Drug interactions in human neuropathic pain pharmacotherapy

The effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and task persistence of 60 boys with attention deficit hyperactivity disorder (ADHD) were investigated. In a balanced-placebo design, boys in 4 groups (received placebo/drug crossed with told placebo/drug) completed the task in success and failure conditions. Medication improved participants' task persistence following failure. Participants' task performance was not affected by whether they thought they had received medication or placebo. Children made internal attributions for success and made external attributions for failure, regardless of medication or expectancy. These findings confirm previous reports that it is the pharmacological activity of MPH that affects ADHD children's self-evaluations and persistence. The results contradict anecdotal reports that MPH causes dysfunctional attributions and confirm previous studies showing that medication does not produce adverse effects on the causal attributions of children with ADHD.     

Effect of Methylphenidate on Time Perception in Children With Attention-Deficit/Hyperactivity Disorder.

The effects of methylphenidate (MPH) on performance of a time-production task were studied in 17 children with attention-deficit/hyperactivity disorder who participated in 1 test session on and 1 off MPH. Participants held a response lever down for at least 10 but no longer than 14 s. Administration of MPH had no effect on the number of correct responses or on the mean duration of lever holds. MPH administration significantly decreased timing response variability, increased holds of 10- to 11-s duration, and decreased lever holds of extremely short durations. These results indicate that administration of MPH resulted in more precise timing performance without changing the mean duration of lever holds, suggesting an enhancement in working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of methylphenidate and expectancy on ADHD children's performance, self-evaluations, persistence, and attributions on a cognitive task.

The effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and task persistence of 60 boys with attention deficit hyperactivity disorder (ADHD) were investigated. In a balanced-placebo design, boys in 4 groups (received placebo–drug crossed with told placebo–drug) completed the task in success and failure conditions. Medication improved participants' task persistence following failure. Participants' task performance was not affected by whether they thought they had received medication or placebo. Children made internal attributions for success and made external attributions for failure, regardless of medication or expectancy. These findings confirm previous reports that it is the pharmacological activity of MPH that affects ADHD children's self-evaluations and persistence. The results contradict anecdotal reports that MPH causes dysfunctional attributions and confirm previous studies showing that medication does not produce adverse effects on the causal attributions of children with ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of methylphenidate and expectancy on performance, self-evaluations, persistence, and attributions on a social task in boys with ADHD.

This study examined the effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and persistence of 137 boys with attention-deficit/hyperactivity disorder (ADHD) in a get-acquainted dyadic interaction with a peer, using a balanced-placebo design. Boys in 4 groups—administered placebo or MPH crossed with being told they received placebo or MPH—interacted with child confederates in experimental situations in which social success and failure were manipulated. In contrast with studies of academic persistence, MPH did not affect boys' task persistence or performance. Boys gave more positive self-evaluations and talked more in the success condition as compared with the failure condition. Boys attributed success to effort and ability and failure to task difficulty, and neither MPH nor expectancy affected this pattern. These findings are consistent with other studies in failing to find debilitating effects of MPH or medication expectancies on ADHD boys' attributions or self-evaluations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of methylphenidate in the classroom: What dosage, for which children, for what problems?

In this study the authors conducted single-case analyses of the dosage and time-course effects of methylphenidate (MPH; Ritalin) on disruptive classroom behavior, math and reading performance, and social engagement. Clear individual differences were demonstrated (a) across children (aged 7 yrs) with attention deficit hyperactivity disorder (ADHD); (b) across academic, behavioral, and social domains of functioning; (c) for dose-response effects; and (d) in the onset and duration of effects. These results are in contrast to the majority of group studies that suggest a generally positive and linear dose-response effect for MPH across both children and domains of functioning. No particular dose-response relationship between disruptive behavior and academic performance was indicated. However, an increasing dosage of MPH was associated with increasing social withdrawal for 2 of the 3 participants. Implications for school-based medication evaluations and for designing optimal comprehensive interventions for children who receive MPH are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Separate and combined effects of methylphenidate and behavior modification on boys with attention deficit-hyperactivity disorder in the classroom

This study evaluated the separate and combined effects of behavior modification and 2 doses of methylphenidate (MPH; 0.3 and 0.6 mg/kg) compared with baseline (no behavior modification and a placebo) on the classroom behavior and academic performance of 31 ADHD (attention deficit-hyperactivity disorder) boys attending a summer treatment program. Results revealed significant effects of both interventions, with the mean effect size of medication being more than twice as great as that of behavior modification. Relatively small incremental value was gained by the higher dose of medication or the addition of behavior modification, compared with the effects of the low dose of MPH. In contrast, the addition of either dose of MPH resulted in improvement beyond the effects of behavior modification alone. These group effects reflected those obtained in analyses of individual differences. Furthermore, comparisons of individual responsiveness showed that boys who responded to one treatment also responded to the other.     

