Jan Born

The memory function of sleep

Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory, depending on the specific conditions of learning and the timing of sleep. Consolidation during sleep promotes both quantitative and qualitative changes of memory representations. Through specific patterns of neuromodulatory activity and electric field potential oscillations, slow-wave sleep (SWS) and rapid eye movement (REM) sleep support system consolidation and synaptic consolidation, respectively. During SWS, slow oscillations, spindles and ripples — at minimum cholinergic activity — coordinate the re-activation and redistribution of hippocampus-dependent memories to neocortical sites, whereas during REM sleep, local increases in plasticity-related immediate-early gene activity — at high cholinergic and theta activity — might favour the subsequent synaptic consolidation of memories in the cortex.

Boosting slow oscillations during sleep potentiates memory

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.

Sniffing neuropeptides: a transnasal approach to the human brain

Neuropeptides act as neuronal messengers in the brain, influencing many neurobehavioral functions. Their experimental and therapeutic use in humans has been hampered because, when administered systemically, these compounds do not readily pass the blood–brain barrier, and they evoke potent hormone-like side effects when circulating in the blood. We administered three peptides, melanocortin(4–10) (MSH/ACTH(4–10)), vasopressin and insulin, intranasally and found that they achieved direct access to the cerebrospinal fluid (CSF) within 30 minutes, bypassing the bloodstream.

Effects of early and late nocturnal sleep on declarative and procedural memory

Recall of paired-associate lists (declarative memory) and mirror-tracing skills (procedural memory) was assessed after retention intervals defined over early and late nocturnal sleep. In addition, effects of sleep on recall were compared with those of early and late retention intervals filled with wakefulness. Twenty healthy men served as subjects. Saliva cortisol concentrations were determined before and after the retention intervals to determine pituitary-adrenal secretory activity. Sleep was determined somnopolygraphically. Sleep generally enhanced recall when compared with the effects of corresponding retention intervals of wakefulness. The benefit from sleep on recall depended on the phase of sleep and on the type of memory: Recall of paired-associate lists improved more during early sleep, and recall of mirror-tracing skills improved more during late sleep. The effects may reflect different influences of slow wave sleep (SWS) and rapid eye movement (REM) sleep since time in SWS was 5 times longer during the early than late sleep retention interval, and time in REM sleep was twice as long during late than early sleep (p < 0.005). Changes in cortisol concentrations, which independently of sleep and wakefulness were lower during early retention intervals than late ones, cannot account for the effects of sleep on memory. The experiments for the first time dissociate specific effects of early and late sleep on two principal types of memory, declarative and procedural, in humans.

Odor cues during slow-wave sleep prompt declarative memory consolidation

Sleep facilitates memory consolidation. A widely held model assumes that this is because newly encoded memories undergo covert reactivation during sleep. We cued new memories in humans during sleep by presenting an odor that had been presented as context during prior learning, and so showed that reactivation indeed causes memory consolidation during sleep. Re-exposure to the odor during slow-wave sleep (SWS) improved the retention of hippocampus-dependent declarative memories but not of hippocampus-independent procedural memories. Odor re-exposure was ineffective during rapid eye movement sleep or wakefulness or when the odor had been omitted during prior learning. Concurring with these findings, functional magnetic resonance imaging revealed significant hippocampal activation in response to odor re-exposure during SWS.

Sleep inspires insight.

Insight denotes a mental restructuring that leads to a sudden gain of explicit knowledge allowing qualitatively changed behaviour. Anecdotal reports on scientific discovery suggest that pivotal insights can be gained through sleep. Sleep consolidates recent memories and, concomitantly, could allow insight by changing their representational structure. Here we show a facilitating role of sleep in a process of insight. Subjects performed a cognitive task requiring the learning of stimulus–response sequences, in which they improved gradually by increasing response speed across task blocks. However, they could also improve abruptly after gaining insight into a hidden abstract rule underlying all sequences. Initial training establishing a task representation was followed by 8 h of nocturnal sleep, nocturnal wakefulness, or daytime wakefulness. At subsequent retesting, more than twice as many subjects gained insight into the hidden rule after sleep as after wakefulness, regardless of time of day. Sleep did not enhance insight in the absence of initial training. A characteristic antecedent of sleep-related insight was revealed in a slowing of reaction times across sleep. We conclude that sleep, by restructuring new memory representations, facilitates extraction of explicit knowledge and insightful behaviour.

