Methylphenidate improves some but not all measures of ATTENTION,as measured by the TEA-Ch in medication-naïve children with ADHD

The Test of Everyday Attention for Children (TEA-Ch) is a reliable neuropsychological assessment of attention control in children. Methylphenidate (MPH) is an effective treatment to improve attentional difficulties in children with attention deficit/hyperactivity disorder (ADHD). Previous studies investigating the effects of MPH on attention performance of children with ADHD have produced mixed results and prior MPH usage may have confounded these results. No previous study has tested the effects of MPH on the entire TEA-Ch battery. This study investigated the effects of MPH on attention performance using the entire TEA-Ch in 51 medication-naïve children with ADHD compared with 35 nonmedicated typically developing children. All children were tested at baseline and after 6 weeks: The children with ADHD were medication-naïve at baseline, received MPH for 6 weeks and were tested whilst on medication at the second testing session. A beneficial effect of MPH administration was found on at least one subtest of each of the three forms of attention (selective, sustained, and attentional control) assessed by the TEA-Ch, independent of practice effects. MPH aided performance on the TEA-Ch tasks that were inherently nonarousing and that might require top-down control of attention. It is recommended that the TEA-Ch measures—Sky Search Count (selective attention),Score! (sustained attention), Creature Counting Time Taken for older children (attentional control), and Same Worlds (attentional control) be prioritized for use in future pharmacological studies using MPH.     

An Investigation of Prospective Memory in Children With ADHD

Prospective memory, defined as the ability to follow through on intended behavior, is believed to be subserved by a number of neuroanatomical substrates, but particularly dependent, at least in part, on the frontal lobes. Children with Attention-Deficit Hyperactivity Disorder (ADHD) traditionally have difficulty on tasks dependent on frontal lobe structures. The present study attempted to determine whether children with ADHD are impaired in prospective memory function. Two studies are described that use a new measure of time-based prospective memory, the CyberCruiser (Kerns, 2000), to compare children with ADHD to a control group consisting of participants who were matched in respect to age, gender, and IQ. The results document prospective memory deficits in ADHD. Prospective memory performance correlated significantly with clinical measures of ADHD as assessed by the Conners' Parent Rating Scale (Conners, 1990) Hyperactivity Index, but was unrelated to intellectual ability. Though psychometric measures of attention correlated with prospective memory performance, they did not account for the differences in prospective memory that were observed between the ADHD and control groups.     

Stimulant Treatment Reduces Lapses in Attention among Children with ADHD: The Effects of Methylphenidate on Intra-Individual Response Time Distributions

Recent research has suggested that intra-individual variability in reaction time (RT) distributions of children with ADHD is characterized by a particularly large rightward skew that may reflect lapses in attention. The purpose of the study was to provide the first randomized, placebo-controlled test of the effects of the stimulant methylphenidate (MPH) on this tail and other RT distribution characteristics. Participants were 49 9- to 12-year-old children with ADHD. Children participated in a 3-day double-blind, placebo-controlled medication assessment during which they received long-acting MPH (Concerta®), with the nearest equivalents of 0.3 and 0.6 mg/kg t.i.d. immediate-release MPH. Children completed a simple two-choice speeded discrimination task on and off of medication. Mode RT and deviation from the mode were used to examine the peak and skew, respectively, of RT distributions. MPH significantly reduced the peak and skew of RT distributions. Importantly, the two medication effects were uncorrelated suggesting that MPH works to improve both the speed and variability in responding. The improvement in variability with stimulant treatment is interpreted as a reduction in lapses in attention. This, in turn, may reflect stimulant enhancement of self-regulatory processes theorized to be at the core of ADHD.     

