Scientific Understanding of Consciousness
Sleep and Dreaming — Recent Research
Science 16 November 2007: Vol. 318. no. 5853, pp. 1147 - 1150
Fast-Forward Playback of Recent Memory Sequences in Prefrontal Cortex During Sleep
David R. Euston, Masami Tatsuno, Bruce L. McNaughton
Arizona Research Laboratories Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, AZ 85724–5115, USA.
As previously shown in the hippocampus and other brain areas, patterns of firing-rate correlations between neurons in the rat medial prefrontal cortex during a repetitive sequence task were preserved during subsequent sleep, suggesting that waking patterns are reactivated. We found that, during sleep, reactivation of spatiotemporal patterns was coherent across the network and compressed in time by a factor of 6 to 7. Thus, when behavioral constraints are removed, the brain's intrinsic processing speed may be much faster than it is in real time. Given recent evidence implicating the medial prefrontal cortex in retrieval of long-term memories, the observed replay may play a role in the process of memory consolidation.
According to memory-consolidation theory, the hippocampus is necessary for the retrieval of recently encoded episodic memories. For remote memories, in contrast, the neocortex is sufficient for recall. The transfer of memories from hippocampal to neocortical control is widely believed to involve replay during sleep of the neural patterns representing the memory.
Among cortical areas, the medial prefrontal cortex (mPFC) apparently plays a unique role in mediating retrieval of consolidated, remote memories.
Accelerated replay may be an important part of the process whereby hippocampus-dependent memories become cortex-dependent.
(end of paraphrase)
Nature 444, 559-560 (30 November 2006)
Neuroscience: A memory boost while you sleep
Robert Stickgold is at the Center for Sleep and Cognition, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
It is generally agreed that sleep aids memory consolidation; researchers have produced a wealth of evidence for at least one function of slumber — the consolidation of memories. A wide range of converging data show that memories are replayed, modified, stabilized and even enhanced as we snooze, but an understanding of how this occurs remains elusive. The proposed mechanisms rely on two effects that are observed in the brain only during sleep: alterations in the levels of chemical neuromodulators and distinctive oscillations of electrical activity. Marshall et al. provide evidence that the direct induction of 'cortical slow oscillations' during sleep can improve the recall of word-pairs memorized the previous night.
Human sleep is divided into rapid-eye-movement sleep (REM) and non-REM sleep (NREM), with NREM sleep further divided into stages 1 to 4. These sleep phases are distinguished, in part, by well-defined patterns of oscillatory electrical activity in the brain, as measured by electroencephalography. Theta waves oscillate at 4–8 Hz, and are characteristic of REM sleep; NREM stage 1 is a transitional phase between full wakefulness and sleep, and is characterized by mixed-frequency waves; sleep spindles (12–14 Hz) typify NREM stage 2; and delta waves (1–4 Hz) distinguish NREM stages 3 and 4, which are known collectively as slow-wave sleep. Sleep spindles and delta waves rise and fall in concert with a yet slower (<1 Hz) oscillatory pattern known as cortical slow oscillations — it is these patterns that Marshall et al. have studied.
(end of paraphrase)
Nature 444, 610-613 (30 November 2006)
Boosting slow oscillations during sleep potentiates memory
Lisa Marshall, Halla Helgadóttir, Matthias Mölleand Jan Born
There is compelling evidence that sleep contributes to the long-term consolidation of new memories. This function of sleep has been linked to slow (<1 Hz) potential oscillations, which predominantly arise from the prefrontal neocortex and characterize slow wave sleep. However, oscillations in brain potentials are commonly considered to be mere epiphenomena that reflect synchronized activity arising from neuronal networks, which links the membrane and synaptic processes of these neurons in time. Whether brain potentials and their extracellular equivalent have any physiological meaning per se is unclear, but can easily be investigated by inducing the extracellular oscillating potential fields of interest. Here we show that inducing slow oscillation-like potential fields by transcranial application of oscillating potentials (0.75 Hz) during early nocturnal non-rapid-eye-movement sleep, that is, a period of emerging slow wave sleep, enhances the retention of hippocampus-dependent declarative memories in healthy humans. The slowly oscillating potential stimulation induced an immediate increase in slow wave sleep, endogenous cortical slow oscillations and slow spindle activity in the frontal cortex. Brain stimulation with oscillations at 5 Hz—another frequency band that normally predominates during rapid-eye-movement sleep—decreased slow oscillations and left declarative memory unchanged. Our findings indicate that endogenous slow potential oscillations have a causal role in the sleep-associated consolidation of memory, and that this role is enhanced by field effects in cortical extracellular space.
