Temporal dynamics of cortical sources underlying spontaneous and peripherally evoked slow waves

Abstract

Slow waves are the most prominent electroencephalographic feature of non-rapid eye movement (NREM) sleep. During NREM sleep, cortical neurons oscillate approximately once every second between a depolarized upstate, when cortical neurons are actively firing, and a hyperpolarized downstate, when cortical neurons are virtually silent (Destexhe et al., 1999; Steriade et al., 1993a, 2001). Intracellular recordings indicate that the origins of the slow oscillation are cortical and that corticocortical connections are necessary for their synchronization (Amzica and Steriade, 1995; Steriade et al., 1993b; Timofeev and Steriade, 1996; Timofeev et al., 2000). The currents produced by the near-synchronous slow oscillation of large populations of neurons appear on the scalp as electroencephalogram (EEG) slow waves (Amzica and Steriade, 1997). Despite this cellular understanding, questions remain about the role of specific cortical structures in individual slow waves. Early EEG studies of slow waves in humans were limited by the small number of derivations employed and by the difficulty of relating scalp potentials to underlying brain activity (Brazier, 1949; Roth et al., 1956). Functional neuroimaging methods offer exceptional spatial resolution, but lack the temporal resolution to track individual slow waves (Dang-Vu et al., 2008; Maquet, 2000). Intracranial recordings in patient populations are limited by the availability of medically necessary electrode placements and can be confounded by pathology and medications (Cash et al., 2009; Nir et al., 2011; Wenneberg 2010). Source modeling of high-density EEG recordings offers a unique opportunity for neuroimaging sleep slow waves. So far, the results have challenged several of the influential topographic observations about slow waves that had persisted since the original EEG recordings of sleep. These recent analyses revealed that individual slow waves are idiosyncratic cortical events and that the negative peak of the EEG slow wave often involves cortical structures not necessarily apparent from the scalp, like the inferior frontal gyrus, anterior cingulate, posterior cingulate, and precuneus (Murphy et al., 2009). In addition, not only do slow waves travel (Massimini et al., 2004), but they often do so preferentially through the areas comprising the major connectional backbone of the human cortex (Hagmann et al., 2008). In this chapter, we will review the cellular, intracranial recording, and neuroimaging results concerning EEG slow waves. We will also confront a long held belief about peripherally evoked slow waves, also known as K-complexes, namely that they are modality independent and do not involve cortical sensory pathways. The analysis included here is the first to directly compare K-complexes evoked with three different stimulation modalities within the same subject on the same night using high-density EEG.

Figure 1. Similarity of scalp and source topographies of K-complex responses

A,B,C: Across subject grand average 256-channel EEG butterfly plot (overlaid traces) of the evoked response during sleep for each stimulation modality. Red-line indicates the time of stimulation. Labeled boxes indicate time periods of evoked responses selected for comparison across modalities. A′,B′,C′: Scalp topography for the N550 time periods. Each map is independently scaled in order to indicate relative topography. Red indicates positivity with respect to the average. Blue indicates negativity. 10-10 approximate locations of AFz and Cz are shown. A″,B″,C″: Flat maps of the cortical sources for the N550 peak. Current sources were z-transformed for each time point before averaging across time. Median z-score current across subjects is displayed. Current hot spots (most current) indicated in red, cold spots in blue. AC=Anterior Cingulate, MFG = Middle Frontal Gyrus, IPL = Inferior Parietal Lobule.

Figure 2. N550 peak shows modality specific differences in cortical sources that include primary cortical areas

A: Reference flat map displaying cortical source voxels which comprise the primary cortical areas. BA 41 (Brodmann area 41) corresponds to primary auditory cortex. BA 1,2,3 (Brodmann areas 1,2,3) corresponds to primary somatosensory cortex. BA 17 (Brodmann area 17) corresponds to primary visual cortex. B: Flat map of significantly different cortical sources across stimulation modalities (Quade test, p<.05). Color-coding of voxels indicates the stimulation with the highest ranking based on the Quade test. Highest rank means the stimulation had the highest current relative to the other stimulation modalities. C: Same as B except significant cortical source voxels are color-coded based on the post hoc procedures (Conover, 1999) for determining the significant comparison. Only comparisons where one stimulation modality is significantly larger than either or both of the other modalities are displayed. Note that there are significantly different cortical sources in left primary visual cortex for which the visual stimulation condition produces significantly higher relative currents compared to either auditory or somatosensory stimulation. A significantly different area also exists that includes the somatosensory cortices bilaterally but extends anteriorly to include supplemental motor areas. A=Auditory, S=Somatosensory, V=Visual.

Figure 3. The initial positive peak (P200), but not N350 or P900, shows modality specific differences in primary cortical areas

Same as Figure 2 except that significantly different areas are shown for the three other components. For the P200 peak, both primary somatosensory and visual areas are significantly different based on the Quade test (p<.05). The somatosensory and visual stimulations account for the most current in these areas respectively (P200, A and B). The N350 peak shows significant areas in medial frontal, superior frontal, cingulate and precuneus, but not the primary cortical areas. Few areas are significantly different during the P900