Differential effects on fast and slow spindle activity, and the sleep slow oscillation in humans with carbamazepine and flunarizine to antagonize voltage-dependent Na+ and Ca2+ channel activity.

STUDY OBJECTIVES: Sleep spindles play an important functional role in sleep-dependent memory consolidation. They are a hallmark of non-rapid eye movement (NREM) sleep and are grouped by the sleep slow oscillation. Spindles are not a unitary phenomenon but are differentiated by oscillatory frequency and topography. Yet, it is still a matter of debate whether these differences relate to different generating mechanisms. As corticothalamic networks are known to be involved in the generation of spindles and the slow oscillation, with Ca2+ and Na+ conductances playing crucial roles, we employed the actions of carbamazepine and flunarizine to reduce the efficacy of Na+ and Ca2+ channels, respectively, for probing in healthy human subjects mechanisms of corticothalamocortical excitability. DESIGN: For each pharmacologic substance a within-design study was conducted on 2 experimental nights in young, healthy adults. MEASUREMENTS AND RESULTS: Results indicate differential effects for slow frontocortical (approximately 10 Hz) and fast centroparietal (approximately 14 Hz) spindles. Carbamazepine enhanced slow frontal spindle activity conjointly with an increment in slow oscillation power (approximately 0.75 Hz) during deep NREM sleep. In contrast, fast centroparietal spindle activity (approximately 14 Hz) was decreased by carbamazepine. Flunarizine also decreased fast-spindle electroencephalogram power, but affected neither slow frontal spindle nor slow oscillation frequency bands. CONCLUSIONS: Our findings indicate a differential pharmacologic response of the two types of sleep spindles and underscore a close linkage of the generating mechanisms underlying the sleep slow oscillation and the slow frontal sleep spindles for the signal transmission processes manipulated in the current study.

Grouping of MEG gamma oscillations by EEG sleep spindles.

Studies have revealed an association between EEG sleep spindles and processing of memories during sleep. Here we investigated whether there is a temporal relation between sleep spindles and MEG oscillatory activity in the gamma frequency band (>30 Hz) which is considered to reflect local cortical processing of memory representations. MEG and simultaneous EEG (at Cz) were obtained in subjects during sleep together with standard polysomnography. As expected EEG spindles were correlated with power increases in MEG spindle (12.5-15.5 Hz) power mainly over prefrontal and occipital cortical areas. During EEG spindles we revealed both transient significant increases and decreases in MEG power, with decreases occurring significantly more often than increases. The modulations in gamma power occurred mainly at sites of increased MEG spindle power, and more often during peaks than troughs within the EEG spindle cycle. Cross-frequency coherence analyses confirmed a strong phase-coupling of gamma band activity with the spindle rhythm. The findings are consistent with the idea that spindles provide a fine-tuned temporal frame for integrated cortical memory processing during sleep.

Sleep selectively enhances memory expected to be of future relevance.

The brain encodes huge amounts of information, but only a small fraction is stored for a longer time. There is now compelling evidence that the long-term storage of memories preferentially occurs during sleep. However, the factors mediating the selectivity of sleep-associated memory consolidation are poorly understood. Here, we show that the mere expectancy that a memory will be used in a future test determines whether or not sleep significantly benefits consolidation of this memory. Human subjects learned declarative memories (word paired associates) before retention periods of sleep or wakefulness. Postlearning sleep compared with wakefulness produced a strong improvement at delayed retrieval only if the subjects had been informed about the retrieval test after the learning period. If they had not been informed, retrieval after retention sleep did not differ from that after the wake retention interval. Retention during the wake intervals was not affected by retrieval expectancy. Retrieval expectancy also enhanced sleep-associated consolidation of visuospatial (two-dimensional object location task) and procedural motor memories (finger sequence tapping). Subjects expecting the retrieval displayed a robust increase in slow oscillation activity and sleep spindle count during postlearning slow-wave sleep (SWS). Sleep-associated consolidation of declarative memory was strongly correlated to slow oscillation activity and spindle count, but only if the subjects expected the retrieval test. In conclusion, our work shows that sleep preferentially benefits consolidation of memories that are relevant for future behavior, presumably through a SWS-dependent reprocessing of these memories.