Responsiveness of children with attention deficit–hyperactivity disorder to reward and response cost: Differential impact on performance and motivation.

Using a within-subject design and both high- and low-interest tasks, this study examined the effects of reward (R), response cost (RC), and no contingency (NR) on performance and motivation of 22 children with attention deficit–hyperactivity disorder (ADHD) and 22 controls. Dependent variables included performance measures, self-rated performance and motivation, and a new measure of behavioral motivation based on a 2-min postcontingency task. Both contingencies benefited some aspects of the performance of ADHD children; relative to R, RC showed stronger effects but at the expense of decreased self-rated motivation on the low-interest task. The performance of controls did not differ across tasks, whereas ADHD children performed relatively better on the high-interest task. Neither contingency decreased motivation measures relative to NR for either group. For ADHD children, motivational effects appeared to be influenced by self-perceptions of performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulant medication improves recognition memory in children diagnosed with attention-deficit/hyperactivity disorder.

The effect of stimulant medication on recognition memory was examined in 18 children with attention-deficit/hyperactivity disorder (ADHD). Recognition memory was assessed using a delayed matching-to-sample task at 6 delays ranging from 1 to 32 s. Each child was tested on 2 separate occasions, once 60 to 90 min after taking stimulant medication and the other at least 18 hr after taking medication. Children performed significantly better on medication than off. Stimulant administration significantly increased accuracy and the number of nickel reinforcers earned. Decreases in observing response latency and correct choice response latency occurred after taking stimulant medication. The results indicate that stimulant medication improved recognition memory for children with ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate

OBJECTIVE: To determine the behavioral, situational, and temporal effects of 4 months of methylphenidate (MPH) treatment for attention-deficit hyperactivity disorder (ADHD). METHOD: Ninety-one children with ADHD were randomly assigned to receive either MPH (titrated to a target dose of 0.7 mg/kg twice a day) or a placebo. Treatment effects were investigated with measures sensitive to various behaviors (core and associated symptoms), situations (home and school), time periods (morning and afternoon, after reaching the target dose, and after 4 months of treatment), and side effects. RESULTS: MPH treatment improved symptoms of ADHD and oppositional behavior at school, both in the morning and afternoon, but not at home. Side effects (increase in physiological and effective symptoms, lack of weight gain) were significantly more frequent with MPH than with placebo treatment. Benefit was evident after titration, but the onset of some side effects was delayed. Side effects were reported by parents but not by teachers. CONCLUSIONS: Positive effects of MPH on behavior are evident in the classroom, but with MPH given twice daily, parents do not report that MPH improves behavior at home. Greater impact on home behavior may require three times daily MPH and combined treatments.     

Performance on two fixed-interval schedules in the absence of neocortex in rats.

Rats with complete surgical removal of the neocortex (neodecorticates) were trained, with milk as the reinforcer, on a 40-sec fixed-interval (FI-40) schedule, then on an FI-120, and finally reexposed to the FI-40. Like controls, neodecorticates developed and appropriately adjusted their postreinforcement pauses and response distributions and showed scallop-type responding on the FI-120 and a positive correlation between running rate and the preceding postreinforcement pause on both FI-40 schedules but not on the FI-120. On some variables neodecorticates reached asymptotic levels of performance more slowly than controls. Extended training on the first FI-40 did not differentially affect neodecorticates' performance. The results suggest that neodecorticates retain a functional timing mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for higher reaction time variability for children with ADHD on a range of cognitive tasks including reward and event rate manipulations.

