Voxel-Based Morphometry in Medicated-naive Boys with Attention-deficit/hyperactivity Disorder (ADHD)_Journal of Biomedical Engineering

Authors：

LIUQi ¹ , CHENLizhou ¹ , LIFei ¹ , CHENYing ² , GUOLanting ² , GONGQiyong ¹ ,  HUANGXiaoqi ¹

1. Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China;
2. Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

HUANGXiaoqi, Email: julianahuang@163.com

Keywords：

attention-deficit/hyperactivity disorder; diffeomorphic anatomical registration through exponential lie algebra; magnetic resonance image

DOI：

10.7507/1001-5515.20160088

Video：

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Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuro-developmental disorders occurring in childhood, characterized by symptoms of age-inappropriate inattention, hyperactivity/impulsivity, and the prevalence is higher in boys. Although gray matter volume deficits have been frequently reported for ADHD children via structural magnetic resonance imaging, few of them had specifically focused on male patients. The present study aimed to explore the alterations of gray matter volumes in medicated-naive boys with ADHD via a relatively new voxel-based morphometry technique. According to the criteria of DSM-IV-TR, 43 medicated-naive ADHD boys and 44 age-matched healthy boys were recruited. The magnetic resonance image (MRI) scan was performed via a 3T MRI system with three-dimensional (3D) spoiled gradient recalled echo (SPGR) sequence. Voxel-based morphometry with diffeomorphic anatomical registration through exponentiated lie algebra in SPM8 was used to preprocess the 3D T1-weighted images. To identify gray matter volume differences between the ADHD and the controls, voxel-based analysis of whole brain gray matter volumes between two groups were done via two sample t-test in SPM8 with age as covariate, threshold at P＜0.001. Finally, compared to the controls, significantly reduced gray matter volumes were identified in the right orbitofrontal cortex (peak coordinates [-2,52,-25], t=4.01), and bilateral hippocampus (Left: peak coordinates [14,0,-18], t=3.61; Right: peak coordinates [-14,15,-28], t=3.64) of ADHD boys. Our results demonstrated obvious reduction of whole brain gray matter volumes in right orbitofrontal cortex and bilateral hippocampus in boys with ADHD. This suggests that the abnormalities of prefrontal-hippocam-pus circuit may be the underlying cause of the cognitive dysfunction and abnormal behavioral inhibition in medicated-naive boys with ADHD.

Citation： LIUQi, CHENLizhou, LIFei, CHENYing, GUOLanting, GONGQiyong, HUANGXiaoqi. Voxel-Based Morphometry in Medicated-naive Boys with Attention-deficit/hyperactivity Disorder (ADHD). Journal of Biomedical Engineering, 2016, 33(3): 526-532. doi: 10.7507/1001-5515.20160088 Copy

