Innovations in neuropsychological assessment using event-related brain potentials.

Historically, clinicians have utilized evoked potentials for evaluating sensory functions and neuropsychological tests for evaluating cognitive functions. However, the clinical implementation of event-related brain potentials (ERPs), an on-line index of cognitive processing, remains to be developed fully. We describe a new method for assessing language functions using neuropsychological tests that are formatted for computer presentation with simultaneous ERP recordings. From its inception, there have been two major objectives of this ERP language assessment research. Practically, we have sought to develop assessment techniques that would enable clinicians to evaluate the language functions of individuals with limited behavioral and communicative abilities. Conceptually, we have endeavored to increase the precision of neuropsychological testing through the development of measures that are sensitive to readily identifiable and objective neural responses. This article summarizes the issues central to the development of ERP assessment techniques, reviews recent normative studies with healthy individuals, and suggests some future avenues of research in this area.     

Olfactory event-related potentials and aging: normative data.

Unlike the clinical usages of evoked potentials (e.g. brain stem auditory evoked potentials for the assessment of auditory function), normative data for the olfactory event-related potential (OERP) have been unavailable. The principal objective was to establish normative data across the human life span for OERPs with a given set of parameters. Participants were 140 persons from seven age groups (16-19, 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years of age), with equal numbers of males and females, screened for nasal health and dementia. The odor stimulus was amyl acetate, presented at nasal temperature in a humidified airstream delivered by an air-dilution olfactometer at a constant flow rate, using a 60-s inter-stimulus interval. OERPs were recorded at Fz, Cz, and Pz electrode sites, amplified and averaged over trials. Amplitudes of the N1/P2 and P3 and latencies of the P2 and P3 were analyzed. Processing speed decreased at a constant rate over decades for the sensory (P2 latency) as well as cognitive (P3 latency) components. Decline in amplitude over decades was also apparent. Normative data will be useful in research on olfactory function and in clinical assessment of olfactory functional status.     

The objective assessment of amnesia in dissociative identity disorder using event-related potentials.

Assessment of amnesia in Dissociative Identity Disorder (DID) typically relies on self-report, the veracity of which cannot often be independently verified. Memory in DID was therefore assessed using an objective method that involved event-related potentials (ERPs) as well as indirect behavioral measures of memory, and that provided statistically supported assessments for each participant. Four participants who met DSM-IV criteria for DID participated in an ERP memory assessment task, in which words learned by one identity (identity A) were then presented to a second identity (identity B). All four participants - tested as identity B - produced ERP and behavioral evidence consistent with recognition of the material learned by identity A. While it would be premature to generalize all cases of DID, the results suggest that there may be reasons to question the veracity of reports by individuals who meet diagnostic criteria for DID on the basis of a structured clinical interview.     

Affective visual event-related potentials: arousal, repetition, and time-on-task

Affective stimulus pictures that differed in valence (unpleasant, neutral, and pleasant) were repeated as targets in an oddball task to elicit event-related potentials (ERPs) in young female adults. Each picture target was repeated consecutively four times, with picture order counterbalanced and time-on-task influences assessed across subjects. Response time decreased from the first to second stimulus presentation and remained stable. Stimulus repetition was associated with voltage increases for N1, P2, N2, and P3, from initial to subsequent presentations. Arousal effects did not interact with stimulus repetition at any latency range. Time-on-task was associated with decreased voltages for the N2 and P3 potentials but was unaffected by stimulus valence. The findings suggest affective arousal, stimulus repetition, and time-on-task independently modulate ERP outcomes at overlapping time ranges. Theoretical implications are discussed.     

Auditory event-related potentials in poor readers.

Although poor readers (PR) are considered the major group among reading-disabled children, there are not event-related potentials (ERP) studies reported of PR on the subject. In this study, attentional and memory processes were studied in an auditory oddball task in PR and normal controls. ERP to auditory stimuli were recorded in 19 leads of the 10/20 system, using linked earlobes as references, in 20 normal children (10 female) and 20 PR (10 female) of the same age (10-12 years old). Two pure tones (1000 and 3000 Hz) were used in an oddball paradigm. No significant differences were observed in the amplitudes and latencies of N100 between the groups. However, N200 to frequent stimuli and P200 to both frequent and infrequent stimuli were of higher amplitude in poor readers than in normal children. There were no differences between groups in the latency and amplitude of P300. The results suggest that PR use more attentional resources in the components occurring before P300 to both frequent and infrequent stimuli than the normal children, and this finding is particularly marked for PR girls.     

Emotion, attention, and the 'negativity bias', studied through event-related potentials.

