Clinical effects of a controlled trial of methylphenidate on adolescents with attention deficit disorder.

Forty-eight attention deficit disorder patients, 12 to 18 years old and without previous stimulant therapy, received a double-blind trial of methylphenidate and placebo for 3 weeks each. Stimulant treatment produced mild side effects and weight reduction. Methylphenidate significantly reduced teachers' and parents' ratings of hyperactivity, inattention, and oppositionality. In addition, patients rated themselves as clinically improved and reported elevated subjective mood during stimulant therapy. Treatment benefits were comparable for patients with and without concurrent conduct or oppositional disorder as well as those with and without past or present depressive disorders. These results support the continued effectiveness of stimulant therapy for attention deficit disorder in adolescence. However, the magnitude of clinical effectiveness reported was smaller than previously found in younger patients.

Effects of sustained-release and standard preparations of methylphenidate on attention deficit disorder.

Nineteen children with attention deficit disorder (ADD) participated in a double-blind trial consisting of four 2-week phases: sustained-release methylphenidate (MPH); standard MPH; a combination of standard and sustained-release MPH; and placebo. Pharmacological treatments were evaluated by means of parent and teacher ratings and open-ended comments, examiner ratings, and patients' performance and event-related potentials during Continuous Performance and Paired-Associate Learning Tests. Results revealed that the MPH conditions were superior to placebo and comparable to one another. Within the limited time frame of the research, the findings suggest comparable effectiveness for sustained-release and standard preparations of MPH.

Methylphenidate reduces abnormalities of stimulus classification in adolescents with attention deficit disorder.

Forty-eight adolescents with attention deficit disorder (ADD) received placebo and methylphenidate (M = 35.21 mg/day) for 3 consecutive weeks each. ADD patients who received placebo in the first phase of treatment were compared with unmedicated normal adolescents. ADD and normal adolescents did not differ in slope of reaction time as a function of memory load in a Sternberg (1969) memory task. These results may be interpreted as reflecting normal rates of memory search in ADD. However, in comparison with normal subjects, ADD subjects made disproportionately more errors to targets and lacked faster latencies of the P3b component of event-related potentials for targets than nontargets. These findings suggest abnormalities in stimulus classification. Methylphenidate did not affect ADD patients' rates of memory search, but it did reduce misclassifications of targets at high memory loads. The drug also evoked the normal pattern of slower P3b latencies for nontargets by shortening latencies for targets. Thus the stimulant reduced ADD adolescents' abnormalities in stimulus classification.

Clinical and cognitive effects of methylphenidate on children with attention deficit disorder as a function of aggression/oppositionality and age.

Children diagnosed with attention deficit disorder (ADD; n = 44), ADD plus aggression/oppositionality (ADD/O; n = 34), and as not meeting ADD criteria (NC; n = 29) received methylphenidate and placebo for 21 consecutive days each. Parents and teachers rated all groups improved under medication, but teachers reported less improvement for NC than for ADD/O children. Methylphenidate and chronological age had generally similar effects in a Sternberg task: greater accuracy and speed (especially for nontargets at low memory loads), larger P3b waves of event-related potentials, more pronounced slowing of P3b latency by memory load, and a greater trend of earlier peaks for targets than for nontargets. Both methylphenidate and maturation promoted more efficient strategies involving differentiated evaluation of targets and nontargets. These results were comparable among ADD groups.

Methylphenidate speeds evaluation processes of attention deficit disorder adolescents during a continuous performance test.

Forty-six 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 event-related 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.

Methylphenidate does not modify the impact of response frequency or stimulus sequence on performance and event-related potentials of children with attention deficit hyperactivity disorder.

Twenty-six children with attention deficit/hyperactivity disorder (ADHD) participated in a double-blind trial consisting of 2 consecutive weeks each of placebo and methylphenidate (M = 26.92 mg/day = 0.78 mg/kg/day). As expected, stimulant therapy resulted in moderate weight loss, increased somatic complaints, and teacher and parent reports of reduced inattentiveness, aggression, and oppositionality. In both phases of the trial, patients were tested in a choice reaction time task assessing two aspects of the task that presumably affect response selection: response frequency (ratio of targets/nontargets = 25/75 vs. 50/50) and stimulus sequence (alternations vs. repetitions). Both manipulations yielded expected results on performance and event-related potentials (ERPs). Stimulant treatment increased accuracy and speed among younger children and curtailed variability of reaction time for the sample as a whole. However, methylphenidate did not affect ERPs. In combination, the results imply that the enhancement of performance by methylphenidate does not involve the demands of response selection examined in this study.

