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.

Response-contingent learning in children at risk.

Ninety-nine male offspring at ages 7 and 10, from schizophrenic, affective psychotic, nonpsychotic patient, and normal control parents performed a nonsense syllable discrimination task administered under each of three reinforcement conditions: neutral information feedback, and two response-contingent conditions, praise and censure. Index (patient) parent diagnosis was determined using DSM-III criteria. Although the four groups did not differ significantly in mean number of errors in learning the task under the neutral condition, when reinforcement was provided by the subject's mother during both praise and censure conditions, schizophrenics' and nonpsychotic patients' offspring made significantly more errors than offspring of affective psychotics and normal controls. Either form of social reinforcement administered by the mother, or merely the mother's voice itself, had a disruptive effect on the learning efficiency of the offspring of schizophrenic and nonpsychotic patients. Chronicity and comprehensibility of these parent's disturbances are considered as possible explanations of their children's performance.

Effect of methylphenidate on young adult's vigilance and event-related potentials.

Two studies were conducted on the effects of methylphenidate (20 mg) on young adults' event-related potentials. Although this stimulant elevated heart rate in study 1 (n = 14), it failed to affect either performance or amplitude of the late positive component (LPC) obtained from two versions of the continuous performance test (CPT). Because performance on these tasks was nearly error-free, we conducted study 2 (n = 23) to test the hypothesis that methylphenidate enlarges LPC amplitude only in more challenging tests than those used in study 1. In study 2, although heart rate was again elevated by the 20 mg dose of methylphenidate, LPC amplitude and performance were again unaffected in the two tasks employed in study 1 or in an easy tone discrimination procedure. However, in a more difficult version of CPT (10% errors of omission), both accuracy and amplitude of the concurrently obtained LPC were increased by methylphenidate. Similarly, in a choice-reaction time test, the stimulant increased speed as well as CNV amplitude. Our interpretation of the results is based on the view that LPC reflects the number of attentional resources committed to a stimulus during the evaluation stage. Thus, increases in LPC amplitude by methylphenidate are obtained only in tasks in which the subject may profit from the recruitment of additional attentional resources.

Learning-disordered children's evoked potentials during sustained attention.

Evoked potentials and performance of 19 learning-disordered (LD) and 19 normally achieving children were studied in two versions of the Continuous Performance Test (CPT). In both CPT procedures, LD children made more errors of omission and commission than did normal children. Evoked potential differences between groups were especially prominent in the more difficult BX version of the CPT. LD children displayed significantly smaller late positive components (LPC) of the evoked potential to critical stimuli in the task. There were no LPC differences between diagnostic groups for noncritical stimulus categories. The results suggest a deficit in behavioral and cortical indices of sustained attention among LD children.

Habituation and conditioning of skin conductance responses in children at risk.

This investigation extends the findings reported by Salzman and Klein (1978) concerning the skin conductance response (SCR) of the offspring of parents who had been hospitalized for a psychiatric illness. Skin conductance during rest and during experiments testing habituation and conditioning of the SCR was recorded in 7-year-old (n = 42) and 10-year-old (n = 57) children. Among the 7-year-olds, 11 had a parent with a diagnosis of schizophrenia, 12 had a parent with a diagnosis of affective psychosis and 19 had a nonpsychotic parent. Among the 10-year-olds, the corresponding distribution was 13 (schizophrenic), 20 (affective), and 24 (nonpsychotic). The results indicate (1) no marked tendency toward either rapid or absent habituation in the offspring of schizophrenics; (2) evidence of significantly greater conditioning among the 10-year-old offspring of schizophrenics; (3) only very weak evidence of greater responsiveness to intense stimuli among the offspring of schizophrenics; (4) no evidence of differences in SCR recovery time among the three groups of children; and (5) differences between diagnostic groups among the 10-year-old children in the pattern of tonic skin conductance levels across experiments. Differences in results between the two age groups were unexpected, but may represent either heterogeneity of diagnosis in the parents or developmental trends in electrodermal activity in the children. In sum, the results of this study produce only partial confirmation of the findings reported in the earlier investigation.

Effects of lithium on evoked potentials and performance during sustained attention.

Two versions of the continuous performance test (CPT) differing in complexity were administered to 15 patients with bipolar affective disorder, manic type before and after treatment with lithium. Reaction time, performance accuracy, and the late positive component (LPC) of the event related potential evoked by the task were measured concurrently. Lithium treatment decreased errors of commission on both CPT tasks, although the difference was significant only for the simpler task. Reaction time was significantly increased by lithium treatment on the more difficult CPT task, LPC amplitude to the target stimulus on the difficult CPT was significantly increased by lithium. The data are interpreted as consistent with an attention-enhancing effect of lithium, coupled with a general reduction in the tendency to respond to stimuli.