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2.	FARAONE S V, SERGEANT J, GILLBERG C, et al. The worldwide prevalence of ADHD:is it an American condition?[J]. World Psychiatry, 2003, 2(2):104-113.
3.	童连,史慧静,臧嘉捷.中国儿童ADHD流行状况Meta分析[J].中国公共卫生,2013,29(9):1279-1283.
4.	POLANCZYK G, DE LIMA M S, HORTA B L, et al. The worldwide prevalence of ADHD:a systematic review and metaregression analysis[J]. Am J Psychiatry, 2007, 164(6):942-948.
5.	ENGELHARDT P E, FERREIRA F, NIGG J T. Priming sentence production in adolescents and adults with attention-deficit/hyper-activity disorder[J]. J Abnorm Child Psychol, 2009, 37(7):995-1006.
6.	NAKAO T, RADUA J, RUBIA K, et al. Gray matter volume abnormalities in ADHD:voxel-based meta-analysis exploring the effects of age and stimulant medication[J]. Am J Psychiatry, 2011, 168(11):1154-1163.
7.	PROAL E, REISS P T, KLEIN R G, et al. Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood[J]. Arch Gen Psychiatry, 2011, 68(11):1122-1134.
8.	PERLOV E, PHILIPSEN A, TEBARTZ VAN ELST L, et al. Hippocampus and amygdala morphology in adults with attention-deficit hyperactivity disorder[J]. J Psychiatry Neurosci, 2008, 33(6):509-515.
9.	HILL D E, YEO R A, CAMPBELL R A, et al. Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children[J]. Neuropsychology, 2003, 17(3):496-506.
10.	NAKAO T, RADUA J, RUBIA K, et al. Gray matter volume abnormalities in ADHD:voxel-based meta-analysis exploring the effects of age and stimulant medication[J]. Am J Psychiatry, 2011, 168(11):1154-1163.
11.	WANG Gongwu, CAI Jingxia. Disconnection of the hippocampal-prefrontal cortical circuits impairs spatial working memory performance in rats[J]. Behav Brain Res, 2006, 175(2):329-336.
12.	ONNINK A M, ZWIERS M P, HOOGMAN M, et al. Brain alterations in adult ADHD:effects of gender, treatment and comorbid depression[J]. Eur Neuropsychopharmacol, 2014, 24(3):397-409.
13.	MEHTA S, GRABOWSKI T J, TRIVEDI Y, et al. Evaluation of voxel-based morphometry for focal lesion detection in individuals[J]. Neuroimage, 2003, 20(3):1438-1454.
14.	TANG Wanjie, HUANG Xiaoqi, LI Bin, et al. Structural brain abnormalities correlate with clinical features in patients with drug-naïve OCD:A DARTEL-enhanced voxel-based morphometry study[J]. Behav Brain Res, 2015, 294:72-80.
15.	COLLOBY S J, O'BRIEN J T, TAYLOR J P. Patterns of cerebellar volume loss in dementia with Lewy bodies and Alzheimer's disease:A VBM-DARTEL study[J]. Psychiatry Res, 2014, 223(3):187-191.
16.	PAN Pinglei, SHI Haicun, ZHONG J G, et al. Gray matter atrophy in Parkinson's disease with dementia:evidence from meta-analysis of voxel-based morphometry studies[J]. Neurol Sci, 2013, 34(5):613-619.
17.	张孟杰,柴超,夏爽.基于体素的形态测量学方法结合最新配准算法临床应用的研究进展[J].国际医学放射学杂志,2015(5):450-454.
18.	卓芝政,苑桂红,李海云.基于VBM-DARTEL的AD脑萎缩特征检测方法[J].北京生物医学工程,2014(3):228-233.
19.	TAKAHASHI R, ISHII K, MIYAMOTO N, et al. Measurement of gray and white matter atrophy in dementia with Lewy bodies using diffeomorphic anatomic registration through exponentiated lie algebra:A comparison with conventional voxel-based morphometry[J]. Am J Neuroradiol, 2010, 31(10):1873-1878.
20.	BERGOUIGNAN L, CHUPIN M, CZECHOWSKA Y, et al. Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression?[J]. Neuroimage, 2009, 45(1):29-37.
21.	FUSTER J. The prefrontal cortex[M]. New York:Academic Press, 2015.