Music and Video as Distractors for Boys with ADHD in the Classroom: Comparison with Controls,Individual Differences,and Medication Effects

This study examined the effects of music and video on the classroom behavior and performance of boys with and without attention deficit hyperactivity disorder (ADHD) and examined the effects of 0.3 mg/kg methylphenidate (MPH). In one study, 41 boys with ADHD and 26 controls worked in the presence of no distractor, music, or video. Video produced significant distraction, particularly for the boys with ADHD, and MPH improved the performance of boys with ADHD across distractor conditions.There were individual differences in response to the music such that some boys were adversely affected and others benefited relative to no-distractor.In a second study, music and MPH were assessed in an additional 86 boys with ADHD to examine further the music results. In the presence or absence of music, MPH improved performance relative to placebo. Similar individual differences were found as in Experiment 1.     

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.     

Methylphenidate,Interstimulus Interval,and Reaction Time Performance of Children with Attention Deficit/Hyperactivity Disorder: A Pilot Study

Thirteen children with attention deficit/hyperactivity disorder (ADHD: DSM-IV-TR) participated in the pilot study. They carried out a Go/No-Go test with a short (2 seconds) and long (6 seconds) interstimulus interval (ISI) when on placebo and a therapeutic dose of methylphenidate (MPH). For the long-ISI placebo condition the responses were slow and inaccurate. This pattern of response may be due to underactivation of the readiness-to-respond state that is not fully controlled by effort allocation. Speed of response and accuracy were enhanced during the short-ISI placebo condition and the long-ISI MPH condition. However, the combined effect (short ISI and MPH) resulted in a fast but inaccurate response style. This pattern of response may be due to overactivation of the readiness-to-respond state. The data of the pilot study support the stimulus shift hypothesis: MPH administration result in deterioration on tests on which children had previously done well (short ISI plus placebo versus short ISI plus MPH). In addition, the data support the idea that ADHD is associated with poor state regulation rather than motivational (delay aversion) theories or temporal-processing/time-estimation theories of ADHD. The pilot study defined empirically an issue for further study with the larger controlled sample.     

Assessment of cognitive domains during treatment with OROS methylphenidate in adolescents with ADHD

Aim: To psychometrically assess cognitive domains in adolescents with ADHD during long-term open treatment with robust dosing of extended-release methylphenidate (OROS MPH).

Methods: Data were derived from a prospective clinical study of adolescent ADHD, employing the Cambridge Neuropsychological Test Automated Battery (CANTAB), before and after up to one year of treatment with OROS MPH. In the absence of placebo control, a similar age and gender group of youth without ADHD served as comparators.

Results: During the course of treatment with OROS MPH, ADHD youth’s performance significantly improved across multiple CANTAB tasks, including spatial working memory, rapid visual processing, verbal recognition memory, set shifting, and inhibition/vigilance. ADHD subjects’ scores in several CANTAB tasks, including spatial working memory, planning, and set shifting, were significantly more impaired at baseline compared to the non-ADHD comparison group; these significant differences were no longer seen at endpoint.

Conclusions: Statistically significant improvements in multiple cognitive domains were observed in a sample of adolescents with ADHD over the course of 12 months of robust treatment with extended-release methylphenidate. Rigorous, monitored stimulant treatment may be associated with objectively determined cognitive benefits; however, practice effects in this open trial cannot be ruled out. Further study on this important topic is warranted.     

The effect of methylphenidate on very low frequency electroencephalography oscillations in adult ADHD

Altered very low-frequency electroencephalographic (VLF-EEG) activity is an endophenotype of ADHD in children and adolescents. We investigated VLF-EEG case-control differences in adult samples and the effects of methylphenidate (MPH). A longitudinal case-control study was conducted examining the effects of MPH on VLF-EEG (.02–0.2 Hz) during a cued continuous performance task. 41 untreated adults with ADHD and 47 controls were assessed, and 21 cases followed up after MPH treatment, with a similar follow-up for 38 controls (mean follow-up = 9.4 months). Cases had enhanced frontal and parietal VLF-EEG and increased omission errors. In the whole sample, increased parietal VLF-EEG correlated with increased omission errors. After controlling for subthreshold comorbid symptoms, VLF-EEG case-control differences and treatment effects remained. Post-treatment, a time by group interaction emerged; VLF-EEG and omission errors reduced to the same level as controls, with decreased inattentive symptoms in cases. Reduced VLF-EEG following MPH treatment provides preliminary evidence that changes in VLF-EEG may relate to MPH treatment effects on ADHD symptoms; and that VLF-EEG may be an intermediate phenotype of ADHD. Further studies of the treatment effect of MPH in larger controlled studies are required to formally evaluate any causal link between MPH, VLF-EEG and ADHD symptoms.     

