Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-23T00:25:29.666Z Has data issue: false hasContentIssue false

An integrated program of computer-presented and physical cognitive training exercises for children with attention-deficit/hyperactivity disorder

Published online by Cambridge University Press:  24 February 2020

Bruce E. Wexler*
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
Lawrence A. Vitulano
Affiliation:
Child Study Center, Yale School of Medicine, New Haven, CT, USA
Christina Moore
Affiliation:
Child Study Center, Yale School of Medicine, New Haven, CT, USA Department of Psychology, University of Delaware, Newark, DE, USA
Liliya Katsovich
Affiliation:
Child Study Center, Yale School of Medicine, New Haven, CT, USA
Stephanie D. Smith
Affiliation:
Child Study Center, Yale School of Medicine, New Haven, CT, USA Department of Psychology, University of Southern Mississippi, Hattiesburg, MS, USA
Cindy Rush
Affiliation:
Department of Statistics, Columbia University, New York, NY, USA
Heidi Grantz
Affiliation:
Child Study Center, Yale School of Medicine, New Haven, CT, USA
Jinxia Dong
Affiliation:
Peking University, Beijing, P.R. China
James F. Leckman
Affiliation:
Child Study Center, Yale School of Medicine, New Haven, CT, USA
*
Author for correspondence: Bruce E. Wexler, E-mail: [email protected]

Abstract

Background

This study integrated an experimental medicine approach and a randomized cross-over clinical trial design following CONSORT recommendations to evaluate a cognitive training (CT) intervention for attention deficit hyperactivity disorder (ADHD). The experimental medicine approach was adopted because of documented pathophysiological heterogeneity within the diagnosis of ADHD. The cross-over design was adopted to provide the intervention for all participants and make maximum use of data.

Methods

Children (n = 93, mean age 7.3 +/− 1.1 years) with or sub-threshold for ADHD were randomly assigned to CT exercises over 15 weeks, before or after 15 weeks of treatment-as-usual (TAU). Fifteen dropped out of the CT/TAU group and 12 out of the TAU/CT group, leaving 66 for cross-over analysis. Seven in the CT/TAU group completed CT before dropping out making 73 available for experimental medicine analyses. Attention, response inhibition, and working memory were assessed before and after CT and TAU.

Results

Children were more likely to improve with CT than TAU (27/66 v. 13/66, McNemar p = 0.02). Consistent with the experimental medicine hypotheses, responders improved on all tests of executive function (p = 0.009–0.01) while non-responders improved on none (p = 0.27–0.81). The degree of clinical improvement was predicted by baseline and change scores in focused attention and working memory (p = 0.008). The response rate was higher in inattentive and combined subtypes than hyperactive-impulsive subtype (p = 0.003).

Conclusions

Targeting cognitive dysfunction decreases clinical symptoms in proportion to improvement in cognition. Inattentive and combined subtypes were more likely to respond, consistent with targeted pathology and clinically relevant heterogeneity within ADHD.

