Effects of stimulant medication, incentives, and event rate on reaction time variability in children with ADHD.
This study examined the effects of methylphenidate (MPH) on reaction time (RT) variability in children with attention deficit hyperactivity disorder (ADHD). Using a broad battery of computerized tasks, and both conventional and ex-Gaussian indicators of RT variability, in addition to within-task manipulations of incentive and event rate (ER), this study comprehensively examined the breadth, specificity, and possible moderators of effects of MPH on RT variability. A total of 93 children with ADHD completed a 4-week within-subject, randomized, double-blind, placebo-controlled crossover trial of MPH to identify an optimal dosage. Children were then randomly assigned to receive either their optimal MPH dose or placebo after which they completed five neuropsychological tasks, each allowing trial-by-trial assessment of RTs. Stimulant effects on RT variability were observed on both measures of the total RT distribution (ie, coefficient of variation) as well as on an ex-Gaussian measure examining the exponential portion of the RT distribution (ie, τ). There was minimal, if any, effect of MPH on performance accuracy or RT speed. Within-task incentive and ER manipulations did not appreciably affect stimulant effects across the tasks. The pattern of significant and pervasive effects of MPH on RT variability, and few effects of MPH on accuracy and RT speed suggest that MPH primarily affects RT variability. Given the magnitude and breadth of effects of MPH on RT variability as well as the apparent specificity of these effects of MPH on RT variability indicators, future research should focus on neurophysiological correlates of effects of MPH on RT variability in an effort to better define MPH pharmacodynamics.
Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. jeff.epstein@cchmc.org
Jeffery N
JN
Epstein
William B
WB
Brinkman
Tanya
T
Froehlich
Joshua M
JM
Langberg
Megan E
ME
Narad
Tanya N
TN
Antonini
Keri
K
Shiels
John O
JO
Simon
Mekibib
M
Altaye
D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002755:Choice Behavior / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use*; D015233:Models, Statistical; D009042:Motivation / Q000187:drug effects*; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000187:drug effects*; D015203:Reproducibility of Results; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D008774:Methylphenidate
Biol Psychiatry. 2005 Jun 1;57(11):1416-23
15950016
Nat Rev Neurosci. 2002 Aug;3(8):617-28
12154363
Nat Neurosci. 2006 Jul;9(7):971-8
16767087
J Abnorm Child Psychol. 1995 Aug;23(4):411-37
7560554
Dev Neuropsychol. 2008;33(2):137-59
18443974
J Int Neuropsychol Soc. 2010 Mar;16(2):388-93
20003583
Neuropsychol Rev. 2010 Mar;20(1):86-102
19757075
J Child Psychol Psychiatry. 2006 May;47(5):446-56
16671928
Dev Neuropsychol. 2005;28(1):459-72
15992251
Biol Psychiatry. 2006 Nov 15;60(10):1088-97
16806097
Neuropsychologia. 1999 Aug;37(9):1005-27
10468365
Child Neuropsychol. 2006 Apr;12(2):125-40
16754533
Neuroimage. 2005 Apr 15;25(3):868-76
15808987
J Clin Exp Neuropsychol. 2005 Apr;27(3):278-98
15969353
Trends Pharmacol Sci. 2005 May;26(5):237-43
15860370
Child Neuropsychol. 2005 Jun;11(3):295-302
16036453
Neuropsychologia. 2007 Mar 2;45(4):630-8
17157885
Neuropsychologia. 2004;42(14):1910-6
15381021
Biol Psychiatry. 2010 Apr 1;67(7):624-31
19914599
J Am Acad Child Adolesc Psychiatry. 2000 Jan;39(1):28-38
10638065
Neuropsychology. 2011 Jul;25(4):427-441
21463041
Neuropsychologia. 2009 Oct;47(12):2389-96
19552927
Psychopharmacology (Berl). 2006 Apr;185(3):315-26
16521033
Brain. 2003 Nov;126(Pt 11):2363-80
12876148
J Am Acad Child Adolesc Psychiatry. 2008 Jul;47(7):808-16
18520957
J Atten Disord. 2009 May;12(6):563-73
19255371
Behav Brain Sci. 2005 Jun;28(3):397-419; discussion 419-68
16209748
J Abnorm Child Psychol. 1996 Oct;24(5):633-50
8956088
Biol Psychiatry. 2005 Jun 1;57(11):1248-55
15949995
J Child Psychol Psychiatry. 2010 Feb;51(2):210-8
19929943
J Am Acad Child Adolesc Psychiatry. 2005 Feb;44(2):169-76
15689730
Acta Psychol (Amst). 2000 May;104(2):167-90
10900704
J Child Psychol Psychiatry. 1992 Feb;33(2):387-98
1564081
Arch Gen Psychiatry. 1999 Dec;56(12):1073-86
10591283
J Child Psychol Psychiatry. 2001 Feb;42(2):199-210
11280416
Neuropsychologia. 2008 Apr;46(5):1532-41
18289615
Br J Psychiatry. 2001 Aug;179:138-43
11483475
J Abnorm Child Psychol. 2009 Aug;37(6):805-16
19291387
J Am Acad Child Adolesc Psychiatry. 2001 Feb;40(2):180-7
11211366
J Child Adolesc Psychopharmacol. 2004 Summer;14(2):219-32
15319019
Dev Neuropsychol. 2002;21(2):117-39
12139195
J Abnorm Child Psychol. 1998 Apr;26(2):141-52
9634136
J Am Acad Child Adolesc Psychiatry. 1992 Mar;31(2):226-34
1564023
Biol Psychol. 2009 Sep;82(1):45-53
19464338
Exp Brain Res. 2006 Jan;168(1-2):218-29
16044297
J Abnorm Child Psychol. 1995 Apr;23(2):235-66
7642836
Neuropsychologia. 2004;42(8):1029-40
15093142
J Abnorm Child Psychol. 1989 Oct;17(5):473-91
2681316
J Am Acad Child Adolesc Psychiatry. 2001 Mar;40(3):355-63
11288778