Hans-Peter Landolt

Electromagnetic fields, such as those from mobile phones, alter regional cerebral blood flow and sleep and waking EEG

Usage of mobile phones is rapidly increasing, but there is limited data on the possible effects of electromagnetic field (EMF) exposure on brain physiology. We investigated the effect of EMF vs. sham control exposure on waking regional cerebral blood flow (rCBF) and on waking and sleep electroencephalogram (EEG) in humans. In Experiment 1, positron emission tomography (PET) scans were taken after unilateral head exposure to 30‐min pulse‐modulated 900 MHz electromagnetic field (pm‐EMF). In Experiment 2, night‐time sleep was polysomnographically recorded after EMF exposure. Pulse‐modulated EMF exposure increased relative rCBF in the dorsolateral prefrontal cortex ipsilateral to exposure. Also, pm‐EMF exposure enhanced EEG power in the alpha frequency range prior to sleep onset and in the spindle frequency range during stage 2 sleep. Exposure to EMF without pulse modulation did not enhance power in the waking or sleep EEG. We previously observed EMF effects on the sleep EEG (A. A. Borbély, R. Huber, T. Graf, B. Fuchs, E. Gallmann and P. Achermann. Neurosci. Lett., 1999, 275: 207–210; R. Huber, T. Graf, K. A. Cote, L. Wittmann, E. Gallmann, D. Matter, J. Schuderer, N. Kuster, A. A. Borbély, and P. Achermann. Neuroreport, 2000, 11: 3321–3325), but the basis for these effects was unknown. The present results show for the first time that (1) pm‐EMF alters waking rCBF and (2) pulse modulation of EMF is necessary to induce waking and sleep EEG changes. Pulse‐modulated EMF exposure may provide a new, non‐invasive method for modifying brain function for experimental, diagnostic and therapeutic purposes.

Effect of age on the sleep EEG: slow-wave activity and spindle frequency activity in young and middle-aged men.

The effect of age on sleep and the sleep EEG was investigated in middle-aged men (mean age: 62.0 years) and in young men (mean age: 22.4 years). Even though the older men reported a higher number of nocturnal awakenings, subjective sleep quality did not differ. Total sleep time, sleep efficiency, and slow wave sleep were lower in the middle-aged, while stage 1 and wakefulness after sleep onset were higher. The differences in wakefulness within nonREM-REM sleep cycles was most pronounced in the third and fourth cycle. In the older men, EEG power density in nonREM sleep was reduced in frequencies below 14.0 Hz, whereas in REM sleep age-related reductions were limited to he delta-theta (0.25-7.0 Hz) and low alpha (8.25-10.0 Hz) band. Slow-wave activity (SWA, power density in the 0.75-4.5 Hz range) decreased in the course of sleep in both age groups. The between-group difference in SWA diminished in the course of sleep, whereas the difference in activity in the frequency range of sleep spindles (12.25-14.0 Hz) increased. It is concluded that frequency and state specific changes occur as a function of age, and that sleep dependent decline in SWA and increase in sleep spindle activity are attenuated with age.

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

We review here the rapid tryptophan depletion (RTD) methodology and its controversial association with depressive relapse. RTD has been used over the past decade to deplete serotonin (5-hydroxy-tryptamine, or 5-HT) in humans and to probe the role of the central serotonin system in a variety of psychiatric conditions. Its current popularity was stimulated by reports that RTD reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) in remitted patients with a history of depression but not in patients treated with antidepressants which promote catecholaminergic rather than serotonergic neurotransmission (such as tricyclic antidepressants or buproprion). However, RTD has inconsistent effects in terms of full clinical relapse in depressed patients. Pooling the data from all published reports, patients who are either unmedicated and/or fully remitted are much less likely to experience relapse (7 of 61, or ∼9%) than patients who are recently medicated and partially remitted (63 of 133, or ∼47%; although, the numbers here may reflect patient overlap between reports). Recently remitted patients who have been treated with non-pharmacological therapies such as total sleep deprivation, electroconvulsive therapy, or bright light therapy also do not commonly show full clinical relapse with RTD. We briefly review RTD effects in other psychiatric disorders, many of which are treated with SSRIs. There is accumulating evidence to suggest that RTD affects central serotonergic neurotransmission. Nevertheless, many questions remain about the ability of RTD to reverse the beneficial effects of SSRIs or MAOIs, or to induce symptoms in unmedicated symptomatic or asymptomatic patients.

