Abstract
The cerebellum is emerging as a key anatomical structure underlying normal attentional and cognitive control mechanisms. Dysregulation within cerebellar circuits may contribute to the core symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). In the present study we aimed to characterize surface morphological features of the cerebellum in ADHD and healthy comparison youths. Further, we studied the association of cerebellar morphology with the severity of ADHD symptoms and the effects of stimulant treatment. We examined 46 youths with ADHD and 59 comparison youths 8–18 years of age in a cross-sectional, case–control study using magnetic resonance imaging. Measures of cerebellar surface morphology were the primary outcome. Relative to comparison participants, youths with ADHD exhibited smaller regional volumes corresponding to the lateral surface of the left anterior and the right posterior cerebellar hemispheres. Stimulant medication was associated with larger regional volumes over the left cerebellar surface, whereas more severe ADHD symptoms were associated with smaller regional volumes in the vermis. We used optimized measures of morphology to detect alterations in cerebellar anatomy specific to ADHD, dimensions of symptomology, and stimulant treatment. Duration of treatment correlated positively with volumes of specific cerebellar subregions, supporting a model whereby compensatory morphological changes support the effects of stimulant treatment.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Akshoomoff NA, Courchesne E, Townsend J (1997). Attention coordination and anticipatory control. Int Rev Neurobiol 41: 575–598.
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Association: Washington, DC, USA.
Bansal R, Staib LH, Whiteman R, Wang YM, Peterson BS (2005). ROC-based assessments of 3D cortical surface-matching algorithms. Neuroimage 24: 150–162.
Barkley RA (1997). Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull 121: 65–94.
Berquin PC, Giedd JN, Jacobsen LK, Hamburger SD, Krain AL, Rapoport JL et al (1998). Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study. Neurology 50: 1087–1093.
Biederman J, Makris N, Valera EM, Monuteaux MC, Goldstein JM, Buka S et al (2008). Towards further understanding of the co-morbidity between attention deficit hyperactivity disorder and bipolar disorder: a MRI study of brain volumes. Psychol Med 38: 1045–1056.
Bledsoe J, Semrud-Clikeman M, Pliszka SR (2009). A magnetic resonance imaging study of the cerebellar vermis in chronically treated and treatment-naive children with attention-deficit/hyperactivity disorder combined type. Biol Psychiatry 65: 620–624.
Bledsoe JC, Semrud-Clikeman M, Pliszka SR (2011). Neuroanatomical and neuropsychological correlates of the cerebellum in children with attention-deficit/hyperactivity disorder—combined type. J Am Acad Child Adolesc Psychiatry 50: 593–601.
Burt SA (2009). Rethinking environmental contributions to child and adolescent psychopathology: a meta-analysis of shared environmental influences. Psychol Bull 135: 608–637.
Bussing R, Grudnik J, Mason D, Wasiak M, Leonard C (2002). ADHD and conduct disorder: an MRI study in a community sample. World J Biol Psychiatry 3: 216–220.
Castellanos FX, Giedd JN, Berquin PC, Walter JM, Sharp W, Tran T et al (2001). Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 58: 289–295.
Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Vaituzis AC, Dickstein DP et al (1996). Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Arch Gen Psychiatry 53: 607–616.
Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK, Clasen LS et al (2002). Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA 288: 1740–1748.
Cooper FE, Grube M, Von Kriegstein K, Kumar S, English P, Kelly TP et al (2012). Distinct critical cerebellar subregions for components of verbal working memory. Neuropsychologia 50: 189–197.
Courchesne E, Townsend J, Akshoomoff NA, Saitoh O, Yeung-Courchesne R, Lincoln AJ et al (1994). Impairment in shifting attention in autistic and cerebellar patients. Behav Neurosci 108: 848–865.
Durston S, van Belle J, de Zeeuw P (2011). Differentiating frontostriatal and fronto-cerebellar circuits in attention-deficit/hyperactivity disorder. Biol Psychiatry 69: 1178–1184.
