Skip to main content Accessibility help

Influence of Methylphenidate on Long-Term Neuropsychological and Everyday Executive Functioning After Traumatic Brain Injury in Children with Secondary Attention Problems

  • Elizabeth LeBlond (a1) (a2), Julia Smith-Paine (a1) (a2), Jacqlyn J. Riemersma (a3), Paul S. Horn (a3) (a4) (a5), Shari L. Wade (a1) (a2) (a3) and Brad G. Kurowski (a2) (a3) (a6) (a7)...


Objective: To investigate the effects of methylphenidate on long-term executive and neuropsychological functioning in children with attention problems following TBI, as well as the relationship between methylphenidate associated changes in lab-based neuropsychological measures of attentional control, processing speed, and executive functioning and parent- or self-report measures of everyday executive functioning. Method: 26 children aged 6–17 years, who were hospitalized for moderate-to-severe blunt head trauma 6 or more months previously, were recruited from a large children’s hospital medical center. Participants were randomized into a double-masked, placebo-controlled cross-over clinical trial. Participants completed a comprehensive neuropsychological battery and parent- and self-report ratings of everyday executive functioning at baseline, and at 4 weeks and 8 weeks following upward titration of medication to an optimal dose or while administered a placebo. Results: Methylphenidate was associated with significant improvements in processing speed, sustained attention, and both lab-based and everyday executive functioning. Significant treatment-by-period interactions were found on a task of sustained attention. Participants who were randomized to the methylphenidate condition for the first treatment period demonstrated random or erratic responding, with slower and more variable response times when given placebo during the second period. Conclusion: Results indicate that methylphenidate treatment is associated with positive outcomes in processing speed, sustained attention, and both lab-based and everyday measures of executive functioning compared to placebo group. Additionally, results suggest sustained attention worsens when discontinuing medication.



Hide All
Abikoff, H., Hechtman, L., Klein, R.G., Weiss, G., Fleiss, K., Etcovitch, J., Cousins, L., Greenfield, B., Martin, D., & 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(7), 802811.
Allen, D.N., Thaler, N.S., Donohue, B., & Mayfield, J. (2010). WISC-IV profiles in children with traumatic brain injury: similarities to and differences from the WISC-III. Psychological Assessment, 22(1), 5764. doi: 10.1037/a0016056
Anderson, V., Brown, S., Newitt, H., & Hoile, H. (2009). Educational, vocational, psychosocial, and quality-of-life outcomes for adult survivors of childhood traumatic brain injury. The Journal of Head Trauma Rehabilitation, 24(5), 303312. doi: 10.1097/HTR.0b013e3181ada830
Antonini, T.N., Raj, S.P., Oberjohn, K.S., Cassedy, A., Makoroff, K.L., Fouladi, M., & Wade, S.L. (2014). A pilot randomized trial of an online parenting skills program for pediatric traumatic brain injury: improvements in parenting and child behavior. Behavior Therapy, 45(4), 455468. doi: 10.1016/j.beth.2014.02.003
Babikian, T., Merkley, T., Savage, R.C., Giza, C.C., & Levin, H. (2015). Chronic aspects of pediatric traumatic brain injury: review of the literature. Journal of Neurotrauma, 32(23), 18491860. doi: 10.1089/neu.2015.3971
Backeljauw, B., & Kurowski, B.G. (2014). Interventions for attention problems after pediatric traumatic brain injury: what is the evidence? PM R, 6(9), 814824. doi: 10.1016/j.pmrj.2014.04.004
Berridge, C.W., Devilbiss, D.M., Andrzejewski, M.E., Arnsten, A.F., Kelley, A.E., Schmeichel, B., Hamilton, C., &. Spencer, R.C. (2006). Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biological Psychiatry, 60(10), 11111120.
Biederman, J., Monuteaux, M.C., Doyle, A.E., Seidman, L.J., Wilens, T.E., Ferrero, F., Morgan, C.L., & Faraone, S.V. (2004). Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children. Journal of Consulting and Clinical Psychology, 72(5), 757.