Methylphenidate slows reactions of children with attention deficit disorder during and after an error.

A Sternberg memory search task was administered under placebo and methylphenidate to 42 children with cross-situational attention deficit disorder (ADD), 31 children with cross-situational ADD plus oppositional features, and 25 patients with marginal ADD. Overall, stimulant medication enhanced accuracy and speed. In addition, patients reacted faster on correct responses not preceded by an error than on errors (especially false alarms) or on correct responses following an error. The slowness during error reactions may reflect decreased confidence or confusion during stimulus classification. This uncertainty may also lead subjects to respond with greater caution, hence more slowly, on correct responses following errors. Notably, methylphenidate increased the slowing of reactions on error trials as well as on correct reactions following an error. Stimulant medication may augment subjects' persistence when they are uncertain or confused, thereby heightening caution and promoting accuracy on succeeding trials. Consistent with previous reports of the generality of enhancement of performance by stimulant medication, the impact of methylphenidate was comparable for the three subtypes of ADD studied.

Computer interpreted fetal electroencephalogram. I. Relative frequency of patterns.

Fetal electroencephalography (FEEG) is a clinical research technique for monitoring the electrical activity of the fetal brain during labor. Because of the massive volume of data, it has not previously been practicable to quantify the frequency of occurrence of the various patterns by visual analysis. With the use of a computer program, which has been shown to be consistent with visual interpretations, records for 11 fetuses, known to be neurologically normal at 1 year of age, were analyzed. Adequate FEEG had been recorded 73.6 per cent of the time during which the fetuses were monitored. In 10,511 10 second epochs of adequate FEEG, the Mixed pattern was found to be dominant, with a relative frequency of 41.2 per cent. The relative frequencies of Trace Alternant and High Voltage Slow activity were 32.3 per cent and 21.5 per cent, respectively. Low Voltage Irregular, Voltage Depression, and Isoelectricity occurred infrequently, accounting for approximately 4.6 per cent of the epochs. The relative frequencies of the various patterns were stable from the onset of monitoring of FEEG through neonatal EEG obtained in the delivery room. These data will form the basis for subsequent studies of FEEG changes associated with various endogenous and exogenous factors.

Computer interpreted fetal electroencephalogram. II. Patterns in infants who were neurologically abnormal at 1 year of age.

A computer program for pattern recognition of fetal electroencephalogram has been used to analyze the records of nine fetuses, known to be neurologically abnormal at 1 year of age. In 4,913 10 second epochs of adequate FEEG, Low Voltage Irregular (LVI) accounted for 17.8 per cent, Mixed activity (MIX) for 30.5 per cent, High Voltage Slow (HVS) for 18.1 per cent, and Trace Alternant (T/A) for 33.2 per cent of the epochs. The numbers of observed FEEG patterns in these abnormal cases appear to be significantly different from those in 11 normal cases (p less than 0.001)3. Specifically, the relative frequency of LVI was found to be increased in the abnormal cases (p congruent to 0.05). Moreover, LVI was significantly associated with visually interpreted prolonged voltage suppression (p less than 0.025) and lowered one-minute Apgar score (p congruent to 0.025). Using discriminant function analysis for LVI, MIX, HVS, and T/A patterns from FEEG recorded during labor, 10 of 11 infants were correctly classified as being neurologically normal at one year of age and 6 of 9 infants were correctly classified as being neurologically abnormal at 1 year of age. These studies confirm previous associations based on visual analysis of FEEG and suggest that the relative frequencies of FEEG patterns may be useful in the prediction of neurologic outcome 1 year later.

Computer interpreted fetal monitoring data. Discriminant analysis or perinatal data as a model for prediction of neurologic status at one year of age.

