Effects of methylphenidate on inhibitory control in hyperactive children

This study investigated the effects of methylphenidate (MPH) on inhibitory control in hyperactive children. A double-blind, placebo-control, within-subject (crossover) design was used in which 12 children, between 6 and 11 years of age, were each tested four times in each drug condition: 0.3 mg/kg and 1.0 mg/kg of methylphenidate, and placebo. Dependent measures included (a) the probability of inhibiting responses to a primary choice reaction time task given a stop signal, on the Stopping Task, and (b) response latency and errors on the Matching Familiar Figures Test (MFFT). MPH improved the efficiency of the central inhibitory mechanism by speeding the inhibitory process, thereby affording the children greater control over their actions and enabling them to increase the probability with which they inhibited responses given a stop signal. MPH increased response latency but did not reduce errors on the MFFT, and observation of the children's task performance highlighted the interpretive problems associated with this task. Performance on both tasks was better at a dosage of 1.0 mg/kg than at 0.3 mg/kg.     

Prepotent response inhibition predicts treatment outcome in attention deficit/hyperactivity disorder

Objective: Inhibition deficits, including deficits in prepotent response inhibition and interference control, are core deficits in ADHD. The predictive value of prepotent response inhibition and interference control was assessed for outcome in a 10-week treatment trial with methylphenidate. Methods: Thirty-four children with ADHD (ages 8–12) received 10 weeks of methylphenidate treatment. At pretest prepotent response inhibition was assessed using the Stop-Signal Task; interference control was assessed using the Stroop Color-Word task. Methylphenidate was individually titrated to an optimal dose. Treatment outcome was assessed by parent- and teacher-rated ADHD behavior. Results: Only stop-signal reaction time of the Stop-Signal Task was a significant predictor of parent-rated levels of inattention and hyperactivity/impulsivity at outcome. Children with lower levels of inhibition showed worse outcome after 10 weeks of treatment, independent of medication dose. Conclusions: Low levels of prepotent response inhibition are associated with worse response to treatment with methylphenidate. Prepotent response inhibition may be an intermediate phenotypical predictor of treatment outcome.     

Delta plots in the study of individual differences: new tools reveal response inhibition deficits in AD/Hd that are eliminated by methylphenidate treatment

The authors highlight the utility of distribution-analytical techniques in the study of individual differences and clinical disorders. Cognitive deficits associated with attention-deficit/hyperactivity disorder (AD/HD) were examined by using delta-plot analyses of performance data (reaction time and accuracy) obtained through the use of a prototypical conflict task, the Eriksen flanker task. In 20 children with AD/HD (compared with matched control participants), overall performance measures indicated a marginal performance deficit. Delta-plot analyses indicated that performance deficits associated with AD/HD involve response inhibition but not automatic response activation. In a within-subjects titration study, the response inhibition deficit was eliminated by methylphenidate treatment, but these effects were highly dose specific. The beneficial effect of methylphenidate was clarified further after correcting for inter-individual variation in sensitivity to medicine dosage.     

Performance and Private Speech of Children with Attention-Deficit/Hyperactivity Disorder While Taking the Tower of Hanoi Test: Effects of Depth of Search,Diagnostic Subtype,and Methylphenidate

We administered the Tower of Hanoi to demographically comparable samples of control participants (n = 34) and children with the Combined (n = 22) and Inattentive subtypes (n = 19) of Attention-Deficit/Hyperactivity Disorder (ADHD). Controls excelled over children with the Inattentive subtype, who outperformed patients with the Combined subtype. These results replicated findings of greater executive deficits in the Combined than in the Inattentive type of ADHD. Double-blind administration of methylphenidate improved task performance only for patients with the Inattentive subtype. In a drug-free Baseline session, children with both subtypes of ADHD made more private verbalizations than controls, particularly when failing puzzles. In later sessions, regardless of drug condition, the inattentive sample exhibited a smaller increase in self-regulatory utterances under failure. In contrast, the combined sample decreased self-regulatory verbalizations under failure only under methylphenidate. The results support some differences between the two subtypes of ADHD in executive functioning and in their response to stimulant therapy. Portions of these results were submitted as part of H. Theresa Chang's PhD dissertation (Chang, 2000) and Helena Kopecky's unpublished master's research, both conducted at the University of Rochester and supervised by Rafael Klorman.     

