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Identifying a consistent pattern of neural function in attention deficit hyperactivity disorder: a meta-analysis

Published online by Cambridge University Press:  13 May 2013

H. McCarthy ,
N. Skokauskas  and
T. Frodl
H. McCarthy
Affiliation:
Department of Psychiatry, Integrated Neuroimaging, Trinity College Dublin, Dublin, Republic of Ireland Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland
N. Skokauskas
Affiliation:
Department of Psychiatry, Integrated Neuroimaging, Trinity College Dublin, Dublin, Republic of Ireland Department of Child and Adolescent Psychiatry, Children's University Hospital, Temple Street, Dublin, Republic of Ireland
T. Frodl*
Affiliation:
Department of Psychiatry, Integrated Neuroimaging, Trinity College Dublin, Dublin, Republic of Ireland Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland
*
*Address for correspondence: T. Frodl, Department of Psychiatry and Institute of Neuroscience, Trinity College Dublin, Lloyd Building, Dublin 2, Republic of Ireland. (Email: [email protected])
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Abstract

Background

The neurobiological underpinnings of attention deficit hyperactivity disorder (ADHD) are inconclusive. Activation abnormalities across brain regions in ADHD compared with healthy controls highlighted in task-based functional magnetic resonance imaging (fMRI) studies are heterogeneous. To identify a consistent pattern of neural dysfunction in ADHD, a meta-analysis of fMRI studies using Go/no-go, Stop and N-back tasks was undertaken.

Method

Several databases were searched using the key words: ‘ADHD and fMRI’ and ‘ADHD and fMRI task’. In all, 20 studies met inclusion criteria comprising 334 patients with ADHD and 372 healthy controls and were split into N-back, Stop task and Go/no-go case–control groups. Using Signed Differential Mapping each batch was meta-analysed individually and meta-regression analyses were used to examine the effects of exposure to methylphenidate (MPH), length of MPH wash-out period, ADHD subtype, age and intelligence quotient (IQ) differences upon neural dysfunction in ADHD.

Results

Across all tasks less activity in frontal lobe regions compared with controls was detected. Less exposure to treatment and lengthier wash-out times resulted in less left medial frontal cortex activation in N-back and Go/no-go studies. Higher percentage of combined-type ADHD resulted in less superior and inferior frontal gyrus activation. Different IQ scores between groups were linked to reduced right caudate activity in ADHD.

Conclusions

Consistent frontal deficits imply homogeneous cognitive strategies involved in ADHD behavioural control. Our findings suggest a link between fMRI results and the potentially normalizing effect of treatment and signify a need for segregated examination and contrast of differences in sample characteristics in future studies.

Keywords

Attention deficit hyperactivity disorderfunctional magnetic resonance imagingmeta-analysistasks
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 4 , March 2014 , pp. 869 - 880
Copyright
Copyright © Cambridge University Press 2013 