A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep.

Caffeine is the most widely used stimulant in Western countries. Some people voluntarily reduce caffeine consumption because it impairs the quality of their sleep. Studies in mice revealed that the disruption of sleep after caffeine is mediated by blockade of adenosine A2A receptors. Here we show in humans that (1) habitual caffeine consumption is associated with reduced sleep quality in self‐rated caffeine‐sensitive individuals, but not in caffeine‐insensitive individuals; (2) the distribution of distinct c.1083T>C genotypes of the adenosine A2A receptor gene (ADORA2A) differs between caffeine‐sensitive and ‐insensitive adults; and (3) the ADORA2A c.1083T>C genotype determines how closely the caffeine‐induced changes in brain electrical activity during sleep resemble the alterations observed in patients with insomnia. These data demonstrate a role of adenosine A2A receptors for sleep in humans, and suggest that a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep.

Caffeine Reduces Low-Frequency Delta Activity in the Human Sleep EEG

In view of the hypothesis that adenosine is involved in sleep regulation, the effects of the adenosine antagonist caffeine on sleep and sleep EEG were investigated in eight young males. Compared to the placebo condition, caffeine (100 mg) administered at bedtime prolonged sleep latency and reduced sleep efficiency and stage 4 of non-rapid eye movement sleep (NREMS). Electroencephalographic slow-wave activity (SWA, spectral power density in the 0.75-4.5-Hz band) was reduced, whereas power density in the spindle frequency range was slightly enhanced. The suppression of SWA was limited to the first NREMS episode. Caffeine reduced the power density mainly in the lowest delta band, in contrast to the changes during physiological sleep that encompass both the delta and theta bands. Caffeine levels in saliva, assessed in a separate experiment, decreased from 7.5 μmol/l in the first hour of sleep to 3.5 μmol/l in the seventh hour. In the night following caffeine administration, stage 4 sleep had reverted to the baseline level, but sleep latency was still increased, and stage 2 sleep, as well as SWA in the first NREMS episode, were reduced. The data show that even a low dose of caffeine affects the sleep EEG. However, the effects of caffeine did not completely mimic the spectral changes observed during physiological sleep.

Exposure to pulse‐modulated radio frequency electromagnetic fields affects regional cerebral blood flow

We investigated the effects of radio frequency electromagnetic fields (RF EMF) similar to those emitted by mobile phones on waking regional cerebral blood flow (rCBF) in 12 healthy young men. Two types of RF EMF exposure were applied: a ‘base‐station‐like’ and a ‘handset‐like’ signal. Positron emission tomography scans were taken after 30 min unilateral head exposure to pulse‐modulated 900 MHz RF EMF (10 g tissue‐averaged spatial peak‐specific absorption rate of 1 W/kg for both conditions) and sham control. We observed an increase in relative rCBF in the dorsolateral prefrontal cortex on the side of exposure. The effect depended on the spectral power in the amplitude modulation of the RF carrier such that only ‘handset‐like’ RF EMF exposure with its stronger low‐frequency components but not the ‘base‐station‐like’ RF EMF exposure affected rCBF. This finding supports our previous observation that pulse modulation of RF EMF is necessary to induce changes in the waking and sleep EEG, and substantiates the notion that pulse modulation is crucial for RF EMF‐induced alterations in brain physiology.

