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Quantitative Brain Magnetic Resonance Imaging in Attention-Deficit Hyperactivity Disorder
Abstract
BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. METHODS: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. RESULTS: Subjects with ADHD had a 4.7% smaller total cerebral volume (P = .02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right > left asymmetry in the caudate (P = .006), smaller right globus pallidus (P = .005), smaller right anterior frontal region (P = .02), smaller cerebellum (P = .05), and reversal of normal lateral ventricular asymmetry (P = .03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. CONCLUSION: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.
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“several (Berquin et al., 1998; Castellanos et al., 1996; Castellanos, 2001; Castellanos et al., 2002a; Hill et al., 2003), but not all (Durston et al., 2004; Filipek et al., 1997; Hynd et al., 1990; Mostofsky et al., 2002), studies report reduced whole brain size in children with ADHD.”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Castellanos et al., 1996
In the citing paper
“Studies have noted reduced volume in several parts of the cerebellum in ADHD (Castellanos et al., 2002a; Castellanos et al., 1996; Durston et al., 2004; Posner & Petersen, 1990) as well as posterior cortical anomalies (Durston et al., 2004; Filipek et al., 1997; Sowell et al., 2003).”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Castellanos et al., 1996
In the citing paper
“Numerous structural MRI studies have reported smaller regions in the prefrontal cortex (PFC) of youth with ADHD (Castellanos et al., 1996; Castellanos et al., 2002a; Durston et al., 2004; Filipek et al., 1997; Hynd, Semrud-Clikeman, Lorys, Novey, & Eliopulos, 1990; Kates et al., 2002; Mostofsky, Cooper, Kates, Denckla, & Kaufmann, 2002; Sowell et al., 2003).”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Castellanos et al., 1996
In the citing paper
“Earlier mental disorder onset shapes brain development (e.g., (123)) and relates to self-injurious behaviors (1).”
From Neural correlates associated with suicide and nonsuicidal self-injury in youth (2021) · cites this paper as [123]
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“ADHD has been studied extensively using quantitative electroencephalography (qEEG) (Arns, Drinkenburg, & Leon Kenemans, 2012; Castellanos et al., 1996; Ogrim, Kropotov, & Hestad, 2012).”
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“A deficit in this region has been found in imaging studies on adult impulsivity (Raine et al., 1997) [29] but not in neuropsychological or imaging studies on childhood disruptive disorders (Carter et al., 1995; Castellanos et al., 1996; Epstein et al., 1997) [9,10,14].”
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Stevenson, J. C., & Williams, D. C. (2000) · Human Nature · doi:10.1007/s12110-000-1010-6 · Cited by 10
Clinical neuroscience and imaging studies of core psychoanalytic constructs
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Chapter 5. Mental Disorders and Disability: Time to Reevaluate the Relationship?
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Attention deficit hyperactivity disorder
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Raising a child with Attention Deficit Hyperactivity Disorder : a parents' perspective
Cosser, C. P. (2009) · Unisa Institutional Repository (University of South Africa) · Cited by 10
Neuroimaging markers for the prediction of treatment response to Methylphenidate in ADHD
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“Some ascribe ADHD symptoms to neurological impairments as a result of brain abnormalities (Barkley, 1997; Castellanos et al., 1996; Fisher, 1996; Fuster, 1997).”
BackgroundTransient hypothyroxinemia of prematurity and problem behavior in young adulthood
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“ORIGINAL ARTICLE Polymorphism of the 30-UTR of the dopamine transporter gene (DAT) in New World monkeys”
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“Several additional studies also have linked right hemisphere dysfunction and ADHD (Casey et al., 1997; Castellanos et al., 1996; Malone, Couitis, Kershner, & Logan, 1994).”
BackgroundAttention-Deficit/Hyperactivity Disorder in Adults: Clinical Information for Primary Care Physicians
Braun, D. L., Dulit, R. A., Adler, D. A., Berlant, J. L., Dixon, L. B., Fornari, V., Goldman, B., Hermann, R. C., Siris, S. G., Sonis, W. A., et al. (2004) · Cited by 9
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Attention-Deficit Hyperactivity Disorder
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EEG-Biocontrol Method in Treating the Attention Deficit Hyperactivity Disorder in Children
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Anatomic Brain Imaging Studies of Normal and Abnormal Brain Development in Children and Adolescents
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Atypical sulcal pattern in boys with attention‐deficit/hyperactivity disorder
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Correlations of ADHD symptoms with neurometabolites measured by 1H magnetic resonance spectroscopy
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“The frontal cortex has been shown to play a key role in cognitive processes, which are related to the impairment of maintaining and shifting attention in ADHD (38, 39).”
