Event-related potentials in schizophrenics

Fifteen schizophrenics and 15 age-matched controls were compared on 3 auditory event-related potential (ERP) paradigms that elicited a variety of components. In one paradigm, tones were given at 0.75, 2.25 and 6.75 sec interstimulus intervals; in another, infrequently occurring targets in a reaction-time task were interspersed with frequent background stimuli; and, in a third, noise bursts or tones were delivered in a random sequence at either 70 or 100 dB SPL. The sensitivity of some of the ERP components in distinguishing schizophrenics from controls depended on the conditions under which the component was elicited. N1 amplitude was smaller in the schizophrenics than in the controls after longer interstimulus intervals. P2 amplitude was smaller in the schizophrenics than in the controls after longer interstimulus intervals. P2 amplitude was smaller in the schizophrenics only at higher stimulus intensities. P2 latency was shorter in schizophrenics except in the paradigm that varied interstimulus intervals. P3 amplitude, however, was much smaller in schizophrenics than controls ragardless of whether P3 was elicited by targets in a task or was elicited by 100 dB SPL stimuli. The loud stimuli also elicited blink reflexes that coincided with N1, but these reflexes did not vary by clinical group. Neither the amplitude of the slow wave following targets nor the sustained potential that accompanies prolonged auditory stimuli differed between schizophrenics and controls.     

Auditory event-related potentials in schizophrenia and depression

Event-related potentials in two auditory target detection paradigms and two auditory paradigms without overt tasks were studied in 22 schizophrenic, 21 depressed, and 28 matched control subjects meeting Research Diagnostic Criteria. In the target detection paradigms, schizophrenics showed a pattern of reduced N120 amplitude and shorter P200 latency to frequently occuring tones, and reduced P300 and Slow Wave amplitude to infrequent target and nontarget tones. This pattern is consistent with impaired selective attention for stimuli. For depressed patients these variables were generally intermediate between those of schizophrenics and controls. In the other paradigms N120 latency was greater for schizophrenics, and P200 amplitude was less for depressed patients.     

Latency variability of the components of auditory event-related potentials to infrequent stimuli in aging, Alzheimer-type dementia, and depression

Auditory event-related potentials (ERPs) were investigated in 15 demented (12 presumed Alzheimer's, 3 cerebrovascular), 8 depressed, and 15 normal older, and 12 normal young, subjects. Both latencies from conventional averages and latency variability measures from single trials were derived for the N100, P200, N200, and P300 components of the ERP recorded from Fz, Cz and Pz scalp placements in a task requiring detection of an infrequent target tone among a series of frequent non-target tones. The P300 component most consistently separated the groups. Demented subjects had longer P300 latencies and greater P300 latency variability than both control groups and the depressed group. Age differences were observed for P300 latency, but not for P300 latency variability. Amplitudes were not significantly different among the groups. Reaction times (RTs) to the targets were longest for the demented subjects and shortest for the young controls, with the depressed and normal older control groups falling in between. Correlations between RT and P300 latency from single trials did not differentiate the groups. Using regression analysis to evaluate the deviation of P300 latency and latency variability for the patients from the predicted values for normal controls, no misclassifications of depressed patients occurred, but only 27% of the demented individuals were correctly classified using P300 variability, and 13% using P300 latency. These findings indicate that ERP measures using the 'oddball' target detection paradigm were useful in describing group differences, but were not sufficiently sensitive to be used in differentiating demented persons on an individual basis for clinical diagnosis.     

Visual detection of motion speed in humans: spatiotemporal analysis by fMRI and MEG

Humans take a long time to respond to the slow visual motion of an object. It is not known what neural mechanism causes this delay. We measured magnetoencephalographic neural responses to light spot motion onset within a wide speed range (0.4-500 degrees /sec) and compared these with human reaction times (RTs). The mean response latency was inversely related to the speed of motion up to 100 degrees /sec, whereas the amplitude increased with the speed. The response property at the speed of 500 degrees /sec was different from that at the other speeds. The speed-related latency change was observed when the motion duration was 10 msec or longer in the speed range between 5 and 500 degrees /sec, indicating that the response is directly related to the speed itself. The source of the response was estimated to be around the human MT+ and was validated by functional magnetic imaging study using the same stimuli. The results indicate that the speed of motion is encoded in the neural activity of MT+ and that it can be detected within 10 msec of motion observation. RT to the same motion onset was also inversely related to the speed of motion but the delay could not be explained by the magnetic response latency change. Instead, the reciprocal of RT was linearly related to the reciprocal of the magnetic response latency, suggesting that the visual process interacts with other neural processes for decision and motor preparation.     