Methylphenidate and cognitive flexibility: Dissociated dose effects in hyperactive children

A randomized, double-blind, placebo-controlled trial was conducted to assess the acute effects of placebo and three doses of methylphenidate (MPH) (0.3, 0.6, 0.9 mg/kg) on cognitive flexibility and overt behavior in 28 children with a confirmed diagnosis of attention deficit-hyperactivity disorder. Two underlying cognitive processes (response inhibition and response reengagement) were assessed by measuring the probability and speed with which subjects could inhibit responses to a primary task (forced-choice letter discrimination) and immediately execute a response to a secondary task (simple reaction time) when given a signal to do so. Results indicated that MPH enhanced cognitive flexibility, although the high dose was less effective than lower doses in enhancing response inhibition. Dissociations of dose effects on cognitive function and behavior were demonstrated: Dose-response functions for changes in behavior were linear, whereas the function for response inhibition was U-shaped. Findings argue against the typical clinical practice of determining the response to stimulant treatment from a single measure such as parent report of child behavior.     

Auditory stimulus intensity gradients and response to methylphenidate in ADD children

Using an auditory stimulus intensity paradigm, we obtained both event related potentials (ERPs) and press and release reaction times (RT) from a large sample of children with Attention Deficit Disorder (ADD). The ERP gradients to three tone intensities were used to classify the children as augmenters (steep gradients), moderates, or reducers (shallow or negative gradients). The RT data were used to classify the children as strong or sensitive, following neo-Pavlovian guidelines. The children were then cross-classified on these two dimensions and compared on cognitive, behavioral, and performance measures. The groups were also compared in response to two dosage levels of methylphenidate. Based on prior studies, we hypothesized that: 1. ERP augmenters would respond as well to the low as high dose but that reducers would respond better to high than low dose; and II. sensitive types (RT measure) would do better on the higher dose and strong types on the low dose. The first hypothesis was confirmed on a performance task but not on behavioral ratings. At the lower dose, augmenters improved most and reducers least on a 10-minute coding task presumed to require sustained attention. There was no support for the second hypothesis either in ratings or performance. The ERP augmentation measure was significantly related to teacher rated attentiveness; i.e., reducers and moderates were rated more adversely. The RT sensitivity measure tended to be related to achievement; i.e., strong types had lower reading and spelling scores. The ERP and RT sensitivity measures were not significantly correlated.     

Effects of methylphenidate (Ritalin) on information processing in hyperactive children

The effect of methylphenidate on information-processing efficiency was studied in 12 hyperactive, nonretarded children. Performance on six efficiency tasks (Posner Letter Matching, Reaction Time, Memory Search, Category Verification, Item Identification, and Word-Span) and a general measure of on-task behavior were compared for children receiving methylphenidate or a placebo. The median drug dosage was .38 mg/kg, and it was ingested 1 1/2 hours prior to testing. Children blind to the drug-placebo condition were tested on 4 days. In general, methylphenidate-related improvements in attention to on-task behaviors were found. An overall analysis of processing speed suggested that methylphenidate improved efficiency. Methylphenidate significantly decreased reaction times to simple and complex stimulus arrays; differences due to the drug remained even when on-task attentive behaviors were statistically removed. Significantly fewer identification errors occurred on the Posner task in the methylphenidate condition. Results indicated that methylphenidate improved general attentional behaviors and positively influenced processes that define perceptual efficiency.The first author was supported by NIH Training Grant No. HD 07184. We appreciate the assistance of Dr. Robert Sweeney in carrying out this research and the useful comments of Ellen B. Ryan and Jeanne D. Day.     

Temperamental contributions to children's performance in an emotion-word processing task: a behavioral and electrophysiological study

Seven-year-old children (N=65) participating in a study of the influence of infant temperament on socioemotional development performed an auditory selective attention task involving words that varied in both affective (positive vs. negative) and social (social vs. nonsocial) content. Parent report of contemporaneous child temperament was also collected, and individual differences in self-regulation in the affective (soothability) and cognitive (attentional control) domains were noted. Overall, children showed slower responses to stimuli that were either social or negative in content, with the largest effect elicited by words that possessed both traits. Children rated high in soothability and attentional control showed slower responses to social negative words. The other children showed little to no differential response patterns across the word categories. ERPs collected during the task indicated that processing differences were evident in the later more cognitive components of the ERP, especially in children low in attentional control. These findings indicate that performance on an auditory selective attention task can assist in identifying underlying patterns of affective processing.     

