Effects of methylphenidate on complex cognitive processing in attention-deficit hyperactivity disorder

Three experiments were conducted to explore the effects of methylphenidate (MPH), attention-deficit hyperactivity disorder (ADHD) diagnosis, and age on performance on a complex visual-memory search task. Results showed that the effects of MPH varied with information load. On low-processing loads, all doses of MPH helped children with ADHD to improve accuracy with no cost to reaction time (RT), whereas on high loads, higher MPH doses improved error rates while slowing RT. Without medication, children with ADHD showed high error rates and slow RTs across both low and high loads, as did younger, normal control children. Because MPH slowed performance on only the most difficult, high-load conditions, it is argued that the drug improves self-regulatory ability, enabling children with ADHD to adapt differentially to high and low loads.     

Ethical Evaluation Bias

The objective of this study was to determine whether Ritalin (methylphenidate, MPH) affects cognitive flexibility and creativity in children with Attention Deficit Hyperactivity Disorder (ADHD). Measures administered included the Wisconsin Card Sorting Test-Revised (WCST-R), the Test of Divergent Thinking (TDT), and the Conners' ADHD rating scale, for both on and off MPH conditions. Comparison of on and off MPH data indicated that MPH administration significantly decreased symptoms of ADHD, as rated by parents on the Conners'. No significant differences were found on the WCST-R as a function of MPH administration. The Elaboration subscale of the TDT was the only scale to show a significant decrease in scores with MPH administration.     

Attention-Deficit/Hyperactivity Disorder and methylphenidate: a dose-response analysis and parent-child comparison of somatic complaints

The authors examined parent and child ratings of somatic complaints in 65 children with Attention-Deficit/Hyperactivity Disorder (ADHD) who received four doses (5 mg, 10 mg, 15 mg, 20 mg) of methylphenidate (MPH) in the context of a double-blind, placebo controlled, within-subject (crossover) experimental design. Results indicated that parent and child ratings of somatic complaints decreased in a linear fashion from baseline levels as a function of increasing MPH dose and showed minimal variation across MPH conditions. Statistical comparisons of specific somatic complaints indicated minimal agreement between parents and children in contrast to the nearly identical parent-child dose-response curves. The paradoxical findings of fewer somatic complaints associated with MPH, importance of obtaining children's perceptions of MPH treatment, and implications for measuring somatic complaints are discussed.     

The Development of Selective Attention in Children With Attention Deficit Hyperactivity Disorder

The influence of age on a selective attention task was studied in a sample of children with and without Attention Deficit Hyperactivity Disorder (ADHD). The impact of methylphenidate (MPH) treatment on selective attention was also investigated in the children with ADHD. Two age groups of children with ADHD and two age groups of control children were tested using a timed computer task. The task consisted of identifying visual target stimuli under various distracter conditions. Distracters varied on the basis of modality (i.e., visual, auditory, or both) and task relevance (i.e., meaningful or irrelevant). Reaction times and accuracy were measured. Children with ADHD were less efficient on the selective attention task than were children without ADHD, and older children were more efficient than younger children in both groups. Children without ADHD were influenced more by the nature of distracters than were children with ADHD. For children with ADHD, MPH improved performance overall.     

An Evaluation of Behavioral Approach in Adults with ADHD

Motivational models emphasizing altered reinforcement sensitivity have been increasingly implicated in etiological accounts of attention-deficit/hyperactivity disorder (ADHD). Overactive behavioral approach tendencies are identified among these motivational models and are addressed within reinforcement sensitivity theory (RST). RST proposes that overactive behavioral approach is associated with over responsiveness to immediately reinforcing stimuli and results from an overactive appetitive motivational subsystem of the brain—the behavioral approach system. The current study tested the hypothesis that behavioral approach would be higher in a clinical sample of adults diagnosed with ADHD relative to a control group. Experimental and self-report measures of behavioral approach were administered. Behavioral approach was higher in the ADHD group across both methods of assessment. Effect size estimates fell within the medium to large range. Implications for how these findings might be incorporated into future ADHD models are discussed.     

