Bert S. Kopell

Clinical application of the P3 component of event-related potentials. II. Dementia, depression and schizophrenia

Patients with dementia, schizophrenia and depression were tested with analogous auditory and visual event-related potential (ERP) paradigms designed to elicit a large P3. The patient groups were compared to age normative predictions derived from a large control sample for a number of ERP and behavioral variables. The results were similar for the auditory and visual paradigms. P3 latency was prolonged two or more S.D.s beyond that predicted by age for less than one-half of the demented patients. This latency prolongation was significant for the group as a whole but would result in too many false negatives if used diagnostically for individuals. Furthermore, increased P3 latency was not specific, as the schizophrenic patients also had later P3s. The amplitude of P3 was reduced in the demented patients, but it was also smaller in other patient groups. The only variable which distinguished the demented patients from both controls and from the other patients was the single trial P3 latency/RT correlation. The demented patients, as a group, had significantly lower P3 latency/RT correlations, but this effect also was not sensitive enough to be diagnostic for individuals. The data from these two paradigms suggest that the P3 amplitude and latency abnormalities observed reflect a common, rather than a diagnostically specific deficit. This study is in contrast to some others which report much more sensitivity and specificity in the use of P3 latency in the diagnosis of dementia. Differences in task demands, patient samples and ERP analysis techniques might explain some of the discrepancy.

Clinical application of the P3 component of event-related potentials. I. Normal aging

Normal adult volunteer subjects ranging in age from 18 to 90 years participated in a study in which analogous auditory and visual paradigms, with infrequently occurring target and non-target events, were used to elicit event-related potentials (ERPs) with a prominent P3 component. Of the 135 subjects participating, 66 completed both auditory and visual paradigms. The amplitude and latency of P3 were analyzed using average ERPs, single trials (adaptive filter) and principal components analysis (PCA). Age regressions were calculated using measures derived from average ERPs and single trials. Single trial measures were better than average ERP measures in demonstrating age-related changes in P3 latency. There was a significant increase in P3 latency with age of 1-1.5 msec/year. The range of normal P3 latency for a given age (1 S.E. of the regression = 40 msec for the visual target stimuli) was much larger than obtained by other investigators. The visual paradigm produced higher P3 latency/age correlations than the auditory paradigm (visual target r = 0.52, non-target r = 0.42; auditory target r = 0.32, non-target r = 0.33). Within individuals, the amplitude and latency of P3 generated by auditory and visual stimuli were highly correlated, though the visual paradigm produced larger and later P3s than the auditory paradigm. There is an apparent change in the scalp topography of P3 with age. In young adults, P3s to target stimuli have a markedly parietal distribution. The distribution of P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave (SW) rather than to changes in the amplitude of P3 per se.

Event-related potentials recorded from young and old adults during a memory retrieval task☆

Six healthy old and 8 healthy young subjects each received a series of trials in a memory retrieval task devised by Sternberg (1966). On each trials, the subject received a memory set of 1-4 digits and was then shown a test digit. The subjects task was to press one of two response buttons indicating whether the test digit was a member of the memory set for that trial. Response time (RT) was found to be an increasing, linear function of the number of items held in memory. The slope of the RT function was a composite measure of the time necessary to process each additional item in memory while the intercept was a measure of stimulus encoding and response processes that do not depend on memory set size (see Sternberg 1966, 1969, 1975). We found that the latency of P3 to the test stimulus also increased with increases in memory set size, although the slope of the P3 was less than that for RT. We have suggested that the intercept of the P3 slope reflects the time it takes to encode the test stimulus before the evaluation of the stimulus starts, while the slope reflects the amount of time per digit needed to evaluate the set. We have suggested that the difference between RT and P3 slopes represents the additional time per digit which the subjects waits before making a response, due to low confidence occurring with more difficult task conditions (i.e., when set size = 4). We further suggest that the intercept of the RT-P3 latency slope is a reflection of pure response processes. Time estimates of these processes are made for young and old subjects.

