Abstract
Methylphenidate is the most common treatment for attention deficit hyperactivity disorder (ADHD) and has been shown to improve attention and behaviour. However, the precise nature of methylphenidate on specific aspects of attention at different dose levels remains unclear. We studied methylphenidate effects in ADHD from a neurophysiological perspective, recording event-related potentials (ERPs) during attention task performance in normal controls and children with ADHD under different dose conditions. Twenty children with ADHD and 20 age matched controls were assessed with a continuous performance task requiring subjects to identify repeating alphabetic characters. ERPs and behavioural measures were recorded and analyzed for trials where a correct response was made. The ADHD group was assessed off drug (baseline) and on placebo, low (0.28 mg/kg) and high (0.56 mg/kg) dose levels of methylphenidate. The results showed that the ADHD group at baseline was more impulsive and inattentive than controls and had shorter P2 and N2 latencies and longer P3 latencies. Low dose methylphenidate was associated with reduced impulsivity (fewer false alarms) and decreased P3 latencies, whereas the higher dose level was associated with reduced impulsivity and less inattention (more hits), as well as increased P2 and N2 latencies and decreased P3 latencies. Amplitudes were unaffected and there were no adverse effects of the higher dose for any of the children. These results suggest differential dosage effects and a dissociation between dose levels and aspects of processing.
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References
Barkley RA . (1994): Impaired delayed responding. In Routh DK (ed), Disruptive Behaviour Disorders in Childhood. New York, Plenum Press
Barkley RA . (1997): Behavioural inhibition, sustained attention, and executive functions; Constructing a unifying theory of ADHD. Psychol Bull 121 (1): 65–94
Breton F, Ritter W, Simson R, Vaughan HGJ . (1988): The N2 component elicited by stimulus matches and multiple targets. Biol Psychol 27: 23–44
Colby CL . (1991): The neuroanatomy and neurophysiology of attention. J Child Neurol 6(suppl):S90–S118.
Conners CK . (1973): Rating scales for use in drug studies with children. (Special Issue: Pharmacotherapy with Children.) Psychopharmacol Bull 9: 24–84
de Sonneville LM, Nijiokiktjien C, Bos H . (1994): Methylphenidate and information processing. Part 1: Differentiation between responders and non responders; Part 2: Efficacy in responders. J Clin Exp Neuropsychol 16: 877–897
Douglas VI, Barr RG, Desilets J, Sherman E . (1995): Do high doses of stimulants impair flexible thinking in ADHD? J Am Acad Child Adolesc Psychiatry 34: 877–885
Dyme IZ, Sahakian BJ, Golinko BE, Rabe EF . (1982): Perservation induced by methylphenidate in children: Preliminary findings. Prog Neuropsychopharmacol Biol Psychiatry 6: 259–273
Friedman D, Boltri J, Vaughan H, Erlenmeyer-Kimling L . (1985): Effects of age and sex on the endogenous brain potential components during two continuous performance tasks. Psychophysiology 22: 440
Gittelman R, Mannuzza S . (1985): Diagnosing ADD-H in adolescents. Psychopharmacol Bull 21: 237–242
Halperin JM, Wolfe LE, Pascualvaca DM, Newcorn JH, Healey JM, O'Brien JD, Morganstein A, Young JG . (1988): Differential assessment of attention and impulsivity in children. J Am Acad Child Adolesc Psychiatry 27: 326–329
Herjanic B . (1983): The Washington University Diagnostic Interview for Children and Adolescents. St. Louis, MO, Washington University Medical Center
Karis D, Fabiani M, Donchin E . (1984): P300 and Memory: Individual differences in the von Restorff Effect. Cogn Psychol 16: 177–216
Klee SH, Garfinkel BD . (1983): The computerized continuous performance task: A new measure of inattention. J Abnorm Child Psychol 11: 87–496
