Fabiana Fratello

The electroencephalographic fingerprint of sleep is genetically determined: a twin study.

Humans have an individual profile of the electroencephalographic power spectra at the 8 to 16Hz frequency during non–rapid eye movement sleep that is stable over time and resistant to experimental perturbations. We tested the hypothesis that this electroencephalographic “fingerprint” is genetically determined, by recording 40 monozygotic and dizygotic twins during baseline and recovery sleep after prolonged wakefulness. We show a largely greater similarity within monozygotic than dizygotic pairs, resulting in a heritability estimate of 96%, not influenced by sleep need and intensity. If replicated, these results will establish the electroencephalographic profile during sleep as one of the most heritable traits of humans. Ann Neurol 2008

Handedness is mainly associated with an asymmetry of corticospinal excitability and not of transcallosal inhibition

OBJECTIVE The study aims to compare transcallosal inhibition (TI), as assessed by the paired-pulse transcranial magnetic stimulation (TMS) technique, in a sample of right-handed subjects (RH) and left-handed subjects (LH). Motor thresholds (MTs) and motor evoked potential (MEP) amplitudes were also measured in the two groups, as an index of corticospinal activity. METHODS Thirty-two normal subjects (16 RH and 16 LH) were recorded with a paired-pulse TMS paradigm (intensity of both pulses=120% of MT). The inter-stimulus intervals (ISIs) were 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20 ms for both motor cortices, and MEP responses were recorded from the abductor digiti minimi muscles. RESULTS Both groups showed a clear TI centred around the 12 ms ISI, but no difference was found as a function of handedness or of hemisphere. On the other hand, the two groups differed in terms of corticospinal activity, since the hand motor dominant hemisphere had lower MTs than the non-dominant one in LH, and larger MEP amplitudes for the right hand were found in RH. CONCLUSIONS Results point to a functional asymmetry of the motor cortex on the hand-dominant versus the non-dominant hemisphere, while handedness does not seem associated with functional differences in callosal inhibition, as measured by the inter-hemispheric paired-pulse TMS technique.

Neurophysiological correlates of sleepiness: A combined TMS and EEG study

Changes of cortical and corticospinal excitability as a function of sleep deprivation have been studied, using EEG power maps and several TMS measures in 33 normal subjects before and after a 40-h sleep deprivation (SD). The effects of SD were independently assessed by subjective and EEG measures of sleepiness, the latter being represented in terms of cortical maps for different frequency bands. Short intracortical facilitation (SICF) and inhibition (SICI) were measured by the paired-pulse TMS technique with different inter-stimulus intervals. Besides standardized motor threshold (MT), lower threshold (LT) and upper threshold (UT) were also determined. Subjective sleepiness severely increased as a consequence of SD, paralleled by a drastic decrease of alertness. EEG topography showed large increases in delta and theta activity, mainly evident at fronto-central areas. Standard MTs, as well as LTs and UTs, all increased as a consequence of SD. SICF also showed a significant increase as compared to pre-deprivation values, but only in females. The increase of theta activity was strongly associated in the left frontal and prefrontal cortex to a smaller decrease of corticospinal excitability, expressed by MTs, and a larger increase of intracortical facilitation, expressed by SICF. TMS and EEG measures converge in indicating that SD has severe effects on both cortical and corticospinal excitability, as shown respectively by the increases of slow-frequency EEG power and MTs. The SICF enhancement in females and the results of the combined topographical analysis of EEG and TMS changes are coherent with the hypothesis that cortical TMS-evoked responses are higher as a consequence of a longer wakefulness. However, the lack of an increase in cortical excitability after prolonged wakefulness in males suggests some caution in the generalization of these effects, that deserve further investigation.

Paradoxes of the first-night effect: a quantitative analysis of antero-posterior EEG topography

OBJECTIVE The first-night effect (FNE) is a common issue in sleep research. Being considered fragmented and poorly efficient, the adaptation night is discarded for data analysis. The present study aims to provide a quantitative and topographical EEG analysis of this phenomenon. METHODS Eight healthy subjects slept for two consecutive nights (adaptation (AD) and baseline (BSL)), and their polysomnography was visually scored and then submitted to spectral power analysis. RESULTS The results showed a decreased quality and quantity of first-night sleep as indicated by more stage 1 and intrasleep wake, paralleled by a reduced sleep efficiency and a longer sleep onset latency. On the other hand, EEG quantitative data showed a more complex and apparently paradoxical picture. An increase in delta power was observed, particularly over the central areas during the first night, paralleled by an increased power in beta bin frequencies solely at posterior scalp locations. CONCLUSIONS These results have been interpreted as caused by, respectively, a reduced total sleep time during the adaptation night and a cortical hyperactivity, typical of psychophysiological insomnia. The present results confirm the need to exclude the laboratory sleep adaptation night from data analysis since it is not a reliable index of sleep on subsequent nights as regards both visual scoring and quantitative EEG analysis. Finally, regional differences between REM and NREM sleep have been confirmed. SIGNIFICANCE This is the first attempt to evaluate the FNE with a quantitative approach to the antero-posterior EEG topography, providing both a Hz-by-Hz and a classical EEG band-based analysis.

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 resonance may have a supportive role for the processing/consolidation of memory.

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.