Modulation of Response Timing in ADHD,Effects of Reinforcement Valence and Magnitude

The present study investigated the impact of reinforcement valence and magnitude on response timing in children with ADHD. Children were required to estimate a 1-s interval, and both the median response time (response tendency) and the intrasubject-variability (response stability) were investigated. In addition, heart rate and skin conductance were measured to examine the autonomic responses to reinforcement. Feedback-only trials were compared to low response cost trials (response cost for incorrect responses), low reward trials (reward for correct responses), high response cost and high reward trials. In feedback-only trials, children with ADHD underestimated more severely the interval and responded more variably than controls. Children with ADHD, unlike controls, were unaffected by the reinforcement conditions in terms of time underestimations. The variability of responding, on the other hand, decreased under conditions of reinforcement to a larger extent in children with ADHD than controls. There were no indications that children with ADHD were abnormally affected by the valence or magnitude of reinforcement. Furthermore, skin conductance responses increased when feedback was coupled with reinforcement, an effect which was larger in children with ADHD than controls. This could be interpreted as demonstrating that children with ADHD suffer from a diminished awareness of the significance of feedback in the feedback-only condition. The current study suggests that children with ADHD suffer from motivation problems when reinforcement was not available, at least when variability in responding was measured. Underestimations of time may reflect more stable deficits in ADHD.     

Asymmetry of reinforcement and punishment in human choice

The hypothesis that a penny lost is valued more highly than a penny earned was tested in human choice. Five participants clicked a computer mouse under concurrent variable-interval schedules of monetary reinforcement. In the no-punishment condition, the schedules arranged monetary gain. In the punishment conditions, a schedule of monetary loss was superimposed on one response alternative. Deviations from generalized matching using the free parameters c (sensitivity to reinforcement) and log k (bias) were compared in the no-punishment and punishment conditions. The no-punishment conditions yielded values of log k that approximated zero for all participants, indicating no bias. In the punishment condition, values of log k deviated substantially from zero, revealing a 3-fold bias toward the unpunished alternative. Moreover, the c parameters were substantially smaller in punished conditions. The values for bias and sensitivity under punishment did not change significantly when the measure of net reinforcers (gains minus losses) was applied to the analysis. These results mean that punishment reduced the sensitivity of behavior to reinforcement and biased performance toward the unpunished alternative. We concluded that a single punisher subtracted more value than a single reinforcer added, indicating an asymmetry in the law of effect.     

Long-Term Follow-Up of Children with Mental Retardation/Borderline Intellectual Functioning and ADHD

Fifty-two children (ages 7 to 14 years) with moderate mental retardation to borderline intellectual functioning were recontacted 12 to 65 months following participation in a double-blind, placebo-controlled trial of methylphenidate (MPH). Sixty-nine percent of subjects continued to be prescribed medication for behavior control at follow-up. While 72% of the sample evidenced improvement, over two-thirds continued to be rated at or above the 98th percentile on the Hyperactivity Index of the Parent Conners. In fact, 22% of subjects had received inpatient psychiatric treatment between the time of the initial MPH trial and follow-up. Finally, subjects with high initial ratings on the Parent Conners Conduct Problems scale were more likely to be suspended from school or receive inpatient psychiatric treatment than subjects with low initial ratings. The results suggested that children with ADHD and mental retardation or borderline intellectual functioning continued to exhibit significant symptoms associated with attention deficit hyperactivity disorder (ADHD) at follow-up and that early conduct problems were predictive of continuing behavioral difficulties.     

Further analysis of the separate and interactive effects of methylphenidate and common classroom contingencies

We evaluated separate and interactive effects between common classroom contingencies and methylphenidate (MPH) on disruptive and off-task behaviors for 4 children with a diagnosis of attention deficit hyperactivity disorder. Analogue conditions consisting of contingent teacher reprimands, brief time-out, no interaction, and alone were conducted in a multielement design. Medication status (MPH or placebo) was alternated across days in a superordinate multielement design. Results indicate that (a) the behavioral effects of MPH were influenced by one or more of the analogue conditions for each participant, and (b) time-out was associated with zero or near-zero levels of both disruptive and off-task behavior for 3 of the 4 participants during MPH and placebo conditions. Implications for the clinical effectiveness of MPH and possible behavioral mechanisms of action of MPH in applied settings are discussed.     