Age-related changes in auditory event-related potentials ☆

Twelve elderly and 12 young women were subjects in a reaction-time task designed to elicit middle and late event-related potentials (ERP). The aged subjects differed from the young in respect to the later occurring ERP components: P2 was larger and later; P3 was later and had a different scalp distribution; the slow wave (SW) was smaller. In contrast, no age-related differences were found for N1 amplitude or latency. It is suggested that the diminution in SW amplitude contributes to the change in scalp distribution of P3 amplitude seen with age. The relationship of reaction time and P3 latency of single trials was examined by the adaptive filter technique. There was no difference between the old and young subjects as both groups revealed signficant, positive P3 latency-reaction time correlations.

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 occurring 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.

Fluctuations in symptoms and moods during the menstrual cycle

Abstract Fifteen married, nulliparous women were studied longitudinally over two menstrual cycles. Changes in menstrual symptoms (pain, water retention, autonomic reactions), mood (anxiety, aggression, depression, pleasantness, activation), and sexual arousal were measured. Results indicated that these variables changed cyclically in relation to the menstrual cycle; that the 15 women were generally consistent from one cycle to another in their degree of symptomatology; that this consistency was greater for the intermenstrual than for the menstrual and premenstrual phases, suggesting greater variability of symptoms in these latter phases; and, that high and low premenstrual tension women tended to differ consistently from each other on negative affect throughout the cycle, as well as on another symptoms in other phases of the cycle. Consistently high premenstrual tension women may thus constitute an especially important group for endocrinologic studies.

Effects of perceptual and cognitive difficulty on P3 and RT in young and old adults

Ten healthy old and 10 healthy young subjects each received a series of trials in a memory retrieval task similar to that devised by Sternberg (1967). On each trial the subject saw a memory set of 2 or 4 digits (set size) followed by a probe. The task was to indicate whether the probe was a positive or negative instance (response type) of the memory set for that trial. On half the trials, the probe digits were degraded by a mask of random dots (stimulus quality). For both young and old subjects, RT was later to probes following the larger set size, later to degraded probes, and later to negative probes. For the young subjects only, P3 latency was delayed by the same variables affecting RT although to a lesser degree. P3 latency in the elderly responded quite differently: it was unaffected by set size or response type. However, P3 was somewhat delayed by the degraded probes suggesting that the failure to reflect set size or ceiling effect in the elderly. The correlation between single-trial P3 latency and RT in the elderly is lower than in the young. The data are discussed in terms of age-related differences in the meaning of P3 latency.

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 subjects 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.

P3 reduction in auditory evoked potentials of schizophrenics

Fifteen schizophrenics and 15 age-matched controls performed a reaction time (RT) task. A Bernoulli sequence of 85 dB SPL, 50 msec, 800 c/sec (P = 0.85) and 1200 c/sec (P = 0.15) tones was presented with an interstimulus interval of 1 sec. Subjects were instructed to press a button quickly upon hearing the 1200 c/sec tone. If a subject failed to respond within 650 msec, a 50 msec white noise burst occurred. In averages synchronized with target tones and computed without respect to RT, P3 was maximal at PZ with a mean latency of 330 msec for both schizophrenics and controls. P3 amplitude at PZ, however, averaged 6 muV in schizophrenics and 14 muV in controls (P < 0.001). Both mean RT and mean within-subject variance were greater in schizophrenices than controls. Other kinds of averages were computed to investigate the possibility that the amplitude differences were associated with different RTs or with differences in P3 latency variability in underlying trails. Averages of trials associated with short RTs (100--286 msec) had larger P3s than averages associated with long RTs (287--600 msec) (P < 0.01). Within each RT range, however, schizophrenic P3s were smaller than control P3s. Neither response-synchronized averaging nor adaptive filtering eliminated P3 amplitude differences between groups, indicating that P3 latency variability cannot account for these differences. We hypothesize that the smaller P3s in schizophrenics represent a deficit in reactivity to unexpected stimuli that is compatible with normal RT performance.