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“This model holds that attention deficit and the characteristic impairments to behavior are linked with difficulties in the inhibition of irrelevant actions which arise in response to morphofunctional changes in the prefrontal cortex and striopallidal system [37].”
BackgroundBases genéticas del trastorno por déficit de atención/hiperactividad
Sánchez‐Mora, C., Marta Ribasés, A., Delgado, F. M., Soutullo, C. A., Fitó, A. S., Pàmias, M., Casas, M., & Ramos‐Quiroga, J. A. (2012) · Revista de Neurología · doi:10.33588/rn.5510.2012344 · Cited by 8
“Además, distintos estudios de neuroimagen han identificado alteraciones en los niveles de SLC6A3 en las regiones implicadas en el trastorno, tales como el núcleo estriado o la corteza prefrontal, en pacientes con TDAH [29-31].”
BackgroundThe Neural and Neurocognitive Determinants of ADHD
Gopin, C. B., & Healey, D. M. (2011) · Journal of Infant Child and Adolescent Psychotherapy · doi:10.1080/15289168.2011.575700 · Cited by 9
“Several (Berquin et al., 1998; Castellanos et al., 1996; Castellanos, 2001; Castellanos et al., 2002; Hill et al., 2003) but not all (Durston et al., 2004; Filipek et al., 1997; Hynd et al., 1990; Mostofsky et al., 2002) studies have reported reduced whole brain size in children with ADHD.”
BackgroundResultInfluentialExecutive emotional system disruption as causal agent in frontal lobishness among abused children
Naudé, H., Preez, C. S. D., & Pretorius, E. (2004) · Early Child Development and Care · doi:10.1080/0300443032000153615 · Cited by 8
“…Mental Health revealed decreased metabolism in the frontal lobes of patients with ADHD using positron emission tomography (Zametkin et al. 1990) and abnormalities in the size and symmetry of the prefrontal cortex and basal ganglia using magnetic resonance imaging (Castellanos et al., 1994, 1996).”
MethodNeurologic Evaluation of Violent Juveniles
Pincus, J. H. (2000) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/s1056-4993(18)30092-0 · Cited by 7
Hyperkinetic disorders and attention deficit hyperactivity disorders
Swanson, J. M. (1997) · Current Opinion in Psychiatry · doi:10.1097/00001504-199707000-00009 · Cited by 8
Aydınlı, F. E., Esen, H. T. Ç., Kirazlı, M. Ç., Çınar, B. Ç., Pektaş, A., Kültür, S. E. Ç., & Aksoy, S. (2016) · Brazilian Journal of Otorhinolaryngology · doi:10.1016/j.bjorl.2016.10.007 · Cited by 8
Kawade, H. M., Borkar, C. D., Shambharkar, A. S., Singh, O., Singru, P. S., Subhedar, N. K., & Kokare, D. M. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.172830 · Cited by 8
Attention Deficit Hyperactivity Disorder and Methylphenidate: When Society Misunderstands Medicine
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Attention-Deficit/Hyperactivity Disorder
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“In a number of studies, the frontal lobes, which are rich in dopamine receptors, have been demonstrated to be smaller in children with ADHD compared with control subjects (Castellanos et al., 1996; Filipek, SemrudClikeman, & Steingard, 1997) and have decreased blood flow.”
ResultNeuropsychologie der Aufmerksamkeitsdefizit/ Hyperaktivitätsstörung (ADHD)
Konrad, K., & Herpertz‐Dahlmann, B. (2010) · Springer eBooks · doi:10.1007/978-3-540-72340-0_22 · Cited by 8
The cerebellum in psychiatric disorders
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“J. Rapoport and colleagues have found cerebellar abnormalities in children with ADHD: Castellanos et al. (1996) first found that in addition to changes in the basal ganglia, boys with ADHD had a smaller cerebella than controls.”