Brain potentials in a memory-scanning task. II. Effects of aging on potentials to the probes

Brain potentials accompanying the classification of probe items as being members of a previously presented list were recorded from subjects ranging in age from 18 to 86 years old. A group of older subjects (average age = 66 years) was compared to a younger group (average age = 29 years). The items tested were verbal (digits) and non-verbal (musical notes). Digits were presented in the auditory and visual modalities, and notes were presented acoustically. Reaction times (RTs) and performance accuracy were computed. Potentials are described in terms of scalp distribution, latency and amplitude as a function of the type of stimulus (verbal/non-verbal, auditory/visual) and age group (younger/older). Evoked potentials to target notes in an auditory target-detection ('odd-ball') task were also recorded for comparison with the memory tasks. Potentials evoked by probes consisted of a sequence of sensory components in the first 250 msec followed by a cognitive component that was positive in polarity and sustained in duration (approximately 700 msec labeled P3), consisting of an earlier frontal component, P3a (mean latency: younger = 385 msec, older = 406 msec), and a large (15 microV) and later parietal constituent, P3b (mean latency: younger = 574 msec, older = 630 msec). The frontal derivation of the younger subjects showed a sustained negative bias of the wave forms in the latency range of 200-500 msec (P2 to P3) compared to the older subjects. Reaction times were longer in older subjects than in younger subjects for all stimulus types and set sizes. For the potentials evoked by the probes the younger group had consistently larger late parietal components (P3b) than the older group, whereas the late frontal potentials (P3a) were larger for the older than younger subjects. Except for visual stimuli, the latencies of the parietal sustained potentials were not influenced by subject age in contrast to the uniform changes in RT for all stimulus types. Significant amplitude and latency effects on the parietal sustained potentials accompanied the different stimulus types and memorized-set sizes which were similar for the two age groups. These results suggest that the effects of aging on short-term memory are primarily on response selection, as evidenced by RT slowing with aging, and not on memory-scanning processes as evidenced by the similarity of the latency measures of the accompanying brain potentials between the two age groups.     

P300 abnormality in schizophrenic subtypes

P300 and other long latency event-related potentials were recorded in 65 schizophrenic subjects and results were compared to findings in 119 healthy controls. Highly significant differences in P300 latency and amplitude were found between the two groups. Forty six per cent of schizophrenics had P300 latency more than two standard deviations longer than the mean for controls, 35% had a P300 amplitude smaller than the mean for controls by the same amount, and 24% were more than two standard deviations outside the mean for controls on both measures. These differences were independent of chronicity of illness, clinical subtype, family psychiatric history or the effects of neuroleptic medication. They confirm that P300 abnormality is present as a stable trait in a high proportion of schizophrenics. The status of abnormal P300 as a biological vulnerability factor for major mental illness is discussed.     

Nerve conduction studies of the sural nerve in childhood

A study of the sural nerve was undertaken to determine latency to onset and peak, duration of action potential, amplitude, and conduction velocity in 33 children, 1 to 7 years old. Multiple tests per patient resulted in 140 measurements per variable. To determine if the interpatient measurement variation was a significant factor compared to the intrapatient differences, one-way analysis of variance was performed. With each variable the F statistic showed the interpatient variation was significantly different (P less than .001) than the intrapatient measurement variation. There was no significant age effect in the latency to onset and peak, the amplitude, and the duration of action potential. The mean value for latency to onset was 2.430 msec, latency to peak 2.997 msec, duration 2.161 msec, and amplitude 8.736 muV. Age was highly significant (P less than .001) with conduction velocities calculated using latency to onset (CV1) and latency to peak (CV2), since distance was less in the younger child, according to the formulas: CV1 = 47.29 + 1.96 (age in years) and CV2 = 38.56 + 1.50 (age in years). Using regression analysis, temperature had no significant effect on CV1 or CV2.     

On the independence of the CNV and the P300 components of the human averaged evoked potential.

We report an experiment designed to assess the interactions between the CNV and the P300 components of human event-related potential. Eight subjects were each presented with series of experimental trials on all of which either a 1200 c/sec or an 800 c/sec tone was presented. There were three independent variables: (a) The presence or absence of a warning flash 1000 msec prior to the tone. (b) The task assigned to the subject--that is subjects were either to make a discriminative response to the tone or, on half the series, to predict prior to the tiral which of the two tones would be presented. (c) The predictability of the tone frequency. On half the series high and low tones alternated from trial to trial. On the other series, tones were chosen randomly on each trial. The data show that the amplitude of the P300 component is not affected by the presence or absence of a warning stimulus. Furthermore, the distributions of P300 and the CNV over the scalp are quite different. These conclusions are supported by a principal component and a discriminant analysis of the data. We conclude that the CNV and the P300 reflect the activity of functionally distinct cortical mechanisms.     