Klorman R, Salzman LF, Borgstedt AD . (1988): Brain event-related potentials in evaluation of cognitive deficits in attention deficit disorder and outcome of stimulant therapy. In Bloomingdale LM (ed), Attention Deficit Disorder, Vol 5. Oxford/New York, Pergamon Press
Klorman R, Salzman LF, Pass HL, Borgstedt AD, Dainer KB . (1983): Effects of two doses of methylphenidate on cross-situational and borderline hyperactive children's evoked potentials. Electroencephalogr Clin Neurophysiol 56: 169–185
Luck SJ, Hillyard SA . (1994): Electrophysiological evidence for parallel and serial processing during visual search. Percept Psychophys 48: 603–617
Malone MA, Kershner JR, Siegel L . (1988): The effects of methylphenidate on levels of processing and laterality in children with attention deficit disorder. J Abnorm Child Psychol 16: 379–395
Malone MA, Kershner JR, Swanson JM . (1994): Hemispheric processing and methylphenidate effects in attention deficit hyperactivity disorder. J Child Neurol 9: 181–189
Mangun GR, Hillyard SA, Luck SJ . (1993): Electrocortical substrates of visual selective attention. In Meyer D, Kornblum S (eds), Attention and Performance XIV. Hillsdale, New Jersey, Erlbaum
McCracken JT . (1991): A two-part model of stimulant action on attention deficit hyperactivity disorder in children. J Neuropsychiatry 3: 201–209
Mefford IN, Potter WZ . (1989): A neuroanatomical and biochemical basis for attention deficit disorder with hyperactivity in children: A defect in tonic adrenaline mediated inhibition of locus ceruleus stimulation. Med Hypotheses 29: 33–42
Mirsky AF, Anthony BJ, Duncan CC, Ahearn MB, Kellam SG . (1991): Analysis of the elements of attention: A neuropsychological approach. Neuropsychol Rev 2: 109–145
Nobre AC, Allison T, McCarthy G . (1994): Word recognition in the human inferior-temporal lobe. Nature 372: 260–263
Novak GP, Solanto M, Abikoff H . (1995): Spatial orienting and focused attention in attention deficit hyperactivity disorder. Psychophysiology 32: 546–559
Pelham WE, Milich R, Murphy D, Murphy HA . (1989): Normative data on the IOWA Conners teaching rating scale. J Clin Child Psychol 18: 259–262
Pennington BF, Ozonoff S . (1996): Executive functions and developmental psychopathology. J Child Psychol Psychiatry 37: 51–87
Picton TW . (1992): The P300 wave of the human event-related potential. J Clin Neurophysiol 9: 456–479
Pliszka SR . (1989): Effects of anxiety on cognition, behaviour, and stimulant response in ADHD. J Am Acad Child Adolesc Psychiatry 28: 882–887
Pliszka SR, McCracken JT, Maas JW . (1996): Catecholamines in attention-deficit hyperactivity disorder: Current perspectives. J Am Acad Child Adolesc Psychiatry 35 (3): 264–272
Posner MI, Cohen A . (1987): Isolating attentional systems: A cognitive-anatomical analysis. Psychobiology 15: 107–121
Schachar R, Tannock R, Logan G . (1993): Inhibitory control, impulsiveness, and attention deficit hyperactivity disorder. Clin Psychol Rev 13: 721–739
Shaywitz BA, Shaywitz SE . (1988): Increased medication use in attention-deficit hyperactivity disorder: Regressive or appropriate. JAMA 260: 2270–2272
Shue KL, Douglas VI . (1992): Attention deficit hyperactivity disorder and the frontal lobe syndrome. Brain Cognit 20 (1): 104–124
Solanto MV, Wender EH . (1989): Does methylphenidate constrict cognitive functioning? J Am Acad Child Adolesc Psychiatry 36: 897–902
Sprague RL, Sleator EK . (1977): Methylphenidate in hyperkinetic children: Differences in dose effects on learning and social behaviour. Science 198: 1274–1276
Stuss DT, Shallice T, Alexander MP, Picton TW . (1995): A multi-disciplinary approach to anterior attentional functions. Ann N Y Acad Sci 769: 191–211