BackgroundComparison of QEEG Reference Databases in Basic Signal Analysis and in the Evaluation of Adult ADHD
White, J. N. (2003) · Journal of Neurotherapy · doi:10.1300/j184v07n03_06 · Cited by 8
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Age-Dependent Sexually-Dimorphic Asymmetric Development of the Ferret Cerebellar Cortex
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“A disturbance of morphological and functional lateralization of the cerebellum is reportedly involved in human neurodevelopmental disorders with cognitive impairments, such as autism [45], schizophrenia [46,47], dyslexia [48], and attention deficit hyperactivity disorder [49].”
BackgroundXKR4 Gene Effects on Cerebellar Development Are Not Specific to ADHD
Shook, D. A., Brouwer, R. M., de Zeeuw, P., Oranje, B., & Durston, S. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00396 · Cited by 6
“Early studies reported smaller total cerebellar volume in children and adolescents with ADHD compared to their typically developing (TD) peers (Castellanos et al., 1996), as well as smaller right cerebellum volume (Durston et al., 2004), and posterior vermis VIII-X volumes (Berquin et al., 1998;…”
BackgroundSleep and Quality of Life in ADHD
Bekker, E. M., Kooij, J. J. S., & Buitelaar, J. K. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-343-5_28 · Cited by 7
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Potential pathomechanisms of ADHD based on neurometabolite changes.
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“Numerous studies have also demonstrated a reduction in cortical GMVs in ADHD, although the exact brain regions involved appeared to differ across studies, including the frontal [7–11], temporal [9], parietal [12], occipital [13], limbic [10], insular [11], and cerebellar [4, 14] cortices.”
Thanellou, A., Schachinger, K. M., & Green, J. T. (2009) · Behavioral Neuroscience · doi:10.1037/a0015567 · Cited by 7
“To this effect, reduced cerebellar volume has been reported in ADHD (Bussing, Grudnik, Mason, Wasiak, & Leonard, 2002, Castellanos et al., 1996, Castellanos et al., 2001; Hill et al., 2003) and it is possible that a decrease in cerebellar neuronal populations is one of the contributing factors to…”
BackgroundEffect of Biofeedback Training of Sensorimotor and β1EEG Rhythms on Attention Parameters
Grin-Yatsenko, V. A., Kropotov, J. D., Ponomarev, V. A., Chutko, L. S., & Yakovenko, E. A. (2001) · Human Physiology · doi:10.1023/a:1010999201899 · Cited by 7
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Rivkin, A., Alexander, R., Knighton, J., Hutson, P. H., Wang, X. J., Snavely, D. B., Rosah, T., Watt, A. P., Reimherr, F. W., & Adler, L. A. (2011) · Journal of Attention Disorders · doi:10.1177/1087054711423633 · Cited by 6
“…the functional impairments seen in ADHD, that is, organization, working memory, attention, impulse inhibition, response selection, and cognition (Castellanos et al., 1996, 2002; Filipek et al., 1997; Mostofsky, Cooper, Kates, Denckla, & Kaufmann, 2002; Seidman, Valera, & Makris, 2005; Wilens et…”
Gross motor skills in children with Attention Deficit Hyperactivity Disorder
Pila-Nemutandani, G. R., Pillay, B. J., & Meyer, A. (2018) · South African Journal of Occupational Therapy · doi:10.17159/2310-3833/20l7/vol48n3a4 · Cited by 14
“Other findings suggest that the balance deficits may reflect cerebellar dysfunctions 38,39 and brain abnormalities at higher levels of cognitive, motor, and vestibular integration 40 .”
