Neurophysiologic Basis of EEG and DC Potentials: Neuronal Membrane Potentials: Intracellular Recordings
Neurophysiologic Basis of EEG and DC Potentials: Neuronal Membrane Potentials: Intracellular Recordings
Neurophysiologic Basis of EEG and DC Potentials: Neuronal Membrane Potentials: Intracellular Recordings
CHAPTER
Neurophysiologic Basis of
EEG and DC Potentials
ERWIN-JOSEF SPECKMANN, CHRISTIAN E. ELGER, AND ALI GORJI
2
T
he clinical electroencephalographer correlates central thousand synapses (2). The glia cells are imbedded between
nervous system (CNS) functions as well as dysfunctions nerve cell somata, dendrites, and axons. They usually have sev-
and diseases with certain patterns of the electroen- eral processes that make contact with somata and processes of
cephalogram (EEG) on an empirical basis. Obviously, this nerve cells; they may also make contact with vessels. This histo-
method has been found valuable in clinical practice. Therefore, logic arrangement results in a cerebral extracellular space con-
why should the clinical electroencephalographer study the basic sisting of very narrow intercellular clefts (De Robertis and
elementary processes underlying the EEG? There is little doubt Carrea, 1965).
that the range of EEG interpretations can be much widened and
misinterpretations avoided when the underlying elementary NEURONAL MEMBRANE POTENTIALS:
processes are also considered. This is true especially for convul-
INTRACELLULAR RECORDINGS
sive disorders and cerebral metabolic disturbances. For exam-
ple, an isoelectric EEG can be caused by selective pCO2 increase Essential potentials that can be demonstrated with intracellular
while the brain is sufficiently supplied with O2. On the other recordings are characterized briefly. When the membrane of the
hand, in the presence of practically normal pCO2 levels, cere- nerve cell body is penetrated by a microelectrode, a potential of
bral hypoxia may be the cause. It will be pointed out below that about 60 to 70 mV with negative polarity in the intracellular
the prognosis may be quite different in these two cases. space can be recorded. This membrane potential is subject to
various fluctuations that are elicited chiefly by synaptic activi-
POTENTIAL GENERATION AT NEURONAL ties. Their mechanisms are shown in greater detail in Figure 2.2.
AND GLIAL ELEMENTS: MEMBRANE As can be derived from this schematic illustration, the neuron
POTENTIALS AND FIELD POTENTIALS
The basic mechanisms that give rise to potentials recorded out-
side the CNS elements will be described. Such extracellular
potentials are generally known as field potentials (1).
In the course of this presentation, the morphology of gener-
ator structures is discussed briefly. Then, the electrical activity
demonstrable with intracellular recordings from neurons and
glia cells is described. On the basis of this information, the prin-
ciples of the generation of extracellular field potentials are out-
lined and the various types of field potentials are characterized.
GENERATOR STRUCTURES
The CNS essentially consists of nerve cells and glia cells. The
arrangement of neurons usually shows a specific type of lami-
nar character. Glia cells are located between neurons. As shown
in Figure 2.1, several processes emerge from the nucleus-con-
taining cellular soma (body) of the nerve cell. These processes
can be divided into two types according to their function. Most
of the processes are dendrites that branch off into numerous
small ramifications. Every cell also has an axon that may split
up into multiple collaterals. Such an axon provides contact with
other nerve cells or with other target organs. In the case of
interneuronal connections, the contact consists of synapses that
cover the dendrites, the soma, and the axon hillock in large Figure 2.1 Schematic drawing of morphology and histology of neu-
numbers. Thus, nerve cells are usually covered with several ronal and glial elements.
1
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intra- and extracellular current flows similar to the ones extension may develop on the basis of the aforementioned
described in reference to neuronal synaptic transmissions mechanisms (1,9,13,14). In view of the above-described
(Fig. 2.2). Glial cells frequently have widespread processes functional interconnections, it is quite likely that in the gen-
and furthermore may have close connections with each other. esis of extracellular field potentials an amplifying effect can
For this reason, potential fields of considerable spatial be attributed to the glial cells.
