|

 

Medpsych.biz

Journal of Learning Disabilities Executive Impairment Determines ADHD Medication Response: Implications for Academic Achievement
James B. Hale, Linda A. Reddy, Margaret Semrud-Clikeman, Lisa A. Hain, James Whitaker, Jessica Morley, Kyle Lawrence, Alex Smith and Nicole Jones J Learn Disabil The online version of this article can be found at: can be found at:
Journal of Learning Disabilities
Additional services and information for
1Hale et al.Journal of Learning Disabilities Hammill Institute on Disabilities 2011 Reprints and permission: Journal of Learning Disabilities44(2) 196 –212 Executive Impairment Determines
Hammill Institute on Disabilities 2011Reprints and permission:sagepub.com/journalsPermissions.nav ADHD Medication Response:
Implications for Academic Achievement
James B. Hale1, Linda A. Reddy2, Margaret Semrud-Clikeman3,
Lisa A. Hain4, James Whitaker5, Jessica Morley4,
Kyle Lawrence4, Alex Smith4, and Nicole Jones4
Abstract
Methylphenidate (MPH) often ameliorates attention-deficit/hyperactivity disorder (ADHD) behavioral dysfunction according
to indirect informant reports and rating scales. The standard of care behavioral MPH titration approach seldom includes
direct neuropsychological or academic assessment data to determine treatment efficacy. Documenting "cool" executive-
working memory (EWM) and "hot" self-regulation (SR) neuropsychological impairments could aid in differential diagnosis
of ADHD subtypes and determining cognitive and academic MPH response. In this study, children aged 6 to 16 with ADHD
inattentive type (IT; n = 19) and combined type (n = 33)/hyperactive-impulsive type (n = 4) (CT) participated in double-blind
placebo-controlled MPH trials with baseline and randomized placebo, low MPH dose, and high MPH dose conditions. EWM/
SR measures and behavior ratings/classroom observations were rank ordered separately across conditions, with nonpara-
metric randomization tests conducted to determine individual MPH response. Participants were subsequently grouped
according to their level of cool EWM and hot SR circuit dysfunction. Robust cognitive and behavioral MPH response was
achieved for children with significant baseline EWM/SR impairment, yet response was poor for those with adequate EWM/
SR baseline performance. Even for strong MPH responders, the best dose for neuropsychological functioning was typically
lower than the best dose for behavior. Findings offer one possible explanation for why long-term academic MPH treatment
gains in ADHD have not been realized. Implications for academic achievement and medication titration practices for children
with behaviorally diagnosed ADHD will be discussed.
Keywords
ADHD, executive function, methylphenidate, medication response
Children with attention-deficit/hyperactivity disorder (ADHD) co-occurs with other psychiatric disorders (Spencer, 2006) exhibit complex and severe neuropsychological and cognitive and is often accompanied by poor academic achievement when deficits that profoundly impact behavioral, social, and aca- executive function deficits are present (Biederman et al., 2004). demic functioning both at home and in school (DuPaul & Many children with ADHD are also diagnosed with specific Stoner, 2004; Reddy & De Thomas, 2006; Willcutt, Doyle, learning disabilities (SLD) in reading, writing, and/or math- Nigg, Faraone, & Pennington, 2005). In addition to telltale ematics (e.g., Capano, Minden, Chen, Schachar, & Ickowicz, signs of developmentally inappropriate inattention, impulsiv-ity, and hyperactivity, these children experience poor planning, organization, self-monitoring, problem-solving, and social 1University of Victoria, Canada skills (Hale, Reddy, Wilcox, et al., 2009). Prevalence rates are Rutgers University, NJ, USA 3Michigan State University, Lansing, USA fairly consistent across class, culture, and race (Barkley, 2006), 4Philadelphia College of Osteopathic Medicine, PA, USA with approximately 5% of children affected with ADHD 5Geisinger Medical Center, Danville, PA, USA worldwide (Polanczyk & Rohde, 2007), making it one of the most common neuropsychiatric childhood disorders (Konrad, Gunther, Hanisch, & Herpertz-Dahlmann, 2004).
James B. Hale, PhD, Associate Professor, Department of Psychology, P.O. Box 3050, University of Victoria, Victoria, British Columbia, Considered by many to be a disruptive behavior disorder (American Psychiatric Association, 2000), ADHD frequently Email: [email protected] Hale et al. 2008; Mayes & Calhoun, 2006; Semrud-Clikeman, 2005). children and adolescents, while lower doses may be best It remains unclear whether these learning problems are due for improving executive control of attention (e.g., Konrad to behavioral interference with learning, such as on-task et al., 2004).
behavior (DuPaul & Stoner, 2004), comorbidities separate and distinct from the ADHD (Isles & Humby, 2006), and/or MPH Effects on Cognitive and core ADHD neuropsychological deficits (e.g., sustained atten-tion, planning, working memory) that may lead to inadequate academic achievement (Goldstein & Naglieri, 2008; Hale, The extant treatment literature suggests that MPH is highly Reddy, Wilcox, et al., 2009).
effective in reducing noncompliant and disruptive behaviors in children with ADHD (e.g., Abikoff et al., 2004; Pearson Methylphenidate Treatment in ADHD et al., 2003; Van der Oord, Prins, Oosterlaan, & Emmelkamp, 2008; Waxmonsky et al., 2008), yet comparatively few inves- With the ADHD diagnostic focus on informant reports of tigations have examined the MPH effects on cognition and/ overt behavior problems, it is not surprising that educators or academic functioning. While some propose MPH improves and clinicians frequently use child and parent behavior train- neuropsychological functioning in children with ADHD (e.g., ing for affected children (e.g., Fabiano et al., 2009) and Bedard, Martinussen, Ickowicz, & Tannock, 2004; Hood, behavioral strategies that improve academic performance Baird, Rankin, & Isaacs, 2005; Langleben et al., 2006; Wilson, (e.g., DuPaul & Stoner, 2004). However, the most common Cox, Merkel, Moore, & Coghill, 2006), others assert that and efficacious form of ADHD treatment remains psychotro- MPH does not show beneficial cognitive effects (e.g., Kemner pic medication, with methylphenidate (MPH) being the most et al., 2004; Kobel et al., 2008; Lufi, Parish-Plass, & Gai, researched and prescribed (Barkley, 2006). MPH is a dopa- 1997). Inconsistent findings may be in part due to differential mine agonist that can impact levels of dopamine and a related MPH dose-response effects on cognitive and behavioral func- neurotransmitter norepinephrine availability in the prefrontal tioning, even within the same child (e.g., Hale, Fiorello, & cortex (Berridge et al., 2006). By blocking the dopmaine trans- Brown, 2005; Konrad et al., 2004; Pearson et al., 2004), with porter, MPH inhibits dopamine reuptake into the presynaptic some arguing MPH dosages above optimal levels may exac- membrane and thus increases overall dopamine concentra- erbate cognitive dysfunction in children with ADHD (e.g., tions in the prefrontal and associated subcortical structures Kuhle et al., 2007).
(Julien, 2005).
One of the earliest MPH studies found positive drug effects Dopamine is a critical neurotransmitter for prefrontal- on cognition and behavior but noted deterioration of cognitive subcortical circuit control of attention and executive function functioning at higher doses (Sprague & Sleator, 1976). High (Lichter & Cummings, 2001) circuits that meta-analyses sug- doses of MPH have been shown to produce "zombie effects" gest are hypoactive in ADHD (Dickstein, Bannon, Castellanos, in which children can become quiet, unresponsive, hypoactive, & Milham, 2006). These frontal-subcortical circuits are highly and hyperfocused, with poorer cognitive performance as a interrelated and may be impacted by different medications that result (Swanson, Cantwell, Lerner, McBurnett, & Hanna, 1991; target cortical (e.g., prefrontal) or subcortical (e.g., striatum) Tannock, Shachar, & Logan, 1995). With response curves structures. MPH appears to influence dopamine and norepi- inconsistent across variables and children diagnosed with nephrine availability in both regions, leading to cognitive (e.g., ADHD, Hoeppner and colleagues (1997) argued for careful attention, response inhibition) and behavioral (e.g., on-task examination of cognitive and behavior MPH dose-response behavior) improvement as a result (Engert & Pruessner, 2008). relationships, particularly for children with ADHD-inattentive Positive effects on hippocampal functioning have been reported type or those with comorbid internalizing disorders, who have also, which could account for improved learning and mem- been found to be poor responders to stimulant treatment (e.g., ory in children with ADHD treated with MPH (Dommett, Barkley, DuPaul, & McMurray, 1991; Tannock, Ickowicz, & Henderson, Westwell, & Greenfield, 2008).
Schachar, 1995).
Animal research suggests that the prefrontal cortex and Despite early findings supporting evaluation of cognitive/ associated circuits are highly sensitive to changes in catechol- neuropsychological and behavioral MPH response in ADHD, amine modulation, with variations affecting executive con- it continues to be a behaviorally diagnosed disorder (McKenzie trol of behavior (Arnsten & Li, 2005). Although MPH clearly & Wurr, 2004), with little attention given to the potential MPH enhances executive modulation of cognition and behavior, effects on cognition. In the 1990s, the movement away from evidence is emerging that differences among dopamine recep- examining cognitive/neuropsychological MPH effects was tors (Floresco & Magyar, 2006) could lead to differential spurred, in part, by contradictory early evidence that suggested MPH effects, with low doses improving attention control and no untoward cognitive effects with increasing MPH dosage working memory and higher doses impairing these functions (Berman, Douglas, & Barr, 1999; Douglas, Barr, Desilets, (Arnsten, 2006b; Berridge et al., 2006). These findings are & Sherman, 1995; Solanto & Wender, 1989), the absence of consistent with results that suggest higher MPH doses may cognitive MPH effects in the presence of robust behavioral be necessary to reduce behavioral intensity and disruption in MPH response (Lufi et al., 1997), and the limited utility of Journal of Learning Disabilities 44(2) neuropsychological tests of executive functioning in ADHD et al., 2005), but findings have not been consistent (e.g., diagnosis (Brown & LaRosa, 2002). Similar executive deficits Tucha & Lange, 2005; Van der Oord et al., 2008). Volkow, are found among other neuropsychiatric disorders (Sergeant, Fowler, Wang, and Swanson (2004) argued that MPH appears Geurts, & Oosterlaan, 2002), leading to what many have to increase reward-related DA availability in the striatum and called the "discriminant validity problem" in using executive associated structures (e.g., nucleus accumbens), thereby function measures for ADHD differential diagnosis (Ozonoff increasing motivation for academic tasks, suggesting MPH & Jensen, 1999).