(end of paraphrase)
Nature 437, 1257-1263 (27 October 2005)
Hypothalamic regulation of sleep and circadian rhythms
Clifford B. Saper, Thomas E. Scammell & Jun Lu
Department of Neurology and Program in Neuroscience, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, USA.
A series of findings over the past decade has begun to identify the brain circuitry and neurotransmitters that regulate our daily cycles of sleep and wakefulness. The latter depends on a network of cell groups that activate the thalamus and the cerebral cortex. A key switch in the hypothalamus shuts off this arousal system during sleep. Other hypothalamic neurons stabilize the switch, and their absence results in inappropriate switching of behavioural states, such as occurs in narcolepsy. These findings explain how various drugs affect sleep and wakefulness, and provide the basis for a wide range of environmental influences to shape wake–sleep cycles into the optimal pattern for survival.
A key finding of studies in the 1970s and 1980s showed that the ascending arousal system largely originates from a series of well-defined cell groups with identified neurotransmitters. This pathway has two major branches. The first branch is an ascending pathway to the thalamus that activates the thalamic relay neurons that are crucial for transmission of information to the cerebral cortex. The major source of upper brainstem input to the thalamic-relay nuclei, as well as to the reticular nucleus of the thalamus, is a pair of acetylcholine-producing cell groups: the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT). The neurons in the PPT/LDT fire most rapidly during wakefulness and rapid eye movement (REM) sleep, which is the stage accompanied by cortical activation, loss of muscle tone in the body and active dreams. These cells are much less active during non-REM (NREM) sleep, when cortical activity is slow. Their input to the reticular nucleus is crucial, as it sits between the thalamic-relay nuclei and the cerebral cortex, acting as a gating mechanism that can block transmission between the thalamus and cerebral cortex, which is important for wakefulness. Other inputs to the thalamic midline and intralaminar nuclei originate more broadly in the upper brainstem, including the reticular formation, the PPT/LDT, the monoaminergic systems and the parabrachial nucleus. The intralaminar and midline nuclei are also believed to have a role in cortical arousal.
Positron-emission tomography studies during sleep in humans with insomnia also show increased activity in corticolimbic sites, including the medial prefrontal cortex and medial temporal lobe, compared with sleeping subjects without insomnia. These inputs might maintain a hyperaroused state, which can be essential in an emergency situation, such as when a doctor must stay awake to care for a sick patient overnight. However, when the arousal systems override the homeostatic and circadian regulation of sleep during periods of behavioural stress or depression, the result might be unwanted and debilitating insomnia.
Because older individuals sleep about half an hour less per day, it is possible that at least some of their cognitive decline and increase in cardiovascular disease might be explained by sleep restriction. Similarly, sleep loss might impair performance among adolescents who arise early for school, shift workers, overnight long-haul truckers and even medical personnel working in hospitals. The public-health implications of sleep loss indicate that there is a great deal at stake in working out the mechanisms that regulate our daily cycles of sleep and wakefulness.
(end of paraphrase)
Nature 441, 589-594 (1 June 2006)
A putative flip–flop switch for control of REM sleep
Jun Lu, David Sherman, Marshall Devor & Clifford B. Saper
Department of Neurology and Program in Neuroscience, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
Department of Cell and Animal Biology, Hebrew University, Jerusalem 91904, Israel
Rapid eye movement (REM) sleep consists of a dreaming state in which there is activation of the cortical and hippocampal electroencephalogram (EEG), rapid eye movements, and loss of muscle tone. Although REM sleep was discovered more than 50 years ago, the neuronal circuits responsible for switching between REM and non-REM (NREM) sleep remain poorly understood. Here we propose a brainstem flip–flop switch, consisting of mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum. Each side contains GABA (gamma-aminobutyric acid)-ergic neurons that heavily innervate the other. The REM-on area also contains two populations of glutamatergic neurons. One set projects to the basal forebrain and regulates EEG components of REM sleep, whereas the other projects to the medulla and spinal cord and regulates atonia during REM sleep. The mutually inhibitory interactions of the REM-on and REM-off areas may form a flip–flop switch that sharpens state transitions and makes them vulnerable to sudden, unwanted transitions—for example, in narcolepsy.