Figure 2.4 Membrane potential (MP) changes of glia cells induced by an increase in the extracellular K concentration
(arrows in the schematic drawings). A: Potassium is applied extracellularly to the glia cell. B: The potassium concentra-
tion is increased due to an activation of a neighboring neuron. (From original tracings from Kuffler SW, Nicholls JG, Orkand
RK. Physiological properties of glial cells in the central nervous system of amphibia. J Neurophysiol. 1966;29:768787.)
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FIELD POTENTIALS
It has been shown in the preceding section that primary trans-
membranous currents generate secondary ionic currents along
the cell membranes in the intra- and extracellular spaces. The
portion of these currents that flows through the extracellular
space is directly responsible for the generation of field poten-
tials (Fig. 2.3). Particular significance must be ascribed to the
synaptic processes as causing events for the field potentials in
question, especially for their time course. In accordance with
these statements, the generation of extracellular field potentials
will be discussed as exemplified by extracellular fields accompa-
nying synaptic activity (4,7,14,15). The discussion of these
events will again make use of a very protracted time axis
(Fig. 2.3). The explanation of the events is given in reference to
the schematic view in Figure 2.5. This figure shows a widely
stretched neuronal element, with one end segment lying close
to the surface of a central nervous structure. At both ends of
this neuronal unit, the microelectrodes ME1 and ME2 are
inserted. At the same time, the extracellular electrodes E1 and E2
are located at the surface and at the deeper end of the neuronal
element. The potentials picked up from the intra- and extracel-
lular electrodes are shown in the vicinity of each electrode. The
potential recorded from the surface of the nervous structure is
accentuated by thicker lines. Figure 2.5 shows active excitatory
and inhibitory synapses, either close to the surface or located in
the depth. As described elsewhere, the activation of an excita-
tory synapse leads to a net inward flow of cations. If this state-
ment is applied to Figure 2.5A1, then it becomes evident that Figure 2.5 Membrane potential (MP) changes and field potentials
the upper end of the neuronal element will be depolarized in (FPs) elicited by the activation of excitatory and inhibitory synapses
comparison with other segments of the same cell. Accordingly, in the central nervous system. The elementary processes are explained
the synaptic current flow causes an EPSP at the microelectrode by means of a neuronal element (hatched area), the one end of which
ME1. This local depolarization then gives rise to further intra- contracts the surface of a structure in the central nervous system. The
and extracellular ionic currents along the nerve cell membrane. MP of the neuron element is recorded at both ends by the microelec-
Because of the intracellular movements of positive charges, trodes ME1 and ME2. The extracellular field is picked up at the surface
depolarization in the area of microelectrode ME2 also takes of the neuronal structure by the electrode E1, as well as in the vicin-
place. This depolarization, however, is less steep and of smaller ity of ME2 by the electrode E2. Active excitatory and inhibitory
amplitude. At the superficially located extracellular electrode synapses are marked by open triangles and black triangles (S), respec-
E2, the inflow of positive charges into the neuronal element tively. A1: The inward current at S generates an EPSP that appears in
causes a negative field potential. The extracellular electrode E2 the region of ME1, as well as in that of ME2. Because S is located
is, metaphorically speaking, approached by positive charges so superficially, the FP generated, due to the direction of the extracellu-
that a positive field potential will develop in this area. The point lar current flow (arrows), is of negative polarity at the surface (E1)
of reversal of the field potentials is localized between electrodes and of positive polarity in the deeper recording (E2). A2: The activa-
E1 and E2. The exact position of the point of reversal depends tion of a deep excitatory synapse elicits a current flow with inverse
on the distribution of extracellular impedances. direction as compared with A1. Therefore, the extracellular FP con-
Current flows of reversed direction (in reference to the sists of a positive deflection at the surface and a negative one at the
recording electrodes) will occur if the active excitatory synapse depth. B1: The outward current at S generates an IPSP in the region
is located at the deeper end of the neuronal element (Fig. of ME2, as well as in that of ME1. Due to the direction of the extracel-
2.5A2). In this case, positive charges approach the superficially lular current flow, the FP generated consists of a positive fluctuation
located electrode (E1) (again speaking metaphorically) and in the depth (E2) and a negative one in the surface recording (E1).