Martin, C. N., & Konopka, L. M. (2011) · Activitas Nervosa Superior · doi:10.1007/bf03379936 · Cited by 6
Rastmanesh, R. (2010) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-010-0033-z · Cited by 6
“Executive dysfunction theory suggests that the symptoms of ADHD arise wholly as a result of a reduction in executive control, which is caused by abnormalities in the structure, function, and biochemical operation of the frontoparietal and frontostriatal neural networks (Arnsten 2006, 2009; Castellanos et al. 1996; Cas…”
BackgroundAnatomical characterization of ADHD using an atlas-based analysis: A diffusion tensor imaging study
Acer, N., Dolu, N., Zararsız, G., Doğan, M. S., Gümüş, K., Özmen, S., Kara, A. Y., Soysal, H., Per, H., & Bilgen, M. (2017) · The EuroBiotech Journal · doi:10.24190/issn2564-615x/2017/01.08 · Cited by 6
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“Ev oked potentials were recorded at the points of maximum mismatch negativity and other components associa ted with attention:Fz, Cz, Pz, as well as C3, C4, F3, and F4 (as per the 10–20 system), as existing data suggest a r elationship between attention deficit syndrome and h ypofunction of the fr ontal cortex, such t…”
Pietschnig, J., Penke, L., Wicherts, J. M., Zeiler, M., & Voracek, M. (2014) · SSRN Electronic Journal · doi:10.2139/ssrn.2512128 · Cited by 6
Moiroud, L., Moscoso, A., Acquaviva, É., Michel, A., Delorme, R., & Bucci, M. P. (2025) · Vision · doi:10.3390/vision9030076 · Cited by 6
“This network includes the frontostriato–parietal circuits [5,8,11], as well as subcortical structures such as the superior colliculus (SC) and omnipause neurons (OPN).”
Ensemble-based Ultrahigh-dimensional Variable Screening
Tu, W. Y., Yang, D., Kong, L., Che, M., Shi, Q., Li, G., & Tian, G. (2019) · International Joint Conference on Artificial Intelligence · doi:10.24963/ijcai.2019/501 · Cited by 5
Morphometric Magnetic Resonance Imaging in Psychiatry
Fleck, D. E., Nandagopal, J. J., Cerullo, M. A., Eliassen, J. C., DelBello, M. P., Adler, C. M., & Strakowski, S. M. (2008) · Topics in Magnetic Resonance Imaging · doi:10.1097/rmr.0b013e3181808152 · Cited by 5
“Studies of the globus pallidus have also shown smaller volumes.(107,109,110,115) Reductions in the volume of the cerebellar vermis, particularly in the posterior-inferior lobules, have been demonstrated consistently in ADHD subjects.”
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“As the rodent cerebellum developed symmetrically [21], ferrets would be useful models for investigating the pathogenesis underlying human neurodevelopmental disorders with disturbances in morphological cerebellar asymmetry, such as autistic spectrum disorder [22], schizophrenia [23,24], dyslexia [25], and attention-de…”
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“Quantitative brain magnetic resonance imaging [13, 14] has revealed that the total volume of the brain (anterior regions of the right frontal lobe, frontal parts of the corpus callosum, right globus pallidus, and cerebellum) in ADHD children is 4.”
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Attention-deficit/hyperactivity disorder
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“A number of results from functional and structural MRI researches have proved this hypothesis.(11,12,23) Structural MR imaging suggests decreased cortical thickness including PFC, cingulate cortex, the motor association area, the basal ganglia, the parietal lobe, the occipital lobe, and cerebellum in ADHD.”
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Metadata
- Authors
- Castellanos, F. X.
- Affiliations
- National Institute of Mental Health (US)
- Corresponding author
- Castellanos, F. Xavier
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1996-07-01
- Volume
- 53
- Issue
- 7
- Pages
- 607
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2097559385
- Cited by
- 1,183
- References
- 102
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 4 · 2023: 14 · 2022: 11 · 2021: 11 · 2020: 20 · 2019: 21 · 2018: 18 · 2017: 19 · 2016: 31 · 2015: 37 · 2014: 40 · 2013: 39 · 2012: 52
- FWCI
- 25.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, brain volumetry, brain volume, caudate nucleus, globus pallidus, cerebellum, corpus callosum, lateral ventricle, hemispheric lateralization, basal ganglia, children, brain structure
- MeSH terms
- Adolescent, Age Factors, Attention Deficit Disorder with Hyperactivity, Basal Ganglia, Body Height, Body Weight, Brain, Caudate Nucleus, Cerebellum, Cerebral Ventricles, Child, Child, Preschool, Frontal Lobe, Globus Pallidus, Humans, Intelligence Tests, Functional Laterality, Magnetic Resonance Imaging, Male, Discriminant Analysis, Prefrontal Cortex
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