Bimodal distribution of REM sleep latencies in depression.

The REM sleep latency of endogenously depressed patients was investigated by analyzing 90 polysomnograms of six patients during depression and 58 polysomnograms of four of these patients after remission. During depression the REM sleep latencies are distributed bimodally with peaks at sleep onset (sleep onset REM phases, SOREMPs) and 60 min later. During the follow-up examinations some time after remission, the occurrence of SOREMPs is very rare. A model is proposed according to which the occurrence of SOREMPs in the sleep of these patients is caused by a reduced amplitude of the circadian rhythm of the arousal system.

Temporal coordination of rest-activity cycle, body temperature, urinary free cortisol, and mood in a patient with 48-hour unipolar-depressive cycles in clinical and time-cue-free environments.

During medication-free observation a 66-year-old male patient showed an almost strict alternation of days with depressed mood and days with normal mood. The experiment consisted of two parts; the first was 4 weeks' observation in the psychiatric ward, while the second was 2 weeks' observation in an experimental unit where the patient was deprived of all known information on local time. In the psychiatric ward the observed circadian rhythms, i.e., the rest-activity cycle, the body temperature, the urinary free cortisol, and the mood rhythm, were all synchronized with the geophysical day. Under isolation from time cues the average rest-activity cycle duration was reduced to about 19.5 hr, whereas the body temperature and the urinary free cortisol continued to show rhythms with near-24-hr periods. The main finding of the study is the persistence of a near-48-hr periodicity in the mood fluctuation under isolation from time cues. Besides this, in the time course of body temperature and urinary free cortisol evoked components correlating with the mood cycles were found.

Interindividual differences in the susceptibility of the cortisol system: an important factor for the degree of hypercortisolism in stress situations?

Whereas in psychophysiological research, the specificity of the individual responses has been assumed to be an important trait variable influencing the investigated parameters in stress experiments or in psychopathological states, in psychoneuroendocrinology, the individual differences in the susceptibility of the investigated neuroendocrine axes have been widely neglected. The present study on the cortisol response of 12 healthy young men to 5 different stress tests is considered to be an initial orientation step into this field. All five stress tests (quiz, arithmetic tasks, stress film, cold pressor test, and physical exercise test) could be proven to be effective stimuli regarding the cortisol system. There was, however, a broad spectrum of cortisol responses among the 12 subjects, with a continuum between complete reactors and nonreactors. This did not correlate with the subjective judgment of stress at all. Although the data showed a tendency toward an augmented dispersion of the response frequencies in comparison with random variation, the limited sample size of subjects and stress tests did not allow a statistically significant proof of a stimulus-independent, individual response specificity. Further experimental clarification seems to be necessary to avoid misinterpretations of neuroendocrine data in psychiatric disorders due to neglect of this variable.

The REM-NREM sleep cycle: renewal process or periodically driven process?

The question of the serial dependence of successive REM-NREM sleep cycles was examined. The experiments were performed in two different settings: 309 sleep episodes of 11 healthy young sleepers (age range, 20-36 years) were recorded under entrained conditions in the sleep laboratory; 5 of these subjects also slept in an isolation unit (underground apartment) with free-running sleep-wake cycles for a total of 107 sleep episodes. The covariances between the first three REM-NREM cycles were computed using an intraindividual cross-night approach. Significant negative covariances were observed. This result confirmed the assumption of serial dependencies between successive REM-NREM cycles. These data agree with the features of a periodically driven process and are incompatible with the alternatively hypothesized renewal model. The periodically driven process is similar in concept to the basic rest-activity cycle.

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.

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.

Size distribution of rhodamine-labelled microspheres retrogradely transported in cultured neurons.

Rhodamine-labelled latex microspheres (RLM), 10-110 nm in diameter, were used as a retrograde tracer in cultured sympathetic neurons. Retrogradely transported RLM were isolated from the cells and measured. These were all smaller than 50 nm in diameter and represented not more than 2% of the original RLM population. The permeability of RLM as a function of size was also estimated and showed a steep decrease between 20 and 30 nm from 100% to less than 20%. Therefore, RLM with a mean diameter of 20 nm would be optimal for retrograde tracing.