Bloom, D.R., Levin, H.S., Ewing-Cobbs, L., Saunders, A.E., Song, J., Fletcher, J.M., & Kowatch, R.A. (2001). Lifetime and novel psychiatric disorders after pediatric traumatic brain injury. Journal of the American Academy of Child & Adolescent Psychiatry, 40(5), 572579. doi: 10.1097/00004583-200105000-00017
Bonfield, C.M., Lam, S., Lin, Y., & Greene, S. (2013). The impact of attention deficit hyperactivity disorder on recovery from mild traumatic brain injury. Journal of Neurosurgery: Pediatrics, 12(2), 97102.
Bryant, R.A., O’donnell, M.L., Creamer, M., McFarlane, A.C., Clark, C.R., & Silove, D. (2010). The psychiatric sequelae of traumatic injury. American Journal of Psychiatry, 167(3), 312320.
Catroppa, C., Anderson, V.A., Morse, S.A., Haritou, F., & Rosenfeld, J.V. (2007). Children’s attentional skills 5 years post-TBI. Journal of Pediatric Psychology, 32(3), 354369. doi: 10.1093/jpepsy/jsl019
Charach, A., & Gajaria, A. (2008). Improving psychostimulant adherence in children with ADHD. Expert Review of Neurotherapeutics, 8(10), 15631571.
Cnaan, A., Laird, N.M., & Slasor, P. (1997). Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Statistics in Medicine, 16(20), 23492380. doi: 10.1002/(Sici)1097-0258(19971030)16:20<2349::Aid-Sim667>3.0.Co;2-E
Conners, C. (2004). Continuous performance test. Technical guide and software manual. North Tonawanda, NY: MultiHealth Systems.
Conners, C.K. (1995). Conners’ continuous performance test computer program 3.0 user’s manual. Toronto, Ontario, Canada: MultiHealth Systems.
Conners, C.K. (2000). Conners’ continuous performance test II. Toronto, Ontario, Canada: MultiHealth Systems.
D’Agati, E., Cerminara, C., Casarelli, L., Pitzianti, M., & Curatolo, P. (2012). Attention and executive functions profile in childhood absence epilepsy. Brain and Development, 34(10), 812817.
De la Torre, G.G., Martin, A., Cervantes, E., Guil, R., & Mestre, J.M. (2017). Attention lapses in children with spina bifida and hydrocephalus and children with attention-deficit/hyperactivity disorder. Journal of Clinical and Experimental Neuropsychology, 39(6), 563573.
Delis, D.C., Kaplan, E., & Kaplan, J. (2001). Delis-Kaplan executive functioning system. San Antonio, TX: Pearson Assesments.
Dennis, M., Wilkinson, M., Koski, L., & Humphreys, R.P. (1995). Attention deficits in the long term after childhood head injury, In Broman, S. & Michel, M.E. (Eds.), Traumatic head injury children (pp. 165187). New York, NY: Oxford University Press.
Donders, J., & Janke, K. (2008). Criterion validity of the Wechsler Intelligence Scale for Children-Fourth Edition after pediatric traumatic brain injury. Journal of the International Neuropsychological Society, 14(4), 651655. doi: 10.1017/S1355617708080752
Dougall, D., Poole, N., & Agrawal, N. (2015). Pharmacotherapy for chronic cognitive impairment in traumatic brain injury. The Cochrane Database of Systematic Reviews, 12, CD009221.
Fenwick, T., & Anderson, V. (1999). Impairments of attention following childhood traumatic brain injury. Child Neuropsychology, 5(4), 213223.
Galbiati, S., Recla, M., Pastore, V., Liscio, M., Bardoni, A., Castelli, E., & Strazzer, S. (2009). Attention remediation following traumatic brain injury in childhood and adolescence. Neuropsychology, 23(1), 4049. doi: 10.1037/a0013409
Gioia, G.A., & Isquith, P.K. (2004). Ecological assessment of executive function in traumatic brain injury. Developmental Neuropsychology, 25(1–2), 135158. doi: 10.1207/s15326942dn2501&2_8
Gioia, G.A., Isquith, P.K., Guy, S.C., & Kenworthy, L. (2000). Behavior rating inventory of executive function. Child Neuropsychology, 6(3), 235238.
Graham, J., Banaschewski, T., Buitelaar, J., Coghill, D., Danckaerts, M., Dittmann, R.W., Döpfner, M., Hamilton, R., Hollis, C., Holtmann, M., Hulpke-Wette, M., Lecendreux, M., Rosenthal, E., Rothenberger, A., Santosh, P., Sergeant, J., Simonoff, E., Sonuga-Barke, E., Wong, I.C.K., Zuddas, A., Steinhausen, H.-C., Taylor, E., & European Guidelines Group. (2011). European guidelines on managing adverse effects of medication for ADHD. European Child & Adolescent Psychiatry, 20(1), 1737.