may make classroom reinforcers more salient (Northup, Fusilier, Swanson, Roane, & Borrero, 1997). This increased Renewed Interest in Assessing availability for learning likely leads to long-term positive MPH-achievement outcomes as measured by both standard- Neuropsychological Response to MPH ized tests and grades (Powers, Marks, Miller, Newcorn, & Given recent meta-analytic evidence confirming frontal- Halperin, 2008). Direct positive MPH effects have been subcortical hypoactivity using MRI/fMRI (Dickstein et al., reported for writing legibility (Tucha & Lange, 2001), math 2006) and response inhibition-executive impairments (Willcutt computation (Gorman, Klorman, Thatcher, & Borgstedt, et al., 2005) in ADHD, there has been renewed interest in 2006), reading performance (Keulers et al., 2006), and listen- direct assessment of neuropsychological medication response. ing comprehension (McInnes et al., 2007), with recent lon- Considering neuropsychological MPH response may be espe- gitudinal evidence suggesting both math and reading cially important given behavioral titration methods alone do improvement with MPH treatment (Scheffler et al., 2009).
not appear to lead to long-term treatment gains (e.g., Jensen Several MPH outcome studies on academic functioning et al., 2007). A recent review found approximately 66% of have also reported that medication produced no effect on math studies showed positive cognitive-MPH effects, with improve- computation accuracy and completion (Benedetto-Nash & ment in attention, visual tracking, planning, cognitive flexibil- Tannock, 1999) and led to poorer handwriting fluency (Tucha ity, vigilance, inhibition, and memory/working memory noted & Lange, 2005). Frankenberger and Cannon (1999) reported (Pietrzak, Mollica, Maruff, & Snyder, 2006). Positive MPH no change in achievement scores for MPH-treated children effects on sustained attention, visual-spatial working memory, with ADHD followed longitudinally. Although behavioral interference control, and response inhibition have also been gains are common, meta-analyses suggest that both MPH reported (e.g., Bedard et al., 2004; Hood et al., 2005; Langleben and psychosocial treatments, even when combined, do not et al., 2006; McInnes, Bedard, Hogg-Johnson, & Tannock, lead to better academic achievement in children with ADHD 2007; Tamm & Carlson, 2007; Wilson et al., 2006), with reduc- (Van der Oord et al., 2008). The nonspecific MPH effects tions in impulsivity cited as the possible source of positive found in many studies led some early researchers to conclude MPH treatment effects (e.g., Huang, Chao, Wu, Chen, & Chen, that only academic task-related behavior improved on medi- 2007). Such a finding would be consistent with Barkley's cation (Balthazor et al., 1991).
(1997) ADHD theory, which argues that response inhibition Inconsistent MPH-achievement findings may be in part due is a core deficit in ADHD. Although MPH-cognitive effects to differences in cognitive and behavioral dose-response rela- are often positive in children with ADHD, such children may tionships. When differential MPH dose-response relationships show slower processing speed as a result, a finding often have been reported, lower doses typically improve academic termed the "speed-accuracy trade-off" (Lajoie et al., 2005).
behavior, with little or no additional benefit found for higher The long-term use of MPH on cognitive functioning has doses. For instance, Chacko et al. (2005) found positive MPH also been studied. Sustained use of MPH has been found to effects on academic and social behavior, but few children showed improve global IQ (Gimpel et al., 2005), executive functioning significant academic improvement with increased dosage. Simi- (Vance, Maruff, & Barnett, 2003), and motor timing deficits, larly, Evans et al. (2001) found improved academic performance but apparently not time perception (Rubia, Noorloos, Smith, (e.g., note-taking, quiz performance, written language, on-task Gunning, & Sergeant, 2003), among ADHD children. A recent behavior, and homework completion) for low MPH dosing, study comparing medicated and nonmedicated children with with high doses improving performance for very few children ADHD found potential benefits in extended MPH treatment and deterioration noted for others. This pattern replicates earlier over time, with normalized or improved attention, working studies that showed academic gains were associated with low memory, interference control, and academic performance in MPH doses, and increasing dosage beyond low to moderate those treated relative to treatment naïve and control children levels produced little additional academic benefit (e.g., Greenhill (Semrud-Clikeman, Pliszka, & Liotti, 2008).
et al., 2001; Pelham & Gnagy, 1999; Smith, Taylor, Brammer, Toone, & Rubia, 1998; Swanson et al., 1995).
MPH Dose-Response Effects on Academic Functioning Purpose of Current Study MPH may improve academic performance in children with The present investigation builds upon previous research docu- ADHD (e.g., Balthazor, Wagner & Pelham, 1991; Chacko menting cognitive and behavioral MPH effects at the single Hale et al. subject (Hale et al., 1998; Reddy & Hale, 2007) and group affecting cognitive or neuropsychological performance; or (Hale, Blaine-Halperin, & Beakley, 2007; Hale et al., 2005; had missing or different instruments for measuring MPH Hale, Mulligan, & Simmerman, 2006; Hoeppner et al., 1997) response (i.e., missing data).
levels of analyses. In this investigation, a double-blind placebo The final sample consisted of 39 males and 17 females controlled study of MPH response in children with ADHD ranging in age from 74 to 200 months (M = 120.84 months, was conducted to examine whether executive-working mem- SD = 30.85). Most participants were in the first through fifth ory (EWM) and self-regulation (SR) neuropsychological grades (n = 43; 77%) and were European American (n = 46; impairments affected cognitive and behavioral MPH response. 82%), with the remainder African American. A majority were There were two predictions. First, it was predicted that level from middle (n = 44) or lower (n = 12) socioeconomic back- and pattern of baseline data obtained from EWM/SR neuro- grounds living in urban (n = 36), suburban (n = 13), or rural psychological measures would differentiate MPH responders (n = 7) communities. Consistent with epidemiological studies from nonresponders. Second, it was predicted that the best (Barkley, 2006), most children were diagnosed with ADHD- MPH dose for improving EWM/SR neuropsychological func- CT (n = 33), with fewer diagnosed with IT (n = 19) and HIT tioning would be lower than the best MPH dose for home/ (n = 4). Comorbid diagnoses included specific learning dis- classroom behavioral functioning.
ability (n = 13), oppositional defiant disorder/conduct disorder (ODD/CD; n = 11), and anxiety/depression (A/D; n = 6). Fairly equal numbers of children in the ADHD-IT (n = 6) and ADHD-CT (n = 7) groups were diagnosed with comorbid LD. Most of the children diagnosed with ODD/CD were in the CT group (n = 9). Consistent with the ADHD and internalizing The study sample was drawn from a group of 65 elementary disorders literature (e.g., Biederman, Faraone, & Lapey, 1992), and high school children diagnosed with ADHD and referred all children diagnosed with A/D were in the IT group (n = 6). by physicians in the northeastern United States for double- Most participants were receiving regular education or inclu- blind placebo controlled MPH trials. The participants had to sion classroom instruction (n = 44; 79%), with the remainder meet several inclusion and exclusion criteria. First, physicians receiving resource or self-contained special education ser- determined if children met diagnostic criteria for ADHD- vices. Available intelligence test data suggested the group to inattentive type (IT), ADHD-hyperactive-impulsive type (HIT), be relatively high functioning compared to most children with or ADHD-combined type (CT) based on semi-structured ADHD (see Barkley, 2006), with global IQ scores in the aver- diagnostic interview, Diagnostic and Statistical Manual of age range (M = 99.56, SD = 6.84; n = 41). All participants Mental Disorders–Fourth Edition–Text Revision (DSM- were either medication naïve or received an appropriate wash- IV-TR; American Psychiatric Association, 2000) criteria, and out period of 2 days before the medication trial began.
behavior rating scales. Second, DSM-IV-TR diagnosis was confirmed independently by a licensed or certified psycholo- gist using a semi-structured interview of parent, child, and/or teacher, including medical, developmental, social, and academic After physician evaluation and referral to the principle inves- histories; DSM-IV-TR; and objective behavior rating scales. tigator for an MPH medication trial, parents were sent an Comorbid diagnoses were also obtained by licensed and/or information packet addressing the medication, potential side certified psychologists in the schools or clinic following com- effects, and medication trial protocol. Those interested were prehensive evaluation of cognitive, academic, and behavior evaluated by a licensed psychologist who conducted a semi- functioning. Third, participants demonstrated significant structured interview, determined DSM-IV-TR and parent attention, hyperactivity, and/or impulse control problems that behavior rating scale inclusion criteria, and obtained informed interfered with a major life function in both home and school consent. A teacher meeting was then held where the treat- settings. Fourth, participants were rated at least 1.5 SDs above ment protocol and classroom observation schedule were the mean (M = 50, SD = 10; higher scores more problematic) discussed. The TRF (Achenbach, 1991) was used for the on at least one of the following rating subscales: Attention classroom behavior baseline assessment only. Four other Problems of the Achenbach (1991) Child Behavior Checklist forms were used for classroom behavior assessment at base- (CBCL) or Teacher Report Form (TRF), or the DSM-IV-TR line and treatment follow-up: the CTRS-R:L, School Situa- Inattention and/or Hyperactive-Impulsive subscales of the tions Questionnaire-Revised (SSQ-R; DuPaul & Barkley, Conners' Parent Rating Scales–Revised: Long Form (CPRS- 1992), Academic Performance Rating Scale (APRS; DuPaul, R:L) or Conners' Teacher Rating Scales–Revised: Long Rapport, & Perriello, 1991), and the Side Effects Rating Scale Form (CTRS-R:L) (Conners, 1997). Participants from this (SERS; Barkley, 1990).
sample were excluded if they had more than one comorbid After the initial parent and teacher meetings were secondary diagnosis; had a history of mental retardation, completed, each 4-week trial (baseline, placebo, low MPH seizure disorder, brain injury, or other medical condition dose, high MPH dose) began with a 45-minute classroom Journal of Learning Disabilities 44(2) observation and a 1-hour baseline assessment. The partici- interrater reliability of the observational methods. All gradu- pants were not medicated during baseline (B) assessment. ate students met .90 or higher interrater reliability after receiv- All medications and placebos were prepared by the study ing training in the observational procedures.