CAFFEINE INTAKE (200 MG) IN THE MORNING AFFECTS HUMAN SLEEP AND EEG POWER SPECTRA AT NIGHT

Adenosine has been implicated in the physiological regulation of sleep propensity. The adenosine-receptor-antagonist, caffeine (100 mg), administered immediately prior to a nocturnal sleep episode, has previously been shown to lower sleep propensity as indexed by a reduced sleep efficiency, a reduced EEG power density in low delta frequencies and enhanced power density in the frequency range of sleep spindles. To further investigate the role of adenosine in sleep regulation we administered 200 mg of caffeine at 07.10 h and analyzed the sleep stages and EEG power spectra during the subsequent night in nine healthy men. Caffeine levels in saliva decreased from a maximum of 17 mumol/l one hour after intake, to 3 mumol/l immediately prior to the sleep episode starting at 23.00 h. Compared to placebo, sleep efficiency and total sleep time were significantly reduced. EEG power density in nonREM sleep was suppressed in the 0.25-0.5 Hz band and enhanced in the frequency range of sleep spindles (11.25-12.0 Hz and 13.25-14.0 Hz). In REM sleep EEG power density was suppressed in the frequency range of 0.75-4.5 and 5.25-6.0 Hz. The data indicate that a saliva level of caffeine as low as 3 mumol/l directly affects sleep propensity or, alternatively, that the presence of caffeine in the central nervous system during the waking episode reduces the progressive increase of sleep propensity associated with wakefulness.

TRAIT-LIKE INDIVIDUAL DIFFERENCES IN THE HUMAN SLEEP ELECTROENCEPHALOGRAM

We aimed to examine whether commonly observed individual differences in sleep architecture and the sleep electroencephalogram reflect individual traits, which are amenable to a genetic investigation of human sleep. We studied intra-individual stability and inter-individual variation in sleep and sleep electroencephalogram spectra across four baseline recordings of eight healthy young men. A similarity concept based on Euclidean distances between vectors was applied. Visually scored sleep variables served as feature vector components, along with electroencephalogram power spectra in non-rapid-eye-movement and rapid-eye-movement sleep. The distributions of similarity coefficients of feature vectors revealed a clear distinction between high within-subject similarity (i.e. stability), and low between-subject similarity (i.e. variation). Moreover, a cluster analysis based on electroencephalogram spectra in both non-rapid-eye-movement and rapid-eye-movement sleep segregated all four baseline nights of each individual into a distinct cluster. To investigate whether high and low sleep pressure affects the similarity coefficients, normalized non-rapid-eye-movement sleep electroencephalogram spectra of the first and second half of the recordings were compared. Because the electroencephalogram changes systematically in the course of the night, within-subject variation no longer differed from between-subject variation. In conclusion, our data provide evidence for trait-like characteristics in the sleep electroencephalogram. Further studies may help to identify distinct phenotypes to search for genes underlying functional aspects of undisturbed human sleep.

Melatonin effect on daytime sleep in men: suppression of EEG low frequency activity and enhancement of spindle frequency activity.

The effect of melatonin (5 mg, p.o.) on electroencephalographic (EEG) activity during sleep was investigated in eight men in a placebo-controlled cross-over design. Melatonin was administered immediately prior to a 4-h daytime sleep episode (13-17 h) after a partial sleep deprivation. The non-REM sleep stages and REM sleep duration were not significantly affected. Melatonin enhanced EEG power density in non-REM sleep in the 13.75-14.0 Hz bin (i.e., within the frequency range of sleep spindles), and reduced activity in the 15.25-16.5 Hz band. In the first 2 h spectral values within the 2.25-5.0 Hz range were reduced. These changes in the EEG are to some extent similar to those induced by benzodiazepine hypnotics and to the contribution of the endogenous circadian pacemaker to the spectral composition of the sleep EEG when sleep occurs at night.

Serotonin-2 Receptors and Human Sleep: Effect of a Selective Antagonist on EEG Power Spectra

To investigate the effect on the sleep EEG, a 1-mg oral dose of SR 46349B, a novel 5-HT2 antagonist, was administered three hours before bedtime. The drug enhanced slow wave sleep (SWS) and reduced stage 2 without affecting subjective sleep quality. In nonREM sleep (NREMS) EEG slow-wave activity (SWA; power within 0.75–4.5 Hz) was increased and spindle frequency activity (SFA; power within 12.25–15 Hz) was decreased. The relative NREMS power spectrum showed a bimodal pattern with the main peak at 1.5 Hz and a secondary peak at 6 Hz. A regional analysis based on bipolar derivations along the antero-posterior axis revealed significant ‘treatment’ × ‘derivation’ interactions within the 9–16 Hz range. In enhancing SWA and attenuating SFA, the 5-HT2 receptor antagonist mimicked the effect of sleep deprivation, whereas the pattern of the NREMS spectrum differed.