Human Cortical Excitability Increases with Time Awake
TL;DR: Noninvasive electrophysiological evidence that wakefulness is associated with a steady increase in the excitability of human cortical circuits that is rebalanced during sleep is provided.
Abstract: Prolonged wakefulness is associated not only with obvious changes in the way we feel and perform but also with well-known clinical effects, such as increased susceptibility to seizures, to hallucinations, and relief of depressive symptoms. These clinical effects suggest that prolonged wakefulness may be associated with significant changes in the state of cortical circuits. While recent animal experiments have reported a progressive increase of cortical excitability with time awake, no conclusive evidence could be gathered in humans. In this study, we combine transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to monitor cortical excitability in healthy individuals as a function of time awake. We observed that the excitability of the human frontal cortex, measured as the immediate (0-20 ms) EEG reaction to TMS, progressively increases with time awake, from morning to evening and after one night of total sleep deprivation, and that it decreases after recovery sleep. By continuously monitoring vigilance, we also found that this modulation in cortical responsiveness is tonic and not attributable to transient fluctuations of the level of arousal. The present results provide noninvasive electrophysiological evidence that wakefulness is associated with a steady increase in the excitability of human cortical circuits that is rebalanced during sleep.
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TL;DR: This Perspective considers the rationale and evidence for the synaptic homeostasis hypothesis (SHY), and points to open issues related to sleep and plasticity.
1,565 citations
Cites background from "Human Cortical Excitability Increas..."
...(B, B0, and B00) Electrophysiological analysis of cortical evoked responses using electrical stimulation (in rats, from Vyazovskiy et al., 2008) and TMS (in humans, from Huber et al., 2013) shows increased slope after wake and decreased slope after sleep....
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...Similarly, in humans, the slope of the early response evoked in frontal cortex by transcranial magnetic stimulation (TMS) increases progressively in the course of 18 hr of continuous wake and returns to baseline levels after one night of recovery sleep (Huber et al., 2013) (Figure 3B0)....
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TL;DR: This review provides a concise overview of how the sleeping brain transforms and builds persisting memories through this process, highlighting hippocampal replay that captures episodic memory aspects and brain oscillations hallmarking slow-wave and rapid-eye movement sleep.
Abstract: Long-term memory formation is a major function of sleep. Based on evidence from neurophysiological and behavioral studies mainly in humans and rodents, we consider the formation of long-term memory during sleep as an active systems consolidation process that is embedded in a process of global synaptic downscaling. Repeated neuronal replay of representations originating from the hippocampus during slow-wave sleep leads to a gradual transformation and integration of representations in neocortical networks. We highlight three features of this process: (i) hippocampal replay that, by capturing episodic memory aspects, drives consolidation of both hippocampus-dependent and non-hippocampus-dependent memory; (ii) brain oscillations hallmarking slow-wave and rapid-eye movement sleep that provide mechanisms for regulating both information flow across distant brain networks and local synaptic plasticity; and (iii) qualitative transformations of memories during systems consolidation resulting in abstracted, gist-like representations.
485 citations
University of Siena1, University of Göttingen2, UCL Institute of Neurology3, City College of New York4, National Institutes of Health5, Brown University6, University of Toronto7, Università Campus Bio-Medico8, Beth Israel Deaconess Medical Center9, Medical University of South Carolina10, Cincinnati Children's Hospital Medical Center11, Aristotle University of Thessaloniki12, Aalto University13, Paris 12 Val de Marne University14, Vita-Salute San Raffaele University15, University of Trento16, Ludwig Maximilian University of Munich17, Harvard University18, Duke University19, University of Messina20, Copenhagen University Hospital21, Fukushima Medical University22, Ben-Gurion University of the Negev23, University of Tübingen24
TL;DR: New operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.
387 citations
Cites background from "Human Cortical Excitability Increas..."
...Sleep deprivation is of particular relevance, as studies using TMS in combination with EEG have reported increases in cortical excitability measures with sleep deprivation even in normal healthy subjects (Huber et al., 2013; Kuhn et al., 2016), although sleep deprivation was also associated with a decreased long-term potentiation (LTP)like plasticity in response to a paired-associative stimulation protocol (Kuhn et al....
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TL;DR: The ties that bind sleep, aging, Glymphatic clearance, and protein aggregation have shed new light on the pathogenesis of a broad range of neurodegenerative diseases, for which glymphatic failure may constitute a therapeutically targetable final common pathway.
Abstract: Sleep is evolutionarily conserved across all species, and impaired sleep is a common trait of the diseased brain. Sleep quality decreases as we age, and disruption of the regular sleep architecture is a frequent antecedent to the onset of dementia in neurodegenerative diseases. The glymphatic system, which clears the brain of protein waste products, is mostly active during sleep. Yet the glymphatic system degrades with age, suggesting a causal relationship between sleep disturbance and symptomatic progression in the neurodegenerative dementias. The ties that bind sleep, aging, glymphatic clearance, and protein aggregation have shed new light on the pathogenesis of a broad range of neurodegenerative diseases, for which glymphatic failure may constitute a therapeutically targetable final common pathway.
328 citations
TL;DR: Evidence on the large variability in individual cortical excitability and response to tES suggests that stimulation may affect individuals differently, depending on the subject’s age, gender, brain state, hormonal levels, and pre-existing regional excitability, which has crucial implications for neurorehabilitation and cognitive enhancement.
Abstract: A current issue in the research of augmentation of brain functions using transcranial electrical stimulation (tES) is the diversity and inconsistency in outcome results. Similar studies often report different results, depending on the parameters and tasks used. Such inconsistencies have led to significant doubts about the efficacy of the method in the broader scientific community, despite its promising potential for patient recovery and treatment. Evidence on the large variability in individual cortical excitability and response to tES suggests that stimulation may affect individuals differently, depending on the subject’s age, gender, brain state, hormonal levels, and pre-existing regional excitability. Certain factors might even lead to the reversal of polarity-dependent effects, and therefore have crucial implications for neurorehabilitation and cognitive enhancement. Research paradigms may have to be refined in the future to avoid the confounding effects of such factors.
293 citations
Cites background from "Human Cortical Excitability Increas..."
...For example, they define tES dosage in terms of the parameters of the electrodes, including the size, number, shape, position and composition, as well as the waveform in terms of intensity and the general form of the waves administered, the pulse shape (wherever relevant), amplitude, width,…...
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...Moreover, with more time staying awake, especially after sleep deprivation, motor cortical excitability gradually increases along with an increase in EEG θ waves, which is commonly observed with prolonged wakefulness (Huber et al., 2013)....
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References
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TL;DR: The after‐effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro‐electrodes in rabbits anaesthetized with urethane.
Abstract: 1. The after-effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro-electrodes in rabbits anaesthetized with urethane.2. In fifteen out of eighteen rabbits the population response recorded from granule cells in the dentate area to single perforant path volleys was potentiated for periods ranging from 30 min to 10 hr after one or more conditioning trains at 10-20/sec for 10-15 sec, or 100/sec for 3-4 sec.3. The population response was analysed in terms of three parameters: the amplitude of the population excitatory post-synaptic potential (e.p.s.p.), signalling the depolarization of the granule cells, and the amplitude and latency of the population spike, signalling the discharge of the granule cells.4. All three parameters were potentiated in 29% of the experiments; in other experiments in which long term changes occurred, potentiation was confined to one or two of the three parameters. A reduction in the latency of the population spike was the commonest sign of potentiation, occurring in 57% of all experiments. The amplitude of the population e.p.s.p. was increased in 43%, and of the population spike in 40%, of all experiments.5. During conditioning at 10-20/sec there was massive potentiation of the population spike (;frequency potentiation'). The spike was suppressed during stimulation at 100/sec. Both frequencies produced long-term potentiation.6. The results suggest that two independent mechanisms are responsible for long-lasting potentiation: (a) an increase in the efficiency of synaptic transmission at the perforant path synapses; (b) an increase in the excitability of the granule cell population.
