Chapter 2

The EEG and the Discovery of the RAS

Edgar Garcia-Rill, PhD*; Christen Simon, PhD┼    * Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA
┼ Scientist, Study Director, Northern Biomedical Research Inc., Spring Lake, MI, USA

Abstract

The electroencephalogram was invented by Hans Berger and was used in combination with brain stem transections to ascertain that the reticular activating system (RAS) was the main determinant of the fast activity seen during waking and rapid eye movement (REM) sleep. Lesions of the RAS or disconnection of the RAS from the forebrain generally led to low-frequency activity as seen during slow-wave sleep, but when the RAS was stimulated or remained connected to the forebrain, fast activity such as that observed during waking and REM sleep was manifested. The main nucleus within the RAS in charge of both waking and REM sleep, two states of low-amplitude, high-frequency activity, is the pedunculopontine nucleus.

Keywords

Electroencephalogram (EEG)

Laterodorsal tegmental nucleus

Pedunculopontine nucleus (PPN)

The EEG and the RAS

Sleep and dreaming have been studied for thousands of years, notably by the Egyptians and Greeks. In 350 BCE., Aristotle wrote "On Sleep and Sleeplessness," where he stated that an awake person is exercising "sense-perception," and "all organs which have a natural function must lose power when they work beyond the natural time-limit of their working period." Sleep occurs when the sense-perception special organ "continues beyond the appointed time-limit of its continuous working period, it will lose its power and will do its work no longer." Therefore, sleep was essentially considered to be a passive event, a turning off of the "sense-perception" organ due to exhaustion (Kirsch, 2011).

Modern sleep science began with the invention of the electroencephalogram (EEG) in 1924 by Hans Berger, whose motivation for developing the technique was the study of telepathy (see a wonderful description by Buzsaki, 2006). Later, the physiologist Frédéric Bremer was one of the first to measure EEG activity following transections of brain stem regions (Figure 2.1). Transection of the brain stem at the junction of the pons and midbrain (cerveau isolé) in the cat anterior to the reticular activating system (RAS) produced a state with cortical high-amplitude, low-frequency EEG patterns similar to that in slow-wave sleep (SWS) (T3 in Figure 2.1). However, transection of the brain stem just rostral to the spinal cord (encéphale isolé) posterior to the RAS produced fluctuating EEG patterns, with spontaneous patterns of low-frequency, high-amplitude activity (as observed during SWS) as well as high-frequency, low-amplitude activity (as observed during waking and rapid eye movement (REM) sleep) (T1 in Figure 2.1) (Bremer, 1973; Kerkhofs and Lavie, 2000). Therefore, the region of the RAS was considered critical for the induction and maintenance of REM sleep and the high-frequency cortical activity that is required for vigilance and consciousness during waking (Gottesmann, 1988).

Figure 2.1 Effects of acute brain stem transections on the EEG. T1. Transections at the medullary-spinal junction allowed the manifestation of high-frequency, low-amplitude cortical EEG immediately after transection. T2. Transections at the midpontine level also permitted the manifestation of high-frequency, low-amplitude EEG activity in the EEG. T3. Midcollicular posthypothalamic transections blocked the manifestation of high-frequency activity, leading to high-amplitude, low-frequency EEG. This occurred despite the fact that this transection left the hypothalamus and basal forebrain connected to the thalamus and cortex. T4. Postcollicular prehypothalamic transections leaving the basal forebrain connected to anterior structures also failed to maintain low-amplitude, high-frequency activity. BF, basal forebrain; LC, locus coeruleus; LH, lateral hypothalamus; PPN, pedunculopontine nucleus.

