Asymmetry in Cortical and Subcortical Structures of the Brain in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Figures & data

Table 1 Demographic and Clinical Characteristics

(a)	ADHD		TD	t/χ^2	P
Characteristic	n=31		n=31
Age	11.67 (1.82)		11.76 (1.82)	0.201	0.841
Sex (boy/girl)	29/2		24/7	2.080	0.149
IQ	106.00 (14.29)		109.35 (15.32)	0.892	0.376
ADHD-RS IV  Inattention  Hyperactivity/Impulsivity	28.29 (3.24) 21.61 (6.01)		15.35 (4.41) 13.307 (3.96)	-13.168 -6.610	0.000* 0.000*
(b)	ADHD-I	ADHD-C	TD	F/χ^2	P
Characteristic	n=20	n=11	n=31
Age	12.00 (1.71)	11.07 (1.93)	11.76 (1.82)	0.976	0.383
Sex (boy/girl)	18/2	11/0	24/7	3.205	0.187
IQ	103.20 (13.78)	111.09 (14.40)	109.35 (15.32)	1.430	0.248
ADHD-RS IV  Inattention  Hyperactivity/Impulsivity	27.85 (2.32) 18.45 (4.73)	29.09 (4.48) 27.36 (3.11)	15.35 (4.41) 13.307 (3.96)	86.664 50.483	0.000* 0.000*

Notes: Continuous variables were expressed as the mean (standard deviation). *Significant at P ≤ 0.05.

Abbreviations: ADHD, attention-deficit/hyperactivity disorder; TD, typically developing; ADHD-I, inattentive attention-deficit/hyperactivity disorder; ADHD-C, combined attention-deficit/hyperactivity disorder; IQ, intelligence quotient; ADHD-RS IV, ADHD Rating Scale IV.

Table 2 The SN Volume AIs Between ADHD and TD Groups

Region	AI			Z	P
SN (mm^3)	ADHD	TD
Thalamus	−1.40 (1.74)	−1.86 (0.34)		0.824	0.410
Caudate	−2.00 (2.30)	−1.52 (0.47)		−0.993	0.321
Putamen	1.78 (2.19)	1.68 (0.29)		0.303	0.762
Pallidum	4.66 (2.99)	5.12 (0.62)		−0.246	0.805
Hippocampus	−1.94 (2.78)	−0.96 (0.45)		−1.232	0.218
Amygdala	0.28 (4.45)	1.09 (0.81)		−0.697	0.486
Accumbens	−3.76 (5.32)	−2.70 (1.08)		−0.641	0.522

Note: Continuous variables were expressed as mean (SEM).

Abbreviations: SN, subcortical nucleus; AI, asymmetry index; ADHD, attention-deficit/hyperactivity disorder; TD, typically developing.

Table 3 The Cortical Thickness AIs Between the Two Subtypes in ADHD and TD Groups

Region	AI			χ^2	P
	ADHD		TD
Cortical regions (mm)	ADHD-I	ADHD-C
Bankssts	−2.77 (0.68)	−0.79 (0.98)	−2.12 (0.52)	2.862	0.239
Caudal anterior cingulate	3.74 (1.05)	3.89 (1.58)	1.80 (0.79)	2.125	0.346
Caudal middle frontal	1.41 (0.47)	−0.42 (0.58)	0.89 (0.39)	5.623	0.060
Cuneus	−0.18 (0.65)	−1.20 (0.90)	−1.02 (0.54)	1.634	0.442
Entorhinal	−3.37 (1.43)	−1.25 (0.95)	−2.02 (0.88)	2.272	0.321
Fusiform	−0.62 (0.35)	−0.61 (0.36)	0.04 (0.37)	1.186	0.553
Inferior parietal	−0.60 (0.23)	−0.48 (0.41)	−0.45 (0.27)	0.476	0.788
Inferior temporal	−1.07 (0.46)	−0.32 (0.47)	−1.78 (0.40)	3.303	0.192
Isthmus cingulate	1.52 (0.66)	1.81 (1.10)	1.17 (0.76)	0.084	0.959
Lateral occipital	−1.77 (0.51)	−2.08 (0.70)	−1.88 (0.38)	0.176	0.916
Lateral orbitofrontal	1.95 (0.47)	2.32 (0.69)	1.51 (0.39)	2.132	0.344
Lingual	−0.53 (0.37)	−0.75 (0.55)	−0.71 (0.38)	0.036	0.982
Medial orbitofrontal	3.16 (0.53)	2.54 (0.60)	0.61 (0.48)	12.245	0.002*
Middle temporal	−0.49 (0.38)	−0.98 (0.63)	−0.05 (0.49)	0.276	0.871
Parahippocampal	0.73 (0.59)	0.05 (1.14)	−0.14 (0.84)	0.263	0.877
Paracentral	0.34 (0.54)	−0.66 (0.58)	1.53 (0.43)	7.269	0.026*
Pars opercularis	−0.70 (0.51)	−0.36 (0.97)	−0.35 (0.39)	0.278	0.870
Pars orbitalis	0.82 (0.70)	−1.07 (1.27)	1.75 (0.75)	5.174	0.075
Pars triangularis	−0.06 (0.50)	−1.22 (0.94)	1.19 (0.47)	6.510	0.039*
Pericalcarine	−0.58 (0.73)	0.93 (0.85)	−1.35 (0.73)	2.768	0.251
Postcentral	0.32 (0.62)	0.81 (0.87)	−0.01 (0.38)	1.890	0.389
Posterior cingulate	3.10 (0.61)	1.82 (0.72)	3.78 (0.54)	4.365	0.113
Precentral	0.86 (0.46)	0.84 (0.43)	0.63 (0.39)	1.349	0.509
Precuneus	1.08 (0.36)	0.12 (0.43)	0.71 (0.39)	3.128	0.209
Rostral anterior cingulate	2.96 (1.11)	2.70 (0.90)	2.80 (0.73)	0.075	0.963
Rostral middle frontal	1.52 (0.41)	0.84 (0.43)	1.11 (0.27)	1.250	0.535
Superior frontal	2.09 (0.33)	1.51 (0.44)	1.78 (0.26)	3.467	0.177
Superior parietal	−0.77 (0.47)	0.51 (0.68)	0.18 (0.26)	5.011	0.082
Superior temporal	−0.63 (0.40)	−0.77 (0.57)	0.08 (0.39)	5.541	0.063
Supramarginal	−0.20 (0.53)	−0.59 (0.50)	0.11 (0.42)	0.478	0.788
Frontal pole	2.57 (0.95)	1.87 (1.83)	0.87 (0.87)	1.175	0.556
Temporal pole	−2.30 (1.08)	−0.25 (1.37)	−0.88 (0.63)	1.402	0.496
Transverse temporal	0.13 (1.10)	−0.09 (0.86)	−0.34 (0.78)	0.262	0.877
Insula	0.12 (0.40)	−1.10 (0.63)	0.36 (0.37)	4.443	0.108