Objective: The purpose of the research study was to examine the manifestation of variability in reaction times (RT) in children with attention deficit hyperactivity disorder (ADHD) and to examine whether RT variability presented differently across a variety of neuropsychological tasks, was present across the two most common ADHD subtypes, and whether it was affected by reward and event rate (ER) manipulations. Method: Children with ADHD-combined type (n = 51), ADHD-predominantly inattentive type (n = 53), and 47 controls completed five neuropsychological tasks (Choice Discrimination Task, Child Attentional Network Task, Go/No-Go task, Stop Signal Task, and N-back task), each allowing trial-by-trial assessment of RTs. Multiple indicators of RT variability including RT standard deviation, coefficient of variation and ex-Gaussian tau were used. Results: Children with ADHD demonstrated greater RT variability than controls across all five tasks as measured by the ex-Gaussian indicator tau. There were minimal differences in RT variability across the ADHD subtypes. Children with ADHD also had poorer task accuracy than controls across all tasks except the Choice Discrimination task. Although ER and reward manipulations did affect children's RT variability and task accuracy, these manipulations largely did not differentially affect children with ADHD compared to controls. RT variability and task accuracy were highly correlated across tasks. Removing variance attributable to RT variability from task accuracy did not appreciably affect between-groups differences in task accuracy. Conclusions: High RT variability is a ubiquitous and robust phenomenon in children with ADHD. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Postreinforcement signal processing.

Demonstrated postreinforcement signal processing by male albino Norway rats (N?=?262) in 6 experiments, using a discrete-trials choice procedure. Exp I assessed the extent to which Ss were able to transfer knowledge about associations between postreinforcement signal durations and choice responses to conditions in which a particular signal duration preceded the opportunity to make a choice response. In Exp II, the generality of the transfer effect was demonstrated by using both signal duration and signal modality as relevant stimulus attributes for the postreinforcement signals. The role of the relative durations of the reinforcement-signal gap and the intertrial interval was investigated in Exp III. To assess the effects of within- and between-trial signal relations on the acquisition of a temporal discrimination, both pre- and postreinforcement signals were presented on each trial in Exps IV and V. The effects of pre- and postreinforcement signal relations on the steady-state performance of a temporal bisection task across 3 signal ranges were studied in Exp VI. Overall results suggest that rats readily process various stimulus attributes of postreinforcement signals and that relations among postreinforcement signals, choice responses, and prereinforcement signals are major determinants of choice behavior. (39 ref) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Enamel hypoplasia in ancestral Puebloan populations from southwestern Colorado: I. Permanent Dentition

Predictions of P. R. Killeen's (1994) mathematical principles of reinforcement were tested for responding on ratio reinforcement schedules. The type of response key, the number of sessions per condition, and first vs. second half of a session had negligible effects on responding. Longer reinforcer durations and larger grain types engendered more responding, affecting primarily the parameter alpha (specific activation). Key pecking was faster than treadle pressing, affecting primarily the parameter delta (response time). Longer intertrial intervals led to higher overall response rates and shorter postreinforcement pauses and higher running rates, and ruled out some competing explanations. The treadle data required a distinction between the energetic requirements and rate-limiting properties of extended responses. The theory was extended to predict pause durations and run rates on ratio schedules.     

Models of ratio schedule performance.

Predictions of P. R. Killeen's (1994) mathematical principles of reinforcement were tested for responding on ratio reinforcement schedules. The type of response key, the number of sessions per condition, and first vs. second half of a session had negligible effects on responding. Longer reinforcer durations and larger grain types engendered more responding, affecting primarily the parameter a (specific activation). Key pecking was faster than treadle pressing, affecting primarily the parameter δ (response time). Longer intertrial intervals led to higher overall response rates and shorter postreinforcement pauses and higher running rates, and ruled out some competing explanations. The treadle data required a distinction between the energetic requirements and rate-limiting properties of extended responses. The theory was extended to predict pause durations and run rates on ratio schedules. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of methylphenidate on discounting of delayed rewards in attention deficit/hyperactivity disorder.

Impulsivity is a central component of attention deficit/hyperactivity disorder (ADHD). Delay discounting, or a preference for smaller, immediate rewards over larger, delayed rewards, is considered an important aspect of impulsivity, and delay-related impulsivity has been emphasized in etiological models of ADHD. In this study, we examined whether stimulant medication, an effective treatment for ADHD, reduced discounting of delayed experiential and hypothetical rewards among 49 children (ages 9–12 years) with ADHD. After a practice day, participants completed a 3-day double-blind placebo-controlled acute medication assessment. Active doses were long-acting methylphenidate (Concerta), with the nearest equivalents of 0.3 and 0.6 mg/kg TID immediate-release methylphenidate. On each testing day, participants completed experiential (real-world money in real time) and hypothetical discounting tasks. Relative to placebo, methylphenidate reduced discounting of delayed experiential rewards but not hypothetical rewards. Broadly consistent with etiological models that emphasize delay-related impulsivity among children with ADHD, these findings provide initial evidence that stimulant medication reduces delay discounting among those with the disorder. The results also draw attention to task parameters that may influence the sensitivity of various delay discounting measures to medication effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nucleus accumbens dopaminergic medication of fixed interval schedule-controlled behavior and its modulation by low-level lead exposure