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References

Bayerl, M, Dielentheis, TF, Vucurevic, G, Gesierich, T, Vogel, F, Fehr, C, Stoeter, P, Huss, M, Konrad, A (2010). Disturbed brain activation during a working memory task in drug-naive adult patients with ADHD. NeuroReport 21, 442–446.CrossRefGoogle ScholarPubMed
Biederman, J, Fried, R, Petty, C, Mahoney, L, Faraone, SV (2012). An examination of the impact of attention-deficit hyperactivity disorder on IQ: a large controlled family-based analysis. Canadian Journal of Psychiatry 57, 608–616.CrossRefGoogle ScholarPubMed
Biederman, J, Mick, E, Faraone, SV (2000). Age-dependent decline of symptoms of attention deficit hyperactivity disorder: impact of remission definition and symptom type. American Journal of Psychiatry 157, 816–818.Google Scholar
Booth, JR, Burman, DD, Meyer, JR, Lei, Z, Trommer, BL, Davenport, ND, Li, W, Parrish, TB, Gitelman, DR, Marsel Mesulam, M (2005). Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD). Journal of Child Psychology and Psychiatry 46, 94–111.Google Scholar
Bush, G, Spencer, TJ, Holmes, J, Shin, LM, Valera, EM, Seidman, LJ, Makris, N, Surman, C, Aleardi, M, Mick, E, Biederman, J (2008). Functional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task. Archives of General Psychiatry 65, 102–114.Google Scholar
Cao, Q, Zang, Y, Zhu, C, Cao, X, Sun, L, Zhou, X, Wang, Y (2008). Alerting deficits in children with attention deficit/hyperactivity disorder: event-related fMRI evidence. Brain Research 1219, 159–168.CrossRefGoogle ScholarPubMed
Cortese, S, Kelly, C, Chabernaud, C, Proal, E, Di Martino, A, Milham, MP, Castellanos, FX (2012). Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. American Journal of Psychiatry 169, 1038–1055.CrossRefGoogle ScholarPubMed
Cubillo, A, Halari, R, Ecker, C, Giampietro, V, Taylor, E, Rubia, K (2010). Reduced activation and inter-regional functional connectivity of fronto-striatal networks in adults with childhood attention-deficit hyperactivity disorder (ADHD) and persisting symptoms during tasks of motor inhibition and cognitive switching. Journal of Psychiatric Research 44, 629–639.Google Scholar
Cubillo, A, Halari, R, Giampietro, V, Taylor, E, Rubia, K (2011). Fronto-striatal underactivation during interference inhibition and attention allocation in grown up children with attention deficit/hyperactivity disorder and persistent symptoms. Psychiatry Research: Neuroimaging 193, 17–27.Google Scholar
Davidson, RJ, Putnam, KM, Larson, CL (2000). Dysfunction in the neural circuitry of emotion regulation – a possible prelude to violence. Science 289, 591–594.Google Scholar
De Zeeuw, P, Schnack, HG, Van Belle, J, Weusten, J, Van Dijk, S, Langen, M, Brouwer, RM, Van Engeland, H, Durston, S (2012). Differential brain development with low and high IQ in attention-deficit/hyperactivity disorder. PLoS ONE 7, e35770.Google Scholar
Dibbets, P, Evers, L, Hurks, P, Marchetta, N, Jolles, J (2009). Differences in feedback- and inhibition-related neural activity in adult ADHD. Brain and Cognition 70, 73–83.Google Scholar
Dickstein, SG, Bannon, K, Castellanos, FX, Milham, MP (2006). The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis. Journal of Child Psychology and Psychiatry and Allied Disciplines 47, 1051–1062.Google Scholar
Dillo, W, Göke, A, Prox-Vagedes, V, Szycik, GR, Roy, M, Donnerstag, F, Emrich, HM, Ohlmeier, MD (2010). Neuronal correlates of ADHD in adults with evidence for compensation strategies – a functional MRI study with a Go/no-go paradigm. German Medical Science. Published online 19 April 2010 . doi:10.3205/000098.Google Scholar
Durston, S (2006). Inhibition-related neural activity in adult ADHD. Brain and Cognition 70, 73–83.Google Scholar
Durston, S, Mulder, M, Casey, BJ, Ziermans, T, Van Engeland, H (2006). Activation in ventral prefrontal cortex is sensitive to genetic vulnerability for attention-deficit hyperactivity disorder. Biological Psychiatry 60, 1062–1070.Google Scholar
Eloyan, A, Muschelli, J, Nebel, MB, Liu, H, Han, F, Zhao, T, Barber, AD, Joel, S, Pekar, JJ, Mostofsky, SH, Caffo, B (2012). Automated diagnoses of attention deficit hyperactive disorder using magnetic resonance imaging. Frontiers in Systems Neuroscience 6, 61.Google Scholar