Children’s Reward and Punishment Sensitivity Moderates the Association of Negative and Positive Parenting Behaviors in Child ADHD Symptoms

Atypical reward processing, including abnormal reward responsivity and sensitivity to punishment, has long been implicated in the etiology of ADHD. However, little is known about how these facets of behavior interact with positive (e.g., warmth, praise) and negative (e.g., hostility, harsh discipline) parenting behavior in the early expression of ADHD symptoms in young children. Understanding the interplay between children’s reward processing and parenting may be crucial for identifying specific treatment targets in psychosocial interventions for ADHD, especially given that not all children benefit from contingency-based treatments (e.g., parent management training). The study consisted of a sample of kindergarten children (N?=?201, 55% male) and their parents, who completed questionnaires about their parenting practices, their child’s behaviors and participated in an observed parent-child play task in the laboratory. Children’s reward responsivity and sensitivity to punishment were positively associated with child ADHD symptoms. However, children with high reward responsivity had more symptoms of ADHD but only under conditions of low negative parenting (self-reported and observed) and high self-reported positive parenting, compared to children with low reward responsivity. Children with high sensitivity to punishment had more ADHD symptoms relative to children with low sensitivity to punishment, but only under conditions in which observed praise was infrequent. Results provide evidence that individual differences in sensitivity to reward/punishment may be an important of marker of risk for ADHD, but also highlights how children’s responses to positive and negative parenting behavior may vary by children’s sensitivities. Clinical and treatment implications are discussed.     

A RAPID METHOD FOR EVALUATING THE NECESSITY FOR BOTH A BEHAVIORAL INTERVENTION AND METHYLPHENIDATE

We examined the effects of a behavioral intervention and methylphenidate (MPH) on inappropriate behavior and sleep disturbance displayed by a 6-year-old boy who had been diagnosed with attention deficit hyperactivity disorder. Results showed that the behavioral intervention was effective in reducing inappropriate behaviors to near-zero levels regardless of the presence or absence of MPH.     

Methodological Issues in the Assessment of Medication Effects in Children Diagnosed with Attention Deficit Hyperactivity Disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed disorders in school-aged children and is usually treated with stimulant medications, including methylphenidate (MPH; Ritalin®, Ritalin-LA®, Concerta®, Metadate®, or Focalin®) and other drug compounds (e.g., Adderall®, Adderall-XR®, or Dexedrine). Assessment of school behavior and performance is a critical component in determining the safety and efficacy of these medications. This paper reviews methodological issues in assessing drug effects in school settings by considering features of the independent variable (the medication), the dependent variables (the endpoints selected for assessment), and the design (the structure of the assessment). In addition, we consider recent conceptual advances in understanding the behavioral mechanisms of action of drugs used to treat ADHD that may influence the structure and interpretation of medication assessments.     

Sequential evaluation of behavioral treatments and methylphenidate dosage for children with attention deficit hyperactivity disorder

We used a sequential approach to evaluate the relative and combined effects of different types of behavioral treatments, as well as dosage of methylphenidate (MPH), on the disruptive behavior of 3 students who had been diagnosed with attention deficit hyperactivity disorder. Results showed that individualized behavioral treatments produced decreases in disruptive behavior equivalent to MPH for all 3 participants and demonstrated the need to evaluate behavioral treatments and medication dosage on an individual basis.     

The Efficacy, Safety, and Practicality of Treatments for Adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD)

Studies examining interventions for adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) were reviewed to evaluate their efficacy. These efficacy findings were supplemented with a preliminary system for judging safety and practicality. Results suggest that the stimulant drug methylphenidate (MPH) is safe and well-established empirically, but has some problems with inconvenience and noncompliance. Preliminary research supports the efficacy, safety, and practicality of some psychotherapeutic interventions, including behavioral classroom interventions, note-taking training, and family therapy. Treatment with tricyclic antidepressants was judged to have minimal empirical support and debatable safety. Very little is known about long-term effectiveness of treatments, long-term compliance, or multimodal treatments for adolescents such as stimulants plus behavior therapy.     