Apparent response incompatibility effects on P3 latency depend on the task

Ten young women were tested with an ERP paradigm that used the words 'left,' 'right,' 'LEFT,' 'RIGHT' as stimuli. The stimulus sequence was presented as several separate runs with varying response instructions. Subjects were instructed to respond according to the meaning of the stimulus in the (WORD task), to the case in which the stimulus was written (CASE task), or to both the case and meaning of the stimulus (CASE/WORD) task. In each task, half the trials called for a response that was incompatible with the stimulus. For the WORD task, compatible and incompatible trials were presented as separate blocks of trials. For all 3 tasks an additional stimulus sequence was presented in which the words were degraded with superimposed visual random noise. Reaction time (RT) in the CASE/WORD task was more than 100 msec later than in the other tasks. In the WORD and CASE/WORD tasks, RT was delayed more than 100 msec when the response was incompatible with the stimulus. Degrading the stimulus additionally delayed RT by about 100 msec. In the WORD and CASE tasks, error RTs were earlier than correct RTs. P3 latency was measured with a single-trial latency adjustment algorithm. P3 latency was delayed in the CASE/WORD task compared to the other 2 tasks. P3 was delayed by degrading the stimuli. Contrary to some previous reports, P3 was delayed by about 70 msec when incompatible responses were required, but only in the WORD task. Taken together with error and RT data, these P3 latency data are consistent with the notion that the task causes subjects to adopt different strategies and hence different types of processing (i.e., serial vs. parallel). Depending on the type of processing, P3 may appear to be affected by response incompatibility.     

Effects of performance feedback on P300 and reaction time in closed head-injured outpatients.

In an earlier study, we have demonstrated that the choice reaction times (RTs) of closed head-injured patients may be reduced significantly by instructions which emphasize speed, thus indicating that this portion of the RT delay was not due to a motor deficit. Despite the reduction in patient RTs, however, they remained significantly longer than those of controls. Furthermore, the RTs of patients were 56 msec longer than their P300 latencies, whereas those of controls occurred at about the same time as P300. The delay which remained in patient RTs was thus not entirely due to longer stimulus evaluation times. The goal of the present study was to further reduce patient RTs using feedback (FB) on response speed and time windows within which subjects were required to respond. When FB on speed and a 'narrow' time window were used, patient RTs occurred at about the same time as P300 latency (as was also the case with controls) indicating that the longer RTs of these patients in our earlier study, and in the other conditions of the present study, could not have been exaggerated beyond P300 latency due to a motor deficit. It was suggested that CHI patients may not be able to internally monitor their responses to the same degree as controls. The provision of external cues may have compensated for this deficit.     

Midlatency auditory evoked responses: differential recovery cycle characteristics

Middle latency responses (MLRs), in the 10-100 msec latency range evoked by click stimuli, were examined in two sets of 7 adult subjects utilizing 5 randomly ordered rates of stimulus presentation: 0.5/sec, 1/sec, 5/sec, 8/sec and 10/sec. Evoked potentials were collected in 250 trial averages for each rate, and a replication across rates yielded 500 trial averages. Peak-to-peak measurements for Pa-Nb and P1-Nb components revealed that the P1 component was reduced in amplitude or absent at the faster rates, while the amplitude of the Pa component remained unchanged across rates. In addition, the latency of Pa was significantly longer for the faster rates of stimulation. These findings were similar across both mastoid and sternovertebral references. Taken together with previous work, these data suggest that the human Pa and P1 potentials reflect different generator systems. Moreover, the physiological similarities between the human P1 potential and the cat wave A suggest that in the human, as in the cat, this potential may be generated within the ascending reticular activating system, whereas the physiological similarities between the human Pa and the cat wave 7, as well as previous clinical data, suggest an auditory cortex origin of this component.     