Selective inhibition in children with attention-deficit hyperactivity disorder off and on stimulant medication

Selective inhibition requires discrimination between auditory signals and is assessed using a modification of the stop-signal task. Selective inhibition was assessed in a group of 59 clinic-referred, DSM-IV-diagnosed children with attention-deficit hyperactivity disorder (ADHD) and compared to that of a community sample of 59 children. Methylphenidate (MPH) effects on selective inhibition were assessed in a subset of the ADHD sample that participated in an acute, randomized, placebo-controlled, crossover trial with 3 fixed doses of MPH. Children with ADHD performed more poorly than controls on the majority of selective stop-signal task parameters: they exhibited more anticipatory (invalid) responses, with less accurate and more variable responses on the response execution task, as well as a slower selective inhibition process. MPH improved speed of both inhibition and response execution processes; it also reduced variability of response execution and decreased nonselective inhibition. On the one hand, findings are consistent with purported inhibition deficit in ADHD, but on the other hand, suggest that neither the impairment itself, nor MPH effects, were restricted to inhibition.     

Methylphenidate influences on both early and late ERP waves of ADHD children in a continuous performance test

Although it has frequently been reported that hyperactive children have abnormally small P3 amplitudes of the event-related potential (ERP), which are normalized by the stimulant drug methylphenidate (MPH), the literature is inconsistent concerning earlier ERP waves. The aim of the present study was to investigate whether the normalizing effect of a 10-mg dose of MPH was also apparent on earlier waves, such as the N1, the P2, and the N2, besides the P3. Twelve attention deficit with hyperactivity disorder (ADHD) children performed a Continuous Performance Test involving a button-press response to the letter X (CPT-X) under the influence of MPH in a double-blind placebo controlled acute dosage design. ERPs were recorded at Oz, Pz, Cz, and Fz. The expected increase of the parietal P3, both to targets and nontargets, was apparent, as well as a significant increase in percentage of hits. There also was a significant increase of an earlier, negative going, wave, the N2, with a frontal maximum, under the influence of MPH. This wave was probably a manifestation of an increase in processing negativity for target stimuli only, after the intake of the stimulant drug. No effect of MPH was found on the N1 or the P2.     

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.     

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.     

Correspondence between children's and adults' ratings of stimulant-induced changes in ADHD behaviours in a crossover trial with medication-naive children

Correspondence between children's and adults' ratings of changes in ADHD behaviours was investigated in a paediatric ADHD stimulant crossover trial. Thirty-one children completed an ADHD self-report scale each week, and comparisons were made with an ADHD questionnaire completed by adults (combined parent and teacher ratings). Children's and adults' ratings demonstrated good internal consistency, were significantly associated with the assessment of ADHD behaviours in the placebo condition and showed comparable responsiveness to stimulants at the group level. Furthermore, a large and significant correlation was detected between the two sets of informants' ratings of changes from placebo to both methylphenidate and dextroamphetamine high-dosage conditions, but not from placebo to low-dosage conditions. Agreement in the categorization of best stimulant condition for individual children was significant, but modest from a clinical perspective. The results indicate that children's ratings correspond adequately with adults' ratings, and thus appear to be a complementary outcome measure.     