Type
Original Articles
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abikoff, H., Gittelman-Klein, R., & Klein, D. F. (1977). Validation of a classroom observation code for hyperactive children. Journal of Consulting and Clinical Psychology, 45, 772783.CrossRefGoogle ScholarPubMed
Abikoff, H., Hechtman, L., Klein, R. G., Weiss, G., Fleiss, K., Etcovitch, J., … Pollack, S. (2004). Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. Journal of the American Academy of Child & Adolescent Psychiatry, 43, 802811.CrossRefGoogle ScholarPubMed
ADHD-200 Consortium (2012). The ADHD-200 consortium: A model to advance the translational potential of neuroimaging in clinical neuroscience. Frontiers in Systems Neuroscience, 6, Article 62, 15.Google Scholar
Allen, A. J., Kurlan, R. M., Gilbert, D. L., Coffey, B. J., Linder, S. L., Lewis, D. W., & Spencer, T. J. (2005). Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology, 65, 19411949.CrossRefGoogle ScholarPubMed
Amador-Campos, J. A., Forns-Santacana, M., Guàrdia-Olmos, J., & Peró-Cebollero, M. (2006). DSM-IV attention deficit hyperactivity disorder symptoms: Agreement between informants in prevalence and factor structure at different ages. Journal of Psychopathology and Behavioral Assessment, 28, 2332.CrossRefGoogle Scholar
Barkley, R. A. (1977). A review of stimulant drug research with hyperactive children. Journal of Child Psychology and Psychiatry, 18, 137165.CrossRefGoogle ScholarPubMed
Barkley, R. A. (1997). Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD. Psychological Bulletin, 121, 6594.CrossRefGoogle ScholarPubMed
Barkley, R. A. (2003). Issues in the diagnosis of attention-deficit/hyperactivity disorder in children. Brain and Development, 25, 7783.CrossRefGoogle Scholar
Barkley, R. A., Anastopoulos, A. D., Guevremont, D. C., & Fletcher, K. E. (1992). Adolescents with attention deficit hyperactivity disorder: Mother-adolescent interactions, family beliefs and conflicts, and maternal psychopathology. Journal of Abnormal Child Psychology, 20, 263288.CrossRefGoogle ScholarPubMed
Barkley, R. A., DuPaul, G. J., & McMurray, M. B. (1990). Comprehensive evaluation of attention deficit disorder with and without hyperactivity as defined by research criteria. Journal of Consulting and Clinical Psychology, 58, 775789.CrossRefGoogle ScholarPubMed
Beck, S. J., Hanson, C. A., Puffenberger, S. S., Benninger, K. L., & Benninger, W. B. (2010). A controlled trial of working memory training for children and adolescents with ADHD. Journal of Clinical Child and Adolescent Psychology, 39, 825836.CrossRefGoogle ScholarPubMed
Bloch, M. H., Landeros-Weisenberger, A., Kelmendi, B., Coric, V., Bracken, M. B., & Leckman, J. F. (2006). A systematic review: Antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Molecular Psychiatry, 11, 622632.CrossRefGoogle ScholarPubMed
Bussing, R., Fernandez, M., Harwood, M., Wei, H., Garvan, C. W., Eyberg, S. M., & Swanson, J. M. (2008). Parent and teacher SNAP-IV ratings of attention deficit hyperactivity disorder symptoms: Psychometric properties and normative ratings from a school district sample. Assessment, 15, 317328.CrossRefGoogle ScholarPubMed
Chacko, A., Bedard, A. C., Marks, D. J., Feirsen, N., Uderman, J. Z., Chimiklis, A., & Ramon, M. (2014). A randomized clinical trial of Cogmed working memory training in school-age children with ADHD: A replication in a diverse sample using a control condition. Journal of Child Psychology and Psychiatry, 55, 247255.CrossRefGoogle Scholar
Chacko, A., Feirsen, N., Bedard, A.-C., Marks, D., Uderman, J. Z., & Chimiklis, A. (2013). Cogmed working memory training for youth with ADHD: A closer examination of efficacy utilizing evidence-based criteria. Journal of Clinical Child and Adolescent Psychology, 42, 769783.CrossRefGoogle ScholarPubMed
Cherkasova, M., Sulla, E. M., Dalena, K. L., Pondé, M. P., & Hechtman, L. (2013). Developmental course of attention deficit hyperactivity disorder and its predictors. Journal of the Canadian Academy of Child and Adolescent Psychiatry, 22, 4754.Google ScholarPubMed