Gupta, S.K. (2011). Intention-to-treat concept: a review. Perspectives in Clinical Research, 2(3), 109112. doi: 10.4103/2229-3485.83221
Hart, J., Kraut, M.A., Womack, K.B., Strain, J., Didehbani, N., Bartz, E., Conover, H., Mansinghani, S., Lu, H., & Cullum, C.M. (2013). Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. JAMA Neurology, 70(3), 326335.
Horton, A.M. Jr, Soper, H.V., & Reynolds, C.R. (2010). Executive functions in children with traumatic brain injury. Applied Neuropsychology, 17(2), 99103.
Ibrahim, K., & Donyai, P. (2015). Drug holidays from ADHD medication: international experience over the past four decades. Journal of Attention Disorders, 19(7), 551568.
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., Williamson, D. & Ryan, N. (1997). Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child & Adolescent Psychiatry, 36(7), 980988.
Kaufmann, P.M., Fletcher, J.M., Levin, H.S., Miner, M.E., & Ewing-Cobbs, L. (1993). Attentional disturbance after pediatric closed head injury. Journal of Child Neurology, 8(4), 348353.
Kim, J., Whyte, J., Patel, S., Europa, E., Wang, J., Coslett, H.B., & Detre, J.A. (2012). Methylphenidate modulates sustained attention and cortical activation in survivors of traumatic brain injury: a perfusion fMRI study. Psychopharmacology (Berl), 222(1), 4757. doi: 10.1007/s00213-011-2622-8
Konrad, K., Günther, T., Hanisch, C., & Herpertz-Dahlmann, B. (2004). Differential effects of methylphenidate on attentional functions in children with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 43(2), 191198.
Kurowski, B.G., Epstein, J.N., Pruitt, D.W., Horn, P.S., Altaye, M., & Wade, S.L. (2018). Benefits of methylphenidate for long-term attention problems after traumatic brain injury in childhood: a randomized, double-masked, placebo-controlled, dose-titration, crossover trial. The Journal of Head Trauma Rehabilitation, 34(2), E1E12
Lakens, D. (2013). Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Frontiers in Psychology, 4, 863. doi: 10.3389/fpsyg.2013.00863
Lavigne, J.V., Dulcan, M.K., LeBailly, S.A., & Binns, H.J. (2012). Can parent reports serve as a proxy for teacher ratings in medication management of attention-deficit hyperactivity disorder? Journal of Developmental and Behavioral Pediatrics, 33(4), 336342. doi: 10.1097/DBP.0b013e31824afea1
Levin, H.S., & Hanten, G. (2005). Executive functions after traumatic brain injury in children. Pediatric Neurology, 33(2), 7993. doi: 10.1016/j.pediatrneurol.2005.02.002
Levin, H.S., Song, J., Ewing-Cobbs, L., Chapman, S.B., & Mendelsohn, D. (2001). Word fluency in relation to severity of closed head injury, associated frontal brain lesions, and age at injury in children. Neuropsychologia, 39(2), 122131.
MacKinnon, D.P., Lockwood, C.M., Hoffman, J.M., West, S.G., & Sheets, V. (2002). A comparison of methods to test mediation and other intervening variable effects. Psychological Methods, 7(1), 83104.
Mackinnon, D.P., Warsi, G., & Dwyer, J.H. (1995). A simulation study of mediated effect measures. Multivariate Behavioral Research, 30(1), 41. doi: 10.1207/s15327906mbr3001_3
Mahalick, D.M., Carmel, P.W., Greenberg, J.P., Molofsky, W., Brown, J.A., Heary, R.F., Marks, D., Zampella, E., & Hodosh, R. (1998). Psychopharmacologic treatment of acquired attention disorders in children with brain injury. Pediatric Neurosurgery, 29(3), 121126.
Massagli, T.L., Fann, J.R., Burington, B.E., Jaffe, K.M., Katon, W.J., & Thompson, R.S. (2004). Psychiatric illness after mild traumatic brain injury in children. Archives of Physical Medicine and Rehabilitation, 85(9), 14281434.
