Divergent Cortical Generators of MEG and EEG during Human Sleep Spindles Suggested by Distributed Source Modeling

Background: Sleep spindles are,1-second bursts of 10–15 Hz activity, occurring during normal stage 2 sleep. In animals, sleep spindles can be synchronous across multiple cortical and thalamic locations, suggesting a distributed stable phaselocked generating system. The high synchrony of spindles across scalp EEG sites suggests that this may also be true in humans. However, prior MEG studies suggest multiple and varying generators. Methodology/Principal Findings: We recorded 306 channels of MEG simultaneously with 60 channels of EEG during naturally occurring spindles of stage 2 sleep in 7 healthy subjects. High-resolution structural MRI was obtained in each subject, to define the shells for a boundary element forward solution and to reconstruct the cortex providing the solution space for a noise-normalized minimum norm source estimation procedure. Integrated across the entire duration of all spindles, sources estimated from EEG and MEG are similar, diffuse and widespread, including all lobes from both hemispheres. However, the locations, phase and amplitude of sources simultaneously estimated from MEG versus EEG are highly distinct during the same spindles. Specifically, the sources estimated from EEG are highly synchronous across the cortex, whereas those from MEG rapidly shift in phase, hemisphere, and the location within the hemisphere. Conclusions/Significance: The heterogeneity of MEG sources implies that multiple generators are active during huma

The reticular formation and the neuromodulatory systems

Almost a century ago, Constantin von Economo observed that in patients with encephalitis lethargica lesions in the upper brain stem and posterior hypothalamus impaired consciousness. From lesion studies in cats and anatomical data, the idea arose that the brain stem reticular formation is the origin of the ascending reticular activating system (ARAS) that would operate through the intralaminar nuclei and activate widespread regions of the cerebral cortex. This view of the reticular formation has been extensively modified, and nowadays the reticular formation is viewed as a series of highly specific cell groups, which closely surround the individual motor and sensory nuclei of the brain stem (Sects. 5.2 and 5.4). The diffuse system, driving arousal and consciousness, is now attributed to the neuromodulatory system, including the serotonergic raphe nuclei, the locus coeruleus and other noradrenergic or adrenergic cell groups and cholinergic cell groups, all close to the reticular formation (Sects. 5.3 and 5.5). The English terms of the Terminologia Neuroanatomica are used throughout. Although the basic notion of the ARAS concept that structures in the brain stem regulate states of consciousness still holds true, a much more complex picture has emerged. Experimental work in laboratory animals suggests that the following structures play key roles in the maintenance and modulation of wakefulness: cholinergic nuclei in the upper brain stem and basal forebrain; noradrenergic nuclei, in particular the locus coeruleus; a histaminergic projection from the tuberomamillary nucleus in the posterior hypothalamus; and dopaminergic and serotonergic pathways from the ventral tegmental area and raphe nuclei, respectively. These nuclei all participate in an ascending activating system to the cerebral cortex (Sect. 5.5). The hypothalamus also contains orexinergic neurons that are crucial for maintaining normal wakefulness and a sleep-promoting region in the ventrolateral preoptic area. These groups have mutually inhibiting connections, known as the sleep switch (Sect. 5.6). Some sleep disorders in which these structures are involved are discussed in Clinical Cases (Sect. 5.7). Damage to the upper brain stem reticular formation is known to cause the most radical disturbance of consciousness, i.e. coma, as illustrated in several Clinical Cases (Sect. 5.8)