Neurochemical substrates and neuroanatomical generators of the event-related P300.

The present review focuses on the current knowledge of the neurochemical processes and neuronal structures involved in the generation of P300. The increasing knowledge in this area facilitates the physiological interpretation of P300 findings as well as the link between P300 research and other research findings in biological psychiatry. Concerning the question of neurochemical substrates, the glutamatergic, GABAergic, cholinergic, noradrenergic, dopaminergic and serotonergic influences on P300 are reviewed. The knowledge of the generating structures of P300 is summarized from intracranial studies, magnetoencephalographic investigations, lesion and animal studies.

Stability of the mismatch negativity under different stimulus and attention conditions.

OBJECTIVE: Mismatch negativities (MMN) elicited by frequency and duration changes in a sequence of repetitive tones were recorded in test and retest sessions from 45 subjects. METHODS: Tones presented with a stimulus onset asynchrony (SOA) of 0.5 s were to be ignored while attention had no instructed focus in one group and was directed to an active visual vigilance task in a second group of subjects. RESULTS: MMN amplitude was larger for duration deviants, the focus of attention had no systematic effect. Individual replicability of the MMN amplitudes was generally better when duration deviants were used. In addition, directing attention to the visual task increased the retest reliability of the duration deviance MMN. In this condition, the test-retest correlation coefficients were above 0.8 at all frontal scalp sites (0.87 at F4). CONCLUSIONS: The study shows that the deviant type as well as the attentional condition may have substantial effects on the stability and replicability of MMN potentials. The choice of the appropriate task condition is essential for using the MMN in group comparisons and as a diagnostic tool in individual cases.

Late auditory evoked potentials (P300) do not discriminate between subgroups of alcohol-dependent patients defined by family history and antisocial personality traits.

Alcohol dependent patients with a family history of alcoholism and with antisocial personality traits were supposed to have frontal brain dysfunction. Late evoked potentials may be useful to discriminate these patients from patients without family history or antisocial behavior. We investigated 56 abstinent patients hypothesizing that four subgroups of abstinent alcoholics with regard to family history (FHP: family history positive, FHN: family history negative) and antisocial behavior (ASP: antisocial traits present, ASN: antisocial traits not present) would exhibit differences in P300, particularly when recorded by frontal electrodes. FHP/ASP patients were expected to show the lowest P300 amplitudes in frontal electrode sites. Beside single electrode recordings, a new method in analyzing P300 scalp data by dipole source analysis (BESA: Brain electric signal analysis) was used. No difference in the P300 values was observed between the FHP/FHN and ASP/ASN groups. Similar results were found by analyzing ASP/ASN and FHP/FHN groups separately. The findings of single electrode recordings were consistent with BESA-dipole results. In conclusion, auditory P300 had a low discriminative power with regards to subgroups of inpatient alcoholics defined by family history and antisocial personality traits. Reasons for the negative findings in this study are discussed.

P300 subcomponents reflect different aspects of psychopathology in schizophrenia.

BACKGROUND: The aim of the study was to investigate abnormalities of P300 subcomponents in schizophrenic patients as well as relationships between these subcomponents and positive versus negative schizophrenic symptoms. METHODS: Nineteen schizophrenic patients and 19 healthy controls were tested with an auditory event-related potential oddball paradigm designed to elicit the P300. The P300 data were analyzed by separating P300 subcomponents with a recently developed dipole source model. RESULTS: Compared to healthy controls, schizophrenic patients showed reduced P300 amplitudes of the temporo-basal dipoles, corresponding mainly to P3b. Positive symptoms of the Positive and Negative Syndrome Scale correlated positively with the temporo-basal but not with temporo-superior dipole P300 activities, whereas negative symptoms correlated positively with the temporo-superior but not with temporo-basal dipole activities. CONCLUSIONS: The P300 subcomponents separated with the dipole model are affected in a different manner by positive versus negative symptoms. Furthermore, the positive correlation between the severity of psychopathology and the P300 amplitudes of the different dipole activities appears to be a state-dependent effect, which has to be separated from the P300 amplitude reduction as a trait marker in schizophrenic patients.

Dipole localization and test-retest reliability of frequency and duration mismatch negativity generator processes.

The mismatch negativity (MMN) is an event related potential component elicited by changes in duration, frequency or intensity of the stimuli during repetitive series of equal standard stimuli. In the present study we compared duration and frequency MMN using dipole source analysis concerning both the test-retest reliability of MMN-amplitudes and the locations of the potential sources. Furthermore, the influence of attention for test-retest-reliability was studied. Therefore, two groups of healthy subjects were investigated with different attentional manipulations. Twenty-one healthy subjects had to perform a visual attention task during the recording and 21 healthy subjects had no additional task to perform. All subjects were studied twice with a time interval of 3 weeks. Test-retest reliability was sufficiently high for the frequency but slightly lower for the duration MMN. The locations of the frequency and duration MMN-dipoles were in the auditory cortex with a more anterior and caudal location for the frequency MMN-dipoles. The latter finding supports the hypothesis that the frequency and duration MMNs have separate neuronal generators.

Dipole source analysis of P300 component of the auditory evoked potential: a methodological advance?

A dipole model of the P300 component of the auditory evoked potential was developed with the aim of separating the overlapping P300 subcomponents and assessing the reliability of P300 dipole parameters compared with other methods such as principal component analysis (PCA). P300 was recorded within an auditory oddball paradigm in 57 healthy subjects. Dipole source analysis was performed with Brain Electrical Source Analysis (BESA). With a temporo-basal and a temporo-superior dipole per hemisphere, most of the variance of scalp-recorded P300 activity can be explained. When dipole source analysis is used, the test-retest reliability of P300-amplitude measurements is enhanced as compared with PCA or single channel analysis. The P300 activity of the temporo-basal dipoles and that of the temporo-superior dipoles differ in several respects (e.g. latency, correlations with age) and thus appear to reflect functionally different neuronal processes. In spite of problems in the interpretation of dipole locations, it is concluded that dipole source analysis enhances both the reliability and physiological validity of P300 parameters.