Max, J.E., Lansing, A.E., Koele, S.L., Castillo, C.S., Bokura, H., Schachar, R., Collings, N., & Williams, K.E. (2004). Attention deficit hyperactivity disorder in children and adolescents following traumatic brain injury. Developmental Neuropsychology, 25(1–2), 159177.
Max, J.E., Schachar, R.J., Levin, H.S., Ewing-Cobbs, L., Chapman, S.B., Dennis, M., Saunders, A., & Landis, J. (2005). Predictors of secondary attention-deficit/hyperactivity disorder in children and adolescents 6 to 24 months after traumatic brain injury. Journal of the American Academy of Child & Adolescent Psychiatry, 44(10), 10411049.
McCauley, S.R., Wilde, E.A., Anderson, V.A., Bedell, G., Beers, S.R., Campbell, T.F., Chapman, S.B., Ewing-Cobbs, L., Gerring, J.P., Gioia, G.A., Levin, H.S., Michaud, L.J., Prasad, M.R., Swaine, B.R., Turkstra, L.S., Wade, S.L., Yeates, K.O., & Pediatric TBI Outcomes Workgroup. (2012). Recommendations for the use of common outcome measures in pediatric traumatic brain injury research. Journal of Neurotrauma, 29(4), 678705. doi: 10.1089/neu.2011.1838
Mulhern, R.K., Merchant, T.E., Gajjar, A., Reddick, W.E., & Kun, L.E. (2004). Late neurocognitive sequelae in survivors of brain tumours in childhood. The Lancet Oncology, 5(7), 399408.
Muscara, F., Catroppa, C., & Anderson, V. (2008). The impact of injury severity on executive function 7-10 years following pediatric traumatic brain injury. Developmental Neuropsychology, 33(5), 623636. doi: 10.1080/87565640802171162
Ornstein, T.J., Sagar, S., Schachar, R.J., Ewing-Cobbs, L., Chapman, S.B., Dennis, M., Saunders, A.E., Yang, T.T., Levin, H.S., & Max, J.E. (2014). Neuropsychological performance of youth with secondary attention-deficit/hyperactivity disorder 6-and 12-months after traumatic brain injury. Journal of the International Neuropsychological Society, 20(10), 971981.
Pangilinan, P.H., Giacoletti-Argento, A., Shellhaas, R., Hurvitz, E.A., & Hornyak, J.E. (2010). Neuropharmacology in pediatric brain injury: a review. PM R, 2(12), 11271140. doi: 10.1016/j.pmrj.2010.07.007
Parisi, P., Moavero, R., Verrotti, A., & Curatolo, P. (2010). Attention deficit hyperactivity disorder in children with epilepsy. Brain and Development, 32(1), 1016.
Shaw, M., Hodgkins, P., Caci, H., Young, S., Kahle, J., Woods, A.G., & Arnold, L.E. (2012). A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment. BMC Medicine, 10(1), 99.
Sinopoli, K.J., & Dennis, M. (2012). Inhibitory control after traumatic brain injury in children. International Journal of Developmental Neuroscience, 30(3), 207215.
Sinopoli, K.J., Schachar, R., & Dennis, M. (2011). Traumatic brain injury and secondary attention-deficit/hyperactivity disorder in children and adolescents: the effect of reward on inhibitory control. Journal of Clinical and Experimental Neuropsychology, 33(7), 805819.
Slomine, B.S., Salorio, C.F., Grados, M.A., Vasa, R.A., Christensen, J.R., & Gerring, J.P. (2005). Differences in attention, executive functioning, and memory in children with and without ADHD after severe traumatic brain injury. Journal of the International Neuropsychological Society, 11(5), 645653. doi: 10.1017/S1355617705050769
Solanto, M.V. (1998). Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behavioural Brain Research, 94(1), 127152.
Strong, C.A.H., Tiesma, D., & Donders, J. (2011). Criterion validity of the Delis-Kaplan executive function system (D-KEFS) fluency subtests after traumatic brain injury. Journal of the International Neuropsychological Society, 17(2), 230237. doi: 10.1017/S1355617710001451
Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management, Wolraich, M., Brown, L., Brown, R.T., DuPaul, G., Earls, M., Feldman, H.M., Ganiats, T.G., Kaplanek, B., Meyer, B., Perrin, J., Pierce, K., Reiff, M., Stein, M.T., & Visser, S. (2011). ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics, 128(5), 10071022.