Faraone, SV, Biederman, J, Mick, E (2006). The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychological Medicine 36, 159–165.Google Scholar
Faraone, SV, Sargeant, J, Gillberg, C, Biederman, J (2003). The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2, 104–113.Google Scholar
Fassbender, C, Schweitzer, JB (2006). Is there evidence for neural compensation in attention deficit hyperactivity disorder? A review of the functional neuroimaging literature. Clinical Psychology Review 26, 445–465.Google Scholar
Fassbender, C, Schweitzer, JB, Cortes, CR, Tagamets, MA, Windsor, TA, Reeves, GM, Gullapalli, R (2011). Working memory in attention deficit/hyperactivity disorder is characterized by a lack of specialization of brain function. PLoS ONE 6, e27240.Google Scholar
Frodl, T (2010). Comorbidity of ADHD and substance use disorder (SUD): a neuroimaging perspective. Journal of Attention Disorders 14, 109–120.Google Scholar
Frodl, T, Skokauskas, N (2012). Meta-analysis of structural mri studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. Acta Psychiatrica Scandinavica 125, 114–126.Google Scholar
Garavan, H, Ross, TJ, Murphy, K, Roche, RA, Stein, EA (2002). Dissociable executive functions in the dynamic control of behavior: inhibition, error detection, and correction. NeuroImage 17, 1820–1829.Google Scholar
Greydanus, DE, Pratt, HD, Patel, DR (2007). Attention deficit hyperactivity disorder across the lifespan: the child, adolescent, and adult. Disease-a-Month 53, 70–131.Google Scholar
Hart, H, Radua, J, Mataix-Cols, D, Rubia, K (2012). Meta-analysis of fMRI studies of timing in attention-deficit hyperactivity disorder (ADHD). Neuroscience and Biobehavioral Reviews 36, 2248–2256.Google Scholar
Hart, H, Radua, J, Nakao, T, Mataix-Cols, D, Rubia, K (2013). Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. JAMA Psychiatry 70, 185–198.CrossRefGoogle ScholarPubMed
Hoekzema, E, Carmona, S, Tremols, V, Gispert, JD, Guitart, M, Fauquet, J, Rovira, M, Bielsa, A, Soliva, JC, Tomas, X, Bulbena, A, Ramos-Quiroga, A, Casas, M, Tobeña, A, Vilarroya, O (2010). Enhanced neural activity in frontal and cerebellar circuits after cognitive training in children with attention-deficit/hyperactivity disorder. Human Brain Mapping 31, 1942–1950.Google Scholar
Huizenga, HM, van Bers, BMCW, Plat, J, van den Wildenberg, WPM, van der Molen, MW (2009). Task complexity enhances response inhibition deficits in childhood and adolescent attention-deficit/hyperactivity disorder: a meta-regression analysis. Biological Psychiatry 65, 39–45.CrossRefGoogle ScholarPubMed
Kessler, RC, Adler, L, Ames, M, Barkley, RA, Birnbaum, H, Greenberg, P, Johnston, JA, Spencer, T, Ustün, TB (2005). The prevalence and effects of adult attention deficit/hyperactivity disorder on work performance in a nationally representative sample of workers. Journal of Occupational and Environmental Medicine 47, 565–572.CrossRefGoogle Scholar
Kessler, RC, Green, JG, Adler, LA, Barkley, RA, Chatterji, S, Faraone, SV, Finkelman, M, Greenhill, LL, Gruber, MJ, Jewell, M, Russo, LJ, Sampson, NA, Van Brunt, DL (2010). Structure and diagnosis of adult attention-deficit/hyperactivity disorder: analysis of expanded symptom criteria from the adult ADHD clinical diagnostic scale. Archives of General Psychiatry 67, 1168–1178.Google Scholar
Kobel, M, Bechtel, N, Weber, P, Specht, K, Klarhöfer, M, Scheffler, K, Opwis, K, Penner, I-K (2009). Effects of methylphenidate on working memory functioning in children with attention deficit/hyperactivity disorder. European Journal of Paediatric Neurology 13, 516–523.Google Scholar
Konrad, K, Neufang, S, Fink, GR, Herpertz-Dahlmann, B (2007). Long-term effects of methylphenidate on neural networks associated with executive attention in children with ADHD: results from a longitudinal functional MRI study. Journal of the American Academy of Child and Adolescent Psychiatry 46, 1633–1641.Google Scholar
Kooistra, L, van der Meere, J, Edwards, J, Kaplan, B, Crawford, S, Goodyear, B (2010). Preliminary fMRI findings on the effects of event rate in adults with ADHD. Journal of Neural Transmission 117, 655–662.CrossRefGoogle ScholarPubMed