remove themselves from the deeply located electrode (E2). This B2: The current flow during the activation of a superficial inhibitory
arrangement of the active synaptic structures causes a positive synapse is inverse as compared with B1. Therefore, the FP recorded
field potential at the surface and a negative one at the deep elec- from the surface consists of a positive fluctuation. Differences in the
trode. The current flows accompanying the activation of time course of the various potentials are caused by the electrical prop-
inhibitory synapses located in deeper and in more superficial erties of the tissue.
areas, respectively, are shown in Figure 2.5B. As can be derived
from this illustration, the activation of a deep inhibitory
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Figure 2.15 Flow charts of neuronal processes possibly responsible for the generation of DC/EEG waves of opposite polar-
ity during a generalized tonicclonic seizure. (Hatched arrows) Symbols for continuous asynchronous input to the cortex;
(heavy lines) symbols for phasic volleys giving rise to single convulsive discharges; (PTC) pyramidal tract cell; (IN)
interneuron; (MP) membrane potential; (UA) extracellularly recorded unit activity. A: During a moderate asynchronous
input to the cortex (small hatched arrow), a burst of UA triggers a paroxysmal depolarization shift in a PTC.
Simultaneously, it leads to a depolarization of superficial neuronal structures and therewith to a negative fluctuation in the
DC/EEG recording at the cortical surface. B: With an increased asynchronous input to the cortex (wide hatched arrow),
the DC potential shifts to a more negative level than in A (1). When in these conditions a phasic volley reaches the cor-
tex, paroxysmal depolarization shifts are also triggered in PTC, whereas the enhanced asynchronous UA is interrupted
mainly due to inactivation. The latter process results in a disfacilitation of the upper neuronal structures and therewith to
a positive fluctuation of the superficial DC/EEG potential (2). (From original tracings from Speckmann EJ, Caspers H,
Jansen RWC. Laminar distribution of cortical fluid potentials in relation to neuronal field activities during seizure dis-
charges. In: Brazier MAB, Petsche H, eds. Architectonics of the Cerebral Cortex. IBRO Monograph Series. Vol 3. New York,
NY: Raven Press; 1978:191209.)
excitatory processes, the paroxysmal depolarization in the characteristic physiologic feature of SD is a negative DC poten-
depth will be coupled with a surface-negative field potential. tial shift with maximal amplitude of 5 to 30 mV and duration
With augmentation of the already existing afferent inflow of of 30 to 90 seconds (Fig. 2.16A) (47). SD recordings by extracel-
impulses, the interneurons involved will necessarily exhibit a lular microelectrodes inserted into the gray matter of the neo-
heightened level of excitation (Fig. 2.15B). If an additional cortex demonstrate that SD can be biphasic or triphasic with
highly synchronized afferent influx of impulses takes place the main negative component. SD begins with a first small pos-
under these conditions, then further PDSs will be triggered in itive component that is sometimes not observed. The main fea-
the pyramidal tract cells, but, in the interneurons, the previ- ture of the SD is a negative wave of high amplitude, which is
ously existing high-frequency activity will be temporarily inter- then followed by a positive-going wave of smaller amplitude,
rupted, chiefly due to inactivation. This causes a decline of the but longer duration. The white matter beneath the neocortical
excitatory inflow of impulses to the superficial cortical struc- gray substance becomes positive, while the gray matter itself
tures. This disfacilitation gives rise to a positive field potential undergoes the negative wave. Apical dendrites were preferen-
at the cortical surface. In this manner, a massive afferent inflow tially involved in the generation of the negative DC deflection.
of impulses provides the basis for a correlation of positive When recordings were made in hippocampal CA1 region,
epicortical field potentials with stereotyped paroxysmal depo- SD invariably started earlier and ended later in the layer of the
larizations and monophasic negative field potentials in the dendritic trees than among the cell body. SD flows in the oppo-
depth (17,44). site direction compared with the current underlying
tonicclonic seizure discharges, which is inward in the neuron
SPREADING DEPRESSION soma layers (47,48).