Time Course of Treatment Effect of OROS(R) Methylphenidate in Children With ADHD

Objective: The authors evaluated the time course of the treatment effect of Osmotic-Release Oral System methylphenidate (OROS(?) MPH) HCl (Concerta(?), Raritan, NJ) CII in children with ADHD. Method: Data were combined from two double-blind, randomized, placebo-controlled, cross-over, analog classroom studies in children (9-12 years) with ADHD. Participants received an individualized dose of placebo or OROS(?) MPH on two laboratory school days. Permanent Product Math Test and Swanson, Kotkin, Agler, M-Flynn, and Pelham scores were evaluated 0.5 hr before dosing and 1, 2, 4, 10, 11, and 12.5 hr post dose. Analysis used a repeated-measures mixed model. Results: Treatment effects were present at all postdose assessment points (p < .0001 for all comparisons, n = 139). Adverse events were similar to previous reports for OROS(?) MPH. Conclusion: A robust treatment effect occurred with OROS(?) MPH; onset was at 1 hr and persisted for at least 12.5 hr after dosing.     

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.     

Methylphenidate and substance abuse: a review of pharmacology,animal, and clinical studies

This article reviews pharmacological, animal, and human evidence regarding the abuse liability of methylphenidate (MPH). Findings are not always consistent, but evidence converges to suggest that although intravenous methylphenidate has some abuse potential, there is very little potential for oral MPH abuse. Furthermore, the available data suggests that children with Attention-Deficit/Hyperactivity Disorder (ADHD) who are treated with MPH are at lower risk for substance use disorder later in life. More longitudinal, prospective studies are needed to assess the long term effects of MPH treatment in ADHD.     

Mechanism of action of methylphenidate: insights from PET imaging studies

Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). We have used Positron Emission Tomography (PET) to investigate the mechanism of action of MPH in the human brain. We have shown (a) that oral MPH reaches peak concentration in the brain 60-90 minutes after its administration, (b) that therapeutic doses of MPH block more than 50% of the dopamine transporters (DAT), and (c) that of the two enantiomers that compose MPH, it is d-threo-methylphenidate (d-MPH) and not l-threo-methylphenidate (l-MPH) that binds to the DAT. We have also shown that therapeutic doses of MPH significantly enhance extracellular dopamine (DA) in the basal ganglia, which is an effect that appears to be modulated by the rate of DA release and that is affected by age (older subjects show less effect). Thus, we postulate (a) that MPH's therapeutic effects are in part due to amplification of DA signals, (b) that variability in responses is in part due to differences in DA tone between subjects, and (c) that MPH's effects are context dependent. Because DA enhances task specific neuronal signaling and decreases noise, we also postulate that MPH-induced increases in DA could improve attention and decrease distractibility; and that since DA modulates motivation, the increases in DA would also enhance the saliency of the task facilitating the 'interest it elicits' and thus improving performance.     

An examination of the psychometric properties of scores on the Family Strain Index (FSI) in a general community sample

Given the potentially harmful effects of parenting stress on parents, children, and their relationship, it is critical to have a reliable and valid measure of parenting stress in clinical and community samples. The Family Strain Index (FSI) is a brief questionnaire designed to measure stress and demand on parents of children with ADHD. The present study is the first to evaluate the psychometric properties of scores on the FSI in a general community sample. Parents (89% mothers) of 550 preschool children (aged 2–5 years; 50% boys) sampled through 17 kindergartens located in Danish cities and villages completed the FSI, the ADHD Rating Scale (RS)‐IV Preschool Version, and a background questionnaire. FSI scores were characterized by restricted range and floor effects. The scale's construct validity was not supported and the measurement repeatability after 1 month was low. The scale did have convergent validity as levels of parenting stress were associated with perceived ADHD behavior in off‐spring, but overall, results did not encourage the use of the FSI as a measure of parenting stress in the general population. Measures that include more normative events may be more appropriate when attempting to capture parenting stress in general community samples.