Manipulation of P3 latency: speed vs. accuracy instructions

Twelve young female subjects were presented with a series of horizontal line-pairs of same or different length in a two-alternative, forced-choice RT task, with 60 of each type pair in each block of trials. In one block (Easy) lines differed by 30%, in another block (Difficult) lines differed by 7%. Subjects were first given 60 practice trials with the Easy discrimination and with the instruction that speed and accuracy should be emphasized equally. For the next block of trials, accuracy was emphasized with a monetary bonus for accurate performance. Finally, in the last block of trials, speed was emphasized with a monetary bonus for speedy performance. Additionally, a penalty was incurred for RTs that exceeded a criterion level based on each individual subject's performance. The order of Easy and Difficult discrimination blocks was maintained within a subject but balanced across subjects. From the latency-adjusted P3s recorded from Pz, we obtained P3 latencies, amplitudes and single-trial P3 latency/RT correlations. RT to correct and incorrect trials and error data were also collected. P3 was considerably larger during the Speed than Accuracy conditions. The single-trial P3 latency/RT correlation was higher in Speed than in Accuracy runs. RT was 235 msec faster and P3 was 40 msec earlier during the Speed than during the Accuracy runs. On the other hand, discrimination difficulty delayed P3 and RT about equally, 28 and 43 msec respectively. This pattern suggests that speed instructions and discrimination difficulty affect stimulus processing time and response production time differently.     

Auditory event-related potentials and electrodermal activity in medicated and unmedicated schizophrenics.

Event-related potentials (ERPs) and electrodermal activity were studied in 14 medicated schizophrenics, 17 unmedicated schizophrenics, and 23 age- and education-matched controls. Subjects were run in three auditory stimulus paradigms differing from the usual ERP paradigms in having interstimulus intervals greater than 12 sec to permit measurement of the longer latency skin conductance response (SCR). In every paradigm medicated but not unmedicated schizophrenics had smaller N120 amplitudes and fewer SCRs than controls. In addition, medicated schizophrenics showed reduced P200 amplitude and latency, longer P320 latency, and reduced skin conductance levels in certain paradigms. These effects cannot easily be attributed to different mental states of medicated and unmedicated patients, since their Brief Psychiatric Rating Scale scores were almost the same. It is more probable that antipsychotic and antiparkinsonian drugs reduced electrodermal activity through anticholinergic mechanisms and that the antipsychotic drugs attenuated N120 through other biological mechanisms.     

Attention and short-term memory in chronic fatigue syndrome patients: an event-related potential analysis.

We recorded event-related brain potentials (ERPs) from 13 patients with chronic fatigue syndrome (CFS) and 13 matched normal controls. To assess attentional and memory deficits in CFS patients, we used a short-term memory task in which events occurred in different spatial locations and the patients made a rapid-response (RT) when a letter in a relevant location matched a letter in the prememorized set (Attention paradigm). Time-on-task effects on the ERP and behavioral measures were assessed over the 2 1/4-hour duration of this task. Both groups also performed a visual Oddball paradigm, with an RT, before and after the Attention paradigm. The patients' RTs were much more variable and, in nine of 13 cases, slower than the mean RT of the controls in both paradigms. The patients' memory performance was not significantly different from that of the controls and there were no group differences in the overall amplitude, latency, or scalp distribution of the N1, P2, N2, or P300 components of the ERP in either paradigm. The ERP and performance data from both paradigms suggest that perceptual, attentional, and short-term memory processes were unaffected in CFS patients and that the differences were limited to response-related processes.     

"Mental set" in controls, postalcoholics, chronic schizophrenics, and "organics"

Subjects consisted of (normal) controls, postalcoholics, chronic schizophrenics, and "organics" (a miscellaneous group of patients with acquired organic brain disorders including posttraumatic encephalopathy, Alzheimer's disease, Beh?et's disease, Huntington's chorea and poststroke encephalopathy). "Mental set" was measured by comparisons of simple auditory-manual reaction times (RTs) at preparatory intervals (PIs) of 2, 5, and 10 sec following "warning" light flashes. First, the PIs were varied randomly over 48 trials (irregular procedure); then, each of the three PIs was held constant for 16 successive trials (regular procedure). Overall RTs increased significantly and progressively from controls to postalcoholics to chronic schizophrenics to organics. Mean differences between irregular and regular RTs at each PI were either significantly less for postalcoholics, chronic schizophrenics, as well as chronic schizophrenics and organics show distinct impairment of "mental set," which may be a sign of organic brain dysfunction, if other factors such as severe cultural deprivation can be excluded.     