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.

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.

Intracerebral injection of different antibodies against endogenous opioids suggests alpha-neoendorphin participation in control of feeding behaviour.

The mechanism of feeding behaviour of rats was examined. We used antibodies to different opioid peptides in order to reduce the tonic activity of various endogenous opioid peptide systems that may underly appetite. Unilateral microinjection of anti-alpha-neoendorphin antibodies into various areas of the ventromedial hypothalamus (VMH) inhibited food and water intake up to 45% in deprived animals. Injections outside this area failed to affect feeding. Administration of anti-beta-endorphin antibodies into the VMH moderately attenuated appetite. A considerable decrease of food and water intake was observed only upon injection of this antibody into the nucleus periventricularis hypothalami, a region generally believed to be involved with feeding. A marginal reduction of appetite was observed with anti-dynorphin antibodies injected into the VMH. These data may suggest that alpha-neoendorphin is involved in the control of food and water intake in the VMH.

Circadian rhythms in endogenous depression.

A comprehensive study of circadian rhythms was carried out in 16 drug-free patients with endogenous depression, 10 of whom were reinvestigated after clinical remission, and 10 healthy controls. No free-running periods were observed in body temperature, urinary excretion of potassium and free cortisol, or any other variable. Moreover, there was little, if any, indication of phase-advance. The circadian variation of several variables was reduced during depression, e.g., motor activity, body temperature, and (less markedly) urinary potassium, but not cortisol. The circadian worsening of mood tended to occur around the time of awakening during depression, i.e., several hours later than after remission or in normal controls. In patients with circadian variation of self-rated mood, the acrophase of this variable correlated significantly with that of urinary free cortisol. This indicates an entrainment of the disease process to the circadian rhythm of cortisol secretion, probably via circadian variations of neurotransmitters in the hypothalamus. The other circadian phenomena observed in depression can adequately be explained by masking effects (negative or positive) of psychopathological symptoms (e.g., early morning awakening) on overt circadian rhythms.

[Studies on the stability of human ultradian rhythms (author's transl)]. / Untersuchungen zur Stabilität ultradianer Rhythmen beim Menschen

It was investigated whether the REM-NREM (rapid eye movement-non-REM) sleep rhythm has a stable period during long-term observations. Sequences of 17 to 31 consecutive sleep records were analyzed for 6 test subjects and 1 patient. Period stability was confirmed for three experimental conditions: a) undisturbed night sleep, b) inversion of the sleep-waking cycle, c) absence of external timing mechanisms. The period of the ultradian REM sleep rhythm is no integral submultiple of 24 h, so that the remainder causes a daily drift in the REM sleep rhythm. It is assumed that the ultradian process is controlled endogenously. In contrast to the circadian rhythm the ultradian rhythm appears to be free-running under normal conditions. The stability of the ultradian period has been shown in long-term observations.

Phase shift in the REM sleep rhythm.

The periodic alternation between REM and NREM sleep was analyzed. Usually, sleep records of consecutive nights of a subject are regarded to be independent events. However, it may be that consecutive nights are realizations of a continuously ongoing rhythm. This was tested in the present study. The temporal patterns of REM and NREM sleep in sequences of about 30 consecutive nights for 3 subjects were analyzed. The results show that only the onset of the first REM sleep phase during any one night may be predicted from the sleep onset time, whereas a systematic phase shift between consecutive nights was observed in the later REM sleep phases. Thus, the onset of later REM sleep phases is better predicted by assuming a rhythm with stable period length which controls the appearance of REM sleep phases in successive nights. Under the experimental conditions the phase shift was between 5 and 10 min per 24 hrs for the 3 subjects. The result is accordance with Kleitman's basic rest activity cycle (BRAC) hypothesis.

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.

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.