Ulrich Hegerl

Auditory-evoked potentials as indicator of brain serotonergic activity first evidence in behaving cats

Due to the increasing importance of the central serotonergic neurotransmission for pathogenetic concepts and as a target of pharmacotherapeutic interventions in psychiatry, reliable indicators of this system are needed. Several findings from basic and clinical research suggest that the stimulus intensity dependence of auditory evoked potentials (AEP) may be such an indicator of behaviorally relevant aspects of serotonergic activity (Hegerl and Juckel 1993, Biol Psychiatry 33:173-187). In order to study this relationship more directly, epidural recordings over the primary and secondary auditory cortex were conducted in chronically implanted cats under intravenous (i.v.) administration of drugs influencing the serotonergic and other modulatory systems (8-OH-DPAT, m-CPP, ketanserin, DOI, apomorphine, atropine, clonidine). The intensity dependence of the cat AEP component with the highest functional similarity to this of the N1/P2-component in humans was significantly changed by influencing 5-HT1a and 5-HT2 receptors, but not 5-HT1c receptors. This serotonergic modulation of the intensity dependence was only found for the primary auditory cortex which corresponds to the known different innervation of the primary and secondary auditory cortex by serotonergic fibers. Our study supports the idea that the intensity dependence of AEP could be a valuable indicator of brain serotonergic activity; however, this indicator seems to be of relative specificity because at least cholinergic effects on the intensity dependence were also observed.

Intensity dependence of auditory evoked dipole source activity

The spatio-temporal approach of dipole source analysis represents a crucial methodological progress in research on individual differences in the dependence of auditory evoked potential amplitude on stimulus intensity (augmenting/reducing) because overlapping subcomponents of the N1/P2-component can be separated and can be related to their generating cortical structures. Basic aspects of the intensity dependence of auditory evoked dipole source activity were analysed in 40 healthy subjects. The evoked responses to binaural 1000-Hz tones at five levels of intensity (60, 70, 80, 90, 100 dB sound pressure level) were recorded at 33 sites across the scalp. The dipole source analysis of the grand average data confirms the reports in the literature that the N1/P2 potentials at the scalp can be explained by two dipoles per hemisphere: a tangential dipole, representing activity of the superior temporal cortex (including primary auditory cortex), and a radial dipole, representing activity of the lateral temporal cortex (secondary auditory areas). The intensity dependence of the tangential dipole activity was significantly more pronounced than that of the radial dipoles, supporting the assumption that radial and tangential dipoles represent different physiological processes. A high reliability of the intensity dependence of the tangential dipole (Pearson correlation: r = 0.88) was found when retesting the subjects after three weeks. Age was negatively correlated with the intensity dependence of the tangential dipole. Dipole source analysis proved to be a reliable method which allows, at least in part, to study separately the intensity dependence of the evoked responses from primary and secondary auditory cortices. This is of importance with regard to the hypothesis that the central serotonergic system modulates the intensity dependence of the evoked N1/P2-response of primary auditory cortex.

Sensory cortical processing and the biological basis of personality

Action-oriented personality traits such as sensation seeking, extraversion, and impulsivity have been related to a pronounced amplitude increase of auditory evoked scalp potentials with increasing stimulus intensity. Dipole source analysis represents a crucial methodological progress in this context, because overlapping subcomponents of the scalp potentials can be separated and can be related to their generating cortical structures. In a study on 40 healthy subjects, it was found that sensation seeking is clearly related to the auditory evoked response pattern (N1/P2-component, stimulus intensities: 60, 70, 80, 90, 100 dB SPL) of the superior temporal plane including primary auditory cortex, but not to that of secondary auditory areas in the lateral temporal cortex. These results support the concept that the serotonergic brain system, which is supposed to modulate sensory processing in primary auditory cortices, is an important factor underlying individual differences in sensation seeking.

Sensation Seeking and Auditory Evoked Potentials

The relationship between auditory evoked potentials (AEP) and the German version of Zuckermans Sensation Seeking Scale was examined. The slope of the amplitude/stimulus intensity function (N1/P2 component) and the N1 latency were particularly studied, as these variables have been found to be potential predictors of the response to lithium prophylaxis. Thirty-three healthy subjects participated in two testing series on the first day and in a third run 3 weeks later. Binaural clicks at four intensity levels (58, 68, 78, 88 dB HL, ISI 2.1 sec) were presented in randomized order by headphone. Eighty responses were averaged at each intensity level. The pattern of correlation between the German version of the Sensation Seeking Scale and a personality inventory (FPI) supports the validity of the Sensation Seeking Scale. Only a tendency toward steeper slopes of the amplitude/stimulus intensity function (ASF) in high sensation seekers was observed in the first run. However, there was a significant interaction of sensation seeking and the test run. Only high sensation seekers showed an influence of retesting on the slope of the ASF, leading to a decrease of the slope in the second, compared with the first run. This might correspond to the psychological pattern of sensation seeking, which is characterized by a permanent need for new and exciting situations and, at the same time, by a rapid loss of interest in these situations. With regard to the N1 latency, a significant interaction of sensation seeking and lead was found. Low sensation seekers showed longer N1 latencies over the right than over the left hemisphere, a finding that accords with some psychophysiological theories on the relation between asymmetric hemispherical activation and certain psychological constructs. Our results support the view that sensation seeking is a personality feature that is closely related to certain physiological variables.

