Cortical Plasticity Induced by Transcranial Magnetic Stimulation during Wakefulness Affects Electroencephalogram Activity during Sleep

BACKGROUND:Sleep electroencephalogram (EEG) brain oscillations in the low-frequency range show local signs of homeostatic regulation after learning. Such increases and decreases of slow wave activity are limited to the cortical regions involved in specific task performance during wakefulness. Here, we test the hypothesis that reorganization of motor cortex produced by long-term potentiation (LTP) affects EEG activity of this brain area during subsequent sleep. METHODOLOGY/PRINCIPAL FINDINGS:By pairing median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex, one can potentiate the motor output, which is presumed to reflect plasticity of the neural circuitry. This paired associative stimulation increases M1 cortical excitability at interstimulus intervals of 25 ms. We compared the scalp distribution of sleep EEG power following paired associative stimulation at 25 ms to that following a control paradigm with 50 ms intervals. It is shown that the experimental manipulation by paired associative stimulation at 25 ms induces a 48% increase in amplitude of motor evoked potentials. This LTP-like potentiation, induced during waking, affects delta and theta EEG power in both REM and non-REM sleep, measured during the following night. Slow-wave activity increases in some frontal and prefrontal derivations and decreases at sites neighboring and contralateral to the stimulated motor cortex. The magnitude of increased amplitudes of motor evoked potentials by the paired associative stimulation at 25 ms predicts enhancements of slow-wave activity in prefrontal regions. CONCLUSIONS/SIGNIFICANCE:An LTP-like paradigm, presumably inducing increased synaptic strength, leads to changes in local sleep regulation, as indexed by EEG slow-wave activity. Enhancement and depression of slow-wave activity are interpreted in terms of a simultaneous activation of both excitatory and inhibitory circuits consequent to the paired associative stimulation at 25 ms

Sleep in the Human Hippocampus: A Stereo-EEG Study

Background. There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. Methodology/Principal Findings. We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i) a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii) a flattening of the time course of the very low frequencies (up to 1 Hz) across sleep cycles, with relatively high levels of power even during REM sleep; iii) a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. Conclusions/Significance. Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonanc

Can an inert sleeping pill affect sleep? Effects on polysomnographic, behavioral and subjective measures

Rationale: Since two recent meta-analyses on sleep changes associated with placebo in clinical trials suggested a beneficial effect of placebo treatments, pointing to a dissociation between subjective and objective measures of sleep, the current experiment was directly aimed to assess the effects of an inert compound, administered with the suggestion that it was a hypnotic substance in subjects with mild sleep complaints. Objectives: The aim of this study was to compare subjective, behavioral, polysomnographic (PSG), and quantitative electroencephalographic (EEG) changes during a night preceded or not by the intake of two 50-mg lactose capsules. Methods: Ten female students, selected by the Pittsburgh Sleep Quality Index, slept for three consecutive nights in a sleep laboratory, with the experimental (EXP) night defined by the administration of two 50-mg lactose pills. Self-ratings of sleep quality and performance were assessed upon morning awakening of baseline (BSL) and EXP nights. Results: The EXP nights were self-rated as more restful and characterized by a decreased number of nocturnal awakenings than the BSL nights. PSG measures showed that wakefulness after sleep onset significantly decreased during the EXP night as compared to the BSL night. The EXP nights also showed an increase of 0.5-4.0 Hz power during nonrapid eye movement sleep and a decrease of EEG activity in the beta frequency range during rapid eye movement sleep only at central brain sites. A specific improvement of behavioral measures was also found upon morning awakening after the EXP night compared to the BSL night. Conclusions: The administration of an inert pill improves both the subjective and objective quality of sleep. The reduced sleep fragmentation and the effects on some quantitative EEG markers of sleep homeostasis suggest that the experimental manipulation induced coherent changes in the subsequent sleep, resembling an enhancement of sleep pressure. The regional differences of EEG activity suggest the involvement of a specific physiological mechanism distinct from that of effective treatments