Epstein JN, Casey BJ, Tonev ST, Davidson MC, Reiss AL, Garrett A et al (2007). ADHD- and medication-related brain activation effects in concordantly affected parent-child dyads with ADHD. J Child Psychol Psychiatry 48: 899–913.
Ferrucci R, Giannicola G, Rosa M, Fumagalli M, Boggio PS, Hallett M et al (2011). Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness. Cogn Emot 26: 786–799.
Frodl T, Skokauskas N (2012). Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. Acta Psychiatr Scand 125: 114–126.
Ghez C, Fahn S (1985). The cerebellum. In: Kandel E.R, Schwartz JH (eds) Principles of Neural Science. Elsevier: New York, NY, USA. pp 502–522.
Golla H, Thier P, Haarmeier T (2005). Disturbed overt but normal covert shifts of attention in adult cerebellar patients. Brain 128: 1525–1535.
Hart H, Radua J, Mataix-Cols D, Rubia K (2012). Meta-analysis of fMRI studies of timing in attention-deficit hyperactivity disorder (ADHD). Neurosci Biobehav Rev 36: 2248–2256.
Hill DE, Yeo RA, Campbell RA, Hart B, Vigil J, Brooks W (2003). Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children. Neuropsychology 17: 496–506.
Hoekzema E, Carmona S, Ramos-Quiroga JA, Barba E, Bielsa A, Tremols V et al (2011). Training-induced neuroanatomical plasticity in ADHD: a tensor-based morphometric study. Hum Brain Mapp 32: 1741–1749.
Hollingshead AB (1975) Four-Factor Index of Social Status. Yale University: New Haven, CT, USA.
Ivanov I, Bansal R, Hao X, Zhu H, Kellendonk C, Miller L et al (2010). Morphological abnormalities of the thalamus in youths with attention deficit hyperactivity disorder. Am J Psychiatry 167: 397–408.
Ivry R (1997). Cerebellar timing systems. Int Rev Neurobiol 41: 555–573.
Ivry RB, Spencer RM, Zelaznik HN, Diedrichsen J (2002). The cerebellum and event timing. Ann N Y Acad Sci 978: 302–317.
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P et al (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36: 980–988.
Kieling C, Goncalves RR, Tannock R, Castellanos FX (2008). Neurobiology of attention deficit hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 17: 285–307 viii.
Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM (1982). Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry 39: 879–883.
Mackie S, Shaw P, Lenroot R, Pierson R, Greenstein DK, Nugent TF 3rd et al (2007). Cerebellar development and clinical outcome in attention deficit hyperactivity disorder. Am J Psychiatry 164: 647–655.
Mostofsky SH, Reiss AL, Lockhart P, Denckla MB (1998). Evaluation of cerebellar size in attention-deficit hyperactivity disorder. J Child Neurol 13: 434–439.
Nakao T, Radua J, Rubia K, Mataix-Cols D (2011). Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. Am J Psychiatry 168: 1154–1163.
Noreika V, Falter CM, Rubia K (2012). Timing deficits in attention-deficit/hyperactivity disorder (ADHD): Evidence from neurocognitive and neuroimaging studies. Neuropsychologia 51: 235–266.
O'Halloran CJ, Kinsella GJ, Storey E (2012). The cerebellum and neuropsychological functioning: a critical review. J Clin Exp Neuropsychol 34: 35–56.
Plessen KJ, Bansal R, Zhu H, Whiteman R, Amat J, Quackenbush GA et al (2006). Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 63: 795–807.
Plomp E, Van Engeland H, Durston S (2009). Understanding genes, environment and their interaction in attention-deficit hyperactivity disorder: is there a role for neuroimaging? Neuroscience 164: 230–240.
Rapoport JL, Gogtay N (2008). Brain neuroplasticity in healthy, hyperactive and psychotic children: insights from neuroimaging. Neuropsychopharmacology 33: 181–197.
Schmahmann JD (2004). Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 16: 367–378.
Seidman LJ, Valera EM, Makris N (2005). Structural Brain Imaging of Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry 57: 1263–1272.
Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D et al (2007). Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci USA 104: 19649–19654.
