Auditory information processing is altered in novelty stress conditions: first session effects in auditory-evoked potentials.

Novelty conditions may elicit stress responses. First session effects are systematic changes in physiological parameters, resulting from the interference of physiological processes with novelty stress. Along with endocrinological changes, these stress responses may be accompanied by alterations of sensory and attentional processes. The present study examines the impact of novelty conditions on event-related potential indicators of auditory information processing and on cortisol. Twenty-two healthy subjects participated in a series of experimental sessions. Auditory-evoked potentials were recorded, and the plasma cortisol levels were determined. The first session causes an activation of the hypothalamo-hypopituitary-adrenal axis. The auditory-evoked potentials show an additional slow negative potential component in the novelty condition. This potential component is maximal at fronto-central electrode sites and reaches its peak at about 240 ms after stimulus onset. Similarities with the processing negativity suggest alterations in attention-related auditory information-processing in the novelty condition encountered in the first session.

Enhanced long-latency somatosensory potentials in major depressive disorder.

Bodily misperceptions are a frequent symptom in major depressive disorder. A reduced ability to deflect attention from somatosensory stimuli may contribute to the generation of unpleasant bodily sensations and co-occur with altered habituation of the brain electric reactions to somatosensory stimuli. The aim of the present study was to explore whether attention-related components of somatosensory evoked potentials (SSEP) and the habituation of these components are altered in major depression. Fifteen patients with major depressive disorder were compared to an age- and gender-matched group of 15 healthy controls. A series of identical, intrusive but not painful electric stimuli were applied to the left index finger for 48 min. Averaged SSEP were computed from multichannel EEG recordings for consecutive recording blocks of the experiment, each block containing 162 stimuli. Based on these data the habituation process of late components of the SSEP was analysed in two latency intervals (50-150, 170-370 ms). Patients showed significantly enhanced reactions throughout the entire experiment. The persistence of enhanced SSEP components throughout the habituation process may be caused by a deficit in reducing the activity of attention-related brain processes concerned with intrusive, yet behaviourally irrelevant, continued stimulation in the state of major depression.

Orienting response and frontal midline theta activity: a somatosensory spectral perturbation study.

OBJECTIVE: Brain electric activity in the theta frequency band has been associated with the encoding of new, and the retrieving of previously stored, information. We studied the time course of stimulus-to-stimulus changes of theta activity under repetitive somatosensory stimulation. MATERIALS AND METHODS: Twelve healthy subjects participated in the study. Repetitive electric stimuli, grouped into 48 stimulus trains, were applied to the left index finger. The stimulus trains contained 27 stimuli (0.9 Hz, 2.5 times sensory threshold). Each stimulus train of 30 s was followed by a stimulus-free break of 30 s. This stimulation paradigm allowed the separate estimation of effects for each position of the stimulus in the train and an analysis of stimulus-to-stimulus changes. Multichannel EEG recordings allowed a topographic analysis of the event-related spectral perturbation effects in the theta frequency band. The brain electric novelty response triggered by the stimulus train onset was analyzed by 3 methods: (1) event-related potentials; (2) event-related power spectra for the investigation of spectral perturbation effects on theta activity; and (3) an approach to break down the stimulus-induced theta activity into phase-locked activity and effects on the spontaneous, ongoing theta activity using digital filtering. RESULTS: The main findings are a frontal midline activation in the theta band with the beginning of the stimulus train, which habituates during the subsequent stimulation cycles, as well as evidence that distinct effects of the first stimulus on the ongoing, non-phase-locked, theta activity exist.

Topography and morphology of heart action-related EEG potentials.

Joint ECG and EEG measurements were performed in 22 healthy subjects under standardized laboratory conditions. Averaged EEG potentials were computed using the R-peaks in the ECG as reference events. Spatio-temporal potential patterns of heart action-related EEG activity were obtained from 26 scalp channels. A heart action-related positive potential was found, peaking over the parietal scalp regions. Its independence from the cardiac electrical field, the source of an EEG artifact that may be confounded with heart action-related brain potentials, is demonstrated. The potential reaches its maximum amplitude of about 0.5 microV at a latency of about 500 ms after the R-peak. Its topography, with peak amplitudes at the parietal electrode locations, is different from the topography of potentials observed in the few comparable experimental studies published so far. This suggests the presence of somatosensory-evoked components in heart action-related potentials and indicates that a renewed discussion of the underlying neuronal processes is necessary.

Cardiac field effects on the EEG.