Clarke, A. R., Barry, R. J., Dupuy, F. E., Heckel, L. D., McCarthy, R., Selikowitz, M., & Johnstone, S. J. (2011). Behavioural differences between EEG-defined subgroups of children with attention-deficit/hyperactivity disorder. Clinical Neurophysiology, 122, 13331341.CrossRefGoogle ScholarPubMed
Coghill, D. R., Seth, S., & Mathews, K. (2014). A comprehensive assessment of memory. Delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: Advancing beyond the three-pathway models. Psychological Medicine, 44, 19892001.CrossRefGoogle ScholarPubMed
Cortese, S., Ferrin, M., Brandeis, D., Buitelaar, J., Daley, D., Dittmann, R. W., & Sonuga-Barke, E. J. S. (2015). Cognitive training for attention-deficit/hyperactivity disorder: Meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials. Journal of the American Academy of Child & Adolescent Psychiatry, 54, 164174.CrossRefGoogle ScholarPubMed
Dalsgaard, S., Østergaard, S. D., Leckman, J. F., Mortensen, P. B., & Pedersen, M. G. (2015). Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: A nationwide cohort study. The Lancet, 385, 21902196.CrossRefGoogle ScholarPubMed
Dovis, S., Van der Oord, S., Wiers, R. W., & Prins, P. J. M. (2015). Improving executive functioning in childen with ADHD: Training multiple executive functions within the context of a computer game. A randomized double-blind placebo controlled trial. PLoS ONE, 10(4), e0121651. doi: 10.1371/journal.pone.0121651.CrossRefGoogle Scholar
Dwan, K., Tianjing, L., Altman, D. G., & Elbourne, D. (2019). CONSORT 2010 Statement: Extension to randomized crossover trials. British Medical Journal, 366, l4378.CrossRefGoogle Scholar
Efron, D., Jarman, J., & Barker, M. (1997). Methylphenidate versus dexamphetamine in children with attention deficit hyperactivity disorder: A double-blind, crossover trial. Pediatrics, 100, 17.CrossRefGoogle ScholarPubMed
Embry, D., (2002). The Good Behavior Game: A best practice candidate as a universal behavioral vaccine. Clinical Child and Family Psychology Review, 5, 273297.CrossRefGoogle Scholar
Erhardt, D., & Hinshaw, S. P. (1994). Initial sociometric impressions of attention-deficit hyperactivity disorder and comparison boys: Predictions from social behaviors and from nonbehavioral variables. Journal of Consulting and Clinical Psychology, 62, 833842.CrossRefGoogle ScholarPubMed
Fair, D. A., Bathula, D, Nikolas, M. A., & Nigg, J. T. (2012). Distinct neuropsychological subgroups in typically developing youth informheterogeneity in children with ADHD. Proceedings of the National Academy of Sciences of the United States, 109, 67696774.CrossRefGoogle ScholarPubMed
Faraone, S. V., Sergeant, J., Gillberg, C. G., & Biederman, J. (2003). The worldwide prevalence of ADHD: Is it an American condition? World Psychiatry, 2, 104113.Google ScholarPubMed
Findling, R. L., Landbloom, R. L., Szegedi, A., Koppenhaver, J., Braat, S., Zhu, Q., & Mathews, M. (2015). Asenapine for the acute treatment of pediatric manic of mixed episode of bipolar 1 disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 54, 10321041.CrossRefGoogle Scholar
Fischer, M., Barkley, R. A., Fletcher, K. E., & Smallish, L. (1993). The stability of dimensions of behavior in ADHD and normal children over an 8-year followup. Journal of Abnormal Child Psychology, 21, 315337.CrossRefGoogle ScholarPubMed
Fried, R., Hirshfeld-Baker, D., Petty, C., Batchelder, H., & Biederman, J. (2015). How informative is the CANTAB to assess executive functioning in children with ADHD? A controlled study. Journal of Attention Disorders, 19, 468475.CrossRefGoogle ScholarPubMed
Gray, S. A., Chaban, P., Martinussen, R., Goldberg, R., Gotlieb, H., Kronitz, R., & Tannock, R. (2012). Effects of a computerized working memory training program on working memory, attention, and academics in adolescents with severe LD and comorbid ADHD: A randomized controlled trial. Journal of Child Psychology and Psychiatry, 53, 12771284.CrossRefGoogle ScholarPubMed
Green, C. T., Long, D. L., Green, D., Iosif, A. M., Dixon, J. F., Miller, M. R., & Schweitzer, J. B. (2012). Will working memory training generalize to improve off-task behavior in children with attention-deficit/hyperactivity disorder? Neurotherapeutics, 9, 639648.CrossRefGoogle ScholarPubMed