Intensity dependence of auditory evoked potentials in behaving cats

The intensity dependence of auditory evoked potentials (AEPs) recorded epidurally over the primary (AI) and secondary (AII) areas of the auditory cortex was studied in behaving cats during wakefulness, sleep and anesthesia. Four kHz tones of 50, 60, 70, and 80 dB SPL, presented in random order every 2 +/- 0.2 s by a bone conductor, elicited clear changes of the AEP amplitudes with increasing stimulus intensity, but individual components displayed different response curves. AEP components from the AI region showed saturation of their amplitude with stimulus intensity (P13, P34) or no amplitude increase (N19), while amplitude and intensity were linearly related in the AII area. The intensity dependence of the first positive component (P12/P13) was consistently stronger for the AEP recorded from the AI than from the AII area, while later components exhibited no difference between AI and AII. During slow wave sleep, the intensity dependence of this first positive component increased in the two areas, while that of later components decreased. Pentobarbital anesthesia abolished almost all later components and depressed the intensity dependence of the first positive component both in the AI and AII area. These results indicate that (I) clear intensity dependence of AEP exists in the cat auditory cortex and (2) this intensity dependence, especially that of the first positive AEP component, shares functional similarities to the human augmenting/reducing phenomenon in the auditory modality concerning regional differences and sleep-waking cycle.

Effect of lithium on the dynamics of electroencephalographic vigilance in healthy subjects

Eleven healthy male volunteers had EEG recordings before lithium, after 10 days of lithium administration and 2 weeks after discontinuation of lithium. As postulated from previous investigations the typical lithium effect on the dynamics of electroencephalographic vigilance proved to consist of: (1) a decrease of non-alpha segments, i.e., an increase of alpha continuity or an enhancement of alpha activity; (2) an increase of the anterior/posterior ratio of absolute alpha power (AQ); (3) a decrease of the dynamic variability of this alpha anteriorization (CV-AQ). In addition the decrease of dynamic variability of alpha anteriorization was found to be associated with an increase in the amplitude of P1/N1 components of auditory evoked potentials.

Ventricle size and P300 in schizophrenia

SummaryBoth ventricular enlargement and reduced P3 amplitudes are consistent findings in schizophrenic patients, suggesting that the two measures reflect a common underlying pathophysiological process in schizophrenia. Investigating 14 stabilized schizophrenic outpatients, a relationship between the size of the lateral ventricles as well as of the third ventricle on CT scans and the auditory event-related P3 amplitude was, however, not found. This negative result suggests that ventricular enlargement and reduced P3 amplitudes in schizophrenics reflect different pathophysiological processes. It is assumed that the P3 amplitude is related rather to abnormalities in the temporal lobe of schizophrenic patients.

Subklassifikation schizophrener Patienten und Prädiktion des Spätdyskinesierisikos mittels ereigniskorrelierter Potentiale

Zahlreiche Studien legen eine Subklassifikation schizophrener Patienten in eine Gruppe, die auf dem Boden einer genetisch bedingten Vulnerabilitat, und eine, die auf dem Boden einer mehr exogen bedingten Vulnerabilitat erkrankt ist, nahe [7, 8, 9, 14]. Zudem gibt es Hinweise, das Patienten mit hirnstrukturellen, vermutlich exogen bedingten Auffalligkeiten ein erhohtes und Patienten mit familiarer Belastung vergleichsweise ein niedriges Spatdyskinesierisiko aufweisen, obwohl die Literatur hierzu keineswegs konsistent ist [1, 2, Review bei 3]. Als Ursache fur eine exogen bedingte Vulnerabilitat sind u. a. pranatale Hirnentwicklungsstorungen zu diskutieren. In mehreren post mortem Untersuchungen an Schizophrenie- Gehirnen sind jeweils bei einer Untergruppe morphologische Auffalligkeiten im medialen Temporalbereich gefunden worden. Diese bestanden u. a. in einer reduzierten Neuronenzahl und einer Fehlanordnung hippokampaler Pyramidenzellen und werden auf Storungen der fotalen Neuroblastenwanderung zuruckgefuhrt. Als mogliche Ursache fur die Storung der Neuroblastenwanderung werden exogene Faktoren wie virale Infektionen der Mutter im 2. Trimenon diskutiert, ein Zusammenhang, den mehrere Arbeiten nahelegen [5, 10].

Diagnostics of extra-cranial carotid stenoses

SummaryIn 98 internal carotid arteries, continuous-wave ultrasound Doppler sonography (USD) and i.v. digital subtraction angiography (DSA) of the internal carotid arteries were performed. The findings were compared with each other prospectively and on the basis of conventional angiography findings. The aim of this investigation was to clarify, whether DSA would show stenoses with lumen restriction of less than 50% more precisely than USD, or whether it would enable clearer localization of any vascular lesions.The results revealed that in cases of haemodynamic effective stenoses and occlusions both procedures correlated well with each other and also with catheter angiography. However, USD and DSA showed increasing discrepancies of findings with decreasing degree of severity of the stenosis. The accuracy for localization of stenoses also decreased markedly for both methods with increasing distance from the carotid bifurcation.In the case of congruent findings of USD and DSA in haemodynamic effective stenoses (degree of stenosis more than 75%) or occlusions conventional angiography did not increase the diagnostic information, and it seems therefore dispensable for vascular surgical decisions. However, in cases with existing clinical symptoms with contradictory or negative USD and DSA findings angiography is still indicated.