The electrical field of the heart propagates throughout the entire body and causes changes in the surface potentials on the scalp that are superimposed on brain electric signals. When heart cycle-related EEG averaging is performed, e.g. in order to measure heart cycle-related brain potentials, the effects of the cardiac electrical field result in a high-amplitude artifact in the surface potentials. The topographic and temporal distributions of the cardiac field artifact were measured in 9 normal subjects. In addition, the effects of head-turning on the field were investigated. The electrocardiac artifact is most prominent during the QRS complex and during the T wave of the heart cycle. In both cases it is distinctly asymmetrical in relation to the hemispheres. A comparison of the scalp potentials and a computed vector ECG showed the 3-dimensional nature of the artifact. Non-computational strategies for the handling of the ECG artifact are discussed. A proper separation of the effects of the cardiac electrical field from heart cycle-related brain potentials is a prerequisite for the study of heart cycle-coordinated brain potentials.

Changes in late auditory evoked potentials induced by corticotropin-releasing hormone and corticotropin fragment 4-9 in male controls.

In order to investigate influences of corticotropin-releasing hormone (CRH) and corticotropin fragment (adrenocorticotropic hormone, ACTH, 4-9) on auditory perception processes, 10 subjects received either a placebo (sodium chloride 0.9%), CRH (100 micrograms) or ACTH 4-9 (Hoe 427, 300 micrograms) intravenously on different days. Late auditory evoked potentials (AEP) were computed and further analyzed using the brain electric source analysis method. As expected, CRH administration was followed by a rise in plasma cortisol and ACTH concentrations, whereas the injection of the ACTH 4-9 fragment did not alter plasma cortisol concentrations. In contrast to these different hormonal responses, both CRH and ACTH 4-9 modulated AEP in a similar manner, differing in quantity rather than in quality. The changes in AEP after the administration of ACTH 4-9 were most likely induced by a direct CNS action, whereas for the CRH effects, an indirect mechanism throughout the release of endogenous ACTH must be considered.

Long-term habituation of brain evoked potential responses and pituitary-adrenal secretion with repeated (placebo) testing.

To study whether changes in late auditory evoked potentials (AEPs) and/or in stress-sensitive hormones of the hypothalamic-pituitary-adrenal (HPA) system take place between a first and a second placebo experiment and if so, whether these changes are possibly related to each other, we conducted two identical placebo sessions (2 ml 0.9% saline) and one cortisol session (50 mg) with 10 subjects on three different days. Plasma cortisol concentrations were significantly higher at the beginning of the first placebo experiment than the second, with a concordant decrease of plasma adrenocorticotropin hormone (ACTH) concentrations. In the AEP domain, a consistently lower P2 amplitude was observed in the first session. Since the change in late auditory processing could not be demonstrated after exogenous administration of cortisol, a direct mediation through an elevation of plasma cortisol concentrations or indirect mediation through a decrease of plasma ACTH concentrations seems unlikely. We rather propose that other stress-sensitive mechanisms, such as CCK, might account for the novelty-induced P2 amplitude lowering.

Changes in late auditory evoked potentials induced by growth hormone-releasing hormone (GHRH) but not somatostatin (SRIF) after peripheral administration in male controls.

To investigate possible influences of growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) on auditory perceptional processes, 12 subjects received either placebo (sodium chloride 0.9%), GHRH (50 micrograms), or SRIF (100 micrograms) on different days. Late auditory evoked potentials (AEP) were computed and further analyzed by using the brain electric source analysis (BESA) method. Reduced late AEP latencies were observed following GHRH administration. In contrast, SRIF had no significant effects on the AEP. The changes in late auditory processing seen after administration of GHRH were most likely induced by a direct central nervous action.

Eyeblinks evoke potentials in the occipital brain region.

The subjects performed voluntary eyeblinks under illuminated and dark laboratory conditions. 32-channel EEG recordings were averaged in relation to the eyeblinks and a brain electric source analysis (BESA) was performed. Two dipoles located near the eyeballs and a third dipole in the occipital region of the brain were found to explain the scalp potentials. The frontally located potentials described electromechanical potentials associated with lid movements and simultaneous eye movements. The occipitally located dipole explained a visually evoked potential with a first peak at about 180 ms after the maximum of the frontal blink potential. The visually evoked potential was observed only under illumination and was probably caused by changes in luminance during the eyeblinks.

2-Nitropropane induces DNA repair synthesis in rat hepatocytes in vitro and in vivo.

The genotoxicity of 2-nitropropane (2-NP) and 1-nitropropane (1-NP) was investigated by measuring the induction of DNA repair synthesis in rat liver cells in vitro and in vivo. 2-NP strongly induced DNA repair synthesis in both cases. When applied in vivo, 2-NP was considerably more effective in hepatocytes from males than in those from females. 1-NP was not active in vitro or in vivo. 2-NP and 1-NP did not induce repair in cell lines of extrahepatic origin derived from rat, mouse, hamster and man. The results are consistent with the reported carcinogenicity of 2-NP in rat liver and suggest that the formation of hepatocarcinomas by 2-NP is due to the generation of a genotoxic metabolite from 2-NP by liver-specific metabolism.