22.	HESSLINGER B, TEBARTZ VAN ELST L, THIEL T, et al. Frontoorbital volume reductions in adult patients with attention deficit hyperactivity disorder[J]. Neurosci Lett, 2002, 328(3):319-321.
23.	SCHILLING C, KVHN S, ROMANOWSKI A, et al. Cortical thickness correlates with impulsiveness in healthy adults[J]. Neuroimage, 2012, 59(1):824-830.
24.	SEIDMAN L J, VALERA E M, MAKRIS N. Structural brain imaging of attention-deficit/hyperactivity disorder[J]. Biol Psychiatry, 2005, 57(11):1263-1272.
25.	BARKLEY R A. Behavioral inhibition, sustained attention, and executive functions:constructing a unifying theory of ADHD[J]. Psychol Bull, 1997, 121(1):65-94.
26.	BOOTH J R, BURMAN D D, MEYER J R, et al. Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD)[J]. J Child Psychol Psychiatry, 2005, 46(1):94-111.
27.	WILBERTZ G, VAN ELST L T, DELGADO M R, et al. Orbitofrontal reward sensitivity and impulsivity in adult attention deficit hyperactivity disorder[J]. Neuroimage, 2012, 60(1):353-361.
28.	LEE J S, KIM B N, KANG E, et al. Regional cerebral blood flow in children with attention deficit hyperactivity disorder:comparison before and after methylphenidate treatment[J]. Hum Brain Mapp, 2005, 24(3):157-164.
29.	SHAW P, LERCH J, GREENSTEIN D, et al. Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder[J]. Arch Gen Psychiatry, 2006, 63(5):540-549.
30.	黄晓科,银晓勇,黄艳秋,等.大鼠海马损毁与学习记忆研究进展[J].中国老年学杂志,2012,32(10):2199-2201.
31.	CHAMBERLAIN S R, ROBBINS T W. Noradrenergic modulation of cognition:therapeutic implications[J]. J Psychopharmacol, 2013, 27(8):694-718.
32.	SANDER M C, LINDENBERGER U, WERKLE-BERGNER M. Lifespan age differences in working memory:a two-component framework[J]. Neurosci Biobehav Rev, 2012, 36(9):2007-2033.
33.	MEDIN T, RINHOLM J E, OWE S G, et al. Low dopamine D5 receptor density in hippocampus in an animal model of attention-deficit/hyperactivity disorder (ADHD)[J]. Neuroscience, 2013, 242:11-20.
34.	LI Yuanyuan, LI Fei, HE Ning, et al. Neural hyperactivity related to working memory in drug-naive boys with attention deficit hyperactivity disorder[J]. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014, 53:116-122.
35.	BUZSÁKI G. Theta oscillations in the hippocampus[J]. Neuron, 2002, 33(3):325-340.
36.	BASTIAANSEN M, HAGOORT P. Event-induced theta responses as a window on the dynamics of memory[J]. Cortex, 2003, 39(4-5):967-992.
37.	BARRY R J, CLARKE A R, JOHNSTONE S J. A review of electrophysiology in attention-deficit/hyperactivity disorder:Ⅰ. Qualitative and quantitative electroencephalography[J]. Clin Neurophysiol, 2003, 114(2):171-183.
38.	LAROCHE S, DAVIS S, JAY T M. Plasticity at hippocampal to prefrontal cortex synapses:dual roles in working memory and consolidation[J]. Hippocampus, 2000, 10(4):438-446.
39.	THIERRY A M, GIOANNI Y, DÉGÉNÉTAIS E, et al. Hippocampo-prefrontal cortex pathway:anatomical and electrophysiological characteristics[J]. Hippocampus, 2000, 10(4):411-419.
40.	PLESSEN K J, BANSAL R, ZHU Hongtu, et al. Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder[J]. Arch Gen Psychiatry, 2006, 63(7):795-807.
41.	LEE T H, LEE C H, KIM I H, et al. Effects of ADHD therapeutic agents, methylphenidate and atomoxetine, on hippocampal neurogenesis in the adolescent mouse dentate gyrus[J]. Neurosci Lett, 2012, 524(2):84-88.