Holmes, J., Gathercole, S. E., Place, M., Dunning, D. L., Hilton, K. A., & Elliott, J. G. (2010). Working memory deficits can be overcome: Impacts of training and medication on working memory in children with ADHD. Applied Cognitive Psychology, 24, 827836.CrossRefGoogle Scholar
Huizink, A. C., Van Lier, P. A. C., & Crijnen, A. A. M. (2008). Attention deficit hyperactivity disorder symptoms mediate early-onset smoking. European Addiction Research, 15, 19.CrossRefGoogle ScholarPubMed
Hyman, S. W. (2010). The diagnosis of mental disorders: The problem of reification. Annual Reviews of Clinical Psychology, 6, 155179.CrossRefGoogle Scholar
Jensen, P. (2003). Longer term effects of stimulant treatments for attention-deficit/hyperactivity disorder. Journal of Attention Disorders, 6, 4556.CrossRefGoogle Scholar
Johnstone, S. J., Roodenrys, S., Blackman, R., Johnston, E., Loveday, K., Mantz, S., & Barratt, M. F. (2012). Neurocognitive training for children with and without AD/HD. ADHD Attention Deficit and Hyperactivity Disorders, 4, 1123.CrossRefGoogle ScholarPubMed
Karalunas, S. L., Fair, D., Musser, E. D., Aykes, K., Iyer, S. P., & Nigg, J. T. (2014). Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: Toward biologically based nosologic criteria. JAMA psychiatry, 71, 0151024.CrossRefGoogle ScholarPubMed
Kaufman, A. S., & Kaufman, N. L. (2004b). Kaufman brief intelligence test (2nd ed.). Bloomington, MN: Pearson.Google Scholar
Kavanaugh, B., Tuncer, O. F., & Wexler, B. E. (2019). Measuring and improving executive function in the classroom. Journal of Cognitive Enhancement, 3(3), 271280. doi: 10.1007/s41465-018-0095-y.CrossRefGoogle Scholar
Klingberg, T., Fernell, E., Olesen, P. J., Johnson, M., Gustafsson, P., Dahlström, K., & Westerberg, H. (2005). Computerized training of working memory in children with ADHD – a randomized, controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry, 44, 177186.CrossRefGoogle ScholarPubMed
Martel, M. M., Von Eye, A., & Nigg, J. T. (2010). Revisiting the latent structure of ADHD: Is there a ‘g’ factor? Journal of Child Psychology and Psychiatry, 51, 905914.CrossRefGoogle Scholar
Melby-Lervåg, M., & Hulme, C. (2013). Is working memory training effective? A meta-analytic review. Developmental Psychology, 49, 270291.CrossRefGoogle ScholarPubMed
Miller, G. (2010). Psychiatry. Beyond DSM: Seeking a brain-based classification of mental illness. Science, 327, 1437.CrossRefGoogle ScholarPubMed
Morimoto, S. S., Wexler, B. E., Liu, J., Hu, W., Seirup, J., & Alexopoulos, G. S. (2014). Neuroplasticity-based computerized cognitive remediation for treatment resistant geriatric depression. Nature Communications, 5, 4579, 17. doi:10.1038/ncomms5579.CrossRefGoogle ScholarPubMed
Nigg, J. T., Willcutt, E. G., Doyle, A. E., & Sonuga-Barke, E. J. (2005). Causal heterogeneity in attention-deficit-hyperactivity disorder: Do we need neuropsychologically impaired subtypes? Biological Psychiatry, 57, 12241230.CrossRefGoogle ScholarPubMed
Pallanti, S., Querciol, L., Sood, E., & Hollander, E. (2002). Lithium and valproate treatment of pathological gambling: A randomized single-blind study. Journal of Clinical Psychiatry, 63, 559564.CrossRefGoogle ScholarPubMed
Popper, CW (1988). Disorders usually first evident in infancy, childhood, or adolescence. In (Talbot, J. A., Hales, R. E., & Yudofsky, S. C. (Eds.), Textbook of psychiatry (pp. 649735). Washington, DC: American Psychiatric Press.Google Scholar
Rapport, M. D., Orban, S. A., Kofler, M. J., & Friedman, L. M. (2013). Do programs designed to train working memory, other executive functions, and attention benefit children with ADHD? A meta-analytic review of cognitive, academic, and behavioral outcomes. Clinical Psychology Review, 33, 12371252.CrossRefGoogle ScholarPubMed
Riddle, M and Science of Behavior Change Working Group (2015). News from the NIH: Using an experimental medicine approach to facilitate translational research. TBM, 5, 486488.Google ScholarPubMed
Rosa, V. O., Franco, A. R., Salum, G. A., Moreora-Maia, C. R., Wagner, F., Simioni, A., & Rhode, L. A. P. (2019). Effects of computerized cognitive training as ass-on treatment to stimulants in ADHD: A pilot fMRI study. Brain Imaging and Behavior, 112. doi:10.1007/s11682-019-00137-0.Google Scholar