pharmacist who randomly assigned children to one of six Following protocol completion, each dependent variable trial orders of the placebo (P), low dose (L), and high dose was rank ordered from 1 to 4 across conditions, with a lower (H) conditions (P-L-H, P-H-L, L-P-H, L-H-P, H-L-P, H-P-L). rank representing better performance or behavior (i.e., ratings For the active drug phase, the doses were calculated at of 1 indicating good performance/behavior and ratings of 0.15 mg/kg/dose for the low dose and 0.30 mg/kg/dose for 4 indicating poor performance/behavior). As has been argued the high dose and rounded to the nearest 2.5 mg (range 2.5 mg in Hale et al. (1998, 2005, 2006) and Hoeppner et al. (1997), to 30 mg per dose). The ground MPH tablet was placed in the instruments utilized have different numbers of items (i.e., lactose-filled opaque capsules for the active drug conditions, sample space) and this procedure ensures that each instrument with lactose only for the placebo condition, and was admin- weighs equally when determining outcome. This assessment istered twice per day. The research assistants, teacher, parents, approach has been found to accurately determine neuropsy- and participants were blind as to the order of conditions. To chological and behavioral medication response (Hale et al., ensure quality control and patient safety, the physician, phar- 1998, 2005, 2006; Hoeppner et al., 1997). For each partici- macist, and principal investigator (PI) were not blind, but pant, mean rank scores were computed separately for the cog- they were not involved in direct data collection.
nitive and behavior ranks and displayed graphically to help Several neuropsychological instruments were used to evaluate individual medication response. Following rank- assess attention, working memory, executive function, inhibi- ordering procedures, the ordinal data was subjected to a non- tion, and self-regulation through auditory, visual, verbal, and parametric randomization test for ranks (NPStat; May, Masson, motor domains. The tests were administered in the same order Hunter, & Wells, 1990), which approximates repeated measures on the last day of each condition by graduate students trained multivariate analysis of variance (MANOVA) in the absence and supervised by the first author. The instruments that were of normal data, to determine individual MPH dose-response administered in the following order include: the Hale-Denckla patterns. After the results were analyzed, the order of condi- Cancellation Task (HDCT; Hale, Reddy, Decker, et al., 2009), tions was revealed.
alternate forms of the Wisconsin Selective Reminding Test (WSRT; Newby, 1999), an audiotaped version of the Go-No Go Test (Go-No Go; Trommer, Hoeppner, & Zecker, 1991), the Conners Continuous Performance Test–II (CPT-II; Conners In a previous study (Hale et al., 2005), structural equation & MHS Staff, 2000), Stroop Color Word Test (Stroop; Golden, modeling (SEM) was used to develop a model of the Executive/ 1978), alternate forms of the Trail Making Test–Part B (TMT-B; Working Memory and Self-Regulation factors, hypothesized Reitan & Wolfson, 1985), constructed by Hale (1997), and to reflect dorsolateral-dorsal cingulate and orbital-ventral Test of Memory and Learning Digits Backward subtest (DB; cingulate frontal-subcortical circuits based on baseline, non- Reynolds & Bigler, 1994). Baseline assessment also included medicated, neuropsychological test performance of children the Wisconsin Card Sorting Test (WCST; Heaton, Chelune, with ADHD. The nonsignificant χ2, Bentler-Bonett Non- Talley, Kay, & Curtiss, 1993) and Controlled Oral Word normed Fit Index, LISREL Goodness of Fit Index, and root Association Test (COWAT; Spreen & Benton, 1977). The utility mean square residual values indicated the model adequately of these reliable and valid instruments when diagnosing ADHD represented the obtained data (see Figure 1; Hale et al., 2005).
and determining treatments effects is well documented in the Hale et al. (2005) hypothesized that the EWM factor would literature (Hale & Fiorello, 2004; Pennington & Ozonoff, be correlated with DSM-IV-TR inattentive symptoms and the 1996; Sergeant et al., 2002; Willcutt et al., 2005), and previous SR factor would correlate with DSM-IV-TR hyperactive/ studies have shown no significant practice effects during medi- impulsive symptoms, but this was not the case. Instead, both cation trials (Hale et al., 2005, 2006; Hoeppner et al., 1997).
the EWM (r = .502, p = .001) and SR (r = .327, p = .034) factors The assessments took place approximately 1 to 2 hours correlated only with hyperactive/impulsive symptoms across after medication was administered. Classroom observations subtypes, consistent with the notion that response inhibition is took place on the same day as neuropsychological testing, the primary deficit associated with ADHD executive impair- approximately 1 to 2 hours after the administration of the ments (Barkley, 1997). As a result, regression-based saved fac- other daily dose of medication. An adaptation of the Restricted tor scores derived from baseline performance were added to Academic Task (RAT; Barkley, 1990) was used to determine produce a combined EWM/SR impairment score, with resultant off-task, fidgeting, vocalizing, playing with objects, and out z scores used to calculate no apparent (N/A; +1.01 or higher), of seat behaviors. The observational procedure included a low (0.01 to +1.00), moderate (0.00 to −1.00), and significant 20-second momentary time sampling technique during class- impairment (−1.01 or lower) executive impairment groups.
room instructional activities. Prior to data collection, the first The medication trial data were subjected to a MANOVA author used videotaped classroom recordings to measure to determine treatment effects, with cognitive ranks and

Hale et al. ADHD-HIT child diagnosed with comorbid ODD/CD in this group. Most of these children were boys (n = 8) and tended to be older than other groups (M = 151.11 months, SD = 39.93), with six of nine children in Grades 7 through 11. An examina-tion of the DSM-IV-TR inattentive (M = 6.60, SD = 1.94) and hyperactive-impulsive (M = 3.20, SD = 2.58) symptoms col-lected during the psychological evaluation revealed this group to have few endorsed ADHD symptoms. Their mean EWM/SR executive impairment determined by saved factor z scores was +2.33 (SD = .45).
For the low impairment group, the 8 females and 13 males were fairly equally represented in the ADHD-CT (n = 10) and ADHD-IT (n = 9) diagnostic groups, but both children with ADHD-HIT were males. More than half of these chil-dren had comorbid diagnoses, including SLD (n = 4), ODD/CD (n = 5), and anxious/depressed (n = 3). Unlike the N/A group, these children tended to be in Grades 1 through 6 (n = 19), with a mean age of 123.19 months (SD = 24.47). The DSM-IV-TR inattentive (M = 7.22, SD = 1.69) and hyperactive-impulsive (M = 5.38, SD = 2.56) symptoms were more consistent, but many in this group failed to meet criteria for CT. EWM/SR executive impairment was +.84 Figure 1. Frontal-subcortical circuit Confirmatory Factor
(SD = .57).
Analysis (CFA).
For the moderate impairment group, 14 of the 16 children Source: Adopted from Hale, Fiorello, and Brown (2005). were classified with ADHD-CT with one ADHD-IT and Note: WCST = Wisconsin Card Sorting Test; CPT-I = Conners Continuous one ADHD-HIT, and most were males (n = 12). Comorbid Performance Test-II; HDCT = Hale-Denckla Cancel ation Task; WSRT = Wisconsin Selective Reminding Test; TOMAL =Test of Memory and Learn- diagnoses included SLD (n = 5) and ODD/CD (n = 3), but ing; COWAT = Controlled Oral Word Association Test.
none of the children were diagnosed with anxiety/depression. All children were in Grades 1 through 5, with a mean age of 110.63 months (SD = 16.40). The DSM-IV-TR inattentive behavior ranks serving as dependent variables in two separate (M = 7.28, SD = 1.48) rather than hyperactive-impulsive equations and impairment group as the independent variables. (M = 7.50, SD = 1.69) symptoms were comparable for this As a result, there were effects calculated for the one within- group. All 16 children were again in Grades 1 through 5, with subject variable for drug conditions (B, P, L, H) and one for a mean age of 110.63 months (SD = 16.40). The EWM/SR the between-subject variable for impairment group and the executive impairment factor z score was -.80, with an associ- interaction of the two. The homogeneity of variance assump- ated SD of .55.
tion was tested using Box's M test for the equality of homo- For the significant impairment group (n = 10), eight of geneity of the covariance matrices, and Mauchly Sphericity the six males and four females were classified as having tests were used to examine the null hypothesis that the error ADHD-CT, with the rest ADHD-IT. Two children in this group covariance matrices of the orthonormalized transformed had comorbid SLD, two had comorbid ODD/CD, and surpris- variables met sphericity assumptions. Levine's test was used ingly one had anxious/depressed comoribidity. In Grades 1 to assess for equality of error variances. Planned contrasts through 4, these children were the youngest of the four impair- were used to determine treatment effects, and orthogonal ment groups (M = 95.50, SD = 16.63). The high executive polynomial contrasts were used to examine linear, quadratic, impairment group had high levels of inattentive (M = 7.75, or cubic trends as previous research has suggested that there SD = 1.38) symptoms, but fewer hyperactive-impulsive is sample heterogeneity in medication response with neuro- symptoms (M = 6.87, SD = 1.46). Their EWM/SR executive psychological response patterns related to treatment efficacy impairment, determined by saved EWM-SR factor z scores, (Hale et al., 1998, 2005; Hoeppner et al., 1997).
was -2.79 (SD = .72).
Cognitive and Behavioral A cross-tabulation of impairment group by diagnosis revealed MPH Response for Impairment Groups that seven of nine children with N/A executive impairment A repeated measures MANOVA was computed with drug con- were diagnosed ADHD-IT, and comorbid diagnoses included dition (B, P, L, H) as the within-subjects factor and impairment SLD (n = 2) and anxious/depressed (n = 2). There was one (N/A, low, moderate, high) serving as the between-subjects Journal of Learning Disabilities 44(2) Table 1. MPH Dose-Response Relationships for EWM/SR Impairment Groups
Note: Lower ranks indicates better performance and behavior; MPH = methylphenidate; EWM/SR = executive-working memory/self-regulation; N/A = no apparent EWM/SR executive impairment.
aLess than baseline with Bonferroni correction.
bLess than placebo with Bonferroni correction.
factor for the cognitive ranks. Although the Mauchly's test of p = .04, with partial η2 = .11, and fairly adequate power = .82. sphericity assumption for drug was met, χ2(5) = 7.52, p = .18, Tests of within-subjects contrasts demonstrated a linear effect as was Levene's test for the equality of error variances for drug, F(1, 49) = 212.00, p < .001, η2= .81, and a quadratic (p range .296 to .884), a multivariate approach to the data could effect as well, F(1, 49) = 13.16, p < .001, η2= .21. Tests of not be completed due to violation of the equality of covariance between-subjects effects for impairment group was not sig- matrices as determined by Box's M test, F(30, 2,905.05) = 2.36, nificant, with an associated F(3, 49) of 2.38 (p = .08), suggest- p < .001. Huynh-Feldt univariate tests of within-subjects effects ing no uniform level of behavior impairment regardless of showed a highly significant effect for drug, F(3, 147) = 44.83, MPH conditions.
p < .001, η2= .47, power = 1.00. The interaction of drug and impairment was also significant, F(9, 147) = 3.11, p = .002, MPH Dose Response η2= .16, power = .97. Tests of within-subjects contrasts demon-strated a linear, F(1, 49) = 94.30, p < .001, η2= .65, and a cubic Differences for Impairment Groups effect, F(1, 49) = 16.09, p < .001, η2= .24, for drug condition, With MANOVA results suggesting that cognitive and behav- suggesting response curves were not uniform. The drug by ioral dose-response curves were different based on level of impairment interaction also demonstrated linear, F(3, 49) = 3.67, EWM/SR impairment, repeated measures MANOVAs were p = .01, η2= .18, and cubic, F(3, 49) = 3.14, p = .03, η2= .16, then computed for each of the four impairment groups, with effects, indicating different response curves for different levels planned Bonferroni contrasts of drug conditions for cognitive of impairment. However, there was no main effect for impair- and behavioral ranks reported in Table 1 and graphically dis- ment group, F(3, 49) = .41, p = .74, η2= .025, suggesting no played in Figure 2 to facilitate interpretation. Mauchly's test defining overall drug trial performance pattern between groups for sphericity was nonsignificant for all analyses, so a multi- across conditions.
variate approach to the data was utilized.
