Subcortico-Cortical Dysconnectivity in ADHD: A Voxel-Wise Mega-Analysis Across Multiple Cohorts
Abstract
Objective:
Methods:
Results:
Conclusions:
Methods
Cohorts and Measures of ADHD
Resting-State Connectivity
Modeling Approach
Results
Variable | ADHD Group (N=1,696) | Control Group (N=6,737) | Statistic | p | Effect Size | CBCL Analyses (N=9,890) | |||
---|---|---|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | | | | Mean | SD |
Age (years) | 10.83 | 2.17 | 10.33 | 1.30 | t=9.53 | <0.001 | d=0.29 | 10.77 | 1.96 |
Minutes of useable data | 12.73 | 4.96 | 15.48 | 4.35 | t=−21.09 | <0.001 | d=−0.59 | 15.05 | 4.93 |
In-scanner motion (mean RMS) | 0.181 | 0.054 | 0.176 | 0.051 | t=3.38 | <0.001 | d=0.09 | 0.174 | 0.05 |
IQ | 100.41 | 16.54 | 105.57 | 16.47 | t=−5.24 | <0.001 | d=−0.31 | 105.93 | 16.83 |
Scaled matrix | 9.66 | 2.91 | 10.32 | 2.85 | t=−6.63 | <0.001 | d=−0.23 | 10.24 | 2.92 |
NIH Toolbox | | | | | | | | | |
Working memory | 94.59 | 15.44 | 97.17 | 16.22 | t=−4.92 | <0.001 | d=−0.16 | 96.63 | 16.12 |
Processing speed | 85.39 | 16.94 | 88.57 | 17.41 | t=−5.55 | <0.001 | d=−0.19 | 88.03 | 17.38 |
Inhibitory control | 92.39 | 11.71 | 94.08 | 13.26 | t=−4.20 | <0.001 | d=−0.14 | 93.76 | 13.08 |
| Median | IQR | Median | IQR | | | | Median | IQR |
CBCL | | | | | | | | | |
Attention problems (raw) | 8 | 6 | 1 | 3 | W=10,735,550 | <0.001 | δ=0.88 | 2 | 5 |
Internalizing (raw) | 7 | 10 | 3 | 5 | W=8,297,186 | <0.001 | δ=0.45 | 3 | 6 |
Externalizing (raw) | 7.5 | 12 | 1 | 4 | W=9,047,786 | <0.001 | δ=0.58 | 2 | 6 |
| N | % | N | % | | | | N | % |
Sex | | | | | χ2=201.97 | <0.001 | OR=2.22 | | |
Male | 1126 | 66.39 | 3,170 | 47.05 | | | | 4,975 | 50.30 |
Female | 570 | 33.61 | 3,567 | 52.95 | | | | 4,915 | 49.70 |
Cash choice task | | | | | χ2=0.46 | 0.50 | OR=1.05 | | |
3 days | 393 | 39.18 | 2,484 | 40.37 | | | | 3,039 | 40.09 |
3 months | 610 | 60.82 | 3,669 | 59.63 | | | | 4,542 | 59.91 |
Race/ethnicity | | | | | χ2=18.40 | 0.001 | V=0.02 | | |
Asian | 23 | 1.35 | 159 | 2.36 | | | | 236 | 2.39 |
Black/African American | 215 | 12.61 | 708 | 10.51 | | | | 1,110 | 11.22 |
Hispanic/Latino | 333 | 19.65 | 1,265 | 18.78 | | | | 1,822 | 18.42 |
Mixed/other | 191 | 11.26 | 660 | 9.80 | | | | 1,001 | 10.12 |
White | 934 | 55.13 | 3,945 | 58.56 | | | | 5,721 | 57.85 |
Household income | | | | | z=−0.51 | 0.61 | OR=0.98 | | |
<$50,000 | 446 | 26.3 | 1,609 | 23.88 | | | | 2,409 | 24.36 |
$50,000–100,000 | 487 | 28.71 | 1,937 | 28.75 | | | | 2,779 | 28.10 |
$100,001–$200,000 | 444 | 26.18 | 2,205 | 32.73 | | | | 3,128 | 31.63 |
>$200,000 | 319 | 18.81 | 986 | 14.64 | | | | 1,574 | 15.92 |
Within-Group Brain Findings
Group Comparison
Cluster | x | y | z | Peak d | Mean d | Size (voxels) | Overlap (%) | Talairach Label |
---|---|---|---|---|---|---|---|---|
Left and right caudate | ||||||||
1 | 64 | −7 | −3 | 0.15 | 0.10 | 17,555 | 9.2 | Left superior temporal gyrus |
| | | | | | | 9.1 | Right superior temporal gyrus |
| | | | | | | 7.7 | Right postcentral gyrus |
| | | | | | | 5.9 | Right insula |
| | | | | | | 5.8 | Left postcentral gyrus |
| | | | | | | 5.3 | Right precentral gyrus |
| | | | | | | 4.1 | Left insula |
| | | | | | | 3.8 | Left precentral gyrus |
| | | | | | | 3.0 | Right inferior parietal lobule |
| | | | | | | 2.9 | Right medial frontal gyrus |
| | | | | | | 2.8 | Left middle temporal gyrus |
| | | | | | | 2.5 | Left medial frontal gyrus |
| | | | | | | 2.4 | Right inferior frontal gyrus |
| | | | | | | 2.3 | Left inferior parietal lobule |
| | | | | | | 1.8 | Right paracentral lobule |
| | | | | | | 1.7 | Left paracentral lobule |
| | | | | | | 1.6 | Right middle temporal gyrus |