Behavioral studies indicate that there exists a 'negativity bias' in the way surrounding events are processed. Particularly, it has been indicated that negative events elicit more rapid and more prominent responses than non-negative events. The objective of the present study was to explore the role of attention in relation to this negativity bias. Three groups of emotional pictures were used as stimuli: positive, negative and neutral. Event-related potentials were recorded from 35 subjects at F5, Fz, F6, C5, Cz, C6, P5, Pz and P6. Valence and arousal content of the stimulation was measured via a questionnaire. The experimental design ensured that subjects whose data were finally analyzed attended to the stimuli. ANOVAs showed that P200, an attention-related component, showed higher amplitudes and shorter latencies in response to negative stimuli than in response to positive stimuli. Additional partial correlation analyses indicated that P200 amplitude, but not latency, significantly associates (at frontal and central sites) with valence content of the stimulation. Therefore, due to the valence-related nature of the bias, it is concluded that intensity aspects (more than timing aspects) of the P200-related attentional processes are particularly involved in the negativity bias.     

Agency attribution: event-related potentials and outcome monitoring

Knowledge about the effects of our actions is an underlying feature of voluntary behavior. Given the importance of identifying the outcomes of our actions, it has been proposed that the sensory outcomes of self-made actions are inherently different from those of externally caused outcomes. Thus, the outcomes of self-made actions are likely to be more motivationally significant for an agent. We used event-related potentials to investigate the relationship between the perceived motivational significance of an outcome and the attribution of agency in the presence of others. In our experiment, we assessed agency attribution in the presence of another agent by varying the degree of contiguity between participants’ self-made actions and the sensory outcome. Specifically, we assessed the feedback correct-related positivity (fCRP) and the novelty P3 measures of an outcome’s motivational significance and unexpectedness, respectively. Results revealed that both the fCRP and participants’ agency attributions were significantly influenced by action–outcome contiguity. However, when action–outcome contiguity was ambiguous, novelty P3 amplitude was a reliable indicator of agency attribution. Prior agency attributions were also found to influence attribution in trials with ambiguous and low action–outcome contiguity. Participants’ use of multiple cues to determine agency is consistent with the cue integration theory of agency. In addition to these novel findings, this study supports growing evidence suggesting that reinforcement processes play a significant role in the sense of agency.     

Syntactic expectancy: an event-related potentials study

Although extensive work has been conducted in order to study expectancies about semantic information, little effort has been dedicated to the study of the influence of expectancies in the processing of forthcoming syntactic information. The present study tries to examine the issue by presenting participants with grammatically correct sentences of two types. In the first type the critical word of the sentence belonged to the most expected word category type on the basis of the previous context (an article following a verb). In the second sentence type, the critical word was an unexpected but correct word category (an article following an adjective) when a verb is highly expected. Event-related potentials (ERPs) were measured to critical words in both sentence types. Brain waves evoked by the correct but syntactically unexpected word revealed the presence of a negativity with a central distribution around 300-500 ms after stimuli onset, an N400, that was absent in the case of syntactically expected words. No differences were present in previous time windows. These results support models that differentiate between the processing of expected and unexpected syntactic structures.     

Passive long-latency event-related potentials in mental retardation.

Long-latency auditory event-related potentials (ERPs) were passively recorded in ten mental retardates and ten age-matched normal controls. Patients were mildly to moderately retarded and had epilepsy controlled with monotherapy, ERPs were recorded from CA-A1+A2, with 1000 and 3000 Hz tones in an "oddball" paradigm. Latency and amplitude of N1, N2, P2, and P3 components were compared in controls and retardates. All ten patients had reproducible AEPs, but these were attenuated in amplitude in four, although amplitudes did not differ significantly from controls. P3 was prolonged in latency in four patients, but patients and controls did not differ significantly. AEP latency and amplitude was not correlated with degree of retardation. These findings suggest that "cognitive" evoked potentials an be recorded passively in persons with impaired cognition, but are not correlated with intellectual ability and may not reflect specific cognitive functions.     

Frontal lobe damage and neuropsychological assessment.

Four cases with neuroradiologically verified frontal lobe damage are reviewed in terms of neuropsychological test performance and behavioral outcome. Frontal damage may result in a wide-spectrum of behavioral and cognitive changes that do not conform to a specific syndrome entity. Many of the traditional neuropsychological measures are insensitive to frontal lobe involvement. Various clinical guidelines are offered.     

Development of face-sensitive event-related potentials during infancy: a review.