To determine if this finding was also relevant for behavioral For the N/A group cognitive ranks, the repeated measures MPH response, a repeated measures MANOVA was computed MANOVA was nonsignificant for drug, F(3, 5) = 1.82, p = .26. with drug condition (B, P, L, H) as the within-subjects factor Power was low (.24) and partial η2 was .51. Orthogonal poly- and impairment (N/A, low, moderate, high) serving as the nomial tests of within-subjects contrasts revealed a linear effect between-subjects factor for the behavioral rank data. There for drug, F(1, 7) = 7.30, p = .03, η2= .51. For behavioral ranks, were no violations of MANOVA assumptions, with Box's the MANOVA was significant for drug, F(3, 5) = 8.32, p = .02, M test, F(30, 2,905.05) = .794, p = .779, Mauchly's test of sphe- η2= .83, power = .80. Orthogonal polynomial within-subjects ricity, χ2(5) = 8.94, p = .112, and Levene's test for the equality contrasts revealed a linear effect for drug, F(1, 7) = 17.06, of error variances (p range .122 to .594) all nonsignificant. p = .004, η2= .70, with quadratic effects approaching signifi- Using the multivariate approach, Hotelling's trace was highly cance, F(1, 7) = 5.45, p = .05. However, Bonferroni adjusted significant for drug, F(3, 47) = 75.64, p < .001, partial η2 = .82, pairwise comparisons revealed that while all blind conditions power = 1.00, across the levels of impairment. The drug by were lower than baseline behavior (indicating better behavior), impairment interaction was also significant, F(9, 137) = 1.96, none of the blind conditions (including placebo) were different

Hale et al. Figure 2. Medication response based on level of frontal-subcortical circuit dysfunction
Note: Lower ranks = better performance and behavior. B = baseline; P = placebo; L = low dose methylphenidate; H = high dose methylphenidate.
from each other. This suggests a placebo effect for behavior For the low impairment group cognitive ranks, the repeated ranks, but no significant MPH treatment effect. As a group, measures MANOVA was significant for drug, F(3, 17) = 7.55, these physician and psychologist behaviorally diagnosed p = .002, η2= .57, power = .95, indicating a difference among children with ADHD did not show EWM/SR impairment cognitive/neuropsychological functioning across drug condi- and did not appear to benefit from MPH treatment as a result.
tions. Orthogonal polynomial tests of within-subjects contrasts Journal of Learning Disabilities 44(2) revealed a linear effect for drug, F(1, 19) = 24.02, p < .001, p < .001, η2= .96, effects found for dosage, and cubic, η2= .55. Bonferroni contrasts revealed cognitive ranks were F(1, 9) = 5.99, p = .03, η2= .40, effects found as well. As was lower (i.e., better performance) during the active drug condi- the case with cognitive response, Bonferroni contrasts tions as compared to baseline, but the high dose condition revealed that the baseline and placebo conditions were dif- was also better than the placebo condition, indicating those ferent from the active drug conditions, but these were not with low impairment did respond to the higher MPH dose. different from each other.
For behavioral ranks, the MANOVA was significant for drug, F(3, 17) = 19.34, p < .001, η2= .77, power = 1.00. Orthogonal Analysis of Single Subject MPH Dose- polynomial contrasts revealed a linear effect for drug, F(1, 19) = 55.04, p < .001, η2= .74, with quadratic effects approach- ing significance, F(1, 19) = 3.95, p = .06. Bonferroni com- With findings demonstrating differential treatment effects parisons revealed that all blinded conditions were lower (better based on level of EWM/SR impairment, an examination of behavior) than baseline, and the high dose condition was lower individual case dose-response relationships based on NPStat than the placebo condition, suggesting that for this group, nonparametric randomization test results was undertaken. MPH improved cognition and behavior at the high dose only. These single subject results were provided to parents and However, placebo effects were also noted for this group.
referring physicians in each child's medication trial report. For the moderate impairment group cognitive ranks, the Although NPStat statistical response does not necessarily repeated measures MANOVA was again significant for drug, reflect clinical response, which was determined by referring F(3, 12) = 16.70, p < .001, η2= .807, power = 1.00, indicating physicians, results suggest that most of those with N/A or low a difference among cognitive/neuropsychological functioning executive impairment tended to be in the ADHD-IT group, across drug conditions. Orthogonal polynomial contrasts and often did not show a significant MPH response. However, revealed linear, F(1, 14) = 33.67, p < .001, η2= .70, quadratic, those with moderate or significant impairment tended to fall F(1, 14) = 4.72, p = .048, η2= .25, and cubic, F(1, 14) = 11.57, into the ADHD-CT group. These individuals were more likely p =.004, η2= .45, effects for drug. This finding suggests cogni- to show a significant cognitive and behavioral medication tive response was not uniform across participants within this response, with no nonresponders found in these impairment group. Unlike the other impairment groups, Bonferroni com- groups, regardless of behavioral ADHD diagnosis.
parisons revealed both active drug conditions to be different from both baseline and placebo, but they were not different from one another. Similarly, there was no difference between baseline and placebo conditions. For the behavior rank In this study, children with behaviorally diagnosed ADHD repeated measures MANOVA, there was again a significant underwent double-blind placebo controlled MPH trials with within-subjects effect, F(3, 12) = 33.52, p < .001, η2= .89, baseline cognitive/neuropsychological direct assessments of power = 1.00, with linear, F(1, 14) = 78.79, p < .001, η2= .84, the child, indirect behavior ratings obtained from parents and and quadratic, F(1, 14) = 6.61, p = .022, η2= .32, effects found teachers, and classroom observations used to calculate cogni- for dosage. This time Bonferroni comparisons revealed all tive and behavioral ranks. These data were subsequently sub- blind conditions to be lower than baseline, and the high dose mitted to NPStat nonparametric randomization tests to to be lower than placebo, but the low dose only approached determine statistical response. Results revealed highly signifi- significance with placebo.
cant MPH treatment effects, but response differences emerged For the significant impairment group, those with significant for children based on the SEM-determined level of EWM/SR baseline EWM/SR deficits, the effect for drug on cognitive executive impairment. For those with N/A baseline EWM/ ranks was highly significant, F(3, 7) = 48.01, p < .001, η2= .954, SR executive impairment, MPH response was poor. For those power = 1.00, even with the small sample size. An examination with significant impairment, every single child showed a sig- of orthogonal polynomials revealed linear, F(1, 9) = 57.69, nificant MPH response. In addition, differential cognitive and p < .001, η2= .86, and cubic, F(1, 9) = 19.45, p = .002, η2= .68, behavioral patterns of MPH response emerged for those with effects, indicating nonuniform response patterns. Bonferroni moderate and significant EWM/SR impairment, with the best contrasts revealed that the baseline and placebo conditions dose for cognition lower than the best dose for behavior.
were different from the active drug conditions, but these were not different from each other. However, it is interesting to MPH Effects on "Hot" Versus "Cool" note that the cognitive rank was qualitatively lower for the low dose than the high dose, where cognition appeared to deteriorate. For the behavior rank repeated measures MANOVA, there Although the exact neurophysiological explanation for these was again a significant drug effect, F(3, 7) = 62.85, p < .001, MPH findings is beyond the scope of this article, some specu- η2= .964, power = 1.00, with strong linear, F(1, 9) = 226.66, lation appears to be warranted given similar findings reported Hale et al. elsewhere (e.g., Arnsten, 2006a; Berridge et al., 2006; Konrad ADHD Subtypes: et al., 2004). Solanto et al. (2001) suggest that the tasks evalu- Are They Distinct Disorders? ating response inhibition or reward or punishment may reflect different types of executive functioning, which explains the This MPH response pattern in this investigation is not surpris- differential findings for EF tasks on and off of medication ing given the preponderance of evidence that response inhibi- found here. Zelazo and Muller (2002) suggest that cognitive tion is the primary deficit in ADHD (Houghton et al., 1999; aspects of EF may be associated with the dorsolateral pre- Willcutt et al., 2005; Wodka et al., 2007), which secondarily frontal cortex and are characterized as "cool" EF. In contrast, affects attention and other more traditional executive functions EF tasks that pull for affect (reward/punishment) are referred (e.g., Barkley, 1997). This assumption is partially supported to as "hot" EF and may be associated with the orbital and by findings in this investigation, where both the EWM and SR medial prefrontal cortices. Castellanos, Sonuga-Barke, Mil- factors reported in Hale et al. (2005) were found to be related ham, and Tannock (2006) suggest that cool EF is associated to DSM-IV-TR hyperactive-impulsive symptoms, but not inat- with more cognitively loaded types of tasks such as IQ, tentive ones, suggesting that ADHD-IT and ADHD-CT may response inhibition, and working memory while hot EF is be distinct disorders (Milich, Balentine, & Lynam, 2001). associated more with risk-taking and externalizing behaviors, Certainly, inattention, or at least intention control (Denckla, but not inattention. Conceptualizing EF as having both cogni- 1996; Hale, Reddy, Decker, et al., 2009), is another primary tive and affective aspects may help explain the differing find- deficit in ADHD. Several studies have suggested that there are ings in children with ADHD, particularly in regard to few differences among ADHD subtypes (e.g., Geurts, Verte, stimulant medication and, as we have demonstrated, with Oosterlaan, Roeyers, & Sergeant, 2005; Nigg, Blaskey, Huang- level of MPH. The phylogenetically older hot ventral circuits Pollock, & Rappley, 2002), with inattentive symptoms associ- are important for behavioral self-regulation or affective deci- ated with executive dysfunction, not hyperactive impulsive sion making, while the younger cool dorsal circuits are involved ones (Chhabildas, Pennington, & Willcutt, 2001), and results in deliberative executive processing and attention control vary based on the study design and methodology. Perhaps (Castellanos, Sonuga-Barke, Milham, & Tannock, 2006; inconsistent findings might be in part due the behavioral defi- Figner, Maklinlay, Wilkening, & Weber, 2009; Roiser et nition of the ADHD populations used in these studies, where al., 2009; Steinberg, 2008).
