Electrophysiological correlates of response inhibition in children and adolescents with ADHD: Influence of gender, age, and previous treatment history MARIO LIOTTI, a,b STEVEN R. PLISZKA, c RICARDO III PEREZ, d BRIAN LUUS, a DAVID GLAHN, c,d and MARGARET SEMRUD-CLIKEMAN e a Department of Psychology, Simon Fraser University, Burnaby, British Columbia, Canada b Department of Psychiatry, University of Nottingham, Nottingham, UK c Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA d Research Imaging Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA e Department of Psychiatry, Michigan State University, East Lansing, Michigan, USA Abstract Deficits in response inhibition may be at the core of the cognitive syndrome in ADHD. Here, inhibitory control mechanisms were studied in 36 ADHD-combined type and 30 healthy children by exploring the event-related brain activity during the Stop Signal task. The influence of age, gender, and previous treatment history was evaluated. The ADHD group showed reduced N200 wave amplitudes. For successful inhibitions, the N200 reduction was greatest over right inferior frontal scalp, and only the control group showed a success-related enhancement of such right frontal N200. Source analysis identified a source of the N200 group effect in right dorsolateral prefrontal cortex. Finally, a late positive wave to failed inhibitions was selectively reduced only in treatment-naı¨ve ADHD children, suggesting that chronic stimulants may normalize late conscious error recognition. Both effects were independent of gender and age. Descriptors: Event-related potentials, Stop signal task, ADHD, N200, NoGo-P3, LPW, Stimulants Attention Deficit-Hyperactivity Disorder (ADHD) is a common behavioral syndrome, estimated to occur in 3%–7% of school- aged children worldwide (Barkley, 1997). Symptoms include low levels of attention and concentration and high levels of activity, distractibility, impulsivity, and the inability to inhibit actions (American Psychiatric Association, 1994). One of the most in- fluential theoretical models of ADHD posits that deficits in in- hibitory control are the core symptoms in ADHD (Barkley, 1997; Schachar & Logan, 1990). The critical neuroanatomical substrate for inhibitory control would be a circuit connecting the basal ganglia to right prefrontal cortex, with its structural/func- tional integrity being impaired in ADHD (Casey et al., 1997; Castellanos, 1997). Other theoretical models emphasize deficits in cognitive control mechanisms, including both conflict mon- itoring and error processing (Nieuwenhuis, Yeung, van den Wildenberg, & Ridderinkhof, 2003), a dysfunction in the regu- lation of motivation and reward, with a preference for immediate versus delayed rewards (delay aversion, e.g., Sonuga-Barke, 2005) or deficits in state/arousal regulation (cognitive-energetic model, e.g. Sergeant, 2000). In support of the inhibitory control model, impairment has been found in children with ADHD on laboratory tasks that tap into the inhibitory control symptoms of ADHD (impulsiveness and inattention), such as the Continuous Performance Test or CPT and the Stop Signal task or SST (for reviews, see Lijffijt, Kenemans, Verbaten, & van Engeland, 2005; Losier, McGrath, & Klein, 1996; Nichols & Waschbusch, 2004). Both the CPTand the SSTare varieties of ‘‘Go/NoGo’’ tasks, requiring subjects to occasionally inhibit an ongoing action or response. In the C-X version of the CPT, subjects are presented with rapid sequences of letters. Twenty percent of the stimuli are the letter C, which is followed 50% of the time by an X and 50% of the time by another letter (e.g., R, V, T, etc). Subjects are instructed to withhold their response when they see an X following a C (‘‘NoGo stimulus’’) but to respond when any other letter follows the letter C (e.g, C-R, C-V, etc., ‘‘Go stimuli’’; Barkley, 1997). The SST imposes greater demands of inhibitory control, in that subjects have to be prepared to withdraw a response on each trial instead of only on 20% of the trials, and probability of the NoGo stimulus is 25% rather than 50%, creating the need of inhibiting a more prepotent response (Logan, Cowan, & Davis, 1984; Schachar & Logan, 1990). In a visual version of the SST (e.g., Pliszka, Borcherding, Spratley, & Irick, 1997; Pliszka, Liotti, & Woldorff, 2000), subjects are presented with either the letter A or The authors thank Kristen Vega, Crystal Mendoza, Kellie Higgins, M.A., and Charlotte Kay, LMSW-ACP, for their assistance on this project. This study was funded by the National Institute of Mental Health grant R01 MH63986 to S.R.P. Address reprint requests to: Mario Liotti, Department of Psychology, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. E-mail: mliotti@sfu.ca Psychophysiology, 44 (2007), 936–948. Blackwell Publishing Inc. Printed in the USA. Copyright r 2007 Society for Psychophysiological Research DOI: 10.1111/j.1469-8986.2007.00568.x 936