Event-related potential (ERP) studies in adults have identified a number of components related to encoding and recognition memory of faces. Although behavioural studies indicate that even very young infants are able to detect faces and recognise familiar individuals, very few ERP studies document the neural correlates of these early abilities. In this article, we review four components (P1, N290, P400, Nc) and slow wave activity that are elicited while infants view faces. Where possible we draw links between these components and their possible equivalents to those observed in children and adults, and we highlight areas where further investigation is required. The theoretical importance of ERP studies of face processing in infants for debates about the origins and domain specificity of the adult cortical face processing system are discussed.     

Affective visual event-related potentials: arousal, valence, and repetition effects for normal and distorted pictures.

Event-related potentials (ERPs) were used to assess arousal (low, high), valence (negative, positive), and stimulus repetition effects for normal and distorted images from the International Affective Pictures System (IAPS). Distorted stimuli were constructed by dividing each image into small squares and rearranging the segments randomly to produce a "scrambled" picture. Event-related potentials (ERPs) were elicited by presenting the normal and scrambled images as target stimuli, with a repeated visual pattern used as the standard stimulus. Participants (N=32) were instructed to press a button to the targets and ignore the standard. Stimulus repetition effects were assessed by presenting each stimulus twice in the normal and scrambled condition. High-arousal stimuli yielded larger late positive components for both the normal and scrambled pictures. No overall valence effects were obtained, but arousal and valence influenced component amplitudes for middle-latency ERPs from the scrambled stimuli. For the normal pictures, stimulus repetition was associated with increased component amplitudes for all potentials and decreased RTs of all affective categories. For the scrambled pictures, no repetition changes were obtained. The findings suggest that stimulus arousal level contributes more than valence to affective ERP measures for normal as well as perceptually distorted pictures. Stimulus repetition engages memory for previous normal picture items but is not influenced by affective category. Theoretical implications are discussed.     

Sentence verification and event-related brain potentials

The purpose of this study was to examine whether the decision process affected scalp recorded event-related brain potentials (ERPs). ERPs were recorded while 10 subjects evaluated the veracity of four types of Japanese sentences; true-affirmative (TA), true-negative (TN), false-affirmative (FA), and false-negative (FN). Each sentence was presented visually, one word at a time in the following order: Subject (S); object (O); and verb (V). This order of words, which is normal in Japanese grammar, allowed the ERP waveforms associated with semantic mismatch between the S and O occurring in the middle of the sentence to be separated from those elicited by the decision concerning the sentence's truth or falsity occurring at the end of the sentence. Semantic mismatch was associated with a negative component (N310) following the O-word. In addition, P3s were elicited by sentence final words. Affirmative sentences elicited larger P3s than did negative sentences, and true sentences elicited earlier P3s than did false sentences. P3s were smaller in amplitude when they followed a mismatch between the S and O words. The result suggested that by using Japanese sentences, it may be possible to examine sentence-level rather than word-level processes.     

Chemosensory perception and event-related potentials in self-reported chemical hypersensitivity.

Anormal chemosensory perception has been identified as a possible mechanism underlying odor intolerance, but research in this domain has yet been rather limited. The main objective of the present study was to investigate total perceived intensity, unpleasantness, sensory irritation, and cortical activity assessed with chemosensory event-related potentials (ERPs) for three concentrations of pyridine ranging from predominantly olfactory to trigeminal in activation. Results from 19 individuals with self-reported chemical hypersensitivity and 19 controls with self-reported normal chemical sensitivity show that the hypersensitive group, compared to controls, rated the pyridine stimuli to be more intense and unpleasant, and that these group differences increased with pyridine concentration. Sensory irritation was also the perceptual dimension found to correlate strongest with score on the chemical sensitivity scale. However, no group differences were found in ERP amplitudes or latencies. These findings suggest that self-reported chemical hypersensitivity (1) can be associated with anormal chemosensory perception, (2) may be more closely related to trigeminal function than to olfaction, and (3) has a neural basis at a higher cortical level than that captured by chemosensory ERPs.     

Time effects on event-related brain potentials and vigilance performance.