7,008 citations
"Human Cortical Excitability Increas..." refers background or methods in this paper
...Accordingly, in vivo long-term potentiation (LTP)-inducing procedures increase LFP amplitude and slope (Bliss and Lomo 1973), whereas long-term depression (LTD) procedures reduce it (Kirkwood et al....
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...In the present work, we assessed the excitability of human cortical circuits by an approach that is closer to the one employed in the animal model, where the amplitude and the slope of the early LFP response to cortical stimulation is measured (Bliss and Lomo 1973; Vyazovskiy et al. 2008)....
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Book•
01 Jan 1989
TL;DR: Part 1: Normal Sleep and Its Variations; Part 2: Abnormal Sleep.
Abstract: 1. Normal Sleep and Its Variations History Of Sleep Physiology And Medicine Normal Human Sleep: An Overview Normal Ageing Daytime Sleepiness And Alertness Sleep Deprivation Phylogeny Of Sleep Regulation Mammalian Sleep 2. Sleep Mechanisms Brain Electrical Activity And Sensory Processing During Waking And Sleep States Brainstem Mechanisms Generating REM Sleep Basic Mechanisms Of Sleep-Wake States Control Of Motoneurons During Sleep 3. Physiology in Sleep Physiological Regulation in Sleep Cardiovascular Physiology: Central and Autonomic Regulation Cardiovascular Physiology: The Peripheral Circulation Respiratory Physiology: Central Neural Control Respiratory Physiology: Control of Ventilation Respiratory Physiology: Breathing in Normal Subjects Respiratory Physiology: Sleep at High Altitudes Host Defense Endocrine Physiology Gastrointestinal Physiology Temperature Regulation **Sleep-related Penile Erections 4. Chronobiology Introduction: Chronobiology Circadian Rhythms in Mammals: Formal Properties and Environmental Influences Anatomy and Physiology of the Mammalian Circadian System Molecular Genetic Basis for Mammalian Circadian System The Human Circadian Timing System and Sleep-Wake Regulation **Sleep Homeostasis and Models of Sleep Regulation Circadian Rhythms in Fatigue, Alertness and Performance Melatonin in the Regulations of Sleep & Circadian Rhythms 5. Pharmacology Hypnotics: Basic Mechanisms and Pharmacology Hypnotics: Efficacy and Adverse Effects Stimulants: Basic Mechanisms and Pharmacology Stimulants: Efficacy and Adverse Effects Drugs Which Disturb Sleep and Wakefulness 6. Psychobiology and Dreaming Approaches to the Study of Dream Content: Methods Measures
4,558 citations
TL;DR: This paper reviews a novel hypothesis about the functions of slow wave sleep-the synaptic homeostasis hypothesis, which accounts for a large number of experimental facts, makes several specific predictions, and has implications for both sleep and mood disorders.
1,864 citations
TL;DR: A microcomputer software system is developed that inputs, edits, transforms, analyzes, and reduces the data from the RT portable audiotapes, for each 10-min trial on the task.
Abstract: The Institute of Pennsylvania Hospital and University of Pennsylvania, Philadelphia, Pennsylvania There is a need for brief, portable performance measures that are free of practice effects but that reliably show the impact of sleep loss on performance during sustained work. Reaction time (RT) tasks hold considerable promise in meeting this need, if the extensive number of responses they typically yield can be processed in ways that quickly provide the essential analyses. While testing the utility of a portable visual RT task during a sustained, quasi-continuous work schedule of 54 h, we developed a microcomputer software system that inputs, edits, transforms, analyzes, and reduces the data from the RT portable audiotapes, for each 10-min trial on the task. With relatively minor modifications, the software system can be used on a minimally configured microcomputer system that supports BASIC. The software is flexible and capable of retrieving distorted data, and it generates a variety of dependent variables reflecting intratrial optimum response capacity, lapsing, and response slowing.
1,471 citations