Left and right putamen | ||||||||
1 | −51 | −3 | −1 | 0.13 | 0.09 | 2,193 | 37.4 | Left superior temporal gyrus |
| | | | | | | 34.1 | Left middle temporal gyrus |
| | | | | | | 10.6 | Left insula |
| | | | | | | 2.9 | Left postcentral gyrus |
| | | | | | | 1.4 | Left inferior temporal gyrus |
| | | | | | | 1.1 | Left fusiform gyrus |
| | | | | | | 1.1 | Left precentral gyrus |
| | | | | | | 1.0 | Left inferior parietal lobule |
2 | 44 | −25 | 8 | 0.12 | 0.09 | 982 | 37.9 | Right superior temporal gyrus |
| | | | | | | 37.4 | Right middle temporal gyrus |
| | | | | | | 7.5 | Right transverse temporal gyrus |
| | | | | | | 5.3 | Right insula |
| | | | | | | 1.8 | Right postcentral gyrus |
| | | | | | | 1.5 | Right inferior temporal gyrus |
3 | −31 | −39 | 44 | 0.12 | 0.09 | 564 | 28.3 | Left inferior parietal lobule |
| | | | | | | 21.3 | Left postcentral gyrus |
| | | | | | | 13.0 | Left precentral gyrus |
| | | | | | | 1.2 | Left superior parietal lobule |
4 | 52 | −29 | 36 | 0.12 | 0.09 | 517 | 54.9 | Right postcentral gyrus |
| | | | | | | 14.2 | Right precentral gyrus |
| | | | | | | 9.0 | Right inferior parietal lobule |
5 | 30 | 20 | −21 | 0.12 | 0.09 | 472 | 41.5 | Right inferior frontal gyrus |
| | | | | | | 29.5 | Right insula |
| | | | | | | 10.7 | Right superior temporal gyrus |
| | | | | | | 8.4 | Right uncus |
| | | | | | | 1.1 | Right middle frontal gyrus |
6 | 58 | 24 | 12 | 0.11 | 0.09 | 367 | 95.6 | Right inferior frontal gyrus |
| | | | | | | 1.0 | Right precentral gyrus |
Left and right nucleus accumbens | ||||||||
1 | 6 | −23 | 68 | 0.12 | 0.09 | 1,179 | 29.6 | Right medial frontal gyrus |
| | | | | | | 10.9 | Left medial frontal gyrus |
| | | | | | | 9.1 | Right paracentral lobule |
| | | | | | | 6.2 | Left precentral gyrus |
| | | | | | | 5.5 | Right cingulate gyrus |
| | | | | | | 3.5 | Right postcentral gyrus |
| | | | | | | 2.1 | Left postcentral gyrus |
| | | | | | | 2.1 | Left paracentral lobule |
2 | 34 | −5 | 12 | 0.13 | 0.09 | 1,141 | 27.0 | Right precentral gyrus |
| | | | | | | 17.7 | Right insula |
| | | | | | | 17.3 | Right postcentral gyrus |
| | | | | | | 14.8 | Right superior temporal gyrus |
| | | | | | | 3.5 | Right inferior parietal lobule |
| | | | | | | 2.8 | Right middle temporal gyrus |
| | | | | | | 2.5 | Right inferior frontal gyrus |
| | | | | | | 1.7 | Right claustrum |
| | | | | | | 1.0 | Right transverse temporal gyrus |
3 | −63 | −19 | 2 | 0.12 | 0.09 | 796 | 42.6 | Left superior temporal gyrus |
| | | | | | | 21.6 | Left insula |
| | | | | | | 11.7 | Left lentiform nucleus |
| | | | | | | 10.2 | Left precentral gyrus |
| | | | | | | 3.7 | Left inferior parietal lobule |
| | | | | | | 2.4 | Left middle temporal gyrus |
| | | | | | | 1.7 | Left claustrum |
4 | −39 | −15 | 50 | 0.13 | 0.09 | 579 | 42.4 | Left precentral gyrus |
| | | | | | | 42.2 | Left postcentral gyrus |
| | | | | | | 7.7 | Left inferior parietal lobule |
Left and right amygdala | ||||||||
1 | −9 | −1 | 42 | 0.11 | 0.09 | 244 | 44.0 | Left cingulate gyrus |
| | | | | | | 22.4 | Right cingulate gyrus |
| | | | | | | 12.6 | Right medial frontal gyrus |
| | | | | | | 12.6 | Left superior frontal gyrus |
| | | | | | | 8.5 | Left medial frontal gyrus |
Associations Between ADHD Traits and Functional Connectivity
Sensitivity Analyses and Robustness Checks
Matching on motion.
Controlling for estimated general intelligence.
Psychostimulant-free subgroup analysis.
Partial correlation analyses.
Alternative seed definitions.
Disorder specificity.
Associations with neuropsychological measures.
Interactions with age.
Discussion
Footnote
Supplementary Material
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