The electroencephalographic substratum of the awakening

The aim of the present study was to characterize the regional electroencephalographic substratum of the awakening process by means of a Hz-by-Hz EEG spectral power analysis. For this purpose, we recorded a group of 25 female subjects who slept for at least two consecutive nights in the laboratory. The post-sleep waking EEG was compared to the one recorded during the presleep wakefulness from four midline derivations (Fz-A1, Cz-A1, Pz-A1, Oz-A1). Results indicated that the first 10 min after awakening are characterized by an increase of EEG power in the low-frequency range (1-9 Hz) compared to the corresponding presleep waking period, and by a significant decrease of EEG power in the beta range (18-24 Hz). As regards topographic differences, the increase of EEG power upon awakening in the delta-theta range showed a parieto-occipital prevalence. Moreover, the occipital derivation showed a larger decrease of power in the beta range as compared to the other derivations. In conclusion, the EEG substratum of the sleep offset period is characterized by a pattern of increased EEG power in the delta-theta and low-alpha bands, and of decreased power in the beta range. This pattern could be considered as the spectral EEG signature of the sleep inertia phenomenon. The state of post-sleep EEG hypo-arousal does not subside in the first 10-min period after awakening considered in the present analysis. Finally, according to our results, the more posterior scalp locations show stronger EEG signs of sleep inertia, and could be the last ones to properly wake up.

Reproducibility of callosal effects of transcranial magnetic stimulation (TMS) with interhemispheric paired pulses

Transcranial magnetic stimulation (TMS) of the motor cortex of one hemisphere (conditioning stimulus (CS)) inhibits EMG responses evoked in distal hand muscles by a later magnetic stimulus given at an appropriate interval, over the opposite hemisphere (test stimulus (TS)). This effect is commonly attributed to an inhibition produced at cortical level via a transcallosal route. The present study assessed the reproducibility of the transcallosal inhibition effects in different sessions in healthy subjects. Within- and between-subject variability, relating to interhemispheric differences was also evaluated. A magnetic CS on one hemisphere effectively inhibited EMG responses of the abductor digiti minimi stimulated by a TS delivered over the opposite hemisphere in a range of intervals centered at 12 ms. Even though group effects were reproduced in separate sessions, the high between- and within-subject variability yielded low test-retest correlations. This differentiation forces the definition of reproducibility (or repeatability), as the replication of the same mean curves of EMG reduction, and of reliability, as the between- or within-subject correlations between values of specific EMG measures.

Interhemispheric transfer deficit in alexithymia: A transcranial magnetic stimulation study

Background: A deficit in interhemispheric transfer was hypothesized in alexithymia more than 30 years ago, following the observation that split-brain patients manifest certain alexithymic characteristics. However, direct evidence of interhemispheric transfer deficit has never been provided. This study investigated the hypothesis of a transcallosal interhemispheric transfer deficit in alexithymia by means of paired-pulse transcranial magnetic stimulation. Methods: A random sample of 300 students was screened for alexithymia using the Italian version of the 20-item Toronto Alexithymia Scale. Eight right-handed males and eight females with high alexithymic scores and an age- and gender-matched group with low alexithymic scores were selected. A first (conditioning) magnetic stimulus was delivered to one motor cortex followed by a second (test) stimulus to the opposite hemisphere at different interstimulus intervals for both motor cortices. Motor evoked responses were recorded from the abductor digit minimi muscles. Results: High alexithymic subjects showed reduced transcallosal inhibition as compared to low alexithymic subjects at interstimulus intervals of 10, 12 and 14 ms in the left-to-right and right-to-left interhemispheric transfer directions. Conclusions: Results point to functional differences in transcallosal interactions in high alexithymic as compared to low alexithymic subjects, supporting the hypothesis of an interhemispheric transfer deficit in alexithymia.

Corticospinal excitability and sleep: a motor threshold assessment by transcranial magnetic stimulation after awakenings from REM and NREM sleep.

Transcranial magnetic stimulation (TMS) is a recently established technique in the neurosciences that allows the non‐invasive assessment, among other parameters, of the excitability of motor cortex. Up to now, its application to sleep research has been very scarce and because of technical problems it provided contrasting results. In fact delivering one single suprathreshold magnetic stimulus easily awakes subjects, or lightens their sleep. For this reason, in the present study we assessed motor thresholds (MTs) upon rapid eye movement (REM) and non‐rapid eye movement (NREM) sleep awakenings, both in the first and in the last part of the night. Taking into account that a full re‐establishment of wake regional brain activity patterns upon awakening from sleep needs up to 20–30 min, it is possible to make inferences about the neurophysiological characteristics of the different sleep stages by analyzing the variables of interest immediately after provoked awakenings. Ten female volunteers slept in the lab for four consecutive nights. During the first night the MTs were collected, following a standardized procedure: 5 min before lights off, upon stage 2 awakening (second NREM period), upon REM sleep awakening (second REM period), upon the final morning awakening (always from stage 2). Results showed that MTs increased linearly from presleep wakefulness to REM sleep awakenings, and from the latter to stage 2 awakenings. There was also a time‐of‐night effect on MTs upon awakening from stage 2, indicating that MTs decreased from the first to the second part of the night. The increase in corticospinal excitability across the night, which parallels the fulfillment of sleep need, is consistent with the linear decrease of auditory arousal thresholds during the night. The maximal reduction of corticospinal excitability during early NREM sleep can be related to the hyperpolarization of thalamocortical neurons, and is in line with the decreased metabolic activity of motor cortices during this sleep stage. On the contrary, the increase of MTs upon REM sleep awakenings should reflect peripheral factors. We conclude that our findings legitimate the introduction of the TMS technique as a new proper tool in sleep research.