Swanson, J., Baler, R.D., & Volkow, N.D. (2011). Understanding the effects of stimulant medications on cognition in individuals with attention-deficit hyperactivity disorder: a decade of progress. Neuropsychopharmacology, 36(1), 207.
Taylor, C.A., Bell, J.M., Breiding, M.J., & Xu, L. (2017). Traumatic brain injury-related emergency department visits, hospitalizations, and deaths – United States, 2007 and 2013. MMWR Surveillance Summaries, 66(9), 118.
Teasdale, G., & Jennett, B. (1974). Assessment of coma and impaired consciousness. A practical scale. Lancet, 2(7872), 8184. doi: 10.1016/S0140-6736(74)91639-0
Toplak, M.E., Bucciarelli, S.M., Jain, U., & Tannock, R. (2008). Executive functions: performance-based measures and the behavior rating inventory of executive function (BRIEF) in adolescents with attention deficit/hyperactivity disorder (ADHD). Child Neuropsychology, 15(1), 5372.
Volkow, N.D., Fowler, J.S., Wang, G., Ding, Y., & Gatley, S.J. (2002). Mechanism of action of methylphenidate: insights from PET imaging studies. Journal of Attention Disorders, 6(Suppl 1), S31S43.
Wade, S.L., Kurowski, B.G., Kirkwood, M.W., Zhang, N., Cassedy, A., Brown, T.M., Nielsen, B., Stancin, T., & Taylor, H.G. (2015). Online problem-solving therapy after traumatic brain injury: a randomized controlled trial. Pediatrics, 135(2), e48795. doi: 10.1542/peds.2014-1386
Wade, S.L., Taylor, H.G., Cassedy, A., Zhang, N., Kirkwood, M.W., Brown, T.M., & Stancin, T. (2015). Long-term behavioral outcomes after a randomized, clinical trial of counselor-assisted problem solving for adolescents with complicated mild-to-severe traumatic brain injury. Journal of Neurotrauma, 32(13), 967975. doi: 10.1089/neu.2014.3684
Warden, D.L., Gordon, B., McAllister, T.W., Silver, J.M., Barth, J.T., Bruns, J., Drake, A., Gentry, T., Jagoda, A., Katz, D.I., Kraus, J., Labbate, L.A., Ryan, L.M., Sparling, M.B., Walters, B., Whyte, J., Zapata, A., & Zitnay, G. (2006). Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. Journal of Neurotrauma, 23(10), 14681501.
Wasserman, R.M., Stoner, A.M., Stern, A., & Holmbeck, G.N. (2016). ADHD and attention problems in children with and without Spina Bifida. Topics in Spinal Cord Injury Rehabilitation, 22(4), 253259.
Wechsler, D. (2003). WISC-IV administration manual. San Antonio, TX: Pearson Assesment.
Wechsler, D., Coalson, D.L., & Raiford, S.E. (2008). WAIS-IV: Wechsler adult intelligence scale. San Antonio, TX: Pearson.
Willmott, C., & Ponsford, J. (2009). Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial. Journal of Neurology, Neurosurgery, and Psychiatry, 80(5), 552557. doi: 10.1136/jnnp.2008.159632
Wolraich, M., Feurer, I., Hannah, J., & Baumgaertel, A. (2003). Vanderbilt ADHD Teacher Rating Scale (VADTRS) and the Vanderbilt ADHD Parent Rating Scale (VADPRS). Oklahoma City, OK: University of Oklahoma Health Sciences Center.
Yeates, K.O., Armstrong, K., Janusz, J., Taylor, H.G., Wade, S., Stancin, T., & Drotar, D. (2005). Long-term attention problems in children with traumatic brain injury. Journal of the American Academy of Child and Adolescent Psychiatry, 44(6), 574584. doi: 10.1097/01.chi.0000159947.50523.64
Yeates, K.O., Swift, E., Taylor, H.G., Wade, S.L., Drotar, D., Stancin, T., & Minich, N. (2004). Short- and long-term social outcomes following pediatric traumatic brain injury. Journal of the International Neuropsychological Society, 10(3), 412426. doi: 10.1017/S1355617704103093
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of the International Neuropsychological Society
  • ISSN: 1355-6177
  • EISSN: 1469-7661
  • URL: /core/journals/journal-of-the-international-neuropsychological-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed