Does Methylphenidate Affect Information Processing? Findings From Two Studies on Performance and P3b Latency

Two studies were conducted to assess the impact of methylphenidate on normal young adults in a fixed version of Steinberg's memory scanning task. Both studies yielded characteristic monotonic increases in reaction time (RT) and P3b latency as a function of memory load. Also, in both studies, methylphenidate speeded up RT as and decreased error rates and intra subject RT variability. However, the slope of RT as a function of memory load, i.e. the rate of memory search, was not altered by the stimulant. In Study 1, P3b latency also was not affected by methylphenidate, a result suggesting that the stimulant brought about the decrease in RT by acting after the completion of evaluation, presumably by accelerating response processes. However, in Study 2, the drug significantly shortened P3b latency and the interval between RT and P3b latency. Thus, a speeding of both evaluation as well as motor processes was achieved. A review of procedural differences between the two studies suggests some possible explanations. In combination, the two studies indicate that methylphenidate consistently shortened the timing of motor processes and, under some circumstances, the duration of evaluation processes as well.     

Effects of Methylphenidate on Young Adults'' Performance and Event-Related Potentials in a Vigilance and a Paired-Associates Learning Test

Twenty-two normal young men received a counterbalanced and double blind administration of 20 mg methylphenidate and placebo. Two tasks were administered in counterbalanced order: an uninterrupted 45-min vigilance test and a paired-associates learning test. As previously reported, under placebo, accuracy and speed decreased monotonically over the course of the vigil. This degradation of performance was significantly reduced by the stimulant drug. Event-related potentials (ERPs) were derived for correctly detected targets and nontargets. The most salient pharmacologic effects involved a late positive wave (P464) identified as P3b. Methylphenidate reversed or reduced the decrease in amplitude and increase in latency of P464 present over phases of the placebo session. The results suggest that the stimulant-induced improvement in performance may be mediated by enhancement of evaluation processes. In the paired-associates test there were no pharmacologic effects. Instead there was an unexpected, pronounced improvement in learning in the second session, irrespective of the substance administered. However, the ERP evoked by the “stimulus” cue of each pair was systematically related to the achievement of learning criteria. A late positive was identified as P3b (P555) increased significantly in amplitude following the attainment of learning. There were no amplitude changes among ERPs evoked in the early post-criterion, late post-criterion, or overlearning “phases.” Nor were there amplitude changes between early and late pre-criterion categories. Thus, ERP amplitude displayed a binary association with the achievement of learning.     

On the Dependence of P300 Latency on Stimulus Evaluation Processes

McCarthy and Donchin (1981) found that the latency of a late positive component of the event-related potential (ERP) was influenced by the presence of noise in a stimulus matrix but not by the compatibility between the stimulus presented and the response required. They concluded that this component is a P300 and that its latency was influenced by stimulus evaluation but not by response selection processes. The present experiments were designed to confirm that the component identified by McCarthy and Donchin was indeed a P300 and to determine if its latency varies systematically with increases in stimulus evaluation time produced by graded changes in noise level. In Experiment 1, subjects performed a standard oddball task in which they were required to count the rarer of two stimuli (the words RIGHT or LEFT) which were, or were not, embedded in a noise matrix (characters from the alphabet). The positive component of the ERP, whose amplitude was larger for rare target stimuli, was labeled a P300, and the latency of this component was longer when the stimuli were embedded in noise. In Experiment 2, subjects performed a choice reaction time task. Following the procedures used by McCarthy and Donchin, stimulus words RIGHT and LEFT required right or left hand responses depending on the presence of a cue word SAME or OPPOSITE which preceded the stimulus. Stimulus words were presented in four different degrees of noise, the levels of which were manipulated by varying the set size of the alphabetic characters which could surround the stimulus words. Reaction time increased both with noise (by 325 ms) and as a function of stimulus-response incompatibility (by 127 ms). In contrast, P300 latency increased substantially with noise (by 200 ms) but, to a much lesser extent (by 14 ms), with response incompatibility. These results indicate that the P300 is sensitive to the ease with which a target stimulus can be discriminated from noise. They confirm that P300 latency can be used as a measure of the timing of stimulus evaluation processes that is relatively independent of response selection and execution.     

The Effects of Age on Human Event-Related Potentials

Event-related brain potentials were recorded from 72 normal subjects aged 20-79 yrs. The event-related potential to a detected improbable signal contained a large late positive component or P3 wave. The latency of the P3 wave in the response to an auditory signal increased regularly with increasing age at a rate of 1.36 ms per year, and its amplitude decreased at a rate of 0.18 μV per year. Similar age-related changes in the P3 wave occurred in the visual and somatosensory modalities. The change in the latency of the P3 wave occurred independently of any change in the reaction time, which showed no significant age-related change. The latency of the P3 wave associated with the detection of an omitted auditory stimulus did not change significantly with age.     

Event-Related Potentials and Autonomic Responses to a Change in Unattended Auditory Stimuli

Event-related brain potentials (ERPs) and autonomic nervous system (ANS) responses to occasional pitch and rise-time changes in a task-irrelevant auditory stimulus repeating at short intervals were measured while the subject performed a difficult intellectual task (Raven Matrices). It was found that deviant stimuli elicited the mismatch negativity (MMN) component of the ERP even when they elicited no ANS response. There was no significant difference in the mismatch negativity between trials in which the skin conductance response was or was not elicited. The pitch deviant tone also elicited heart rate deceleration, whereas the rise-time deviant tone tended to elicit a later heart rate acceleration. Neither heart rate change correlated with the mismatch negativity. The pattern of results obtained suggests that the mismatch negativity is generated by an automatic discrimination process associated with the cerebral events initiating the orienting response to stimulus change, but does not necessarily lead to the orienting response elicitation. Longer-latency ERP components tended to show slight covariation with ANS responses. The P3 was larger when a skin conductance response was elicited than when it was not elicited. Further, heart rate change trials tended to be accompanied by larger slow waves than trials with no heart rate response. Heart rate acceleration trials were accompanied by a larger slow parietal positivity and a smaller frontal negativity than were heart rate deceleration trials.     

Effects of Stimulus Probability and Task-Relevance on Event-Related Potentials

Stimuli were delivered to 12 subjects in a sequence that included regularly occurring standard tone pips, random warning tone pips, and random while noise bursts. Half the noise bursts were preceded by warning tones (high probability), and half were not (low probability). There were four runs, each having one of two noise burst intensities, and each having the warning tone and noise bursts either both task-relevant to a reaction time task or both task irrelevant. Event-related potentials (ERPs) were obtained by signal averaging in F₂, C₂, P₂ and eye leads. The P₃ to the warning tone was largest in P, and was not affected by task relevance. CNV_s preceded all the high probability noise bursts. These CNV_s had an amplitude of 5μV even when the bursts were task irrelevant. Low probability noise bursts elicited larger P3_s in all leads for the task-irrelevant condition, but only in P_z for the task-relevant conditions. In C_z, the amplitudes of NI. P₂, and P₃ to the high probability. task-relevant noise bursts correlated with the amplitude of the preceding CNV.     

Parietal P3 Response as an Indicator of Stimulus Categorization: Increased P3 Amplitude to Categorically Deviant Target and Nontarget Stimuli

Two experiments were performed in which we compared the effects of selected non-deviant versus categorically deviant stimuli on parietal P3 under a variety of conditions in which one, both, or neither stimulus was a target of an experimental task. Subjects were repeatedly presented with series of 8 numeric stimuli and 1 alphabetic (Deviant) stimulus. P3 amplitudes to target and nontarget Deviant stimuli were consistently and significantly larger than to other, non-deviant targets and nontargets, respectively. Nontarget Deviant stimuli evoked P3 amplitudes comparable to those evoked by low-probability non-deviant targets. The observed differences indicate that P3 amplitude is a sensitive indicator of perceived category differences, and that the effect of category deviance on parietal P3 amplitude is independent of task response classification (target or nontarget) and of response probability.     

Late Components of Auditory Event-Related Potentials to Eight Equiprobable Stimuli in a Target Detection Task

Fourteen normal subjects undertook a target detection task in which eight different but equiprobable stimuli were presented in an unpredictable sequence (four tone frequencies to either the left or the right ear). One tone/ear combination was designated as a target, to be responded to with a rapid button press. Event-related potentials were recorded from an array of six scalp electrodes. In Condition 1 no responses were required; in Condition 2 a response was required to the highest tone in one designated ear; in Condition 3 a response was required to the second highest tone in the ear opposite to the Condition 2 target. Event-related potentials to the no-task condition (1) included a P3-type late positive component. P3 increased in amplitude to target tones in Conditions 2 and 3, but showed equally large amplitude increases and some decrease in latency to nontarget tones in those conditions. However, a frontal Slow Wave component was elicited more specifically by target stimuli. An attended ear effect was evident in a processing negativity that extended for some hundreds of milliseconds prefrontally, but tended to be comprised of two separate negativities over fronto-central locations.     

Effects of Foveal Task Load on Visual-Spatial Attention: Event-Related Brain Potentials and Performance

The effects of foveal task difficulty on the processing of events in the visual periphery were investigated through an analysis of event-related brain potentials and performance measures. Subjects performed a foveally presented continuous monitoring task both separately and together with an arrow discrimination task that was presented at three different retinal eccentricities. The subjects detected occasional failures in the monitoring task while also responding to designated targets in the left and right visual fields. The analysis of the event-related brain potentials elicited by discrete events in the arrow discrimination task indicated that the amplitude of the N190 and P300 components decreased with both the introduction of the foveal task and an increase in its difficulty. The N160 component was sensitive to the distribution of attention within a task but was uninfluenced by dual task demands. These findings suggest that the N160 reflects the distribution of attention to different spatial locations within a task while the N190 may index the distribution of general purpose perceptual resources. P300 appears to index the allocation of perceptual/central processing resources. The implications of the results for models of resource allocation and attentional gradients are discussed.     

Event-Related Potentials and Recognition Memory For Pictures and Words: The Effects of Intentional and Incidental Learning

Event-related potentials were recorded under conditions of intentional or incidental learning of pictures and words, and during the subsequent recognition memory test for these stimuli. Intentionally learned pictures were remembered better than incidentally learned pictures and intentionally learned words, which, in turn, were remembered better than incidentally learned words. In comparison to pictures that were ignored, the pictures that were attended were characterized by greater positive amplitude frontally at 250 ms and centro-parietally at 350 ms and by greater negativity at 450 ms at parietal and occipital sites. There were no effects of attention on the waveforms elicited by words. These results support the view that processing becomes automatic for words, whereas the processing of pictures involves additional effort or allocation of attentional resources. The N450 amplitude was greater for words than for pictures during both acquisition (intentional items) and recognition phases (hit and correct rejection categories for intentional items, hit category for incidental items). Because pictures are better remembered than words, the greater late positive wave (600 ms) elicited by the pictures than the words during the acquisition phase is also consistent with the association between P300 and better memory that has been reported.     

The Effects of Serial Order in Long Sequences of Auditory Stimuli on Event-Related Potentials

The generalizability of the model relating P300 amplitudes to subjective probabilities, developed by Squires et al. (1976) for random series of events, was examined with respect to long sequences of repetitions, which had been restricted in randomness, allowing only for sequences of between 4 and 12 frequent clicks. Subjects were asked to silently count either the rarer of two clicks, presented with a probability of .10, or light stimuli occurring with the same temporal distribution. Within these limits there was an increase in P300 amplitude not only to the rare clicks, but also—contrary to predictions from the model—to the frequent non-target clicks following longer series of repetitions, provided that clicks had to be counted. A plausible interpretation might be that the longer the series of repetitions in long non-random sequences with low predictability, the more the subjects become involved in the “stimulus evaluation” of both kinds of events. A similar increase across serial position was found for the N100 component to frequent clicks when the auditory modality was defined as task relevant, and was interpreted as progressive focusing of selective attention. For the rare clicks there occurred a decrease in a slow Negative Shift with peak amplitude at 220 msec after long series of non-targets, possibly reflecting a facilitative effect of the focused attention on decision processes related to target detection. There were no differences between normals and chronic alcoholics with respect to the above-mentioned effects.     

The Effects of Semantic Priming and Word Repetition on Event-Related Potentials

Event-related potentials (ERPs) were recorded during the performance of a lexical decision task, in which a proportion of the words were either semantic associates or repetitions of the preceding word. Reaction times were faster to both the second member of associated pairs (targets) and repeated words, with the latter facilitatory effect being more than twice that of the former. ERPs to the semantic primes were more negative-going than those to targets. This difference peaked around 400–450 ms after stimulus onset. Comparison of unrepeated and repeated words revealed a larger and temporally more extended difference, with a similar scalp topography. The prime-target differences are interpreted as a further example of the sensitivity of the ‘N400’ component of the ERP to semantic relationships between words. The differences between the repetition and priming effects in ERPs are considered equivocal with respect to the view that the associated behavioural effects are caused by different cognitive mechanisms.     