1. BARKLEY R A, BIEDERMAN J. Toward a broader definition of the age-of-onset criterion for attention-deficit hyperactivity disorder[J]. J Am Acad Child Adolesc Psychiatry, 1997, 36(9):1204-1210.
2. FARAONE S V, SERGEANT J, GILLBERG C, et al. The worldwide prevalence of ADHD:is it an American condition?[J]. World Psychiatry, 2003, 2(2):104-113.
3. 童连,史慧静,臧嘉捷.中国儿童ADHD流行状况Meta分析[J].中国公共卫生,2013,29(9):1279-1283.
4. POLANCZYK G, DE LIMA M S, HORTA B L, et al. The worldwide prevalence of ADHD:a systematic review and metaregression analysis[J]. Am J Psychiatry, 2007, 164(6):942-948.
5. ENGELHARDT P E, FERREIRA F, NIGG J T. Priming sentence production in adolescents and adults with attention-deficit/hyper-activity disorder[J]. J Abnorm Child Psychol, 2009, 37(7):995-1006.
6. NAKAO T, RADUA J, RUBIA K, et al. Gray matter volume abnormalities in ADHD:voxel-based meta-analysis exploring the effects of age and stimulant medication[J]. Am J Psychiatry, 2011, 168(11):1154-1163.
7. PROAL E, REISS P T, KLEIN R G, et al. Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood[J]. Arch Gen Psychiatry, 2011, 68(11):1122-1134.
8. PERLOV E, PHILIPSEN A, TEBARTZ VAN ELST L, et al. Hippocampus and amygdala morphology in adults with attention-deficit hyperactivity disorder[J]. J Psychiatry Neurosci, 2008, 33(6):509-515.
9. HILL D E, YEO R A, CAMPBELL R A, et al. Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children[J]. Neuropsychology, 2003, 17(3):496-506.
10. NAKAO T, RADUA J, RUBIA K, et al. Gray matter volume abnormalities in ADHD:voxel-based meta-analysis exploring the effects of age and stimulant medication[J]. Am J Psychiatry, 2011, 168(11):1154-1163.
11. WANG Gongwu, CAI Jingxia. Disconnection of the hippocampal-prefrontal cortical circuits impairs spatial working memory performance in rats[J]. Behav Brain Res, 2006, 175(2):329-336.
12. ONNINK A M, ZWIERS M P, HOOGMAN M, et al. Brain alterations in adult ADHD:effects of gender, treatment and comorbid depression[J]. Eur Neuropsychopharmacol, 2014, 24(3):397-409.
13. MEHTA S, GRABOWSKI T J, TRIVEDI Y, et al. Evaluation of voxel-based morphometry for focal lesion detection in individuals[J]. Neuroimage, 2003, 20(3):1438-1454.
14. TANG Wanjie, HUANG Xiaoqi, LI Bin, et al. Structural brain abnormalities correlate with clinical features in patients with drug-naïve OCD:A DARTEL-enhanced voxel-based morphometry study[J]. Behav Brain Res, 2015, 294:72-80.
15. COLLOBY S J, O'BRIEN J T, TAYLOR J P. Patterns of cerebellar volume loss in dementia with Lewy bodies and Alzheimer's disease:A VBM-DARTEL study[J]. Psychiatry Res, 2014, 223(3):187-191.
16. PAN Pinglei, SHI Haicun, ZHONG J G, et al. Gray matter atrophy in Parkinson's disease with dementia:evidence from meta-analysis of voxel-based morphometry studies[J]. Neurol Sci, 2013, 34(5):613-619.
17. 张孟杰,柴超,夏爽.基于体素的形态测量学方法结合最新配准算法临床应用的研究进展[J].国际医学放射学杂志,2015(5):450-454.
18. 卓芝政,苑桂红,李海云.基于VBM-DARTEL的AD脑萎缩特征检测方法[J].北京生物医学工程,2014(3):228-233.
19. TAKAHASHI R, ISHII K, MIYAMOTO N, et al. Measurement of gray and white matter atrophy in dementia with Lewy bodies using diffeomorphic anatomic registration through exponentiated lie algebra:A comparison with conventional voxel-based morphometry[J]. Am J Neuroradiol, 2010, 31(10):1873-1878.
20. BERGOUIGNAN L, CHUPIN M, CZECHOWSKA Y, et al. Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression?[J]. Neuroimage, 2009, 45(1):29-37.
21. FUSTER J. The prefrontal cortex[M]. New York:Academic Press, 2015.