some children have "primary" ADHD-IT, while others have A differential effect by MPH on the hot (e.g., SR; secondary or "pseudo" ADHD due to other psychiatric and/or orbital-medial-ventral cingulate) and cool (e.g., EWM; learning problems (Hale, Reddy, Wilcox, et al., 2009).
dorsolateral-dorsal cingulate) frontal-striatal-thalamic Results from this study suggest that there are multiple circuits (Castellanos et al., 2006; Kelly, Sonuga-Barke, causes of inattention symptoms in children behaviorally diag- Scheres, & Castellanos, 2007) may explain the difference nosed as ADHD, suggesting informant reports and behav- in improvement in behavior versus cognition. MPH has ioral rating scales are insufficient for differential diagnosis. been demonstrated to increase activation in the areas asso- Although behavior rating scales are important sources of ciated with behavioral and risk-taking behaviors compared information in a multimethod, multisource evaluation, they to those involved with higher level executive functioning remain summative behavioral judgments of children, effec- (Zametkin et al., 1990). Support for this conclusion comes tively intertwining subjective source opinion with objective from an fMRI study that showed less activation in the facts about the child (Demaray, Elting, & Schaefer, 2003; dorsolateral region in children with ADHD, particularly DuPaul, 2006). When multiple causes of attention problems those with no history of medication treatment (Pliszka et al., are subsumed under a heterogeneous ADHD behavioral 2006). Moreover, a comparison of event-related potentials umbrella, the diagnostic sensitivity and specificity of our in children with a history of MPH or no history of MPH tools is reduced, and treatment efficacy is likely attenuated on a task requiring inhibition found less activation to (Hale, Reddy, Decker, et al., 2009).
"failed" trials than to "successful" trials (Liotti, Pliszka, Evidence for this assertion can be seen in the lower cor- Perez, Glahn, & Semrud-Clikeman, 2008). In these cases relation between EWM and SR factors and DSM-IV-TR children with a history of MPH treatment showed improve- inattention symptoms in this study. Also, the four EWM/SR ment in the areas involved in inhibitory skills (behavior) executive impairment groups differed on DSM-IV-TR compared to those without such a history. Thus, children hyperactive-impulsive symptoms but did not differ on DSM- with a history of MPH at generally accepted levels were IV-TR inattention ones, suggesting that only those with "true" found to show improvement in the hot circuit even when ADHD and hot circuit involvement are more likely to respond off medication. Perhaps MPH is more likely to have a strongly to MPH. The cool dorsolateral and dorsal anterior cingulate linear effect on the hot circuit, but a curvilinear one for circuits also cause attention deficits in other disorders, such the cool circuit, where balance of catecholamines becomes as depression (Liotti & Mayberg, 2001), so perhaps the MPH more important.
nonresponder ADHD-IT children in this study have this type Journal of Learning Disabilities 44(2) of impairment or another form of "pseudo" ADHD such as If MPH titration was based on maximizing cognitive func- parietal lobe dysfunction (Hale, Reddy, Wilcox, et al., 2009).
tioning and adjunct behavior therapy was used to help reduce These arguments are consistent with findings that the problematic behaviors not adequately addressed by the lower ADHD-IT is likely to be a heterogenous disorder (e.g., Hale, MPH dose, perhaps then we would see long-term academic Reddy, Decker, et al., 2009; Johansen, Aase, Meyer, & and behavior improvement in children with ADHD.
Sagvolden, 2002) in that only some of these children display The results presented here suggest that practitioners need subthreshold behavioral/self-regulation/response inhibition to reconsider use of standard indirect behavioral approaches problems that are characteristic of children with ADHD-CT to ADHD diagnosis and determining MPH treatment efficacy. (Weiss, Worling, & Wasdell, 2003). A subsequent chart review Instead, it may be useful to incorporate direct measurement of the ADHD-IT group in this study supported this conclu- of cognitive, neuropsychological, academic, and behavioral sion, with children with ADHD-IT and comorbid anxiety/ functioning when conducting comprehensive evaluations to depression often showing low executive impairment and no ensure children referred for attention problems do indeed MPH response, and those with higher impairment had sub- have "true" ADHD (Hale, Reddy, Decker, et al., 2009). Even threshold reported hyperactive-impulsive symptoms and for those with "true" ADHD, many have comorbid behavioral showed good MPH response. It is clear that multiple data and academic concerns, and differential cognitive, academic, sources, including informant reports, neuropsychological and behavioral MPH dose-response relationships appear to assessment of executive functions, and careful clinical evalu- be common, so it may be useful to compare short- and long- ation of child and family histories, is essential practice for term MPH treatment effects on all of these critical functions. determining the various causes of attention problems (Hale, Multimethod, multisource evaluations using both neuropsy- Reddy, Wilcox, et al., 2009; Reddy & Hale, 2007).
chological and behavioral assessment methods minimize the individual limitations of both approaches, and in combination Implications for Academic can construct a better diagnostic picture for clinicians, thereby leading to targeted interventions tailored to individual needs Achievement in ADHD and better treatment efficacy as a result.
When medication is considered for a child with ADHD, some teachers may be most immediately concerned about MPH Limitations and Future Directions effects on improving overt behavior problems. However, the results presented here and reported in the literature (e.g., Several study limitations are worth noting. First, the sample Chacko et al., 2005; Evans et al., 2001; Horrigan & Barnhill, included children aged 6 to 16, with a majority of the children 2000; Pliszka, Liotti, Bailey, Perez, Glahn, & Semrud-Clike- in Grades K through 5. Developmental differences in ADHD man, 2006; Teicher, Polcari, & McGreenery, 2008) suggest neuropsychological and behavioral functioning are well the best MPH dose for cognition may be lower than the best known (Barkley, 1997), so future research should examine MPH dose for behavior. These differential dose-response if these MPH findings are consistent across age ranges. Sec- relationships for children with ADHD could explain why ond, the neuropsychological tests used here were not coun- long-term treatment MPH efficacy remains limited (e.g., terbalanced and analyzed for order effects; however, they Jensen et al., 2007) and that MPH has equivocal effects on were specifically chosen because order effects have not been academic achievement (Balthazor et al., 1991; Frankenberger found in previous studies (e.g., Hale et al., 2005; Hoeppner et al., & Cannon; 1999; Van der Oord et al., 2008) because clinical 1997). Third, research assistants who conducted classroom attention has been focused on MPH behavior control, not observations were proficient at collecting reliable observa- maximizing cognitive functioning. If the optimal dose for tional data before medication trials, but future research could behavior is chosen, children will likely struggle with learning, also examine interrater reliability during MPH trials. Fourth, memory, and achievement because the higher dosage limits all participants were thought to have average intellectual func- executive attention control/working memory functions (e.g., tioning by report, but only some of the children had been admin- Berridge et al., 2006).
istered a standardized intelligence test prior to the medication The cool dorsolateral-dorsal cingulate executive functions trial. Although the baseline and placebo conditions in part guard such as sustained attention, executive planning, flexible prob- against intelligence differences, future research should at least lem solving, fluid reasoning, processing speed, and working include a cognitive screening of all children. Finally, it will be memory are important predictors of academic domains such important to consider teacher, instructional, or classroom man- as math calculation and reasoning, reading comprehension, agement practices in future research to determine if these vari- written expression, higher level implicit language, and read- ables influence or moderate MPH treatment response.
ing, math, and writing fluency (e.g., Biederman et al., 2004; Future research could examine children with MPH titration Bryan & Hale, 2001; Decker, Hill, & Dean, 2007; Denckla, based on direct neuropsychological baseline function com- 1996; Goldstein & Naglieri, 2008; Hale & Fiorello, 2004). pared to those who receive standard indirect behavioral titration Hale et al. approaches to determine if cognitive, academic, and behav- Barkley, R. A. (1990). Attention-deficit hyperactivity disorder: ioral outcomes are differentially affected. In addition, further A handbook for diagnosis and treatment. New York, NY: research examining MPH response in relation to, and in com- bination with, other interventions is needed. While this study Barkley, R. A. (1997). ADHD and the nature of self control. provides additional evidence supporting evaluation of both New York, NY: Guilford.
cognitive and academic MPH response, the exact neurophysi- Barkley, R. A. (2006). Attention-deficit/hyperactivity disorder. In ological nature of differential MPH response curves was not D. A. Wolfe & E. J. Mash (Eds.), Behavioral and emotional directly evaluated. These response curves could also differ disorders in adolescents: Nature, assessment, and treatment for alternative ADHD medications (e.g., Adderall, Strattera) (pp. 91–152). New York, NY: Guilford.
or MPH dosing regimens (e.g., Concerta, Metadate). Addi- Barkley, R. A., DuPaul, G. J., & McMurray, M. B. (1991). Attention tional research is needed to explore MPH response for the deficit disorder with and without hyperactivity: Clinical different hot orbital-ventral cingulate and cool dorsolateral- response to three dose levels of methylphenidate. Pediatrics, dorsal cingulate circuits, how this impacts SR and EWM. This empirical work could help determine whether MPH dose- Bedard, A. C., Martinussen, R., Ickowicz, A., & Tannock, R. response curves differ for the circuits and ultimately lead to (2004). Methylphenidate improves visual-spatial memory in better titration practices that foster academic achievement children with attention-deficit/hyperactivity disorder. Journal and psychosocial functioning for children with ADHD.
of the American Academy of Child and Adolescent Psychiatry, 43, 260–268.
