Sleep Spindles in Humans: Insights from Intracranial EEG and Unit Recordings

Abstract

Sleep spindles are an electroencephalographic (EEG) hallmark of non-rapid eye movement (NREM) sleep and are believed to mediate many sleep-related functions, from memory consolidation to cortical development. Spindles differ in location, frequency, and association with slow waves, but whether this heterogeneity may reflect different physiological processes and potentially serve different functional roles remains unclear. Here we utilized a unique opportunity to record intracranial depth EEG and single-unit activity in multiple brain regions of neurosurgical patients to better characterize spindle activity in human sleep. We find that spindles occur across multiple neocortical regions, and less frequently also in the parahippocampal gyrus and hippocampus. Most spindles are spatially restricted to specific brain regions. In addition, spindle frequency is topographically organized with a sharp transition around the supplementary motor area between fast (13-15Hz) centroparietal spindles often occurring with slow wave up-states, and slow (9-12Hz) frontal spindles occurring 200ms later on average. Spindle variability across regions may reflect the underlying thalamocortical projections. We also find that during individual spindles, frequency decreases within and between regions. In addition, deeper sleep is associated with a reduction in spindle occurrence and spindle frequency. Frequency changes between regions, during individual spindles, and across sleep may reflect the same phenomenon, the underlying level of thalamocortical hyperpolarization. Finally, during spindles neuronal firing rates are not consistently modulated, although some neurons exhibit phase-locked discharges. Overall, anatomical considerations can account well for regional spindle characteristics, while variable hyperpolarization levels can explain differences in spindle frequency.

Sleep- and wake-dependent changes in neuronal activity and reactivity demonstrated in fly neurons using in vivo calcium imaging

“…Instead, the results are more in line with recent findings in mammals suggesting that sleep may not be as global as previously thought. For example, intracranial recordings in epileptic patients have shown that the slow waves and spindles of NREM sleep often occur in some cortical areas but not in others (54) and frequently involve only small groups of neurons (55,56), a finding that was confirmed in rats (15). Recordings of evoked responses in the rat barrel cortex after whisker stimulation also suggest the possible occurrence of "local wake during sleep": responses sometimes appear sleeplike in one cortical column but wake-like in another (57).…”

Rotating waves during human sleep spindles organize global patterns of activity that repeat precisely through the night

“…Early animal sleep spindle studies, using up to 8 electrodes in a linear array (Andersen et al, 1967;Kim et al, 1995;Contreras et al, , 1997, in addition to preliminary EEG evidence in the human (Achermann and Borbély, 1998), proposed that spindles involve global synchronization of cortical circuits, raising the possibility that this sleep oscillation places neocortex into a specialized state for consolidation of long-term memories. In recent years, several studies have reported a mixture of 'local' and 'global' spindles using amplitude-duration thresholding approaches Andrillon et al, 2011). By carefully studying the phase information in the spindle frequency band recorded on large-scale ECoG arrays, we have uncovered that a substantial number of spindle oscillation cycles are organized into global, hemisphere-spanning patterns of rotating and expanding waves (Figure 1-figure supplement 7).…”

Sleep Spindles – As a Biomarker of Brain Function and Plasticity

“…They further report that fast spindles often occur with slow-wave up-states and that spindle variability across regions may reflect the underlying TC projections. They do not find a consistent modulation of neuronal firing rates during spindles [47]. They also report that most sleep slow waves and spindles are predominantly local inferring therefore that the underlying active and inactive neuronal states also occur locally [48].…”

“…An important recent study has provided valuable insights by characterizing sleep spindles in humans by pooling together simultaneous recordings of intracranial depth EEG and unit spiking activities in multiple brain regions in the hippocampus and cortex of 13 individuals undergoing presurgical localization of pharmacologically resistant epilepsy [47][48]. The authors of these studies report that spindles occur across multiple neocortical regions, and less frequently also in the parahippocampal gyrus and hippocampus.…”