Methylphenidate Conditions Research Articles

Effect of methylphenidate on oculomotor function in individuals with multiple sclerosis: a pilot randomized placebo-controlled trial

IntroductionIndividuals with multiple sclerosis (MS) frequently experience visual and oculomotor symptoms that may impact and confound neuropsychological assessments of information processing speed (IPS). In this study, we examined the effect of the psychostimulant methylphenidate on oculomotor function and the association between change in oculomotor speed and change in information processing speed.MethodsWe used a repeated measures crossover design in which a sample of 11 participants with MS were randomly assigned to one of two treatment arms: one that received methylphenidate for 4 weeks and another that received a placebo for 4 weeks. After a 7-day washout period, the treatments were crossed over. The King Devick test, the Symbol Digit Modalities Test, and the Paced Auditory Serial Addition Test were administered at baseline and after each of the two study arms.ResultsWe found a significant improvement in oculomotor speed in the methylphenidate condition as compared to placebo. This improvement was significantly correlated with improvement on a visuomotor assessment of IPS (Symbol Digit Modalities Test), but no such association was found for an auditory-verbal assessment of IPS (Paced Auditory Serial Addition Test).DiscussionThese findings suggest that individuals with MS experience improved oculomotor speed while taking methylphenidate, which may, in turn, improve performance on assessments of IPS with visuomotor demands.

Discriminating cocaine use from other sympathomimetics using wearable electrocardiographic (ECG) sensors

BackgroundOur group has established the feasibility of using on-body electrocardiographic (ECG) sensors to detect cocaine use in the human laboratory. The purpose of the current study was to test whether ECG sensors and features are capable of discriminating cocaine use from other non-cocaine sympathomimetics. MethodsEleven subjects with cocaine use disorder wore the Zephyr BioHarness™ 3 chest band under six experimental (drug and non-drug) conditions, including 1) laboratory, intravenous cocaine self-administration, 2) after a single oral dose of methylphenidate, 3) during aerobic exercise, 4) during tobacco use (N=7 who smoked tobacco), and 5) during routine activities of daily inpatient living (unit activity). Three ECG-derived feature sets served as primary outcome measures, including 1) the RR interval (i.e., heart rate), 2) a group of ECG interval proxies (i.e., PR, QS, QT and QTc intervals), and 3) the full ECG waveform. Discriminatory power between cocaine and non-cocaine conditions for each of the three outcomes measures was expressed as the area under the receiver operating characteristics (AUROC) curve. ResultsAll three outcomes successfully discriminated cocaine use from unit activity, exercise, tobacco, and methylphenidate conditions with a mean AUROC values ranging from 0.66 to 0.99 and with least squares means values all statistically different/higher than 0.5 among all subjects [F(3, 99) = 3.38, p =0.02] and among those with tobacco use [F(4, 84) = 5.39, p = 0.0007]. ConclusionsThese preliminary results support discriminatory power of wearable ECG sensors for detecting cocaine use.

Time-varying SUVr reflects the dynamics of dopamine increases during methylphenidate challenges in humans

Dopamine facilitates cognition and is implicated in reward processing. Methylphenidate, a dopamine transporter blocker widely used to treat attention-deficit/hyperactivity disorder, can have rewarding and addictive effects if injected. Since methylphenidate’s brain uptake is much faster after intravenous than oral intake, we hypothesize that the speed of dopamine increases in the striatum in addition to its amplitude underly drug reward. To test this we use simulations and PET data of [11C]raclopride’s binding displacement with oral and intravenous methylphenidate challenges in 20 healthy controls. Simulations suggest that the time-varying difference in standardized uptake value ratios for [11C]raclopride between placebo and methylphenidate conditions is a proxy for the time-varying dopamine increases induced by methylphenidate. Here we show that the dopamine increase induced by intravenous methylphenidate (0.25 mg/kg) in the striatum is significantly faster than that by oral methylphenidate (60 mg), and its time-to-peak is strongly associated with the intensity of the self-report of “high”. We show for the first time that the “high” is associated with the fast dopamine increases induced by methylphenidate.