Intrapartum fetal monitoring may be useful in discriminating short-term and long-term infant outcomes. In order to develop a model for the classification of infants for measures of outcome and to evaluate the discriminatory value of selected perinatal data, 61 data files, which included computer interpreted fetal electroencephalogram and fetal heart rate, one and five minute Apoar scores, results of neonatal neurologic examination, and results of neurologic examination at one year of age, were submitted to computerized discriminant function analysis. For the classification of infants for neurologic status at one year, using FEEG patterns alone, 64% of the 42 normal infnats and 63% of the 19 abnormal infants were correctly classified. Using intrapartum FEEG and FHR patterns simultaneously, 69% of the 42 normal infants and 63% of the 19 abnormal infants were correctly classified. Combining intrapartum data with postpartum data, including one minute and five minute Apgar scores and neonatal neurologic examinations, 81% of the 42 normal infants and 79% of the 19 abnormal infants could be correctly classified. These results suggest that brain damage may already be present before birth, during labor, and that the risk of abnormal neurologic outcome at one year can be detected for a large percentage of infants using computer interpreted monitoring data during labor.

Fetal electroencephalography. Relationship to neonatal and one-year developmental neurological examinations in high-risk infants.

Sharp wave activity in fetal electroencephalograms was found to have a significant relation to neurological findings at 1 year of age but not to neurological findings obtained during the neonatal period. Neonatal neurological findings were significantly related to those at 1 year of age.

Effects of methylphenidate on processing negativities in patients with attention-deficit hyperactivity disorder.

This study compared the impact of methylphenidate on patients with Attention-deficit Hyperactivity Disorder (ADHD) with and without aggressive/noncompliant features in an oddball test consisting of a randomly ordered series of loud (frequent) tones, soft (rare) tones, bright (frequent) lights, and dim (rare) lights. In alternate conditions, subjects were required to respond to either the rare tones or the rare lights. These tasks were administered in a drug-free baseline session and after a counterbalanced treatment of 14 days each of methylphenidate (0.3 mg/Kg b.i.d.) and placebo (lactose b.i.d.). In comparison with placebo, methylphenidate resulted in greater accuracy and speed of reactions to targets of both modalities. The amplitude of N1 to auditory nontargets was larger when the target was a rare tone as opposed to a rare light, and this attention-related effect was increased by methylphenidate. The same differential amplitude enhancement by stimulant treatment was found for an early area measure of difference ERPs. In contrast, for N1 to visual nontargets the effect of selective attention (larger amplitude when the target was a rare light vs. a rare tone) was not significant and was not affected by stimulant medication. All these findings were comparable for the three ADHD subgroups, a result attesting to the generality of stimulant effects on information processing.

Effects of two doses of methylphenidate on cross-situational and borderline hyperactive children's evoked potentials.

This study involved 27 children displaying cross-situational hyperactivity and 14 youngsters with borderline hyperactivity. For all patients, evoked potentials were recorded after receiving 0 (placebo), 0.3 and 0.6 mg/kg methylphenidate. Under each pharmacologic condition, subjects were administered: a photic stimulation procedure; two versions of the Continuous Performance Test (CPT), which varied in difficulty level; and a discrimination ('oddball') test. Under photic stimulation, methylphenidate reduced the impact of increasing brightness levels on the rates of amplitude increment and latency decrease in the P208 component of the visual evoked response. These results are similar to those obtained by Buchsbaum and Wender (1973) for hyperactive patients with a positive clinical response to amphetamine. In CPT and the discrimination test, the two active dosages of methylphenidate brought about a comparable reduction of placebo levels of errors and reaction time. Analogously, in both versions of CPT, the two active dosages resulted in comparable increases in the amplitude of two components of the late positive complex (LPC; P510 and P740). P510 was identified as a classical P300. In the discrimination test, the effect of the stimulant on the response evoked by the visual non-target was to increase the amplitude of a component (P463) previously identified as P300. These pharmacologic results were nearly identical for borderline and cross-situational patients. In general, the results confirmed previous observations that methylphenidate improves hyperactive children's performance and increases the amplitude of their LPC. Further, these findings support previous observations that hyperactive patients' cognitive processing is optimized by a dosage of 0.3 mg/kg methylphenidate. Finally, the similarity between findings for cross-situational and borderline hyperactive patients is consistent with other evidence that stimulant effects are not limited to classically hyperactive children.