Schachar, R. (2014). Genetics of attention deficit hyperactivity disorder (ADHD): Recent updates and future prospects. Current Developmental Disorders Reports, 1, 4149.CrossRefGoogle Scholar
Shalev, L., Tsal, Y., & Mevorach, C. (2007). Computerized progressive attentional training (CPAT) program: Effective direct intervention for children with ADHD. Child Neuropsychology, 13, 382388.CrossRefGoogle ScholarPubMed
Sibley, M. H., Altszuler, A. R., Morrow, A. S., & Merrill, B. M. (2014). Mapping the academic problem behaviors of adolescents with ADHD. School Psychology Quarterly, 29, 422437.CrossRefGoogle ScholarPubMed
Smith, S. D., Crowley, M. J., Ferrey, A., Ramsey, K., Wexler, B. E., Leckman, J. F., & Sukhodolsky, D. G. (2019). Effects of integrated brain, body, and social (IBBS) intervention on ERP measures of attentional control in children with ADHD. Psychiatry Research, 278, 248257.CrossRefGoogle ScholarPubMed
Smith, S. D., Vitulano, L. A., Katsovich, L., Li, S., Moore, C., Li, F., & Leckman, J. F. (2016). A randomized controlled trial of an integrated brain, body, and social intervention for children with ADHD. Journal of Attention Disorders, 115. doi: 10.1177/1087054716647490Google ScholarPubMed
Sonuga-Barke, E., Bitsakou, P., & Thompson, M. (2010). Beyond the dual pathway model: Evidence for the dissociation of timing, inhibitory, and delay-related impairments in attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 49(4), 345355.Google ScholarPubMed
Sonuga-Barke, E. J., Brandeis, D., Cortese, S., Daley, D., Ferrin, M., Holtmann, M., & Dittmann, R. W. (2013). Nonpharmacological interventions for ADHD: Systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. American Journal of Psychiatry, 170, 275289.CrossRefGoogle ScholarPubMed
Storch, E. A., Lewin, A. B., De Nadai, A. S., & Murphy, T. K. (2010). Defining treatment response and remission in obsessive-compulsive disorder: A signal detection analysis of the children's Yale-Brown Obsessive Compulsive Scale. Journal of the American Academy of Child & Adolescent Psychiatry, 49, 708717.Google ScholarPubMed
Suzuki, T., Remington, G., Mulsant, B. H., Uchida, H., Rajji, T. K., Graff-Guerrero, A., & Mamo, D. C. (2012). Defining treatment-resistant schizophrenia and response to antipsychotics: A review and recommendation. Psychiatry research, 197, 16.CrossRefGoogle ScholarPubMed
Swanson, J. M. (1992). School-Based assessments and interventions for ADD students. Irvine, CA: KC Publishing.Google Scholar
van Dongen-Boomsma, M., Vollebregt, M. A., Slaats-Willemse, D., & Buitelaar, J. K. (2013). A randomized placebo-controlled trial of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder. Journal of Clinical Psychiatry, 74, 821827.CrossRefGoogle ScholarPubMed
Wahkstedt, C., Thorell, L. B., & Bohlin, G. (2008). ADHD symptoms and executive function impairment: Early predictors of later behavioral problems. Developmental Psychology, 33, 160178.Google Scholar
Walsh, B. T., Seidman, S. N., Sysko, R., & Gould, M. (2002). Placebo response in studies of major depression. JAMA, 287, 18401847.CrossRefGoogle ScholarPubMed
Wexler, B. E. (1992). Beyond the Kraepelinean dichotomy. Biological Psychiatry, 31, 539541.CrossRefGoogle ScholarPubMed
Wexler, B. E., & Bell, M. D. (2005). Cognitive remediation and vocational rehabilitation for schizophrenia. Schizophrenia Bulletin, 31, 931941.CrossRefGoogle Scholar
Whalen, C. K., Henker, B., & Dotemoto, S. (1980). Methylphenidate and hyperactivity: Effects on teacher behaviors. Science, 208, 12801282.CrossRefGoogle ScholarPubMed
Wilens, T. E., Biederman, J., Brown, S., Monuteaux, M., Prince, J., & Spencer, T. J. (2002). Patterns of psychopathology and dysfunction in clinically referred preschoolers. Journal of Developmental and Behavioral Pediatrics, 23, S31S36.CrossRefGoogle ScholarPubMed
Wykes, T., Huddy, V., Cellard, C., McGurk, S. R., & Czobor, P. (2011). A meta-analysis of cognitive remediation for schizophrenia: Methodology and effect sizes. The American Journal of Psychiatry, 168, 472485.CrossRefGoogle ScholarPubMed
Supplementary material: File

Wexler et al. supplementary material

Wexler et al. supplementary material

Download Wexler et al. supplementary material(File)
File 14 KB