Shaw P, Lerch J, Greenstein D, Sharp W, Clasen L, Evans A et al (2006). Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 63: 540–549.
Shaw P, Sharp WS, Morrison M, Eckstrand K, Greenstein DK, Clasen LS et al (2009). Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder. Am J Psychiatry 166: 58–63.
Sobel LJ, Bansal R, Maia TV, Sanchez J, Mazzone L, Durkin K et al (2010). Basal ganglia surface morphology and the effects of stimulant medications in youth with attention deficit hyperactivity disorder. Am J Psychiatry 167: 977–986.
Steinlin M (2008). Cerebellar disorders in childhood: cognitive problems. Cerebellum 7: 607–610.
Stoodley CJ, Valera EM, Schmahmann JD (2012). Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. Neuroimage 59: 1560–1570.
Strick PL, Dum RP, Fiez JA (2009). Cerebellum and nonmotor function. Annu Rev Neurosci 32: 413–434.
Tiemeier H, Lenroot RK, Greenstein DK, Tran L, Pierson R, Giedd JN (2010). Cerebellum development during childhood and adolescence: a longitudinal morphometric MRI study. Neuroimage 49: 63–70.
Tobe RH, Bansal R, Xu D, Hao X, Liu J, Sanchez J et al (2010). Cerebellar morphology in Tourette syndrome and obsessive-compulsive disorder. Ann Neurol 67: 479–487.
Valera EM, Faraone SV, Murray KE, Seidman LJ (2007). Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biol Psychiatry 61: 1361–1369.
Xu D, Hao X, Bansal R, Plessen KJ, Geng W, Hugdahl K et al (2007). Unifying the analyses of anatomical and diffusion tensor images using volume-preserved warping. J Magn Reson Imaging 25: 612–624.
Xu D, Hao X, Bansal R, Plessen KJ, Peterson BS (2008). Seamless warping of diffusion tensor fields. IEEE Trans Med Imaging 27: 285–299.
Acknowledgements
This project was supported by grants NIMH K0274677, NIMH MH068318, MH59139, the Tom Klingenstein and Nancy Perlman Family Fund, and the Suzanne Crosby Murphy endowment at Columbia University. Dr Ivanov has received honorarium from Lundbeck unrelated to the current report and has also received travel support from the American Psychological Association, American College of Psychopharmacology, Alcohol Medical Scholar Program and American Professional Society of ADHD and Related Disorders. Dr Murrough is supported by a Career Development Award from the NIMH (K23MH094707) and receives additional research support from the American Foundation for Suicide Prevention, the Doris Duke Charitable Foundation, Janssen Research & Development and Avanir Pharmaceuticals. Dr Peterson has received investigator-initiated research support from Eli Lilly and Pfizer. The work contained herein is solely the responsibility of the authors and does not necessarily reflect the views of the NIH, NIMH, or other funding body.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on the Neuropsychopharmacology website
Supplementary information
Rights and permissions
About this article
Cite this article
Ivanov, I., Murrough, J., Bansal, R. et al. Cerebellar Morphology and the Effects of Stimulant Medications in Youths with Attention Deficit-Hyperactivity Disorder. Neuropsychopharmacol 39, 718–726 (2014). https://doi.org/10.1038/npp.2013.257
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/npp.2013.257
Keywords
This article is cited by
-
The ability to maintain rhythm is predictive of ADHD diagnosis and profile
BMC Psychiatry (2023)
-
Structural and functional deficits and couplings in the cortico-striato-thalamo-cerebellar circuitry in social anxiety disorder
Translational Psychiatry (2022)
-
Abnormal hemispheric asymmetry of both brain function and structure in attention deficit/hyperactivity disorder: a meta-analysis of individual participant data
Brain Imaging and Behavior (2022)
-
Viewing the Personality Traits Through a Cerebellar Lens: a Focus on the Constructs of Novelty Seeking, Harm Avoidance, and Alexithymia
The Cerebellum (2017)
-
The Cerebellum and Neurodevelopmental Disorders
The Cerebellum (2016)