Influence of Methylphenidate on Long-Term Neuropsychological and Everyday Executive Functioning After Traumatic Brain Injury in Children with Secondary Attention Problems.

To investigate the effects of methylphenidate on long-term executive and neuropsychological functioning in children with attention problems following TBI, as well as the relationship between methylphenidate associated changes in lab-based neuropsychological measures of attentional control, processing speed, and executive functioning and parent- or self-report measures of everyday executive functioning. 26 children aged 6-17 years, who were hospitalized for moderate-to-severe blunt head trauma 6 or more months previously, were recruited from a large children's hospital medical center. Participants were randomized into a double-masked, placebo-controlled cross-over clinical trial. Participants completed a comprehensive neuropsychological battery and parent- and self-report ratings of everyday executive functioning at baseline, and at 4 weeks and 8 weeks following upward titration of medication to an optimal dose or while administered a placebo. Methylphenidate was associated with significant improvements in processing speed, sustained attention, and both lab-based and everyday executive functioning. Significant treatment-by-period interactions were found on a task of sustained attention. Participants who were randomized to the methylphenidate condition for the first treatment period demonstrated random or erratic responding, with slower and more variable response times when given placebo during the second period. Results indicate that methylphenidate treatment is associated with positive outcomes in processing speed, sustained attention, and both lab-based and everyday measures of executive functioning compared to placebo group. Additionally, results suggest sustained attention worsens when discontinuing medication. (JINS, 2019, 25, 740-749).

Effects of methylphenidate on the ERP amplitude in youth with ADHD: A double-blind placebo-controlled cross-over EEG study.

Methylphenidate (MPH) is a first line drug for attention-deficit/hyperactivity disorder (ADHD), yet the neuronal mechanisms underlying the condition and the treatment are still not fully understood. Previous EEG studies on the effect of MPH in ADHD found changes in evoked response potential (ERP) components that were inconsistent between studies. These inconsistencies highlight the need for a well-designed study which includes multiple baseline sessions and controls for possible fatigue, learning effects and between-days variability. To this end, we employ a double-blind placebo-controlled cross-over study and explore the effect of MPH on the ERP response of subjects with ADHD during a Go/No-Go cognitive task. Our ERP analysis revealed significant differences in ADHD subjects between the placebo and MPH conditions in the frontal-parietal region at 250ms-400ms post stimulus (P3). Additionally, a decrease in the late 650ms-800ms ERP component (LC) is observed in frontal electrodes of ADHD subjects compared to controls. The standard deviation of response time of ADHD subjects was significantly smaller in the MPH condition compared to placebo and correlated with the increased P3 ERP response in the frontoparietal electrodes. We suggest that mental fatigue plays a role in the decrease of the P3 response in the placebo condition compared to pre-placebo, a phenomenon that is significant in ADHD subjects but not in controls, and which is interestingly rectified by MPH.

Predicting the ergogenic response to methylphenidate.

Methylphenidate (MPH) and other stimulants have been shown to enhance physical performance. However, stimulant research has almost exclusively been conducted in young, active persons with a normal BMI, and may not generalize to other groups. The purpose of this study was to determine whether the ergogenic response to MPH could be predicted by individual level characteristics. We investigated whether weekly minutes of moderate-to-vigorous physical activity (MVPA), age, and BMI could predict the ergogenic response to MPH. In a double-blind, cross-over design 29 subjects (14M, 15F, 29.7 ± 9.68 years, BMI: 26.1 ± 6.82, MVPA: 568.8 ± 705.6min) ingested MPH or placebo before performing a handgrip task. Percent change in mean force between placebo and MPH conditions was used to evaluate the extent of the ergogenic response. Mean force was significantly higher in MPH conditions [6.39% increase, T(25) = 3.09, p = 0.005 118.8 ± 37.96 (± SD) vs. 111.8 ± 34.99Ns] but variable (coefficient of variation:163%). Using linear regression, we observed that min MVPA (T(25)=-2.15, β=-0.400, p = 0.044) and age [T(25)=-3.29, β=-0.598, p = 0.003] but not BMI [T(25) = 1.67, β = 0.320 p = 0.109] significantly predicted percent change in mean force in MPH conditions. We report that lower levels of physical activity and younger age predict an improved ergogenic response to MPH and that this may be explained by differences in dopaminergic function. This study illustrates that the ergogenic response to MPH is partly dependent on individual differences such as habitual levels of physical activity and age.