Effects of methylphenidate on working memory in pigeons

To assess the effects of methylphenidate on working memory, pigeons were trained in a delayed matching-to-sample task. Delay interval duration (0.2, 1, 3, 6, or 12 sec) was varied within sessions in order to separate delay-dependent from delay-independent effects of the drug on performance. A reduction in the sample response requirement from five responses to one response effectively reduced attention to the stimulus and impaired overall accuracy. Methylphenidate was administered in doses of 0.0 (saline control), 0.25, 2.5, and 10 mg/kg. Relative to performance with saline, accuracy was significantly reduced with 10 mg/kg methylphenidate to the same extent in both fixed ratio (FR) 1 and FR 5 conditions. The smaller doses had no effect, and there was no evidence that accuracy improved with drug administration. Intercepts and slopes of exponential functions fitted to measures of discriminability plotted as a function of delay showed that methylphenidate affected delay-independent aspects of performance (initial discriminability), but not delay-dependent aspects (rate of forgetting).     

Effects of methylphenidate on the persistence of ADHD boys following failure experiences

We examined the effects of methylphenidate on the task persistence of 21 boys with attention-deficit hyperactivity disorder (ADHD), after they had been exposed to both solvable and insolvable problems. The boys attempted to solve 10 different find-a-word puzzles on each of 4 days, involving the crossing of medication (placebo vs. 0.3 mg/kg) and prior task difficulty (solvable vs. insolvable). The results revealed that medication prevented the decrement in performance following the insolvable problems that was evident with the placebo days. In addition, on medication compared with placebo, the boys were more likely to make external attributions for failure and internal attributions for success. The results are discussed in terms of the impact of medication on ADHD boys' performance as medicated by cognitivemotivational state mechanisms.This study was undertaken in the 1989 Summer Treatment Program conducted at Western Psychiatric Institute and Clinic. We thank the staff of the program for their cooperation, particularly Mary Vodde-Hamilton, Karen Greenslade, and Gary Vallano. The authors thank Monica Harris for her helpful comments.     

Methylphenidate speeds evaluation processes of Attention Deficit Disorder adolescents during a continuous performance test

Fortysix Attention Deficit Disorder (ADD) adolescents took a Continuous Performance Test (CPT) under placebo and methylphenidate (35.33 mg/day). The task required pressing one button for targets (p=133),and another button for nontargets. Subjects displayed a strong bias to make the more frequent negative response before completely evaluating stimuli. Consistent with this assumption, subjects responded faster (by an average of 87 ms) to nontargets than to targets. Methylphenidate increased accuracy and speeded reaction times (RTs) to targets. The drug also increased the amplitude of the P3b component of the eventrelated potential for nontargets and shortened the latency of P3b for both targets and nontargets. These results suggest increased capacity allocation to and faster evaluation of task stimuli. Finally, the stimulant lengthened relative motor processing time (RT-P3b latency) for nontargets, a finding implying that response processing was accomplished with the benefit of earlier completion of evaluation processes for these stimuli.Portions of these findings were reported at the meeting of the Society for Research in Child and Adolescent Psychopathology, Costa Mesa, California, January 24–26, 1990. This research was supported by NIMH grant MH38118 to the first author. We thank the late Helen Pollock and the University of Rochester's Strong Memorial Hospital Pharmacy Manufacturing Department for their help.     

Acute Stimulant Treatment and Reinforcement Increase the Speed of Information Accumulation in Children with ADHD