Martinussen, R, Hayden, J, Hogg-Johnson, S, Tannock, R (2005). A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 44, 377–384.Google Scholar
Mulligan, RC, Knopik, VS, Sweet, LH, Fischer, M, Seidenberg, M, Rao, SM (2011). Neural correlates of inhibitory control in adult attention deficit/hyperactivity disorder: evidence from the Milwaukee longitudinal sample. Psychiatry Research 194, 119–129.Google Scholar
Owen, AM, McMillan, KM, Laird, AR, Bullmore, E (2005). N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Human Brain Mapping 25, 46–59.Google Scholar
Passarotti, AM, Sweeney, JA, Pavuluri, MN (2010). Neural correlates of response inhibition in pediatric bipolar disorder and attention deficit hyperactivity disorder. Psychiatry Research 181, 36–43.Google Scholar
Pliszka, SR, Glahn, DC, Semrud-Clikeman, M, Franklin, C, Perez, R III, Xiong, J, Liotti, M (2006). Neuroimaging of inhibitory control areas in children with attention deficit hyperactivity disorder who were treatment naive or in long-term treatment. American Journal of Psychiatry 163, 1052–1060.Google Scholar
Posner, J, Maia, TV, Fair, D, Peterson, BS, Sonuga-Barke, EJ, Nagel, BJ (2011). The attenuation of dysfunctional emotional processing with stimulant medication: an fMRI study of adolescents with ADHD. Psychiatry Research 193, 151–160.Google Scholar
Proal, E, Reiss, PT, Klein, RG (2011). Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood. Archives of General Psychiatry 68, 1122–1134.CrossRefGoogle ScholarPubMed
Radua, J, Mataix-Cols, D, Phillips, ML, El-Hage, W, Kronhaus, DM, Cardoner, N, Surguladze, S (2012). A new meta-analytic method for neuroimaging studies that combines reported peak coordinates and statistical parametric maps. European Psychiatry 27, 605–611.CrossRefGoogle ScholarPubMed
Rasmussen, ER, Neuman, RJ, Heath, AC, Levy, F, Hay, DA, Todd, RD (2004). Familial clustering of latent class and DSM-IV defined attention-deficit/hyperactivity disorder (ADHD) subtypes. Journal of Child Psychology and Psychiatry 45, 589–598.Google Scholar
Rubia, K, Cubillo, A, Smith, AB, Woolley, J, Heyman, I, Brammer, MJ (2010). Disorder-specific dysfunction in right inferior prefrontal cortex during two inhibition tasks in boys with attention-deficit hyperactivity disorder compared to boys with obsessive–compulsive disorder. Human Brain Mapping 31, 287–299.Google Scholar
Rubia, K, Cubillo, A, Woolley, J, Brammer, MJ, Smith, A (2011 a). Disorder-specific dysfunctions in patients with attention-deficit/hyperactivity disorder compared to patients with obsessive-compulsive disorder during interference inhibition and attention allocation. Human Brain Mapping 32, 601–611.Google Scholar
Rubia, K, Halari, R, Cubillo, A, Mohammad, A-M, Brammer, M, Taylor, E (2009 a). Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task. Neuropharmacology 57, 640–652.Google Scholar
Rubia, K, Halari, R, Mohammad, A-M, Taylor, E, Brammer, M (2011 b). Methylphenidate normalizes frontocingulate underactivation during error processing in attention-deficit/hyperactivity disorder. Biological Psychiatry 70, 255–262.Google Scholar
Rubia, K, Halari, R, Smith, AB, Mohammad, M, Scott, S, Brammer, MJ (2009 b). Shared and disorder-specific prefrontal abnormalities in boys with pure attention-deficit/hyperactivity disorder compared to boys with pure CD during interference inhibition and attention allocation. Journal of Child Psychology and Psychiatry 50, 669–678.Google Scholar
Rubia, K, Overmeyer, S, Taylor, E, Brammer, M, Williams, SC, Simmons, A, Bullimore, ET (1999). Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. American Journal of Psychiatry 156, 891–896.Google Scholar
Rubia, K, Overmeyer, S, Taylor, E, Brammer, M, Williams, SCR, Simmons, A, Andrew, C, Bullmore, ET (2000). Functional frontalisation with age: mapping neurodevelopmental trajectories with fMRI. Neuroscience and Biobehavioral Reviews 24, 13–19.CrossRefGoogle ScholarPubMed
Rubia, K, Smith, AB, Halari, R, Matsukura, F, Mohammad, M, Taylor, E, Brammer, MJ (2009 c). Disorder-specific dissociation of orbitofrontal dysfunction in boys with pure conduct disorder during reward and ventrolateral prefrontal dysfunction in boys with pure ADHD during sustained attention. American Journal of Psychiatry 166, 83–94.Google Scholar