Methylphenidate alters brain connectivity after enhanced physical performance

Muscle fatigue is a disturbed homeostatic state characterized by a temporary inability to maintain force output and has lasting effects on the brain in the period immediately after exercise, such as decreased interhemispheric functional connectivity (FC). Stimulants that increase dopamine and norepinephrine neurotransmission can enhance performance during muscle fatiguing exercise (i.e. are ergogenic). We recently demonstrated that methylphenidate (MPH) increased force output and increased FC between the insular (IC) and hand motor cortex during a fatiguing handgrip task. However, whether resting FC is altered in the recovery period after enhanced force is unknown. The objective of these follow-up analyses was to examine the effects of performing a fatiguing handgrip task with MPH on subsequent resting state FC. In a double-blind counter-balanced design, participants ingested placebo or MPH and in a magnetic resonance imaging scanner performed: a six-minute pre-task resting scan, a fatiguing handgrip task during scanning, and then a six-minute post-task resting scan. We investigated task-related force and resting state FC pre- and post-task between: (1) interhemispheric motor cortices (M1) and (2) the right IC and left hand motor area. We found 1) a post-task reduction in M1 interhemispheric FC and that the extent of reduciton was negatively correlated with enhanced mean trial force in MPH conditions. 2) MPH but not placebo increased post-task FC between the right IC and left hand motor area. This study demonstrates that using MPH during a muscle fatiguing task has lasting effects on the brain that are markedly different from drug naïve conditions.

Methylphenidate Enhances Grip Force and Alters Brain Connectivity.

A central fatigue theory proposes that force output during fatiguing exercise is limited to maintain homeostasis. The self-awareness of the body's homeostatic state is known as interoception. Brain regions thought to play a role in interoception, such as the insular and orbital frontal cortex, have been proposed as sites for the upstream regulation of fatiguing exercise. Methylphenidate (MPH) can improve force output during exercise and may alter central processes during fatiguing exercise. However, the ergogenic neural underpinnings of MPH are unknown. This study examines the effect of MPH on force output and brain functional connectivity during a muscle-fatiguing handgrip task. In a double-blind, crossover design, 15 subjects (mean age = 28.4 ± 5.2; 9 males and 6 females) ingested MPH or placebo before performing a muscle-fatiguing handgrip task during functional magnetic resonance imaging. We examined force output and brain connectivity (psychophysiological interactions and functional connectivity) throughout the task as well as in the few seconds just before releasing the grip dynamometer (i.e., pretask failure). We show that in the MPH condition, subjects increased grip force throughout but not during pretask failure. Brain connectivity was altered throughout the task between the insular and the hand motor cortex, as well as between the insular and the orbital frontal cortex. There were no differences in connectivity during pretask failure. For the first time, we show that brain connectivity can be influenced by MPH during muscle-fatiguing exercise. This study provides additional support that the CNS acts to regulate motor drive subservient to homeostasis.

The effect of single-dose methylphenidate on resting-state network functional connectivity in ADHD.