Effects of Stimulus Repetition, Duration, and Rise Time on Startle Blink and Automatically Elicited P300

Intense auditory stimuli of sudden onset evoke not only startle blinks but also an event-related potential component resembling classic P300, even when subjects have no assigned task. To more closely examine the relationship of this P300 to startle, event-related potentials and eyeblink were recorded from 16 young adults in three paradigms designed to produce wide variation in startle amplitude: an Habituation series of 30-ms, 105dBA white noise bursts, a Duration paradigm which presented 105dB noise bursts for 3, 10, 30, or 90 ms, and a Rise Time paradigm which varied the rise/fall times (3, 15, 30, and 45 ms) of 110dBA, 1000-Hz tone bursts. Subjects received two runs of each paradigm. Only on the final Duration and Rise Time runs were stimuli explicitly task relevant; on those runs subjects rated verbally, midway in each 8.4-s interstimulus interval, the disturbingness of the prior sound. Although even the briefest noise bursts evoked parietal P300 as well as startle blink, P300 did not behave like startle. P300 habituated more slowly than did blink amplitude, was more responsive to sustained noise than were blink, N110, and P190, and most importantly, did not show the sensitivity to stimulus rise time manifested by these measures. These findings suggest that the amplitude of automatically elicited P300 is not governed by the same mechanisms as startle amplitude, but behaves more like a defense response.     

Normalizing Effects of Methylphenidate on Hyperactive Children's Vigilance Performance and Evoked Potentials

Evoked potentials during the × and B-X versions of the Continuous Performance Test (CPT) were evaluated in 29 hyperactive children after ingestion of placebo or methylphenidate (0.3 mg/Kg). Twenty-one age matched normal children were also assessed twice but without any drugs. In both tests, placebo-treated hyperactives made more omission and commission errors and displayed smaller late positive components (LPC) of the evoked response to salient experimental cues. Methylphenidate ameliorated hyperactives’ performance in both tasks and enlarged their LPCs in CPT-X. Several of these drug effects and diagnostic differences were absent for older hyperactive subjects, probably because some of the procedures were too easy for them. For younger patients the present tasks were sufficiently challenging, and the results reflect normalization of their deficits in sustained attention.     

The Identification of Concealed Memories Using the Event-Related Potential and Implicit Behavioral Measures: A Methodology for Prediction in the Face of Individual Differences

The development and validation of an event-related potential (ERP) memory assessment procedure is detailed. The procedure identifies learned material with high rates of accuracy, whether or not subjects give intentional responses indicating they had previously learned it. Because the traditional analysis of variance approach fails to provide probabilistic conclusions about any given individual, Bayesian posterior probabilities were computed, indicating the probability for each and every person that material was learned. The method was developed on a sample of 20 subjects, and then cross-validated on two additional samples of 20 subjects each. Across the three samples, the method correctly defined over 94% of learned material as learned, and misclassified 4% of the unlearned material. Additionally, in a simple oddball task performed by the same subjects, the method classified rare and frequent material with perfect accuracy. Finally, combining two implicit behavioral measures--mean reaction time and the number of incorrect responses--in Bayesian fashion yielded classification accuracy that actually exceeded that of the ERP-based procedure overall, but the two methods provided identical accuracy in classifying the most critical material as recognized.     

Effects of Visual Field, Stimulus Degradation, and Level of Practice on Event-Related Potentials of the Brain

The present study reports the results of an experiment in which subjects were instructed to indicate whether letter-pairs that were randomly presented in the center and peripheral (left and right) visual fields were semantically same or different. Letter-pairs could be either intact or perceptually degraded, and all subjects participated in 3 consecutive sessions of the experiment. The results showed that event-related-potential (ERP) components were strongly affected by the visual field of presentation of stimuli. Center field stimuli elicited late positive components (P630, SW) of larger amplitude than peripheral field stimuli, at all electrode locations. At lateral electrode sites, N200 components were always larger (more negative), and late positive components were consistently smaller (less positive) to contralaterally than ipsilaterally presented stimuli. However, the contralateral negativity of N200 was much larger over the right than left regions of the scalp, while positive ERP components showed a more symmetrical distribution of the contra- vs. ipsilateral stimulation effect. These results are discussed in relationship to cognitive aspects of information processing, as well as the neural origin of endogenous ERP components.     