Sleep forms memory for finger skills

Practicing a motor skill triggers a process of memory consolidation that continues for hours after practice has ended, and becomes manifest in an improved skill at later testing. We used a sequential motor task (finger-to-thumb opposition task) to show that, in humans, the formation of motor skill memories essentially benefits from sleep. Independent of whether placed during daytime or nighttime, sleep after practice enhanced speed of sequence performance on average by 33.5% and reduced error rate by 30.1% as compared with corresponding intervals of wakefulness. The effect of sleep after learning proved to be stable when retesting was postponed for another night, to exclude effects of sleep loss and to assure that all subjects had sufficient sleep before retrieval testing. Also, the consolidating effect of sleep was specific for the motor sequence learned. It did not generalize to a similar sequence containing identical movement segments in a different order. Retention periods of wakefulness improved performance only moderately and only if placed during daytime. The observations demonstrate a critical role of sleep for storing and optimizing motor skills.

Intranasal insulin improves memory in humans.

Previous studies have suggested an acutely improving effect of insulin on memory function. To study changes in memory associated with a prolonged increase in brain insulin activity in humans, here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment. Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration, we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function. Also, improvements in mood were expected. We investigated the effects of 8 weeks of intranasal administration of insulin (human regular insulin 4 x 40 IU/d) on declarative memory (immediate and delayed recall of word lists), attention (Stroop test), and mood in 38 healthy subjects (24 males) in a double blind, between-subject comparison. Blood glucose and plasma insulin levels did not differ between the placebo and insulin conditions. Delayed recall of words significantly improved after 8 weeks of intranasal insulin administration (words recalled, Placebo 2.92 +/- 1.00, Insulin 6.20 +/- 1.03, p < 0.05). Moreover, subjects after insulin reported signs of enhanced mood, such as reduced anger (p < 0.02) and enhanced self-confidence (p < 0.03). Results indicate a direct action of prolonged intranasal administration of insulin on brain functions, improving memory and mood in the absence of systemic side effects. These findings could be of relevance for the treatment of patients with memory disorders like in Alzheimers disease.

The contribution of sleep to hippocampus-dependent memory consolidation

There is now compelling evidence that sleep promotes the long-term consolidation of declarative and procedural memories. Behavioral studies suggest that sleep preferentially consolidates explicit aspects of these memories, which during encoding are possibly associated with activation in prefrontal-hippocampal circuitry. Hippocampus-dependent declarative memory benefits particularly from slow-wave sleep (SWS), whereas rapid-eye-movement (REM) sleep seems to benefit procedural aspects of memory. Consolidation of hippocampus-dependent memories relies on a dialog between the neocortex and hippocampus. Crucial features of this dialog are the neuronal reactivation of new memories in the hippocampus during SWS, which stimulates the redistribution of memory representations to neocortical networks; and the neocortical slow (<1Hz) oscillation that synchronizes hippocampal-to-neocortical information transfer to activity in other brain structures.

Sleep to Remember

Recently, compelling evidence has accumulated that links sleep to learning and memory. Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory. Consolidation is an active process that is presumed to rely on the covert reactivation and reorganization of newly encoded representations. Hippocampus-dependent memories benefit primarily from slow-wave sleep (SWS), whereas memories not depending on the hippocampus show greater gains over periods containing high amounts of rapid eye movement sleep. One way sleep does this is by establishing different patterns of neurotransmitters and neurohormone secretion between sleep stages. Another central role for consolidating memories is played by the slow oscillation, that is, the oscillating field potential change dominating SWS. The emergence of slow oscillations in neocortical networks depends on the prior use of these networks for encoding of information. Via efferent pathways, they synchronize the occurrence of sharp wave ripples accompanying memory reactivations in the hippocampus with thalamocortical spindle activity. Thus, hippocampal memories are fed back into neocortical networks at a time when these networks are depolarized and, because of concurrent spindle activity, can most sensitively react to these inputs with plastic changes underlying the formation of long-term memory representations.