A review of the literature showed that in vigilance or oddball tasks, changes over time in event-related potentials (ERPs) and performance measures often seem to be unrelated, but a number of studies had some shortcomings. In the present study a visual vigilance experiment was carried out, in which single-trial ERPs and performance data of 40 males were obtained. A relationship between time trends in behavioral and ERP measures was found: an early P3 amplitude and response latency (RT) showed an inversely varying relation over time. Analysis of covariance showed that the two linear trends tap the same aspect of processing: both trends became insignificant when adjusted for common variance. A negative correlation between mean values of P3 amplitude and RT rather than for change scores has been observed in previous studies, but has been ignored in the literature. However, correlations with RT have also been reported for other ERP deflections. Although there were several correlations between mean scores, most time-induced changes in ERP parameters appeared to be unrelated to worsening performance, for which several explanations are advanced. The ERP results do not support the hypothesis that a decrement in performance is caused by increasing difficulty discriminating targets from nontargets. A gradual decline in effort or resources allocated to the task might be an alternative explanation of performance deterioration. However, an effort-hypothesis cannot easily be tested. Effort is often invoked post hoc, and has previously been associated with many ERP components. The relationship between ERPs and the signal detection measures "sensitivity" d' and "response bias" beta is discussed.     

Clinical application of event-related potentials in dementing illness: issues and problems.

Many of the problems associated with the clinical application of event-related potentials (ERPs) are well recognized. These include the broad inter-subject variability of peak latencies and amplitudes in control groups, as well as the apparent non-specificity of some ERP tests. In addition, it is often the case that the same test yields a different proportion of 'hits' (in terms of identification of abnormality in patients classified by other means as having dementia) when used by different research groups. This is almost certainly due to differences in the disease state of the patients being tested. The difference between hit rates identifies another important factor which is not often considered in the application of ERP tests in clinical medicine. This is that although an ERP test may identify abnormality in the later stages of disease, the true task for the test is to identify abnormality in early disease when evidence of cognitive dysfunction will be different and less frank than in later stages of the disorder. It is therefore, necessary to identify the cognitive deficits associated with the early stages of dementia and devise appropriate ERP tests to detect these deficits. A recent paper by Fox et al. (Fox, N.C., Warrington, E.K., Seiffer, A.L., Agnew, S.K., Rossor, M.N., 1998. Presymptomatic cognitive deficits in individuals at risk of familial Alzheimer's disease. A longitudinal prospective study. Brain 121, 1631-1639.) suggests that ERP tests of verbal memory function may be the most sensitive for detecting the early stages of Alzheimer's disease.     

Age and novelty: event-related brain potentials and autonomic activity

Our aim was to study age-related differences in the habituation of orienting reaction by using novel visual stimuli. We intended to fill a gap in habituation research by recording both autonomic and ERP components of orienting to visual stimuli in the same sample and in highly related paradigms. We report data showing that in young subjects repetition of visual novels yielded fast habituation of both skin conductance responses and ERP components (P3(novel), N2b) whereas elderly people displayed no sign of habituation. However, cardiac deceleration--thought conventionally to be part of the orienting reaction--did not habituate in either group. Overall, most of our results harmonize with those obtained by using auditory stimuli; therefore we conclude that there is no significant modality specificity in age-related deterioration of habituation processes.     

Brain event-related potentials: diagnosing early-stage Alzheimer's disease

A pattern of components from brain event-related potentials (ERPs) (cognitive non-invasive electrical brain measures) performed well in separating early-stage Alzheimer's disease (AD) subjects from normal-aging control subjects and shows promise for developing a clinical diagnostic for probable AD. A Number-Letter task elicited brain activity related to cognitive processes. In response to the task stimuli, brain activity was recorded as ERPs, whose components were measured by principal components analysis (PCA). The ERP component scores to relevant and irrelevant stimuli were used in discriminant analyses to develop functions that successfully classified individuals as belonging to an early-stage Alzheimer's disease group or a like-aged Control group, with probabilities of an individual belonging to each group. Applying the discriminant function to the developmental half of the data showed 92% of the subjects were correctly classified into either the AD group or the Control group with a sensitivity of 1.00. The two crossvalidation results were good with sensitivities of 0.83 and classification accuracies of 0.75-0.79. P3 and CNV components, as well as other, earlier ERP components, e.g. C145 and the memory "Storage" component, were useful in the discriminant functions.     

Pesticide exposure and neuropsychological impairment in migrant farm workers.

The chronic, long-term effects from exposure to many frequently used pesticides have yet to be fully documented. Migrant Hispanic farm workers who are the frequent victims of such exposures are rarely studied. A neuropsychological test battery was administered to 21 migrant farm workers acutely exposed to Phosdrin, Lannate and Maneb on two occasions, and to 11 controls matched for age, sex, education, socioeconomic status, and ethnicity. Results revealed that two years after the pesticide exposures, the exposed group was significantly more impaired than controls on tests of psychomotor speed, dexterity, and visuospatial memory. Disturbing emotional symptoms were reported with significantly greater frequency by the exposed group in comparison to controls. Results are consistent with the previously reported constellation of symptoms and neuropsychological deficits associated with pesticide exposure.