Journal of Neuroscience and Neuroengineering Vol. 3, pp. 1–5, 2014 (www.aspbs.com/jnsne)
Copyright © 2014 by American Scientific Publishers All rights reserved. Printed in the United States of America
Electroencephalogram Mapping of Brain States German Torres∗ , Michael P. Cinelli, Alexander T. Hynes, Ian S. Kaplan, and Joerg R. Leheste Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine Old Westbury, New York, 11568 USA
KEYWORDS: Action Potentials, Anesthetics, Brain Pathologies, Neuronal Cell Types, Sleep-Wake Cycles.
INTRODUCTION Action potentials are the information-processing elements of the nervous system. Although the sequence of events underlying action potentials is relatively understood at the microscopic level, its functional significance at the macroscopic level is far from clear. Nevertheless, action potentials are usually viewed as two regenerative electrochemical cycles (i.e., depolarization and hyperpolarization cycles) conveying graded information to the neuron, synapse, neural circuit and eventually to the entire brain. Action potentials can be gauged indirectly at the macroscopic level through the use of brain imaging and quantitative electroencephalogram (EEG) readouts. For example, EEGs measure summations of excitatory (i.e., depolarizing) and inhibitory (i.e., hyperpolarizing) postsynaptic action potentials across cortical cells, more specifically, pyramidal neurons of the external (Layer III) and internal (Layer V) layers of the cerebral cortex [1]. As pyramidal neurons represent the primary output for the cerebral cortex to the ipsilateral or contralateral hemisphere [2], EEG readouts are thought to translate local streams of abstract information to subcortical targets in the forebrain, brainstem or spinal cord. Because of its noninvasive nature, and adequate temporal and spatial resolutions, the EEG has become an excellent experimental tool for deciphering global patterns of neural activity regulating brain states.
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Author to whom correspondence should be addressed. Email:
[email protected] Received: xx Xxxx xxxx Accepted: xx Xxxx xxxx
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MECHANISMS OF THE ELECTROENCEPHALOGRAM The EEG, as first described by the German psychiatrist Hans Berger, measures voltage or electrical potential (V ) differences between two electrodes placed on the scalp of a human subject [3]. The mechanism behind the EEG is based upon the theory of volume conduction which describes the passage of ion currents from a biological system (i.e., the brain) to a source of measurement. It should be noted that summation of ion currents from thousands of pyramidal neurons represents the primary source of V as cortical interneurons (e.g., -amino-butyric acid, GABA) or glial cells (e.g., astrocytes) provide little or no contribution to voltage differences. The synaptic activity of all pyramidal neurons having the same approximate vertical orientation to the scalp is eventually relayed to the EEG machine as a synchronous signal amplified approximately 10,000× (Fig. 1). Current EEG systems measure V differences between 4 to 256 electrodes, with most laboratories using a 21-electrode tracing system [4]. Electrodes normally detect synchronous signals ranging from 20–150 V elapsed over intervals of 0.5 to 60 Hz (cycles per second). Electrode placement on the human scalp is now a rigorously standardized procedure aimed to provide reliability across studies and to develop valid hypotheses with internal and external validity (Fig. 2). In general, the EEG allows scientists to gauge the overall conscious state of a patient, as each state of consciousness (e.g., asleep, wake, anesthetized) is correlated with particular electroencephalographic wave patterns. However, electroencephalographic recordings do not reveal brain structures, nor can they indicate the functioning of specific brain structures.
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doi:10.1166/jnsne.2014.1098
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Neurons of the nervous system continuously generate output signals that can be gauged indirectly by quantitative electroencephalogram readouts. This recording procedure measures changes in depolarization pulses from cortical and thalamic circuits in response to streams of abstract information provided by sensory receptors. In this brief review, we discuss the electroencephalograph in terms of its use in detecting regional differences in brain electrical activity, and describe a wide range of clinical phenomena revealed by the application of quantitative electroencephalogram mapping.
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Electroencephalogram Mapping of Brain States
Fig. 1. A schematic diagram depicting an electroencephalographic design for gauging neural activity during a state of consciousness. Electrodes made of a silver/silver chloride moiety are placed on the scalp of a human subject. Action potentials generated by pyramidal neurons residing within cortical structures (e.g., F3, left frontal cortex; T4, right temporal lobe) are amplified (2×) and filtered (2×) against potential EEG artifacts (e.g., EMG, EOG, rhythmic patterns of respiratory inspiration/expiration indices). The use of additional electrodes significantly allows for the increased resolution of synchronous signals from the brain parenchyma. A reference (A1/A2; pink) and ground (Fpz; yellow) electrodes are anatomically placed on each ear to provide baseline features of physiological activity. Eventually, the synchronous signal is transformed to a digital index via an analog-to-digital converter. The final electroencephalographic pattern depicts differences in V over time (cycles per second; ms, milliseconds). A1, left earlobe; A2, right earlobe.
