df-1950.cluster-level effect on the reduced gray matter volumes of the significant WE<0.001)and the posterior occipital cortex (x=-15, ers by group comparisons of ver-medicated patients =91.5,z=112 voxels;peakt 32.df=1 and site. and anterior insula,and the posterior occipital cluster was mainly in the left cuneus and extended to the left calcarine RESULTS tex (Figure 1).Thes not confounded by a的baine Ca地oiag became insignificant after controlling for the inattention memory,intrasubject variability,and delay discounting score but remained significant after controlling for the were positively associated with ADHD symptoms,and the hyperactivity-impulsivity score (prefrontal cluster:r=-0.08, .September 2020 additionally controlling for handedness and total intracranial volume. Validation. We applied the same preprocessing pipeline of structural neuroimaging data as that used in IMAGEN to the ADHD-200 clinical sample. Using a mask of the significant clusters identified in IMAGEN, the gray matter volume of each cluster was extracted for analyses. We tested 1) whether patients with ADHD had lower gray matter volumes of the significant clusters by comparing patients with control subjects; 2) which ADHD patient subtype had the lowest gray matter volumes of the significant clusters by comparing between two ADHD subtypes (hyperactive/impulsive sub￾type was excluded because of a small sample size of eight) and control subjects; and 3) whethermedication had any remedial effect on the reduced gray matter volumes of the significant clusters by group comparisons of never-medicated patients, medicated patients, and control subjects. All analyses were controlled for age, sex, handedness, total intracranial volume, and site. RESULTS Descriptive Statistics In the IMAGEN cohort at baseline (Table 1), working memory, intrasubject variability, and delay discounting were positively associated with ADHD symptoms, and the correlations were not confounded by one another (Table 2). There was no significant correlation between ADHD symptoms and stop-signal reaction time (p.0.05), and therefore it was not included in further analyses. Delay discounting rate was positively associated with working memory errors (r=0.13, df=1952, p,0.001, 95% CI=0.08, 0.17) and increased intrasubject variability (r=0.09, df=1835, p,0.001, 95% CI=0.04, 0.13). Neuroanatomical Correlates of Inattention in a Population-Based Cohort In IMAGEN at baseline, we found that higher ADHD total score was associated with lower gray matter volumes of two brain clusters in both the prefrontal cortex (x=219.5, y=49.5, z=3; 3,357 voxels; peak t=24.29, df=1950, cluster-level pFWE,0.001) and the posterior occipital cortex (x=21.5, y=91.5, z=15; 1,295 voxels; peak t=24.32, df=1950, cluster-level pFWE=0.025). The prefrontal cluster covered the left ven￾tromedial prefrontal cortex, dorsal anterior cingulate cortex, and anterior insula, and the posterior occipital cluster was mainly in the left cuneus and extended to the left calcarine cortex (Figure 1). These associations were not confounded by either site (see Figure S1 in the online supplement) or IQ (see eResults 2 in the online supplement). These associations became insignificant after controlling for the inattention score but remained significant after controlling for the hyperactivity-impulsivity score (prefrontal cluster: r=20.08, TABLE 2. Associations of neuropsychological variables with ADHD symptoms and gray matter volumes of the significant clustersa ADHD Symptoms Gray Matter Volume Total Score Hyperactivity￾Impulsivity Inattention Prefrontal Cluster Posterior occipital Cluster Measure r 95% CI r 95% CI r 95% CI r 95% CI r 95% CI Working memoryb 0.19*** 0.15, 0.24 0.09*** 0.05, 0.14 0.21*** 0.16, 0.25 20.04 20.08, 0.01 20.08*** 20.12, 20.03 Delay discountingb 0.13*** 0.08, 0.17 0.06** 0.02, 0.11 0.14*** 0.09.0.18 20.07** 20.11, 20.02 20.06* 20.10, 20.01 Intrasubject variabilityc 0.14*** 0.10, 0.19 0.09*** 0.04, 0.14 0.14*** 0.10, 0.19 20.05* 20.10, 20.01 20.06** 20.11, 20.01 Working memory corrected for delay discounting and intrasubject variability 0.16*** 0.12, 0.21 0.07** 0.03, 0.12 0.18*** 0.13, 0.22 20.04 20.09, 0.005 20.07** 20.11, 20.02 Delay discounting corrected for working memory and intrasubject variability 0.10*** 0.05, 0.15 0.05* 0.001, 0.10 0.11*** 0.06, 0.15 20.05* 20.09, 20.002 20.05* 20.09, 23.3e–4 Intrasubject variability corrected for working memory and delay discounting 0.12*** 0.08, 0.17 0.08** 0.03, 0.13 0.12*** 0.07, 0.16 20.04 20.09, 0.005 20.05* 20.10, 20.01 a ADHD symptoms were adjusted for age, sex, and site. Gray matter volume was adjusted for age, sex, handedness, site, and total intracranial volume. Confidence intervals were estimated by bootstrap 5,000 times. b N=1,963. c N=1,846. *p,0.05. **p,0.01. ***p,0.001. Am J Psychiatry 177:9, September 2020 ajp.psychiatryonline.org 847 SHEN ET AL