The current studies utilized drift diffusion modeling (DDM) to examine how reinforcement and stimulant medication affect cognitive task performance in children with ADHD. In Study 1, children with (n = 25; 88 % male) and without ADHD (n = 33; 82 % male) completed a 2-choice discrimination task at baseline (100 trials) and again a week later under alternating reinforcement and no-reinforcement contingencies (400 trials total). In Study 2, participants with ADHD (n = 29; 72 % male) completed a double-blind, placebo-controlled trial of 0.3 and 0.6 mg/kg methylphenidate and completed the same task utilized in Study 1 at baseline (100 trials). Children with ADHD accumulated information at a much slower rate than controls, as evidenced by a lower drift rate. Groups were similar in nondecision time and boundary separation. Both reinforcement and stimulant medication markedly improved drift rate in children with ADHD (ds = 0.70 and 0.95 for reinforcement and methylphenidate, respectively); both treatments also reduced boundary separation (ds = 0.70 and 0.39). Reinforcement, which emphasized speeded accuracy, reduced nondecision time (d = 0.37), whereas stimulant medication increased nondecision time (d = 0.38). These studies provide initial evidence that frontline treatments for ADHD primarily impact cognitive performance in youth with ADHD by improving the speed/efficiency of information accumulation. Treatment effects on other DDM parameters may vary between treatments or interact with task parameters (number of trials, task difficulty). DDM, in conjunction with other approaches, may be helpful in clarifying the specific cognitive processes that are disrupted in ADHD, as well as the basic mechanisms that underlie the efficacy of ADHD treatments.     

A linear growth curve analysis of inpatient treatment response by conduct‐disordered,ADHD, and comorbid preadolescents

Conduct disorder (CD) comorbid with attention deficit hyperactivity disorder (ADHD) is widely reputed to be treatment refractory, particularly when accompanied by aggression and early‐onset symptoms. Few studies, however, have assessed inpatient treatment response among early onset CD/ADHD children in detail. In the present investigation, behavioral and rating scale data were compared among CD (n=13), ADHD (n=20), and CD/ADHD (n=45) preadolescents during one‐month of multimodal inpatient treatment that included methylphenidate administration. As expected, linear growth curve analyses revealed that CD/ADHD children were the most symptomatic of the three groups. However, all groups benefited from hospitalization, with few differences in treatment responsiveness observed. Analyses of residualized symptoms suggested that methylphenidate administration was effective in curbing impulsive but not aggressive behaviors. Aggr. Behav. 29:440–456, 2003. © 2003 Wiley‐Liss, Inc.     

Event-Related Potential and Behavioral Measures of Attention in 5-, 7-, and 9-Year-Olds

In 2 experiments, the development of auditory selective attention in children was assessed. The participants, aged 5, 7, and 9 years, responded to target stimuli in the left ear for 1 series (ignoring the standard stimuli) and in the right ear for the other series. In Experiment 1, event-related potentials (ERPs) evoked by the auditory stimuli were recorded from frontal, central, and parietal sites. The 9-year-olds showed a greater processing negativity (Nd) to the attended channel compared with the 5-year-olds. Both 7-and 9-year-olds showed significantly larger amplitudes for the P3 component of ERPs in the attended vs. ignored condition. Behaviorally, the 5-year-olds made fewer hits and more false alarms than did older children, and the 9-year-olds made significantly more false alarms than did the 7-year-olds. The results of Experiment 2 showed that the detriment in the performance of the 9-year-olds was a result of task parameters. The inability of 5-year-olds to attend selectively appears to involve problems with the inhibition of the processing of irrelevant information and with selection of the correct response.     

Event-related potential and behavioral measures of attention in 5-, 7-, and 9-year-olds

In 2 experiments, the development of auditory selective attention in children was assessed. The participants, aged 5, 7, and 9 years, responded to target stimuli in the left ear for 1 series (ignoring the standard stimuli) and in the right ear for the other series. In Experiment 1, event-related potentials (ERPs) evoked by the auditory stimuli were recorded from frontal, central, and parietal sites. The 9-year-olds showed a greater processing negativity (Nd) to the attended channel compared with the 5-year-olds. Both 7- and 9-year-olds showed significantly larger amplitudes for the P3 component of ERPs in the attended vs. ignored condition. Behaviorally, the 5-year-olds made fewer hits and more false alarms than did older children, and the 9-year-olds made significantly more false alarms than did the 7-year-olds. The results of Experiment 2 showed that the detriment in the performance of the 9-year-olds was a result of task parameters. The inability of 5-year-olds to attend selectively appears to involve problems with the inhibition of the processing of irrelevant information and with selection of the correct response.     