Schneider, MF, Krick, CM, Retz, W, Hengesch, G, Retz-Junginger, P, Reith, W, Rösler, M (2010). Impairment of fronto-striatal and parietal cerebral networks correlates with attention deficit hyperactivity disorder (ADHD) psychopathology in adults – a functional magnetic resonance imaging (fMRI) STUDY. Psychiatry Research 183, 75–84.Google Scholar
Schulz, KP, Fan, J, Bédard, AC, Clerkin, SM, Ivanov, I, Tang, CY, Halperin, JM, Newcorn, JH (2012). Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder. Archives of General Psychiatry 69, 952–961.CrossRefGoogle ScholarPubMed
Schulz, KP, Newcorn, JH, Fan, JIN, Tang, CY, Halperin, JM (2005). Brain activation gradients in ventrolateral prefrontal cortex related to persistence of ADHD in adolescent boys. Journal of the American Academy of Child and Adolescent Psychiatry 44, 47–54.Google Scholar
Schweitzer, JB, Lee, DO, Hanford, RB, Zink, CF, Ely, TD, Tagamets, MA, Hoffman, JM, Grafton, ST, Kilts, CD (2004). Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: normalization of behavior but not related brain activity. Biological Psychiatry 56, 597–606.Google Scholar
Sebastian, A, Gerdes, B, Feige, B, Klöppel, S, Lange, T, Philipsen, A, Tebartz Van Elst, L, Lieb, K, Tüscher, O (2012). Neural correlates of interference inhibition, action withholding and action cancelation in adult ADHD. Psychiatry Research 202, 132–141.Google Scholar
Simmonds, DJ, Pekar, JJ, Mostofsky, SH (2008). Meta-analysis of Go/no-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent. Neuropsychologia 46, 224–232.Google Scholar
Smith, AB (2006). Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder. American Journal of Psychiatry 163, 1044–1051.Google Scholar
Solanto, MV, Schulz, KP, Fan, J, Tang, CY, Newcorn, JH (2009). Event-related fMRI of inhibitory control in the predominantly inattentive and combined subtypes of ADHD. Journal of Neuroimaging 19, 205–212.Google Scholar
Suskauer, SJ, Simmonds, DJ, Caffo, BS, Denckla, MB, Pekar, JJ, Mostofsky, SH (2008). fMRI of intrasubject variability in ADHD: anomalous premotor activity with prefrontal compensation. Journal of the American Academy of Child and Adolescent Psychiatry 47, 1141–1150.CrossRefGoogle ScholarPubMed
Tamm, L, Menon, V, Ringel, J, Reiss, AL (2004). Event-related fMRI evidence of frontotemporal involvement in aberrant response inhibition and task switching in attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 43, 1430–1440.Google Scholar
Vaidya, CJ, Austin, G, Kirkorian, G, Ridlehuber, HW, Desmond, JE, Glover, GH, Gabrieli, JDE (1998). Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. Proceedings of the National Academy of Sciences of the USA 95, 14494–14499.Google Scholar
Valera, EM, Brown, A, Biederman, J, Faraone, SV, Makris, N, Monuteaux, MC, Whitfield-Gabrieli, S, Vitulano, M, Schiller, M, Seidman, LJ (2010). Sex differences in the functional neuroanatomy of working memory in adults with ADHD. American Journal of Psychiatry 167, 86–94.CrossRefGoogle ScholarPubMed
Valera, EM, Faraone, SV, Biederman, J, Poldrack, RA, Seidman, LJ (2005). Functional neuroanatomy of working memory in adults with attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 439–447.Google Scholar
Vloet, TD, Gilsbach, S, Neufang, S, Fink, GR, Herpertz-Dahlmann, B, Konrad, K (2010). Neural mechanisms of interference control and time discrimination in attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 49, 356–367.Google Scholar
Volkow, ND, Swanson, JM (2003). Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. American Journal of Psychiatry 160, 1909–1918.Google Scholar
Volkow, ND, Wang, G-J, Fowler, JS, Logan, J, Franceschi, D, Maynard, L, Ding, Y-S, Gatley, SJ, Gifford, A, Zhu, W, Swanson, JM (2002). Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications. Synapse 43, 181–187.Google Scholar
Zhou, Y, Yu, CS, Zheng, H, Liu, Y, Song, M, Qin, W, Li, KC, Jiang, TZ (2010). Increased neural resources recruitment in the intrinsic organization in major depression. Journal of Affective Disorders 121, 220–230.Google Scholar
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