Responses to methylphenidate in Attention-Deficit/Hyperactivity Disorder and normal children: update 2002

Since the positive effects of stimulants on disruptive behavior were described (Bradley & Bowen, 1941), further pediatric studyhas been limited almost exclusively to samples of hyperkinetic school-age children. Because these agents normally were viewed as arousing in their effects on the central nervous system, but were calming in their therapeutic effects on these children, stimulant effects on Attention Deficit Disorder (ADD) were interpreted as being 'paradoxical.' Investigation of effects in normal children and adolescents and in those with disorders unrelated to Attention-Deficit/Hyperactivity Disorder (ADHD), as well as in young adult samples, however, indicate that stimulants appear to have similar behavioral effects in normal and in hyperactive children. This brief report is an update (as of August 2002) on studies of stimulants in ADHD and normal children, with particular focus on MPH.     

The effect of reinforcement variables on inhibition in children with ADHD.

Behavioral inhibition, often cited as a central deficit in children with ADHD, has been shown to change in response to reinforcement. In this preliminary investigation, children with ADHD (n= 20) and matched controls (ages 7 to 12) completed a new version of the stop signal paradigm, the Fire Fighter Game, a measure of inhibition of a prepotent motor response, under three conditions: (1) no reinforcement; (2) immediate reinforcement; and (3) delayed reinforcement. In all conditions, the stop signal reaction time (SSRT) of children with ADHD was consistently longer than controls. Both groups improved significantly with reinforcement, and there was no strong evidence that immediate reinforcement was more effective than delayed reinforcement. However, it appeared that the reason for the changes in SSRT in response to reinforcement differed between the groups. Children in the control group responded faster on go trials, whereas children with ADHD improved their ability to inhibit responding with shorter stop delays. The relevance of these findings is discussed in terms of current theories of ADHD.     

Improving Working Memory in Children with Attention-Deficit/Hyperactivity Disorder: The Separate and Combined Effects of Incentives and Stimulant Medication

Working memory (WM) is considered a core deficit in Attention-Deficit/ Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was assessed using a visuo-spatial n-back task. Study 1 compared children (ages 9-12?years) with ADHD-Combined type (n?=?24) to a group of typically developing (TD) children (n?=?32). Study 1 replicated WM deficits among children with ADHD. Incentives improved WM, particularly among children with ADHD. The provision of incentives reduced the ADHD-control group difference by approximately half but did not normalize WM. Study 2 examined the separate and combined effects of incentives and stimulant medication among 17 children with ADHD-Combined type. Both incentives and a moderate dose of long-acting methylphenidate (MPH; ~0.3?mg/kg t.i.d. equivalent) robustly improved WM relative to the no-incentive, placebo condition. The combination of incentives and medication improved WM significantly more than either incentives or MPH alone. These studies indicate that contingencies markedly improve WM among children with ADHD-Combined type, with effect sizes comparable to a moderate dose of stimulant medication. More broadly, this work calls attention to the role of motivation in studying cognitive deficits in ADHD and in testing multifactorial models of ADHD.     

Dopamine transporter gene moderates response to behavioral parent training in children with ADHD: a pilot study

There is great variability in the degree to which children with attention deficit/hyperactivity disorder (ADHD) improve through behavioral treatments. This study investigates the influence of the dopamine transporter gene (SCL6A3/DAT1) on outcome of behavioral parent training (BPT). Study subjects were a subsample (n = 50, for whom DAT1 genotypes were available) of a randomized controlled BPT effectiveness study (N = 94) comparing BPT plus ongoing routine clinical care (RCC) versus RCC alone in referred children (4-12 years old) with ADHD. Treatment outcome was based on parent-reported ADHD symptoms and behavioral problems. Presence of 2 versus no or 1 DAT1 10-repeat allele served as moderator variable. Time × Treatment × Genotype effect was analyzed with repeated-measures analysis of variance, controlling for baseline medication status. Results indicate that DAT1 moderated treatment response (p = .009). In children with no or 1 DAT1 10-repeat allele, superior treatment effects of BPT + RCC compared with RCC alone were present (p = .005), which was not the case in children with 2 DAT1 10-repeat alleles (p = .57). Our findings suggest that genetic differences in DAT1 in children with ADHD influence their susceptibility to a behavioral intervention directed at shaping their environment through their parents. The role of the dopamine system in motivation and learning and in the aberrant sensitivity to reinforcement in children with ADHD may explain this moderating effect, given that the management of contingencies is typically addressed in BPT.