22. HESSLINGER B, TEBARTZ VAN ELST L, THIEL T, et al. Frontoorbital volume reductions in adult patients with attention deficit hyperactivity disorder[J]. Neurosci Lett, 2002, 328(3):319-321.
23. SCHILLING C, KVHN S, ROMANOWSKI A, et al. Cortical thickness correlates with impulsiveness in healthy adults[J]. Neuroimage, 2012, 59(1):824-830.
24. SEIDMAN L J, VALERA E M, MAKRIS N. Structural brain imaging of attention-deficit/hyperactivity disorder[J]. Biol Psychiatry, 2005, 57(11):1263-1272.
25. BARKLEY R A. Behavioral inhibition, sustained attention, and executive functions:constructing a unifying theory of ADHD[J]. Psychol Bull, 1997, 121(1):65-94.
26. BOOTH J R, BURMAN D D, MEYER J R, et al. Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD)[J]. J Child Psychol Psychiatry, 2005, 46(1):94-111.
27. WILBERTZ G, VAN ELST L T, DELGADO M R, et al. Orbitofrontal reward sensitivity and impulsivity in adult attention deficit hyperactivity disorder[J]. Neuroimage, 2012, 60(1):353-361.
28. LEE J S, KIM B N, KANG E, et al. Regional cerebral blood flow in children with attention deficit hyperactivity disorder:comparison before and after methylphenidate treatment[J]. Hum Brain Mapp, 2005, 24(3):157-164.
29. SHAW P, LERCH J, GREENSTEIN D, et al. Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder[J]. Arch Gen Psychiatry, 2006, 63(5):540-549.
30. 黄晓科,银晓勇,黄艳秋,等.大鼠海马损毁与学习记忆研究进展[J].中国老年学杂志,2012,32(10):2199-2201.
31. CHAMBERLAIN S R, ROBBINS T W. Noradrenergic modulation of cognition:therapeutic implications[J]. J Psychopharmacol, 2013, 27(8):694-718.
32. SANDER M C, LINDENBERGER U, WERKLE-BERGNER M. Lifespan age differences in working memory:a two-component framework[J]. Neurosci Biobehav Rev, 2012, 36(9):2007-2033.
33. MEDIN T, RINHOLM J E, OWE S G, et al. Low dopamine D5 receptor density in hippocampus in an animal model of attention-deficit/hyperactivity disorder (ADHD)[J]. Neuroscience, 2013, 242:11-20.
34. LI Yuanyuan, LI Fei, HE Ning, et al. Neural hyperactivity related to working memory in drug-naive boys with attention deficit hyperactivity disorder[J]. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014, 53:116-122.
35. BUZSÁKI G. Theta oscillations in the hippocampus[J]. Neuron, 2002, 33(3):325-340.
36. BASTIAANSEN M, HAGOORT P. Event-induced theta responses as a window on the dynamics of memory[J]. Cortex, 2003, 39(4-5):967-992.
37. BARRY R J, CLARKE A R, JOHNSTONE S J. A review of electrophysiology in attention-deficit/hyperactivity disorder:Ⅰ. Qualitative and quantitative electroencephalography[J]. Clin Neurophysiol, 2003, 114(2):171-183.
38. LAROCHE S, DAVIS S, JAY T M. Plasticity at hippocampal to prefrontal cortex synapses:dual roles in working memory and consolidation[J]. Hippocampus, 2000, 10(4):438-446.
39. THIERRY A M, GIOANNI Y, DÉGÉNÉTAIS E, et al. Hippocampo-prefrontal cortex pathway:anatomical and electrophysiological characteristics[J]. Hippocampus, 2000, 10(4):411-419.
40. PLESSEN K J, BANSAL R, ZHU Hongtu, et al. Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder[J]. Arch Gen Psychiatry, 2006, 63(7):795-807.
41. LEE T H, LEE C H, KIM I H, et al. Effects of ADHD therapeutic agents, methylphenidate and atomoxetine, on hippocampal neurogenesis in the adolescent mouse dentate gyrus[J]. Neurosci Lett, 2012, 524(2):84-88.

Journal of Biomedical Engineering

Voxel-Based Morphometry in Medicated-naive Boys with Attention-deficit/hyperactivity Disorder (ADHD)

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