We examined the effect of a single dose of methylphenidate (MPH) on whole brain functional connectivity, assessed using resting state functional MRI (rsfMRI), in young people with ADHD. 16 young people with ADHD participated in two rsfMRI scans in a randomized, placebo-controlled study with an acute dose of MPH (20mg). 15 typically developing controls also performed the task under placebo conditions. The network-based statistic (NBS) was used to identify differential connectivity patterns between the MPH and placebo conditions in the ADHD group. Mean connectivity of the resulting sub-network was examined in the ADHD and control groups. Resting state functional connectivity (RSFC) analysis revealed significantly reduced connectivity under MPH compared to placebo in young people with ADHD. Findings were robust across a range of thresholds. No sub-networks of increased connectivity were found at any threshold. Mean connectivity of the identified sub-network was significantly higher in ADHD individuals in the placebo condition compared to controls, however there was no difference between MPH condition and controls. We demonstrated a significant MPH-related reduction in RSFC in a large, robust network primarily involving occipital, temporal and cerebellar regions, and visual, executive and default mode networks. These findings suggest that MPH is 'normalising' a higher RSFC in young people with ADHD. This study is a novel addition to the understanding of treatment effects on the brain in ADHD.

Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial.

Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. To determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function. A randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment-naive status. Treatment with either methylphenidate or a matched placebo for 16 weeks. Change in the cerebral blood flow response to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses. Among 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receive methylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI, 0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95% CI, 0.7-14.8; P = .03). We confirm preclinical data and demonstrate age-dependent effects of methylphenidate treatment on human extracellular dopamine striatal-thalamic circuitry. Given its societal relevance, these data warrant replication in larger groups with longer follow-up. identifier: NL34509.000.10 and trialregister.nl identifier: NTR3103.

Commentary on Konsteniuset al. (2014): On medication development for stimulant addiction

The effort to identify a medication, any medication, to treat the broad group of individuals who become dependent on stimulants (methamphetamine, amphetamine) is one of the most significant tasks facing addiction research. This situation may make it tempting to over-interpret the generally positive findings in the Konstenius et al. report in this issue 1. Indeed, the results from the trial are impressive. Participants assigned to high-dose extended release methylphenidate condition were significantly more likely than participants assigned to placebo to reduce attention deficit hyperactive disorder (ADHD) symptoms and to provide scheduled urine samples that were negative both for amphetamine and for other drug metabolites. Time to relapse was longer for those in the active medication condition, as was retention in treatment. The size of the effects of the differences between the medication and placebo groups for both ADHD and drug use outcomes were apparent, even without checking the P-values. The authors are to be congratulated for this achievement. Nevertheless, it is the rarity of this positive report that underscores its importance. If the medication evaluated were anything other than a stimulant, these findings would energize replication trials and in broad groups of stimulant-dependent individuals not comorbid with ADHD; but that is not the case. A probably lackluster response among funders and scientists will highlight that the significant effort to develop medications for stimulant addiction is driven as much by politics as by data. None.

Methylphenidate and brain activity in a reward/conflict paradigm: Role of the insula in task performance

Psychostimulants, such as methylphenidate, are thought to improve information processing in motivation–reward and attention-activation networks by enhancing the effects of more relevant signals and suppressing those of less relevant ones; however the nature of such reciprocal influences remains poorly understood. To explore this question, we tested the effect of methylphenidate on performance and associated brain activity in the Anticipation, Conflict, Reward (ACR) task. Sixteen healthy adult volunteers, ages 21–45, were scanned twice using functional magnetic resonance imaging (fMRI) as they performed the ACR task under placebo and methylphenidate conditions. A three-way repeated measures analysis of variance, with cue (reward vs. non-reward), target (congruent vs. incongruent) and medication condition (methylphenidate vs. placebo) as the factors, was used to analyze behaviors on the task. Blood oxygen level dependent (BOLD) signals, reflecting task-related neural activity, were evaluated using linear contrasts. Participants exhibited significantly greater accuracy in the methylphenidate condition than the placebo condition. Compared with placebo, the methylphenidate condition also was associated with lesser task-related activity in components of attention-activation systems irrespective of the reward cue, and less task-related activity in components of the reward–motivation system, particularly the insula, during reward trials irrespective of target difficulty. These results suggest that methylphenidate enhances task performance by improving efficiency of information processing in both reward–motivation and in attention-activation systems.