SLEEP-WAKE CYCLES A neural activity commonly studied by the EEG is sleepwake cycles. From this particular technique, we know that sleep cycles between two states, rapid-eye-movement (REM) and non-REM sleep that occur at regular 90-minute intervals. Non-REM sleep has three distinct EEG stages, whereas REM sleep is characterized by skeletal-muscle hypotonia [5]. It should be noted that the brain is active during both sleep states with different bouts of neuronal activity traced to each sleep state. For example, before a person goes to sleep (i.e., eyes closed and quietly resting), the brain shows prominent alpha waves (∼10 Hz), whereas during non-REM sleep, the brain exhibits EEG tracings of delta waves (∼1 to 4 Hz). Thus brain activity during a relaxed, awake state is quite different from that of the non-REM phase of sleep where the EEG shows high-voltage, slow wave epochs [6]. The fact that switches of brain activity corresponds to changes in behavioral states indicates that sleep-awake transitions are regulated by different populations of neurons that promote behavioral arousal or sleep [7]. For example, acetylcholine-, norepinephrine-, serotonin-, histamine- and dopamine-containing neurons from the ascending reticular activating system and hypothalamus promote wakefulness, whereas GABA- and galanin-containing neurons from the ventro-lateral preoptic nucleus of the hypothalamus promote sleep [8, 9]. In addition, orexin (hypocretin) neurons housed in the lateral hypothalamus maintain wakefulness 2
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as degeneration of these neurons leads to narcolepsy with cataplexy [10]. Based upon EEG tracings, a desynchronized state (low voltage, fast EEG) is associated with behavioral arousal, whereas a synchronized state (high voltage, slow EEG) is linked to sleep. This pattern of brain activity is complemented by measuring muscle tone activity through the use of electromyography (EMG) recordings. During nonREM sleep, skeletal muscle is reduced, whereas during REM sleep, there is complete loss of skeletal-muscle tone despite the EEG showing a desynchronized pattern of neural activity that is remarkable similar to the wake state [6, 11]. Another commonly used technique to map sleep bouts is the electro-oculogram (EOG) which records eye position and movement. When the brain enters a REM state of sleep, the EOG shows bilateral eye movements which dominate this particular state of sleep, further allowing a clear-cut distinction from the wake state (Fig. 3). Other encephalographic patterns observed during sleep cycles, include sleep spindles (or sigma thalamic-derived wavebands), K complexes and theta waves (∼4–7 Hz) which are seen during non-REM sleep. Despite considerable knowledge about the mechanisms underlying the aforementioned brain wave patterns, their functional significance to sleep behavior remains poorly understood.
BRAIN PATHOLOGIES The EEG is also used as a diagnostic tool for predicting signs of brain pathology [12]. For instance, EEG technology has been used for detecting abnormal neural activity in prion-based diseases such as Creutzfeldt-Jakob and in patients with debilitating deficiencies in motor function such as those seen in hepatic encephalopathy [13]. EEG readouts from these patients often show tri-phasic wave activity which is thought to reflect abnormalities in cortical-thalamic connections [14]. It should be noted that tri-phasic waves are also detected in peripheral conditions, including individuals with uremia, hyponatremia and autoimmune thyroiditis [15]. In general, tri-phasic waves are of high-amplitude (≥70 V) with three negativepositive-negative phases that repeat periodically at a lower amplitude and at the rate of ∼1–2 Hz. Thus, neural activity patterns in the form of tri-phasic waves appear to occur as abnormalities in electrical circuits with different clinical end points. Predicting awareness outcome in patients who survive acute brain damage but have slipped into a comatose state is an additional strength of EEG technology. For instance, EEGs can confirm clinical diagnoses of brain death which are defined as neural activity below the 2 V range. However, for patients in a permanent vegetative state, EEG readouts cannot confirm diagnosis nor predict chances of recovery because conscious awareness is absent from purposeful motor behavior [16]. In this regard, EEGs are J. Neurosci. Neuroeng., 3, 1–5, 2014