Notes: Continuous variables were expressed as mean (SEM). *Significant at P≤ 0.05.

Abbreviations: AI, asymmetry index; ADHD, attention-deficit/hyperactivity disorder; TD, typically developing; ADHD-I, inattentive attention-deficit/hyperactivity disorder; ADHD-C, combined attention-deficit/hyperactivity disorder.

Table 4 Pairwise Comparisons of the Cortical Thickness AIs Between the Two Subtypes in ADHD and TD Groups

Cortical regions (mm)	ADHD-I vs TD	ADHD-C vs TD	ADHD-C vs ADHD-I
	adjusted P	adjusted P	adjusted P
Medial orbitofrontal	0.003*	0.119	1.000
Paracentral	0.359	0.029*	0.659
Pars triangularis	0.238	0.062	1.000

Notes: Bonferroni correction was used in pairwise comparisons. *Significant at P≤ 0.05.

Abbreviations: AI, asymmetry index; ADHD, attention-deficit/hyperactivity disorder; TD, typically developing; ADHD-I, inattentive attention-deficit/hyperactivity disorder; ADHD-C, combined attention-deficit/hyperactivity disorder.

Table 5 The Cortical Gray-Matter Volume and SN Volume AIs Between the Two Subtypes in ADHD and TD Groups

Region	AI			χ^2	P
	ADHD		TD
Cortical regions (mm^3)	ADHD-I	ADHD-C
Bankssts	4.36 (2.23)	0.43 (3.05)	0.38 (1.77)	1.322	0.516
Caudal anterior cingulate	−9.35 (2.69)	4.42 (4.70)	−7.61 (2.60)	6.390	0.041*
Caudal middle frontal	6.02 (2.15)	6.72 (2.59)	7.68 (1.70)	0.137	0.934
Cuneus	−4.74 (1.41)	−6.68 (2.30)	−2.35 (1.86)	1.783	0.410
Entorhinal	2.26 (2.49)	10.13 (2.48)	3.22 (2.12)	4.760	0.093
Fusiform	1.75 (1.51)	0.38 (1.34)	1.52 (1.04)	0.615	0.735
Inferior parietal	−8.90 (1.19)	−9.15 (1.27)	−9.75 (0.95)	0.213	0.899
Inferior temporal	−0.91 (1.51)	2.41 (2.34)	0.96 (1.23)	2.777	0.249
Isthmus cingulate	3.71 (1.31)	9.97 (1.56)	3.86 (1.29)	7.616	0.022*
Lateral occipital	−1.53 (1.12)	−2.24 (2.11)	−0.05 (0.99)	1.771	0.412
Lateral orbitofrontal	2.87 (0.84)	1.51 (1.18)	1.93 (0.69)	0.501	0.779
Lingual	−0.73 (1.11)	−1.76 (0.83)	−2.44 (0.86)	1.419	0.492
Medial orbitofrontal	−0.12 (1.55)	−2.06 (1.52)	−1.59 (1.02)	0.352	0.839
Middle temporal	−5.40 (1.29)	−4.30 (1.88)	−2.98 (0.92)	2.267	0.322
Parahippocampal	1.46 (1.28)	3.37 (2.10)	2.50 (1.54)	1.044	0.593
Paracentral	−5.22 (2.03)	−9.00 (2.04)	−3.79 (1.43)	3.874	0.144
Pars opercularis	7.97 (1.88)	10.57 (2.14)	8.88 (1.90)	1.076	0.584
Pars orbitalis	−11.49 (1.70)	−13.20 (1.61)	−8.66 (1.25)	4.126	0.127
Pars triangularis	−7.15 (1.75)	−10.88 (2.11)	−7.99 (1.59)	1.616	0.446
Pericalcarine	−4.73 (1.17)	−8.45 (1.25)	−7.48 (1.51)	5.137	0.077
Postcentral	1.66 (1.47)	2.86 (1.41)	3.65 (1.27)	1.438	0.487
Posterior cingulate	2.00 (2.17)	5.51 (2.30)	0.64 (1.42)	4.066	0.131
Precentral	0.41 (1.11)	1.61 (1.38)	−0.26 (0.69)	2.099	0.350