Methylphenidate‐mediated reduction in prefrontal hemodynamic responses to working memory task: a functional near‐infrared spectroscopy study

Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique for bedside evaluation of cerebral metabolism that has clinical potential for monitoring the efficacy of pharmacological treatment. In this pilot study, we investigated the cognitive effects of methylphenidate (MP) on prefrontal function using fNIRS in healthy subjects. Thirteen right-handed healthy subjects underwent working memory tasks (0-back and 2-back) after a single oral dose of MP (20 mg) or placebo administered in a double-blind crossover design on two different days separated by 1-3 days. We measured changes in oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) concentrations during the tasks in bilateral prefrontal regions after MP or placebo administration using two-channel fNIRS. There were significantly more correct responses and fewer missed responses during the 2-back task performance after MP treatment as compared with placebo. Baseline-corrected oxy-Hb was significantly decreased after MP treatment compared with the placebo in the 2-back task in the right frontal region but was not different in the 0-back task. Baseline-corrected deoxy-Hb and total-Hb concentrations were not significant between MP and placebo conditions in either of the cognitive tasks. These data are consistent with previous positron emission tomography findings of MP-mediated reduction in lateral prefrontal activity accompanied by improved cognitive performance.

Neurochemical Enhancement of Conscious Error Awareness

How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited. We conducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors.

Methylphenidate Normalizes Fronto-Striatal Underactivation During Interference Inhibition in Medication-Naïve Boys with Attention-Deficit Hyperactivity Disorder

Youth with attention deficit hyperactivity disorder (ADHD) have deficits in interference inhibition, which can be improved with the indirect catecholamine agonist methylphenidate (MPH). Functional magnetic resonance imaging was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naïve ADHD boys. Medication-naïve boys with ADHD were scanned twice, in a randomized, double-blind design, under either a single clinical dose of MPH or placebo, while performing a Simon task that measures interference inhibition and controls for the oddball effect of low-frequency appearance of incongruent trials. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of healthy age-matched comparison boys. During incongruent trials compared with congruent–oddball trials, boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition, including right inferior prefrontal cortex, left striatum and thalamus, mid-cingulate/supplementary motor area, and left superior temporal lobe. MPH relative to placebo upregulated brain activation in right inferior prefrontal and premotor cortices. Under the MPH condition, patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions. Effect size comparison, furthermore, showed that these normalization effects were significant. MPH significantly normalized the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition, but did not affect medial frontal or temporal dysfunction. MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation.

The Adolescent Outcome of Children with Attention Deficit Hyperactivity Disorder Treated with Methylphenidate or Methylphenidate Combined with Multimodal Behaviour Therapy: Results of a Naturalistic Follow‐up Study

Children with attention deficit hyperactivity disorder (ADHD) who participated in a randomized clinical trial, which compared a brief intensive multimodal behaviour therapy combined with optimally titrated methylphenidate to optimally titrated methylphenidate alone (n = 45), were re-assessed at adolescence in a naturalistic follow-up 4.5 to 7.5 years after treatment. Also a matched normal control group was recruited (n = 23). Assessments at follow-up included diagnostic status, ADHD symptoms, oppositional and conduct behaviour, substance abuse symptoms and parenting stress. Of the 24 adolescents participating in the follow-up study, 50% still met diagnostic criteria for ADHD. There were no significant differences between adolescents at follow-up and those lost for follow-up. At follow-up, adolescents in the combined treatment condition used significantly less medication than children in the methylphenidate condition; there were no other significant differences between the treatment conditions. The adolescents showed a significant decline in hyperactivity/impulsivity, oppositional and conduct disorder symptoms from post-test to follow-up. Only inattention symptoms increased from post-test to follow-up but not to pre-test levels. The adolescents originally diagnosed with ADHD fared significantly worse than the matched controls on all outcomes, except on conduct disorder and substance abuse symptoms. Our study shows in adolescents, diagnosed with ADHD in childhood, age-dependent decline of ADHD symptoms, although they still fared significantly worse than matched normal controls. Implications of results are restricted by small samples size, and the results may be subject to chance findings and need replication before firm conclusions can be drawn.