To examine the assertion that changes in nucleus accumbens (NAC) dopamine (DA) activity serve as a mechanism of lead (Pb)-induced disruption of fixed interval (FI) schedule-controlled behavior, the effects of intra-NAC administration of the irreversible DA antagonist EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihyroquinoline) and of dopamine itself on FI performance were compared in rats that had been chronically exposed to 0, 50 or 500 ppm Pb acetate in drinking water from weaning. Pb exposure per se (500 ppm), as in past studies, increased FI response rates, primarily by shortening interresponse times. Although DA, which produced rate-dependent effects, increased FI rates at low doses in the 0 and 50 ppm groups, it did so by decreasing postreinforcement pause times. All DA doses decreased rates in the 500 ppm group. In contrast, the DA antagonist EEDQ suppressed FI response rates, effects that were not strongly rate dependent, by increasing both postreinforcement pause values and mean interresponse times. Pb exposure (500 ppm) delayed the recovery of response rates to control levels at the highest EEDQ dose, raising the possibility of a delay in receptor production rate. Collectively, these data suggest that NAC DA activity may be an important modulator of FI response rates. Enhanced NAC DA activity may contribute to Pb-associated increases in FI rates and may underlie the differential response of control and 500 ppm Pb-treated groups to intra-NAC DA administration. The different processes by which DA and Pb increase FI rates, however, suggests that additional mechanisms are operative in the case of Pb.     

Transdermal Methylphenidate, Behavioral, and Combined Treatment for Children With ADHD.

Stimulant medication and behavioral treatments are evidence-based for children with attention-deficit/hyperactivity disorder, but the combination of the 2 treatments has been understudied. In this investigation, methylphenidate (MPH) was crossed with 2 levels of behavior modification (BMOD) in a summer treatment program. Twenty-seven children with attention-deficit/hyperactivity disorder, aged 6-12, participated. Children received placebo and 3 doses of transdermal MPH (12.5 cm2, 25.0 cm2, and 37.5 cm2). BMOD was implemented on alternating weeks. Both treatments produced large and significant effects. Combined treatment was superior to either treatment alone. The effects of transdermal MPH were comparable to those found in this setting in previous studies with multiple stimulant medications and formulations. Consistent with other research, low doses of MPH--even lower than in previous studies--yielded enhanced effects in combination with behavior modification. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study

Functional MRI revealed differences between children with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls in their frontal-striatal function and its modulation by methylphenidate during response inhibition. Children performed two go/no-go tasks with and without drug. ADHD children had impaired inhibitory control on both tasks. Off-drug frontal-striatal activation during response inhibition differed between ADHD and healthy children: ADHD children had greater frontal activation on one task and reduced striatal activation on the other task. Drug effects differed between ADHD and healthy children: The drug improved response inhibition in both groups on one task and only in ADHD children on the other task. The drug modulated brain activation during response inhibition on only one task: It increased frontal activation to an equal extent in both groups. In contrast, it increased striatal activation in ADHD children but reduced it in healthy children. These results suggest that ADHD is characterized by atypical frontal-striatal function and that methylphenidate affects striatal activation differently in ADHD than in healthy children.     

Executive function in children with Tourette syndrome and/or attention deficit hyperactivity disorder

Tourette Syndrome (TS) in children is associated with various neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD). Children with TS and ADHD show some difficulties with neuropsychological tasks, but we do not know if children with TS alone have neuropsychological deficits. To assess specific cognitive differences among children with TS and/or ADHD, we administered a battery of neuropsychological tests, including 10 tasks related to executive function (EF), to 10 children with TS-only, 48 with ADHD-only, and 32 with TS + ADHD. Children in all groups could not efficiently produce output on a timed continuous performance task [Test of Variables of Attention (TOVA) mean reaction time and reaction time variability]. Children with TS-only appeared to have fewer EF impairments and significantly higher perceptual organization scores than children with TS + ADHD or ADHD-only. These findings suggest that deficiencies in choice reaction time and consistency of timed responses are common to all three groups, but children with TS-only have relatively less EF impairment than children with TS + ADHD or ADHD-only.