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more powerful gauges of consciousness than magnetic resonance imaging (MRI) or computed tomographic (CT) scanning as these imaging techniques cannot detects signs of conscious awareness; they only visualized structural damage to the brain parenchyma. In general, EEGs from comatose patients frequently resemble the high-amplitude, low-frequency activity (∼13–25 Hz; paradoxical excitation) seen during propofol-induced anesthesia [5]. The EEG is also isoelectric (a completely flat EEG readout) during the most profound state of general anesthesia (i.e., Phase 4). During Phase 1 of general anesthesia, the EEG readout shows a significant decrease of beta waves (∼13–30 Hz) and increases of delta waves (∼1–4 Hz). This light state of general anesthesia is followed by Phase 2 which is characterized by increases in alpha and delta waves, a phenomenon known as anteriorization [17, 18]. Of interest, the EEG in this particular Phase of general anesthesia (the intermediate state) resembles that of stage 3 of the non-REM sleep cycle. Phase 3 is a deeper state of general anesthesia and the EEG is characterized by isoelectric periods intermingled with periods of alpha and beta waves, a phenomenon known as burst suppression [19]. Surgery is usually performed during Phases 2 and 3 [5]. From these sequences of brain EEG events, it is J. Neurosci. Neuroeng., 3, 1–5, 2014
clear that general anesthesia is a reversible state of druginduced coma. Another brain disorder in which EEGs provide information on certain aspects of pathogenesis and pathophysiology is epilepsy. Although there are more than a dozen clinical phenotypes of epilepsy (e.g., absence seizures), they are generally classified as generalized epilepsy (e.g., tonic-clonic epilepsy), partial epilepsy (usually limited to a specific brain region), frontal-lobe epilepsy and temporal-lobe epilepsy [20, 21]. Regardless of pathogenesis, epilepsy is characterized by neurons whose resting potential parameters are closely aligned to thresholds of depolarization. Under these aberrant conditions, the probability of action potentials significantly increases causing overtly-excited glutamate neurons to fire action potentials uncontrollably. Alternatively, a decline in GABAA receptor signaling could also trigger hyperactive states of depolarization cycles. The end result of unimpeded action potentials is an epileptic seizure with a synchronized, high frequency “spike wave” pattern across broad populations of cortical and thalamic neurons [22]. It should be noted that an isoelectric EEG is often induced by the administration of a barbiturate (e.g., pentobarbital), 3
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Fig. 2. A semi-schematic diagram depicting dorsal and sagittal views of the human skull and brain framed with a 21-electrode tracing system. Standardized electrode placement distribution is based on the International 10–20 EEG system as described by Khazi et al. [30]. Electrodes on the right side of the brain are denoted with even numbered electrodes, whereas electrodes on the left size of the brain are denoted with odd numbered electrodes. Nomenclature of brain structures is shown on adjacent table. The denotation “z” is for zero or midline electrode placement. In addition to the EEG, optical coherence tomography and functional near-infrared spectroscopy (specific spectra: 700–1000 nm) are also used to gauge brain activity in terms of oxygenation and blood volume at micrometer (m) resolutions [31]. Diagram adapted and modified from 3D4 Medical [32].
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Electroencephalogram Mapping of Brain States
Fig. 3. Representative EEG, EMG and EOG readouts during an awake and sleep cycle. Beta waves (∼15–40 Hz) occur during a wake state, whereas alpha waves (∼10 Hz) occur during a drowsy-like state. Stage 1 of the sleep cycle often shows theta waves in the range of ∼3–7 Hz, whereas stage 2 exhibits brain waves in the range of ∼12–14 Hz. Stage 2 of the sleep cycle is characterized by the presence of sleep spindles and K complexes. Delta waves in the range of ∼1–4 Hz predominates stages 3 and 4 of the sleep cycle. Note that during REM sleep, the EEG and EOG readouts resemble the wave patterns of the wake state. The EMG tracing is highest during waking and lowest during REM sleep. In general, periods of non-REM and REM sleep are interwoven during a sleep bout.
propofol or etomidate to minimize cell damage during neurosurgery or to stop generalized seizures [23]. The striking changes of ensemble neural activity observed in epilepsy, unfortunately, are not seen in other brain disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD) or clinical depression. In severely demented patients, the EEG is dominated by slow wave activity (e.g., delta wave, ∼1 to 4 Hz) over frontal and temporal lobes [24]. It should be noted, however, that AD appears to be caused by multiple pathological processes and therefore electroencephalographic readouts may vary in terms of etiologies and mechanisms underlying each pathological process. This complexity also extends to clinical depression where the definition of pathology, source of pathology (e.g., genomes, epigenetic reprogramming and/or environments) and mechanisms of disease are particularly challenging as well. Regardless, frontal and parietal electroencephalographic band asymmetries (