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.

Methylphenidate modulates activity within cognitive neural networks of patients with post-stroke major depression: A placebo-controlled fMRI study

Methylphenidate (MP) is a dopamine- and noradrenaline-enhancing agent beneficial for post-stroke depression (PSD) and stroke recovery due to its therapeutic effects on cognition, motivation, and mood; however, the neural mechanisms underlying its clinical effects remain unknown. This study used functional magnetic resonance imaging (f MRI) to investigate the effect of MP on brain activity in response to cognitive tasks in patients with PSD. Nine stroke outpatients with DSM IV defined major depression underwent fMRI during two cognitive tasks (2-back and serial subtraction) on four occasions, on the first and third day of a three-day treatment of MP and placebo. Nine healthy control (HC) subjects matched for age and sex scanned during a single session served as normative data for comparison. The main outcome measure was cognitive task-dependent brain activity. For the 2-back task, left prefrontal, right parietal, posterior cingulate, and temporal and bilateral cerebellar regions exhibited significantly greater activity during the MP condition relative to placebo. Less activity was detected in rostral prefrontal and left parietal regions. For serial subtraction, greater activity was detected in medial prefrontal, biparietal, bitemporal, posterior cingulate, and bilateral cerebellar regions, as well as thalamus, putamen, and insula. Further, underactivation observed during the placebo condition relative to HC improved or reversed during MP treatment. No significant differences in behavioral measures were found between MP and placebo conditions or between patients and HC. Short-term MP treatment may improve and normalize activity in cognitive neuronal networks in patients with PSD.

Unexpected Effects of Methylphenidate in Attention-Deficit/Hyperactivity Disorder Reflect Decreases in Core/Secondary Symptoms and Physical Complaints Common to All Children

Abstract Hypotheses concerning unexpected, psychostimulant-related effects reported in previous studies were examined by separating behavioral/physical complaints highly specific to methylphenidate (MPH) from those that (a) may mimic core/secondary symptoms of the disorder, or (b) are commonly reported by unmedicated children in the general population. Sixty-five children with attention-deficit/hyperactivity disorder (ADHD) participated in a double-blind, placebo-controlled, within-subject (crossover) experimental design and received a placebo and four MPH doses in counterbalanced order following baseline assessment. Behavioral and physical complaints were significantly higher under baseline relative to placebo and the four immediate-release MPH conditions (5 mg, 10 mg, 15 mg, and 20 mg) across three symptom categories: ADHD core/secondary symptoms; symptoms commonly reported in the general population, including unmedicated children with ADHD; and symptoms highly specific to MPH. No significant differences were found among active drug conditions. Past unexpected findings of psychostimulant effects in ADHD may be due to the inclusion of scale items that reflect core/secondary features of ADHD and normally occurring behavioral/physical complaints in children.

The reliability, validity, and unique contributions of self-report by adolescents receiving treatment for attention-deficit/hyperactivity disorder.

Participants were 36 adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) who completed a summer treatment program. Self-report measures included the IOWA Conners Inattention/Overactivity and Oppositional/Defiant subscales, peer and staff interaction ratings, and a daily guess if the placebo or methylphenidate was given during a double-blind medication trial. Self-reports were reliable, and some of the self-report measures distinguished between placebo and methylphenidate conditions. However, the self-report measures exhibited weak correlations with observed frequencies of negative behavior and did not make a unique contribution beyond what was reported by adults. This study replicates previous findings that adolescents may be poor sources of information about ADHD symptoms, but adolescents receiving treatment for ADHD may be able to provide valid self-reports about negative social behavior.