Relationships between stimulus intensity and amplitude of visual and auditory event related potentials.

Event related potentials were recorded from subjects presented with separate trains of lights and tones of three intensity levels (75, 240 and 750 fl and 60, 77 and 95 dB respectively). The auditory P1-N1 and N1-P2 components increased linearly with loudness, whereas in visual evoked responses, these components were maximal at an intermediate brightness. There was no correlation between responses to the two modalities. The results are examined in relation to current theories of cortical stimulus processing.

The late positive component of the evoked response in acute schizophrenics during a test of sustained attention.

To investigate the relationship between behavioral and cortical measures of impaired attention in schizophrenia, 17 hospitalized acute schizophrenics and 16 hospitalized nonpsychotic patients were studied. Event-related potentials (ERP) were obtained while subjects performed the Continuous Performance Test (CPT) under three conditions: First base line, Auditory-Visual Distraction, and Second base line. Schizophrenics made more errors of omission and commission and had longer reaction times. Analysis of the Late Positive Component (LPC) of the ERP revealed that both groups had an attenuated LPC during distraction and a larger LPC to the critical compared to the noncritical stimulus throughout all conditions. Schizophrenics had a smaller LPC and a smaller amplitude difference between the critical and noncritical stimulus than the nonpsychotics throughout all conditions.

Censure-praise learning of children at risk.

Twelve high risk and 27 low risk 10-year-old male children performed a nonsense syllable discrimination task administered under each of three reinforcement conditions: neutral information feedback, and two response-contingent conditions, praise and censure. Risk status was determined on the basis of index parent diagnosis (schizophrenic or nonschizophrenic) using DSM-III criteria. Although the two groups did not differ significantly in the mean number of errors made in learning the task under the neutral condition, when reinforcement was provided by subject's mother during both praise and censure conditions, schizophrenics' offspring made approximately twice as many errors as did offspring of controls. Either form of social reinforcement administered by the mother, or merely the mother's voice itself, has a uniquely disruptive effect on the learning efficiency of the offspring of schizophrenics.

The effect of distraction on acute schizophrenics' visual tracking.

To examine the nature of impaired smooth pursuit eye movement (SPEM) in schizophrenia, 16 hospitalized schizophrenics in the acute phase and 16 hospitalized nonpsychotic patients were studied. The experiment consisted of five 30-sec visual tracking phases: (i) base line (no distraction); (ii) auditory-visual distraction; (iii) middle base line; (iv) dichotic listening; and (v) final base line. Schizophrenics were characterized by significantly more velocity arrests throughout all phases of the experiment. Auditory-visual distraction did not impair either group's SPEM relative to base line performance. In contrast, dichotic listening significantly increased both groups' velocity arrests. This form of distraction also tended to produce greater impairment among schizophrenics. The failure of apparently intense auditory-visual distraction to significantly disrupt schizophrenics' SPEM suggests that inattentiveness alone does not account for schizophrenics' tracking impairment. This notion is supported by the finding that only the more intense distraction by dichotic listening produced a (trend toward) greater impairment in schizophrenics.

Habituation and conditioning of electrodermal responses in high risk children.

Measures of skin conductance during rest and during experiments testing habituation and conditioning of the skin conductance response were obtained from 42 10-year-old male children, of whom 12 were at risk for schizophrenia and 30 constituted low risk controls. While typical habituation curves for skin conductance response were obtained from both sets of offspring, no differences were found between high and low risk subjects on trials to habituation, response magnitude, latency, or number of spontaneous responses. However, there was evidence suggestive of differential conditioning in the two groups of children as a function of risk status. High risk offspring produced significantly larger skin conductance responses to conditioning test trials than low risk offspring. High risk subjects were also significantly more responsive to the unconditioned stimulus (loud white noise) than low risk subjects, but half-amplitude recovery time did not differentiate between the two groups of children. Finally, high risk offspring manifested lower levels of tonic conductance during conditioning, but not during resting or habituation. These results lend support to two important recent findings by Mednick concerning autonomic differences between high and low risk children, but do not confirm his findings regarding generalization and half-amplitude recovery time.

An independent study program within a medical curriculum.

The Independent Study Program (ISP) at the University of Rochester School of Medicine and Dentistry is described and its objectives are specified. Experimental (ISP) students and two matched (non-ISP students from the same class) groups were studied in two successive second-year medical school classes. Data were gathered only post-ISP for the first class and both pre- and post-ISP for the second. The data included measures of achievement, personality characteristics, and academic-professional experience. Experimental and control groups were not significantly different on achievement and academic-professional measures but did differ on certain measures of personality and values. The groups also differed on their evaluations of curriculum and reports of study habits. Fache ISP program was considered, and it was found that the ISP is less expensive of faculty time than is the regular curriculum but involves higher nonfaculty costs.