Latent Inhibition and Asymmetrical Visual-Spatial Attention in Children with ADHD

The research was designed to determine whether the purported hemispheric asymmetries that are associated with attention deficit/hyperactivity disorder (ADHD) affect performance on a selective attention visual search task, and whether any obtained asymmetry will be modulated by methylphenidate. Two groups of children (8–15 years) with ADHD, one with methylphenidate treatment (ADHD+) and one without (ADHD+), were compared to matched controls on a two-stage visual search task. The task assessed right–left visual field asymmetries and the effects of changing a previous distractor into a target. Such a procedure, related to latent inhibition (LI; poorer performance to a previously irrelevant stimulus than to a novel one), can provide evidence for dysfunctional processing of irrelevant stimuli. All three groups exhibited the LI effect. The ADHD group, however, exhibited less LI for left- than right-side targets, an effect absent in the control and ADHD+ groups, suggesting a lateralized attentional deficit for ADHD+ that was normalized by methylphenidate.     

Latent inhibition and asymmetrical visual-spatial attention in children with ADHD.

The research was designed to determine whether the purported hemispheric asymmetries that are associated with attention deficit/hyperactivity disorder (ADHD) affect performance on a selective attention visual search task, and whether any obtained asymmetry will be modulated by methylphenidate. Two groups of children (8-15 years) with ADHD, one with methylphenidate treatment (ADHD+) and one without (ADHD+), were compared to matched controls on a two-stage visual search task. The task assessed right-left visual field asymmetries and the effects of changing a previous distractor into a target. Such a procedure, related to latent inhibition (LI; poorer performance to a previously irrelevant stimulus than to a novel one), can provide evidence for dysfunctional processing of irrelevant stimuli. All three groups exhibited the LI effect. The ADHD group, however, exhibited less LI for left- than right-side targets, an effect absent in the control and ADHD+ groups, suggesting a lateralized attentional deficit for ADHD+ that was normalized by methylphenidate.     

RITALIN VS. RESPONSE COST IN THE CONTROL OF HYPERACTIVE CHILDREN: A WITHIN-SUBJECT COMPARISON

A within-subject comparison was made of the effects of methylphenidate (Ritalin) and response cost in reducing the off-task behavior of two boys, 7 and 8 years of age, who had been diagnosed as having an attentional deficit disorder with hyperactivity. Several dosages of Ritalin (5 to 20 mg/day) were evaluated with the results indicating varying effects of the drug for both children. Response cost (with free-time as the reinforcer) was superior to Ritalin in raising levels of on-task behavior and in improving academic performance.     

Attention and gaze shifting in dual-task and go/no-go performance with vocal responding

Evidence from go/no-go performance on the Eriksen flanker task with manual responding suggests that individuals gaze at stimuli just as long as needed to identify them (e.g., Sanders, 1998). In contrast, evidence from dual-task performance with vocal responding suggests that gaze shifts occur after response selection (e.g., Roelofs, 2008a). This difference in results may be due to the nature of the task situation (go/no-go vs. dual task) or the response modality (manual vs. vocal). We examined this by having participants vocally respond to congruent and incongruent flanker stimuli and shift gaze to left- or right-pointing arrows. The arrows required a manual response (dual task) or determined whether the vocal response to the flanker stimuli had to be given or not (go/no-go). Vocal response and gaze shift latencies were longer on incongruent than congruent trials in both dual-task and go/no-go performance. The flanker effect was also present in the manual response latencies in dual-task performance. Ex-Gaussian analyses revealed that the flanker effect on the gaze shifts consisted of a shift of the entire latency distribution. These results suggest that gaze shifts occur after response selection in both dual-task and go/no-go performance with vocal responding.     

冲突观察能诱发冲突适应

重复启动效应和一致试次所占的比例都会影响冲突适应效应。采用词-色Stroop任务, 本研究在控制了重复启动效应和一致试次的比例之后, 通过三个实验共同探讨反应执行和冲突观察对冲突适应效应的影响。实验一发现当前试次的Stroop干扰效应, 但没有得到冲突适应效应; 在实验二中, 先前试次为四选一的选择反应时任务, 当前试次为词-色Stroop任务, 得到反转的冲突适应效应; 实验三和实验一程序相似, 但在先前试次上不执行反应, 得到了稳定的冲突适应效应。这些结果证明, 冲突观察能够诱发冲突适应机制, 提升当前的操作表现。