Precuneus	−0.28 (1.25)	−1.88 (1.31)	−0.43 (0.98)	1.187	0.552
Rostral anterior cingulate	9.91 (2.39)	15.38 (4.77)	12.31 (2.27)	1.197	0.550
Rostral middle frontal	2.22 (1.30)	−1.77 (0.87)	−1.22 (0.64)	3.079	0.215
Superior frontal	3.61 (0.89)	0.39 (0.91)	2.32 (0.59)	6.000	0.050*
Superior parietal	−0.08 (1.31)	1.86 (1.67)	0.63 (0.83)	2.465	0.292
Superior temporal	1.90 (1.03)	2.36 (1.20)	3.09 (0.79)	0.231	0.891
Supramarginal	5.37 (1.39)	3.31 (1.84)	4.16 (1.21)	1.113	0.573
Frontal pole	−11.72 (2.18)	−15.39 (3.50)	−14.05 (1.46)	2.413	0.299
Temporal pole	3.86 (1.84)	7.86 (2.56)	4.32 (1.33)	1.326	0.515
Transverse temporal	14.76 (1.45)	18.00 (2.29)	14.93 (1.30)	1.913	0.384
Insula	−1.32 (0.98)	−0.61 (0.54)	−0.28 (0.81)	0.753	0.686
SN (mm^3)
Thalamus	−1.03 (0.37)	−2.08 (0.53)	−1.86 (0.34)	3.537	0.171
Caudate	−1.89 (0.53)	−2.20 (0.67)	−1.52 (0.47)	1.076	0.584
Putamen	1.50 (0.48)	2.29 (0.70)	1.68 (0.29)	1.212	0.546
Pallidum	3.92 (0.72)	6.00 (0.61)	5.12 (0.62)	3.623	0.163
Hippocampus	−1.66 (0.59)	−2.45 (0.92)	−0.96 (0.45)	2.062	0.357
Amygdala	0.20 (1.07)	0.42 (1.19)	1.09 (0.81)	0.487	0.784
Accumbens	−3.28 (1.27)	−4.64 (1.43)	−2.70 (1.08)	1.224	0.542

Notes: Continuous variables were expressed as mean (SEM). *Significant at P≤ 0.05.

Abbreviations: SN, subcortical nucleus; AI, asymmetry index; ADHD, attention-deficit/hyperactivity disorder; TD, typically developing; ADHD-I, inattentive attention-deficit/hyperactivity disorder; ADHD-C, combined attention-deficit/hyperactivity disorder.

Table 6 Pairwise Comparisons of the Cortical Gray-Matter Volume AIs Between the Two Subtypes in ADHD and TD Groups

Cortical regions (mm^3)	ADHD-I vs TD	ADHD-C vs TD	ADHD-C vs ADHD-I
	adjusted P	adjusted P	adjusted P
Caudal anterior cingulate	1.000	0.076	0.050*
Isthmus cingulate	1.000	0.032*	0.036*
Superior frontal	0.520	0.407	0.045*

Notes: Bonferroni correction was used in pairwise comparisons. *Significant at P≤ 0.05.

Abbreviations: AI, asymmetry index; ADHD, attention-deficit/hyperactivity disorder; TD, typically developing; ADHD-I, inattentive attention-deficit/hyperactivity disorder; ADHD-C, combined attention-deficit/hyperactivity disorder.

Figure 1 Correlation between the cortical thickness AI in the medial orbitofrontal and the severity of ADHD symptoms on the inattention subscale score.

Figure 2 Correlation between the cortical thickness AI in the paracentral and the severity of ADHD symptoms on the inattention subscale score.

Figure 3 Correlation between the cortical gray-matter volume AI in the isthmus cingulate and the severity of ADHD symptoms on the hyperactivity/impulsivity subscale score.