Declaration of Conflicting Interests
Benedetto-Nash, E., & Tannock, R. (1999). Math computation, The author(s) declared no conflicts of interest with respect to the error patterns and stimulant effects in children with attention authorship and/or publication of this article.
deficit hyperactivity disorder. Journal of Attention Disorders, 3, 121–134.
Berman, T., Douglas, V. I., & Barr, R. G. (1999). Effects of methyl- The authors disclosed receipt of the following financial support for phenidate on complex cognitive processing in attention-deficit/ the research and/or authorship of this article: This research was hyperactivity disorder. Journal of Abnormal Psychology, 108, made possible in part by funding from the Neuropsychiatric Research Institute, Fargo, ND, USA.
Berridge, C. W., Devilbiss, D. M., Andrzejewski, M. E., Arnsten, A. F., Kelley, A. E., Schmeichel, . . Spencer, R. C. (2006). Methyl- phenidate preferentially increases catecholamine neurotrans- Abikoff, H., Hechtman, L., Klein, R.G., Weiss, G., Fleiss, K., mission with in prefrontal cortex at low doses that enhance Etcovich, J., . . Pollack, S. (2004). Symptomatic improvement cognitive function. Biological Psychiatry, 60, 1111–1120.
in children with ADHD treated with long-term methylpheni- Biederman, J., Faraone, S. V., & Lapey, K. (1992). Comorbidity date and multimodal psychosocial treatment. Journal of the of diagnosis in attention-deficit hyperactivity disorder. In American Academy of Child and Adolescent Psychiatry, 43, G. Weiss (Ed.), Child and adolescent psychiatry clinics of North America: Attention deficit hyperactivity disorder Achenbach, T. M. (1991). Integrative guide for the 1991 CBCL/4–18, (pp. 335–360). Philadelphia, PA: Saunders.
YSR, and TRF profiles. Burlington, VT: University of Vermont, Biederman, J., Monuteaux, M. C., Doyle, A. E., Seidman, L. J., Department of Psychiatry.
Wilens, T. E., Ferraro, F., . . Faraone, S. V. (2004). Impact of American Psychiatric Association. (2000). Diagnostic and statistical executive function deficits and attention-deficit/hyperactivity manual of mental disorders (4th ed., Text Rev.). Washington, disorder (ADHD) on academic outcomes in children. Journal of Consulting and Clinical Psychology, 72, 757–766.
Arnsten, A. F. (2006a). Fundamentals of attention-deficit/hyperactivity Brown, R. T., & LaRosa, A. (2002). Recent developments in the disorder: Circuits and pathways. Journal of Clinical Psychiatry, pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD). Professional Psychology, Research and Practice, 33, Arnsten, A. F. (2006b). Stimulants: Therapeutic actions in ADHD. Bryan, K. L., & Hale, J. B. (2001). Differential effects of left and right Arnsten, A. F., & Li, B. M. (2005). Neurobiology of executive func- cerebral vascular accidents on language competency. Journal tions: Catecholamine influences on prefrontal cortical functions. of the International Neuropsychological Society, 7, 655–664.
Biological Psychiatry, 57, 1377–1384.
Capano, L., Minden, D., Chen, S. X., Schachar, R. J., & Ickowicz, A. Balthazor, M. J., Wagner, R. K., & Pelham, W. E. (1991). The (2008). Mathematical learning disorder in school-age children specificity of the effects of stimulant medication on classroom with attention-deficit/hyperactivity disorder. Canadian Journal learning-related measures of cognitive processing for attention of Psychiatry, 53, 392–399.
deficit disorder children. Journal of Abnormal Psychology, 19, Castellanos, F. X., Sonuga-Barke, E. J. S., Milham, M. P., & Tannock, R. (2006). Characterizing cognition in ADHD: Journal of Learning Disabilities 44(2) Beyond executive dysfunction. Trends in Cognitive Science, Evans, S. W., Smith, B. H., Gnagy, E. M., Pelham, W. E., Bukstein, O., Greiner, A. R., . . Baron-Myak, C. (2001). Dose-response Chacko, A., Pelham, W. E., Gnagy, E. M., Greiner, A., Vallano, G. effects of methylphenidate on ecologically valid measures of Bukstein, O., & Rancurello, M. (2005). Stimulant medication academic performance and classroom behavior in adolescents effects in a summer treatment program among young children with ADHD. Experimental and Clinical Psychopharmacology, with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 44, Fabiano, G. A., Pelham, Jr., W. E., Coles, E. K., Gnagy, E. M., Chronis-Tuscano, A., & O'Connor, B. C. (2009). A meta-anal- Chhabildas, N., Pennington, B. F., & Willcutt, E. G. (2001). A com- ysis of behavioural treatments treatments for attention-deficit/ parison of neuropsychological profiles of the DSM-IV subtypes hyperactivity disorder. Clinical Psychology Review, 29, of ADHD. Journal of Abnormal Child Psychology, 29, 529–540.
Conners, K. (1997). Conners' Parent and Teacher Rating Scale– Figner, B., Mackinlay, R. J., Wilkening, F., & Weber, E. U. (2009). Revised. North Tonawanda, NY: Multi-Health Systems.
Affective and deliberative processes in risky choice: Age dif- Conners, K., & MHS Staff. (2000). Conners' Continuous Perfor- ferences in risk taking in the Columbia Card Task. Journal of mance Test–II user's manual. Toronto, Canada: Multi-Health Experimental Psychology: Learning, Memory, and Cognition, Decker, S. L., Hill, S. K., & Dean, R. S. (2007). Evidence of con- Floresco, S. B., & Magyar, O. (2006). Mesocortical dopamine struct similarity in executive functions and fluid reasoning abili- modulation of executive functions: Beyond working memory. ties. International Journal of Neuroscience, 117, 735–748.
Demaray, M. K., Elting, J., & Schaefer, K. (2003). Assessment of Frankenberger, W., & Cannon, C. (1999). Effects of Ritalin on aca- attention-deficit/hyperactivity disorder (ADHD): A compara- demic achievement from first to fifth grade. International Journal tive evaluation of five commonly used, published rating scales. of Disability, Development, and Education, 46, 199–221.
Psychology in the Schools, 40, 341–361.
Geurts, H. M., Verte, S., Oosterlaan, J., Roeyers, H., & Sergeant, J. A. Denckla, M. B. (1996). Biological correlates of learning and atten- (2005). ADHD subtypes: Do they differ in their executive tion: What is relevant to learning disability and attention-deficit/ functioning profile? Archives of Clinical Neuropsychology, 20, hyperactivity disorder? Journal of Developmental & Behavioral Pediatrics, 17, 114–119.
Gimpel, G. A., Collett, B. R., Veeder, M. A., Gifford, J. A., Dickstein, S. G., Bannon, K., Castellanos, F. X., & Milham, M. P. Sneddon, P., Bushman, B., . . Odell, J. D. (2005). Effects of (2006). The neural correlates of attention deficit hyperactivity stimulant medication on cognitive performance of children disorder: An ALE meta-analysis. Journal of Child Psychology with ADHD. Clinical Pediatrics, 44, 405–411.
and Psychiatry, 47, 1051–1062.
Golden, J. C. (1978). Stroop Color and Word Test. Chicago, IL: Dommett, E. J., Henderson, E. L., Westwell, M. S., & Greenfield, S. A. (2008). Methylphenidate amplifies long-term plasticity in the hip- Gorman, E. B., Klorman, R., Thatcher, J. E., & Borgstedt, A. D. pocampus via noradrenergic mechanisms. Learning & Memory, (2006). Effects of methylphenidate on subtypes of attention- deficit/hyperactivity disorder. Journal of the American Academy Douglas, V. I., Barr, R. G., Desilets, J., & Sherman, E. (1995). Do of Child and Adolescent Psychiatry, 45, 808–816.
high doses of stimulants impair flexible thinking in attention- Greenhill, L. L., Swanson, J. M., Vitiello, B., Davies, M., deficit/hyperactivity disorder? Journal of the American Acad- Clevenger, W., Wu, M., . . Wigal, T. (2001). Impairment and emy of Child and Adolescent Psychiatry, 34, 877–885.
deportment responses to different methylphenidate doses in chil- DuPaul, G. J. (2006). Academic achievement in children with dren with ADHD: The MTA titration trial. Journal of the Ameri- ADHD. Journal of the American Academy of Child and Ado- can Academy of Child and Adolescent Psychiatry, 40, 180–187.
lescent Psychiatry, 45, 766–767.
Goldstein, S., & Naglieri, J. (2008). The school neuropsychology of DuPaul, G. J., & Barkley, R. A. (1992). Situational variability of ADHD: Theory, assessment, and intervention. Psychology in attention problems: Psychometric properties of the Revised the Schools, 45, 859–874.
Home and School Situations Questionnaires. Journal of Clinical Hale, J. B. (1997). Development of alternate forms of the Hale Child Psychology, 21, 178–188.
Cancellation Task and Trail-Making Test for use in ADHD DuPaul, G. J., Rapport, M. D., & Perriello, L. M. (1991). Teacher rat- medication trials. Unpublished manuscript, Rochester Institute ings of academic skills: The development of the Academic Perfor- of Technology.
mance Rating Scale. School Psychology Review, 20, 284–300.
Hale, J. B., Blaine-Halperin, D., & Beakley, K. (2007, February). DuPaul, G. J., & Stoner, G. (2004). ADHD in the schools: Assessment Executive impairment determines ADHD response to methylphe- and intervention strategies (2nd ed.). New York, NY: Guilford.
nidate treatment. Paper presented at the 35th Annual Meeting of Engert, V., & Pruessner, J. C. (2008). Dopaminergic and noradren- the International Neuropsychological Society, Portland, OR.
ergic contributions to functionality in ADHD: The role of methyl- Hale, J. B., & Fiorello, C. A. (2004). School neuropsychology: phenidate. Current Neuropharmacology, 6, 322–328.
A practitioner's handbook. New York, NY: Guilford.
Hale et al. Hale, J. B., Fiorello, C. A., & Brown, L. (2005). Determining medi- Jensen, P. S., Arnold, L. E., Swanson, J. M., Vitiello, B., Abikoff, H. B., cation treatment effects using teacher ratings and classroom Greenhill, L. L. . Hur, K. (2007). 3-year follow up of the observations of children with ADHD: Does neuropsychological NIMH MTA study. Journal of the American Academy of Child impairment matter? Educational and Child Psychology, 22, and Adolescent Psychiatry, 46, 989–1002.