Age differences in P3-reaction time associations

Eight healthy old and 12 healthy young women had event-related potentials (ERPs) recorded during the performance of a memory retrieval task. For each subject the single trial data recorded at Pz were analyzed using Woody's adaptive filter technique. The old subjects differed from the young in several respects: P3 amplitude at Pz was smaller, P3 latency and reaction time (RT) were greater, the relationship between P3 latency and RT was considerably altered. The adaptive filter increased the amplitude of P3 but the age-related amplitude difference persisted, suggesting that this difference is not due to increased latency variability with age. The old subjects had lower single trial P3-RT correlations and longer elapsed time from P3 peak to the response than did the young subjects. Both groups had greater RTs for outset items ('negative' responses) than for inset items ('positive' responses). For the young subjects P3 latency was also greater for the outset compared to the inset items but the difference was not found for the old subjects. Thus, the relationship between P3 latency and RT is altered in the aged--P3 and RT are less tightly coupled than in the young.     

Task difficulty, probability, and inter-stimulus interval as determinants of P300 from auditory stimuli

The P300 event-related potential was elicited with auditory stimuli in 4 experiments which manipulated combinations of stimulus target probability (10% vs. 30%), task difficulty (easy vs. hard), and inter-stimulus interval (5 sec vs. 2 sec). P300 amplitude was smaller and peak latency longer for the more difficult relative to the easier tasks across experiments. Increases in stimulus target probability generally diminished P300 amplitude and shortened peak latency more for the easy relative to difficult task conditions. Increasing the number of non-target stimulus tones decreased P300 amplitude reliably, but increased latency only slightly. Task difficulty did not interact with variations in inter-stimulus interval which produced generally weak effects for both amplitude and latency. These findings suggest that P300 amplitude and latency obtained from auditory discrimination paradigms reflect processing difficulty independently of stimulus target probability unless differences in task requirements affect stimulus encoding.     

On hemispheric differences in evoked potentials to speech stimuli.

Eight subjects listened to lists of speech sounds (pa or ba) or pure tones (250 or 600 c/sec). Within each list one of the sounds (the "frequent") occurred more often than the other (the "target") in a ratio of approximately 4:1. Subjects were required to count the targets in each list; concurrently, evoked responses to both targets and frequents were being separately averaged from electrodes at vertex at symmetrical left and right parietal locations. The evoked responses show the expected sequence of deflections at all three electrode sites, including large P3 waves (about 350 msec latency) to the target stimuli. However, the left and right hemispheric responses to speech or tones, either frequent or target, were strikingly similar, both to the eye and by statistical tests intended to reveal differences between them.     

Sequence-dependent deterioration in the visual evoked potential in the absence of drowsiness.

When visual evoked potentials (VEPs) are tested patients are often expected to focus on a pattern screen for prolonged periods of time. This may lead to fatigue, failure of concentration and drowsiness, and consequently to a deterioration in the recorded VEP. To determine whether there may be time-dependent changes in the VEP of normal subjects independent of the degree of alertness, attention and altertness were controlled using a reaction time (RT) task in which the subjects were required to re-illuminate the fixation point in the middle of the stimulating screen for the VEP. It was first established that the switching of the fixation point produced little contamination of the background VEP to pattern reversal and that the latency and amplitude of P100 to pattern reversal were identical whether or not the subject was engaged in the RT task. A sequence of 16 averages of the VEP to 256 pattern reversals was recorded, alternately with or without the RT task. The measured RTs decreased during the sequence, presumably due to practice. There was a progressive decrease in the amplitude N70-P100, accompanied by an increase in the variability of the latency of P100. These changes cannot be attributed to lack of alertness, given the improvement in RT. Clinicians should be aware of the possibility of a deterioration in the VEP due to physiological mechanisms when the testing protocol involves multiple averages.     

Midlatency auditory evoked responses: differential effects of sleep in the human

Middle latency responses (MLRs) in the 10-100 msec latency range, evoked by click stimuli, were studied in 14 adult volunteer subjects during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. Evoked potentials were collected in 500 trial averages during continuous presentation of 1/sec clicks during initial awake recordings and thereafter during a 2 h afternoon nap or all-night sleep session. Continuously recorded EEG, EOG and EMG were scored for wakefulness, stages 2-4 of slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. The major components included in this study and their latency ranges, as determined by peak latency measurements from the awake records, were: ABR V, 5-8 msec, Pa, 30-40 msec, Nb, 45-55 msec, and P1, 55-80 msec. In agreement with previous reports, ABR V and Pa showed no amplitude changes from wakefulness to either SWS or REM. Not previously reported, however, was the dramatic decrease and disappearance of P1 during SWS and its reappearance during REM to an amplitude similar to that during wakefulness. This unique linkage between a particular evoked potential component and sleep-wakefulness indicates that its generator system must be functionally related to states of arousal. Relevant data from the cat model suggest that the generator substrate for P1 may be within the ascending reticular activating system.