The Italian Giuseppe Moruzzi and the American Horace Magoun also greatly contributed to waking and sleep research through the use of the EEG. These scientists discovered that stimulation of the brain stem reticular formation abolished low-frequency activity and induced high-frequency activity in the cortical EEG (Moruzzi and Magoun, 1949). This high-frequency activity was identical to that observed by Bremer in the encéphale isolé preparation. Moruzzi and Magoun concluded, "the possibility is considered that a background maintained activity within the ascending brain stem activating system may account for wakefulness, while reduction of its activity either naturally, by barbiturates, or by experimental injury and disease, may respectively precipitate normal sleep, contribute to anesthesia or produce pathological somnolence" (Moruzzi and Magoun, 1949).

Further transection studies concluded that the "maintained influence of the ascending brain stem activating system underlies wakefulness, while absence of this influence precipitates sleep" (Lindsley et al., 1949). In later studies, Moruzzi transected the brain stem at the pontomidbrain junction, a few millimeters caudal to the original cerveau isolé preparation. These transections at midpontine pretrigeminal levels produced spontaneous EEG patterns and eye movements, like those observed for the encéphale isolé preparation (T2 in Figure 2.1) (Moruzzi, 1972). Similar midpontine transections were performed by Steriade that led to waking EEG signs, while postcollicular-premammillary transections (T4 in Figure 2.1) led to SWS EEG (Steriade et al., 1969). Therefore, nuclei near the pons-midbrain junction were implicated in the generation of high-frequency EEG patterns.

Nathaniel Kleitman was a prominent sleep researcher at the University of Chicago and, along with two of his graduate students Eugene Aserinsky and William Dement, correlated dreams, increased respiration, heart rate, and eye movements to high-frequency EEG patterns during REM sleep (Aserinsky and Kleitman, 1953, 1955). They also proposed the dual nature of sleep: REM sleep is a completely different state than SWS, even though they both occur while asleep. Michel Jouvet expanded on these results to show that REM sleep, termed "paradoxical sleep," is accompanied by muscle atonia and rostropontine transections preserved muscle atonia during REM sleep (Jouvet, 1962).

The above studies led to the formulation of three distinct arousal states in the human and other mammals: waking, SWS, and REM sleep. Furthermore, they established the importance of the brain stem reticular formation in generating these states. However, later studies were required to more carefully analyze the role of specific brain stem nuclei in modulating wake-sleep states. It should be noted that the transections used in the above studies assessed EEG features soon after the lesion, that is, acutely. However, when animals were transected and maintained for days or weeks after the transection, the Chilean neuroscientist Jaime Villablanca found that prethalamic transections disconnected the RAS from the forebrain and cats did indeed ultimately recover some waking-like EEG activity (Villablanca, 2004). These results suggest that partial recovery of low-amplitude, high-frequency activity can take place in the forebrain but after chronic transections. Villablanca, however, did conclude that "true waking behavior depended on the cholinergic reticular core" (Villablanca, 2004). In Chapter 3, we will discuss some of the regions anterior to the RAS that could be mediating the recovery of some of the fast activity after such chronic lesions.

Limitations of the EEG

Gold cup electrodes with conducting paste are applied to the scalp in a designated system to record the EEG. The electrodes pick up electrical signals from the brain, which are somewhat distorted by the intervening bone and hair. The signals originate from thousands of neurons in the underlying cortex in which the largest cells, the pyramidal cells, are arranged radially and have apical dendrites extending to the most superficial layers with axons extending into the white matter. Since the cortex has a columnar organization, most cells are oriented perpendicularly to the surface, making current flow calculations simple for the gyri, although the presence of sulci creates a complex problem for calculating current flow. In general, the activity of as many as 500,000 neurons over a range of 3-5 mm may be measured by a single electrode. EEG amplifiers, however, typically measure activity that is filtered. The typical high-pass filter settings are at 1 Hz and in some cases 0.1 Hz. This eliminates very slow brain activity and drift in the electrodes. The typical low-pass settings are at 70 Hz and in some cases as high as 200 Hz. This eliminates high-frequency activity. That means that the EEG amplifier has inappropriate band-pass filters for detecting events as fast as action potentials, which occur in the...