(end of paraphrase)
Science 22 May 2009: Vol. 324. no. 5930, pp. 1084 - 1087
The Human K-Complex Represents an Isolated Cortical Down-State
Sydney S. Cash,1 Eric Halgren,2 Nima Dehghani,2 Andrea O. Rossetti,5 Thomas Thesen,3 ChunMao Wang,3 Orrin Devinsky,3 Ruben Kuzniecky,3 Werner Doyle,3 Joseph R. Madsen,4 Edward Bromfield,5 Loránd Erss,6 Péter Halász,7,9 George Karmos,8,9 Richárd Csercsa,8 Lucia Wittner,6,8 István Ulbert6,8,9
1 Department of Neurology, Epilepsy Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K-complex (KC), which occurs in slow-wave sleep. Here, we show that KCs are generated in widespread cortical areas by outward dendritic currents in the middle and upper cortical layers, accompanied by decreased broadband EEG power and decreased neuronal firing, which demonstrate a steep decline in network activity. Thus, KCs are isolated "down-states," a fundamental cortico-thalamic processing mode already characterized in animals. This correspondence is compatible with proposed contributions of the KC to sleep preservation and memory consolidation.
Although the electroencephalogram (EEG) is known to directly and instantaneously reflect synaptic and active transmembrane neuronal currents, the specific channels, synapses, and circuits that generate particular EEG elements in humans remain poorly specified. Much of the EEG is composed of repeated wave forms with characteristic morphologies, durations, amplitudes, frequency content, evoking events, and background states. The largest of these EEG "graphoelements" is the KC, characterized by a short surface-positive transient followed by a slower, larger surface-negative complex with peaks at 350 and 550 ms, and then a final positivity peaking near 900 ms, followed sometimes by 10- to 14-Hz "spindles". KCs occur in non–rapid-eye-movement (non-REM) sleep, especially stage 2. Deeper sleep (stages 3 to 4) is characterized by slow waves, demonstrated in extensive animal studies to consist of a "slow oscillation" between periods of intense firing by both excitatory and inhibitory cortical neurons (termed "up-states") and periods of neuronal silence ("down-states"). Using micro- and macro-electrode arrays placed in patients undergoing evaluation for epilepsy, we demonstrate that the microphysiological characteristics of human KCs appear identical to those of down-states recorded in the same patients.
This study provides strong evidence that KCs are induced cortical down-states. The recordings demonstrate that KCs are generated in widespread cortical locations. Previous extracranial EEG, magnetoencephalogram (MEG), and intracranial EEG recordings have not provided unambiguous localization of KC generators because of difficulties in localizing widely distributed sources.
Sleep is thought to perform essential restorative and mnestic functions. Maintaining sleep is therefore crucial, but so is awakening in the face of danger. Our finding that the KC represents an isolated down-state supports the theory that it suppresses cortical activity and, thus, arousal in response to stimuli that are judged by the sleeping brain not to be dangerous. Increasing evidence supports a strong contribution to memory consolidation of stage 2 sleep, characterized by KC and spindles. The cortical down-state may provide a period when the near absence of neural activity induces a blanket suppression of synaptic strengths, balancing the synaptic enhancement occurring during waking and up-states and thus preserving the signal-to-noise ratio in network representations. In addition, during the recovery from the down-state, cortical firing "reboots" in a systematic order, which allows the potential for engrams encoded in dynamic assemblies of neuronal firing to be repeatedly practiced and thus consolidated.
(end of paraphrase)
Return to — Sleep and Dreaming