Johansen, E. B., Aase, H., Meyer, A., & Sagvolden, T. (2002). Hale, J. B., Hoeppner, J. B., DeWitt, M. B., Coury, D. L., Attention-deficit/hyperactivity disorder (ADHD) behaviour Ritacco, D. G., & Trommer, B. (1998). Evaluating medication explained by dysfunctioning reinforcement and extinction pro- response in ADHD. Journal of Learning Disabilities, 31, cesses. Behavioural Brain Research, 130(1-2), 37–45.
Julien, R. M. (2005). A primer of drug action. New York, NY: Worth Hale, J. B., Mulligan, C. A., & Simmerman, K. L. (2006, February). Quantifying medication response in ADHD: Does neuropsycho- Kelly, C., Sonuga-Barke, E. J. S., Scheres, A., & Castellanos, F. X. logical impairment matter? Poster presentation at the 34th (2007). Functional neuroimaging of the reward and motiva- Annual Meeting of the International Neuropsychological Society, tional pathway in ADHD. In M. Fitzgerald, M. Bellgrove, & M. Gill (Eds.), Handbook of Attention Deficit Hyperactivity Hale, J. B., Reddy, L. A., Decker, S. L., Thompson, R., Henzel, J., Disorder. (pp. 209–235). Hoboken, NJ: John Wiley & Sons.
Teodori, A., . . Denckla, M. B. (2009). Development and vali- Kemner, C., Jonkman, L. M., Kenemans, J. L., Bocker, K. B., dation of an executive function and behavior rating screening Verbaten, M. N., & Engeland, H. (2004). Sources of auditory battery sensitive to ADHD. Journal of Clinical and Experimental selective attention and the effects of methylphenidate in chil- Neuropsychology, 1, 1–16.
dren with attention-deficit/hyperactivity disorder. Biological Hale, J. B., Reddy, L. A., Wilcox, G., McLaughlin, A., Hain, L., Psychiatry, 55, 776–778.
Stern, A., . . Eusebio, E. (2009). Assessment and intervention Keulers, E. H. H., Hendriksen, J. G. M., Feron, F. J. M., for children with ADHD and other frontal-striatal circuit dis- Wassenberg, R., Wuisman-Frerker, M. G. F., Jolles, J., & orders. In D. C. Miller (Ed.), Best practices in school neuro- Vles, J. S. (2006). Methylphenidate improves reading perfor- psychology: Guidelines for effective practice, assessment and mance in children with attention deficit hyperactivity disorder evidence-based interventions (pp. 225–280). New York, NY: and comorbid dyslexia: An unblinded clinical trial. European Journal of Paediatric Neurology, 11(1), 21–28.
Heaton, R. K., Chelune, G. J., Talley, J. L., Kay, G. G., & Curtiss, Kobel, M., Bechtel, N., Weber, P., Specht, K., Klarhofer, M., G. (1993). Wisconsin Card Sorting Test (WCST) manual Scheffler, K., . . Penner, I. K. (2008). Effects of methylpheni- revised and expanded. Odessa, FL: Psychological Assessment date on working memory functioning in children with attention deficit/hyperactivity disorder. European Journal of Paediatric Hoeppner, J. B., Hale, J. B., Bradley, A., Byrns, M., Coury, D. L., Neurology, 13, 516–523.
& Trommer, B. L. (1997). A clinical protocol for determining Konrad, K., Gunther, T., Hanisch, C., & Herpertz-Dahlmann, B. methylphenidate dosage levels in ADHD. Journal of Attention (2004). Differential effects of methylphenidate on attentional Disorders, 2, 19–30.
functions in children with attention-deficit/hyperactivity disor- Hood, J., Baird, G., Rankin, P. M., & Isaacs, E. (2005). Immediate der. Journal of the American Academy of Child and Adolescent effects of methylphenidate on cognitive attention skills of chil- Psychiatry, 43, 191–198.
dren with attention-deficit/hyperactivity disorder. Developmental Kuhle, H., Kinkebur, J., Andes, K., Heidorn, F., Zeyer, S., Medicine & Child Neurology, 47, 408–414.
Rautzenberg, P., . . Jansen, F. (2007). Self-regulation of visual Horrigan, J. P., & Barnhill, L. J. (2000). Low-dose amphetamine attention and facial expression of emotions in ADHD children. salts and adult attention deficit/hyperactivity disorder. Journal Journal of Attention Disorders, 10, 350–358.
of Clinical Psychiatry, 61, 414–417.
Lajoie, G., Anderson, V., Anderson, P., Tucker, A. R., Robertson, I. H., Houghton, S., Douglas, G., West, J., Whiting, K., Wall, M., & Manly, T. (2005). Effects of methylphenidate on attention Langsford, S., . . Carroll, A. (1999). Differential patterns of skills in children with attention deficit/hyperactivity disorder. executive function in children with attention-deficit hyperactiv- Brain Impairment, 6(1), 21–32.
ity disorder according to gender and subtype. Journal of Child Langleben, D. D., Monterosso, L., Elman, I., Ash, B., Krikorian, G., Neurology, 14, 801–805.
& Austin, G. (2006). Effects of methylphenidate on Stroop Huang, Y., Chao, C., Wu, Y., Chen, Y., & Chen, Y. (2007). Acute Color-Word task performance in children with attention-deficit/ effects of methylphenidate on performance during the Test hyperactivity disorder. Psychiatry Research, 141, 315–320.
of Variables of Attention in children with attention deficit/ Lichter, D. G., & Cummings, J. L. (Eds.). (2001). Frontal-subcortical hyperactivity disorder. Psychiatry and Clinical Neurosciences, circuits in psychiatric and neurological disorders. New York, NY: Guilford.
Isles, A. R., & Humby, T. (2006). Modes of imprinted gene action in Liotti, M., & Mayberg, H. S. (2001). The role of functional neuro- learning disability. Journal of Intellectual Disability Research, imaging in the neuropsychology of depression. Journal of Clinical and Experimental Neuropsychology, 23, 121–136.
Journal of Learning Disabilities 44(2) Liotti, M., Pliszka, S. R., Perez, R., Glahn, D. C., & Semrud- Pennington, B. F., & Ozonoff, S. (1996). Executive functions and Clikeman, M. (2008). Electrophysiological correlates of response developmental psychopathology. Journal of Child Psychology inhibition in children and adolescents with ADHD: Influence of and Psychiatry, 37, 51–87.
gender, age, and previous treatment history. Psychophysiology, Pietrzak, R. H., Mollica, C. M., Maruff, P., & Snyder, P. J. (2006). Cognitive effects of immediate-release methylphenidate in chil- Lufi, D., Parish-Plass, J., & Gai, E. (1997). The effect of methyl- dren with attention-deficit/hyperactivity disorder. Neuroscience phenidate on the cognitive and personality functioning of and Behavioral Reviews, 30, 1225–1245.
ADHD children. Journal of Psychiatry and Related Services, Pliszka, S. R., Glahn, D. C., Semrud-Clikeman, M., Franklin, C., Perez, R., Xiong, J., & Liotti, M. (2006). Neuroimaging of May, R. B., Masson, M. E. J., Hunter, M. A., & Wells, J. (1990). inhibitory control areas in children with attention deficit hyper- NPStat 3.01 [Computer software]. Victoria, Canada: University activity disorder who were treatment naive or in long-term of Victoria.
treatment. American Journal of Psychiatry, 163, 1052–1060.
Mayes, S. D., & Calhoun, S. L. (2006). Frequency of reading, math, Pliszka, S. R., Liotti, M., Bailey, B. Y., Perez, R., Glahn, D., & and writing disabilities in children with clinical disorders. Semrud-Clikeman, M. (2007). Electrophysiological effects of Learning and Individual Differences, 16, 145–157.
stimulant treatment on inhibitory control in children with atten- McInnes, A., Bedard, A. C., Hogg-Johnson, S., & Tannock, R., tion-deficit/hyperactivity disorder. Journal of Child and Ado- (2007). Preliminary evidence of beneficial effects of methylphe- lescent Psychopharmacology, 17, 356–366.
nidate on listening comprehension in children with attention- Polanczyk, G., & Rohde, L. A. (2007). Epidemiology of attention- deficit/hyperactivity disorder. Journal of Child and Adolescent deficit/hyperactivity disorder across the lifespan. Current Opinion in Psychiatry, 20, 386–392.
McKenzie, I., & Wurr, C. (2004). Diagnosing and treating atten- Powers, R. L., Marks, D. J., Miller, C. J., Newcorn, J. H., & tional difficulties: A nationwide survey. Archives of Diseases in Halperin, J. M. (2008). Stimulant treatment in children with Childhood, 89, 913–916.
attention-deficit/hyperactivity disorder moderates adolescent Milich, R., Balentine, A. C., & Lynam, D. R. (2001). ADHD academic outcome. Journal of Child and Adolescent Psycho- combined type and ADHD predominantly inattentive type are pharmacology, 18, 449–459.
distinct and unrelated disorders. Clinical Psychology, Science Reddy, L. A., & De Thomas, C. (2006). Assessment of ADHD and Practice, 8, 463–488.
children and adolescents. In S. R. Smith & L. Handler (Eds.), Newby, R. F. (1999). Wisconsin Selective Reminding Test. Milwaukee, The clinical assessment of children and adolescents: A practitio- WI: Medical College of Wisconsin.
ner's guide. (pp. 367–387). Mahwah, NJ: Lawrence Erlbaum.
Nigg, J. T., Blaskey, L. G., Huang-Pollock, C. L., & Rappley, M. D. Reddy, L. A., & Hale, J. (2007). Inattentiveness. In A. R. Eisen (2002). Neuropsychological executive functions and DSM-IV (Ed.), Treating childhood behavioral and emotional disorders: ADHD subtypes. Journal of the American Academy of Child A step-by-step evidence-based approach (pp. 156–211). and Adolescent Psychiatry, 41, 59–66.
New York, NY: Guilford.
Northup, J., Fusilier, I., Swanson, V., Roane, H., & Borrero, J. Reitan, R. M., & Wolfson, D. (1985). Neuroanatomy and neuro- (1997). An evaluation of methylphenidate as a potential estab- pathology: A guide for neuropsychologists. Tucson, AZ: Neuro- lishing operation for some common classroom reinforcers. psychology Press.
Journal of Applied Behavior Analysis, 30, 615–625.
Reynolds, C. R., & Bigler, E. D. (1994). Test of memory and learning. Ozonoff, S., & Jensen, J. (1999). Specific executive function pro- Austin, TX: Pro-Ed.
files in three neurodevelopmental disorders. Journal of Autism Roiser, J. P., Cannon, D. M., Ghandi, S. K., Taylor-Tavares, J., & Developmental Disorders, 29, 171–177.