Sunohara GA, Voros JG, Malone MA, Taylor MJ . (1997): Effects of methylphenidate in children with attention deficit hyperactivity disorder: a comparison of event-related potentials between medication responders and non-responders. International J Psychophys 27: 9–14
Swanson JM, Kinsbourne M, Roberts W, Zucker K . (1978): Time-response analysis of the effect of stimulant medication on the learning ability of children referred for hyperactivity. Pediatrics 61: 21–29
Swanson J, Nolan R, Pelham W . (1988): Swanson, Nolan and Pelham rating scale (SNAP). Pittsburgh, PA, Department of Psychiatry, Western Psychiatric Institute and Clinic
Swanson JM, Cantwell D, Lerner M, McBurnett K, Hanna G . (1991): Effects of stimulant medication on learning in children with ADHD. J Learn Disab 24: 219–230
Swanson JM, McBurnett K, Christian DL, Wigal T . (1995): Stimulant medications and the treatment of children with ADHD. In Ollendick TH, Prinz J (eds), Advances in Clinical Child Psychology, Vol 17. New York, Plenum Press
Szatmari P, Offord DR, Boyle MH . (1989): Ontario child health study: Prevalence of attention deficit disorder with hyperactivity. J Child Psychol Psychiatry 30: 219–230
Tannock R, Schachar R . (1992): Methylphenidate and cognitive perseveration in hyperactive children. J Child Psychol Psychiatry 33: 1217–1228
Tannock R, Schachar RJ, Carr RP, Logan GD . (1989): Dose-response effects of methylphenidate on academic and overt behaviour in hyperactive children. Pediatrics 84: 648–657
Taylor MJ, Voros JG, Logan WJ, Malone MA . (1993): Changes in event-related potentials with stimulant medication in children with attention deficit hyperactivity disorder. Bio Psychol 36: 139–156
Thurston CM, Sobol MP, Swanson J, Kinsbourne M . (1979): Effects of methylphenidate on selective attention in hyperactive children. J Abnorm Child Psychol 7: 471–481
van der Meere JJ, Sergeant JA . (1987): A divided attention experiment with pervasively hyperactive children. J Abnorm Psychol 15: 279–392
van der Meere JJ, Sergeant JA . (1988): Controlled processing and vigilance in hyperactivity: Time will tell. J Abnorm Child Psychol 15: 279–292
van der Meere J, Wekking E, Sergeant J . (1991): Sustained attention and pervasive hyperactivity. J Child Psychol Psychiatry 21: 275–284
Verbaten MN, Overtoom CC, Koelga HS, Swaab-Barneveld H, van der Gaag RT, Buitelaar J, van Engeland H . (1994): Methylphenidate influences on both early and late ERP waves of ADHD children in a continuous performance test. J Abn Child Psychol 22: 561–578
Voeller KS . (1991): Toward a neurobiologic nosology of attention deficit hyperacticity disorder. J Child Neurol 6(suppl):S2–S8
Wechsler D . (1991): Wechsler Intelligence Scale for Children -Third Edition. Toronto, Harcourt Brace & Company
Wender PH . (1987): The hyperactive child, adolescent, and adult. New York, Oxford University Press
Whalen CK, Henker B . (1991): Social impact of stimulant medication treatment for hyperactive children. J Learn Disab 24: 231–241
Acknowledgements
This study was conducted in partial fulfillment of Glen Sunohara's Ph.D. dissertation. It was supported by a RESTRACOM graduate studentship from the Research Institute at The Hospital for Sick Children. Special appreciation is extended to the staff at the Child Development Centre at The Hospital for Sick Children for facilitating this work.
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Sunohara, G., Malone, M., Rovet, J. et al. Effect of Methylphenidate on Attention in Children with Attention Deficit Hyperactivity Disorder (ADHD): ERP Evidence. Neuropsychopharmacol 21, 218–228 (1999). https://doi.org/10.1016/S0893-133X(99)00023-8
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DOI: https://doi.org/10.1016/S0893-133X(99)00023-8
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