Multiple Sources of P3b Associated with Different Types of Information

This experiment investigated how the P3a, P3b, and Slow Wave components of the event-related brain potential (ERP) respond to manipulations of the nature, timing, and extent of information delivery. There were two experiments in which the total amount of task information was distributed between pairs of successive stimuli (S1 and S2) within each trail. The task was to predict the relation between S1 and S2. In Experiment 1, the S1 could resolve no, partial, or all uncertainty with respect to the prediction outcome (correct or incorrect). Each S1 delivered three types of information: 1) outcome information--which resolved the subjects' uncertainty about the correctness of their prediction; 2) procedural information--which resolved uncertainty about how much outcome information would be delivered by S1; and 3) memory information--the identity of S1, which had to be stored for subsequent comparison with S2. In Experiment 2, the activity of these components was contrasted in two conditions in which the S1 delivered either memory information alone or both memory and procedural information. P3a and Slow Wave were sensitive only to outcome information. P3b was sensitive to all three types of information, and its scalp topography varied as a function of the type of information. The topographic variations indicate that P3b is not a unitary phenomenon but rather is a composite of activity arising from multiple intracranial sources of bioelectric activity.     

Parsing the late positive complex: mental chronometry and the ERP components that inhabit the neighborhood of the P300

Falkenstein, Hohnsbein, and Hoorman (1994) suggested that common measures of P300 latency confound a "P-SR" component whose latency corresponds to stimulus evaluation time and a "P-CR" component whose latency varies with response-selection time, thus casting doubt on work in mental chronometry that relies on P300 latency. We report here a replication and extension of Falkenstein et al. (1994) using a high-density 129-electrode montage with 11 subjects. Spatiotemporal PCA was used to extract the components of the ERP. A centroid measure is also introduced for detecting waveform-timing changes beyond just peak latency. In terms of componentry, we argue that the P-SR and the P-CR, correspond to the P3a/Novelty P3 and the P300, respectively. Conceptually, we dispute the proposed distinction between stimulus evaluation and response selection. We suggest a four-stage ERP model of information processing and place the P3a and the P300 in this framework.     

Attention to Color: An Analysis of Selection, Controlled Search, and Motor Activation, Using Event-Related Potentials

In this study the organization of information processing in a selective search task was examined by analyzing event-related potentials. This task consisted of searching for target letters in a relevant (attended) color. The ERPs revealed two different effects of attention: an early occipital negativity (+/- 150 ms) reflecting feature-specific attention, and a later, central N2b component (+/- 240 ms) reflecting covert orienting of attention. A later, prolonged negativity (search-related negativity) (+/- 300 ms), maximal at Cz, was related to controlled search to letters in the attended color. Detection of relevant targets resulted in a parietal P3b component. Depending on stimulus presentation conditions an earlier response to both attended and unattended targets was found: an N2 component (+/- 250 ms). In these same conditions, C'3-C'4 asymmetries (Corrected Motor Asymmetries--CMA) suggested motor activation at +/- 300 ms, in the same time range as search-related negativity. It was argued that N2 and CMA suggest the existence of a preattentive target detection system, operating in parallel with a slower serial attentive system, as reflected by N2b and search negativity.     

Effects of Methylphenidate on Hyperactive Children's Evoked Responses During Passive and Active Attention

Eighteen hyperactive clinical responders to methylphenidate were taken off medication and tested in two sessions during which they received an acute dose of methylphenidate and placebo in counterbalanced order. Seventeen normal boys of comparable age were tested without drugs. For both samples, evoked potentials were recorded during a Continuous Performance Test. Normal children made fewer errors of commission and omission and displayed faster reaction times than hyperactives tested under placebo. In addition, under active attention, the late positive component (LPC) of placebo-treated hyperactive boys' evoked responses exhibited smaller amplitude than normal controls'. Methylphenidate increased the amplitude of hyperactive patients' LPC and generally ameliorated their performance, especially commission errors and reaction times. The results confirmed previous findings of attentional disturbance in hyperactivity and normalization by methylphenidate of these patients' performance and electrophysiological activity during sustained attention.