Erickson, K., Wood, S., . . Drevets, W. C. (2009). Hot and Pearson, D. A., Santos, C. W., Casat, C. D., Lane, D. M., Jerger, S. W., cold cognition in unmedicated depressed subjects with bipolar Roache, J. D., . . Cleveland, L. A. (2004). Treatment effects disorder. Bipolar Disorders, 11, 178–189.
of methylphenidate on cognitive functioning in children with Rubia, K., Noorloos, J., Smith, A., Gunning, B., & Sergeant, J. mental retardation and ADHD. Journal of the American Acad- (2003). Motor timing deficits in community and clinical boys emy of Child and Adolescent Psychiatry, 43, 677–685.
with hyperactive behavior: The effect of methylphenidate on Pearson, D. A., Santos, C. W., Roache, J. D., Casat, C. D., motor timing. Journal of Abnormal Child Psychology, 31, Loveland, K. A., Lachar, D., . . Cleveland, L. A. (2003). Treat- ment effects of methylphenidate on behavioral adjustment in Scheffler, R. M., Brown, T. T., Fulton, B. D., Hinshaw, S. P., Levine, children with mental retardation and ADHD. Journal of the P., & Stone, S. (2009). Positive association between attention-def- American Academy of Child and Adolescent Psychiatry, 42, icit/ hyperactivity disorder medication use and academic achieve- ment during elementary school. Pediatrics, 123, 1273–1279.
Pelham, W. E., & Gnagy, E. M. (1999). Psychosocial and combined Semrud-Clikeman, M. (2005). Neuropsychological aspects for treatments for ADHD. Mental Retardation and Developmental evaluating learning disabilities. Journal of Learning Disabilities, Disabilities Research Reviews, 5, 225–236.
Hale et al. Semrud-Clikeman, M., Pliszka, S., & Liotti, M. (2008). Executive Teicher, M. H., Polcari, A., & McGreenery, C. E. (2008). Utility of functioning in children with attention-deficit/hyperactivity dis- objective measures of activity and attention in the assessment order: Combined type with and without a stimulant medication of therapeutic response to stimulants in children with attention- history. Neuropsychology, 22, 329–340.
deficit/hyperactivity disorder. Journal of Child and Adolescent Sergeant, J. A., Geurts, H., & Oosterlaan, J. (2002). How specific is a deficit in executive functioning for attention-deficit/hyperactivity Trommer, B. L., Hoeppner, J. B., & Zecker, S. G. (1991). The go- disorder? Behavioural Brain Research, 130, 3–28.
no-go test in attention deficit disorder is sensitive to methyl- Smith, A. B., Taylor, E., Brammer, M., Toone, B., & Rubia, K. phenidate. Journal of Child Neurology, 6(Suppl.), S128–S131.
(2006). Task-specific hypoactivation in prefrontal and tempo- Tucha, O., & Lange, K. W. (2001). Effects of methylphenidate on roparietal brain regions during motor inhibition and task kinematic aspects of handwriting in hyperactive boys. Journal switching in medication-naïve children and adolescents with of Abnormal Child Psychology, 29, 351–356.
attention-deficit/hyperactivity disorder. American Journal of Tucha, O., & Lange, K. W. (2005). The effect of conscious control Psychiatry, 163, 1044–1051.
on handwriting in children with attention-deficit/hyperactivity Solanto, M. V., Abikoff, H., Sonuga-Barke, E. J. S., Schachar, R. J., disorder. Journal of Attention Disorders, 9, 323–332.
Logan, G. D., Wigal, T., . . Turkel, E. (2001). The ecological Vance, A., Maruff, P., & Barnett, R. (2003). Attention deficit hyper- validity of delay aversion and response inhibition as measures activity disorder, combined type: Better executive function perfor- of impulsivity in AD/HD: A supplement to the NIMH multi- mance with longer-term psychostimulant medication. Australian modal treatment study of AD/HD. Journal of Abnormal Child and New Zealand Journal of Psychiatry, 37, 570–576.
Psychology, 29, 215–228.
Van der Oord, S., Prins, P. J., Oosterlaan, J., & Emmelkamp, P. M. Solanto, M. V., & Wender, E. H. (1989). Does methylphenidate con- (2008). Efficacy of methylphenidate, psychosocial treatments strict cognitive functioning? Journal of the American Academy and their combination in school-aged children with ADHD: A of Child and Adolescent Psychiatry, 28, 897–902.
meta-analysis. Clinical Psychology Review, 28, 783–800.
Spencer, T. J. (2006). ADHD and comorbidity in childhood. Journal Volkow, N. D., Fowler, J. S., Wang, G. J., & Swanson, J. M. (2004). of Clinical Psychiatry, 67, 27–31.
Dopamine in drug abuse and addiction: Results from imaging Sprague, R. L., & Sleator, E. K. (1976). Methylphenidate in hyper- studies and treatment implications. Molecular Psychiatry, 9, kinetic children: Differences in dose effects on learning and social behavior. Science, 198, 1274–1276.
Waxmonsky, J., Pelham, W. E., Gnagy, E., Cummings, M. R., Spreen, O., & Benton, A. L. (1977). Neurosensory center compre- O'Connor, B., Majumdar, A., . . Robb, J. A. (2008). The effi- hensive examination for aphasia (NCCEA). Victoria, Canada: cacy and tolerability of methylphenidate and behavior modifi- University of Victoria Neuropsychology Laboratory.
cation in children with attention-deficit/hyperactivity disorder Steinberg, L. (2008). A social neuroscience perspective on adoles- and severe mood dysregulation. Journal of Child and Adolescent cent risk-taking. Developmental Review, 28, 78–106.
Swanson, J. M., Cantwell, D., Lerner, M., McBurnett, K., & Weiss, M. D., Worling, D. E., & Wasdell, M. B. (2003). A chart Hanna, G. (1991). Effects of stimulant medication on learning review study of the inattentive and combined types of ADHD. in children with ADHD. Journal of Learning Disabilities, 24, Journal of Attention Disorders, 7, 1–9.
Willcutt, E. G., Doyle, A. E., Nigg, J. T., Faraone, S. V., & Swanson, J. M., Flockhart, D., Udrea, D., Cantwell, D., Connor, D., Pennington, B. F. (2005). Validity of the executive function & Williams, L. (1995). Clonodine in the treatment of ADHD: theory of attention-deficit/hyperactivity disorder: A meta- Questions about safety and efficacy. Journal of Child and analytic review. Biological Psychiatry, 57, 1336–1346.
Adolescent Psychopharmacology, 5, 301–304.
Wilson, H. K., Cox, D. J., Merkel, R. L., Moore, M., & Coghill, D. Tamm, L., & Carlson, C.L. (2007). Task demands interact with sin- (2006). Effect of extended release stimulant-based medications gle and combined effects of medication and contingencies on on neuropsychological functioning among adolescents with children with ADHD. Journal of Attention Disorders, 10, attention-deficit/hyperactivity disorder. Archives of Clinical Tannock, R., Ickowicz, A., & Schachar, R. (1995). Differential Wodka, E. L., Mahone, E. M., Blanker, J. G., Gidley-Larson, J. C., effects of methylphenidate on working memory in ADHD chil- Fotedar, S., Denckla, M.B., & Mostofsky, S. H. (2007). Evidence dren with and without comorbid anxiety. Journal of American that response inhibition is a primary deficit in ADHD. Journal Academy of Child and Adolescent Psychiatry, 34, 886–896.
of Clinical and Experimental Neuropsychology, 29, 345–356.
Tannock, R., Schachar, R., & Logan, G. (1995). Methylphenidate Zametkin, A. J., Nordahl, T. E., Gross, M., King, A. C., Semple, W. E., and cognitive flexibility: Dissociated dose effects in hyperac- Rumsey, J., . . Cohen, R. M. (1990). Cerebral glucose metabo- tive children. Journal of Abnormal Child Psychology, 23, lism in adults with hyperactivity of childhood onset. New England Journal of Medicine, 323, 1361–1366.
Journal of Learning Disabilities 44(2) Zelazo, P. D., & Muller, U. (2002). Executive function in typical professor at Michigan State University with a joint appointment and atypical development. In U. Goswami (Ed.), Blackwell in Psychology and Psychiatry.
handbook of childhood cognitive development (pp. 445–469). Malden, MA: Blackwell Publishing.
Lisa A. Hain, PsyD, NCSP, ABSNP, is an Assistant Professor and
Practicum Coordinator in the Department of Psychology at the
About the Authors
Philadelphia College of Osteopathic Medicine. Dr. Hain's research James B. Hale, PhD is an Associate Professor of Clinical
interests center on the application and integration of neuropsycho- Neuropsychology in the Department of Psychology at the logical principles in the field of school psychology. University of Victoria. He specializes in applying brain-behavior relationships to high incidence disorders, and linking neuropsy- James Whitaker, PsyD, is a consultant with the Pearson Clinical
chological assessment data to academic and behavioral Assessment group and an adjunct instructor in the school psychol- ogy programs at Philadelphia College of Osteopathic Medicine and Bucknell University.
Linda A. Reddy, PhD is an Associate Professor in the Graduate
School of Applied and Professional Psychology at Rutgers
Jessica Morley, EdS, NCSP, is a School Psychologist at the Chester
University. She specializes in the assessment and intervention of County Intermediate Unit in Pennsylvania. She provides psycho- ADHD and ADHD-related disorders, test development and valida- educational services to students with high incidence disorders in tion, and school interventions.
secondary alternative education settings.
Margaret Semrud-Clikeman, PhD received her doctorate from
Kyle Lawrence is a graduate student in the School Psychology
the University of Georgia in 1990 and completed an internship Program at the Philadelphia College of Osteopathic Medicine.
and postdoctoral fellowship at the Massachusetts General Hospital/Harvard Medical school (MGH). She continues her research inter- Alex Smith is a graduate student in the School Psychology Program
ests in the areas of ADHD and educational neuroscience. Dr. at the Philadelphia College of Osteopathic Medicine.
Semrud-Clikeman was awarded the 1999 Early Career Contributions award from the National Academy of Nicole Jones is a graduate student in the School Psychology Program
Neuropsychology. She has published more than 60 articles, 45 at the Philadelphia College of Osteopathic Medicine. She works as chapters and five books. Dr. Semrud-Clikeman is currently a a therapist for young children with Autism Spectrum Disorders.

Source: http://medpsych.biz/pdfs/Hale%20et%20al.%202011.pdf