A brief period of excitation heralds SD, which is immediately
In this section, the generation and propagation of cortical field followed by prolonged neuronal activity depression. This is
potentials during spreading depression (SD) is discussed. SD is replaced by a sustained increase in the neuronal activity; SD
a strong and rapid depolarization of neuronal tissues and prop- also produces transient suppression of synaptic transmission
agates slowly (3 to 5 mm/min) as a wave in brain tissue (46). that is replaced by a sustained increase in the efficacy of synap-
The SD phenomenon is exclusive to the CNS and appears to tic transmission. SD significantly enhanced the amplitude of
influence both the neuronal and the glial cells. The most fEPSP following a transient suppressive period and increased
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pulmonary and circulatory function is disturbed or when the With isolated increment of the CO2 tension in the cerebral
local cerebral blood flow is inadequate. tissue by means of the apnea technique, the amplitude of the
First, the alterations of epicortical field potentials during conventional EEG decreases progressively. This amplitude
selective hypercapnia are discussed; then, those associated with reduction affects first the waves of higher frequency and then
primary asphyxia are considered. It is shown that EEG changes those of lower frequency. Prior to the extinction of normal
may be similar under both conditions. The cortical DC poten- EEG activity, there is once again a phase characterized by
tial, however, shows typical shifts that permit inferences con- high-frequency EEG activity in the range of 50 to 70 Hz
cerning the cause of the accompanying EEG changes. The (1,56). The extinction of the EEG is associated with a shift of
discussion of the effects of gas tension alterations on the bio- the DC potential in a positive direction. If the CO2 tension is
electrical activity of the CNS is based, again, on data derived then lowered again by reventilation, the EEG waves return in
from experimental work in animals. the original spectral composition after a short latency. At the
same time, the positive DC shift resolves (Fig. 2.17).
Hypercapnia Experiments in animals have shown that, with reduction of
If the CO2 tension in the brain tissue is increased in a selective the pCO2, the EEG returns to normal activity even though the
manner, typical reactions of the cortical field potentials as well hypercapnia-induced suppression lasted for 1 hour or more.
as of the membrane potential and the postsynaptic potentials of In these cases, a positive DC deflection of monophasic charac-
individual neurons are found. These findings are shown in a ter was found to occur during the whole period of apnea
summarized schematic view in Figure 2.17. (32,56,57).
The animal experiments on which Figure 2.17 is based were Under the aforementioned conditions, the recording of the
carried out with the use of the so-called apnea technique. With membrane potential of a cortical nerve cell shows a hyperpolar-
this technique, interference of the effects of hypercapnia with ization while the CO2 tension is increased. Extensive experi-
simultaneous effects of hypoxia could be avoided. According to mental studies in animals have demonstrated that such a
this technique, the experimental animal is ventilated for at least hyperpolarization is caused primarily by a reduction of the
a half hour with pure oxygen. Thereafter, artificial ventilation is EPSP (Fig. 2.17; also see Ref. 57). Consideration of field poten-
discontinued while the trachea of the animal remains con- tials, membrane potentials, and EPSP shows that epicortical DC
nected with the O2 reservoir. Under these conditions, the CO2 potentials reflect neuronal hyperpolarization. The disappear-
tension progressively rises in the tissue for about 15 minutes ance of the EEG waves is presumed to be caused mainly by the
without a concomitant fall of the oxygen tension below the reduction of postsynaptic activity.
baseline level.
Asphyxia
Primary asphyxia exemplified by respiratory arrest after air ven-
tilation is associated with combined CNS effects of hypercapnia
and hypoxia. The effects of gas tension changes on the field
potentials and on the membrane potential of individual neu-
rons are schematically shown in Figure 2.18. In the correspon-
ding animal experiments, the artificial ventilation with air was
either temporarily (Fig. 2.18A) or persistently (Fig. 2.18B)
interrupted.
With such an interruption of artificial ventilation with
air, the conventional EEG waves disappear within less than
1 minute. This process is accompanied by a negative DC poten-
tial shift from the baseline, which has been characterized as ini-
tial negativity (1 in Fig. 2.18). While the EEG shows an
isoelectric line in the further course of asphyxia, additional
potential shifts are detectable with DC recording technique.
The initial negativity is followed by a positive DC shift termed
Figure 2.17 Effects of an isolated hypercapnia on epicortical field intermediate positivity (2 in Fig. 2.18). If reventilation is per-
potentials (EEG, DC/EEG) and on membrane potential (MP). With formed in this phase of asphyxia, an additional positive DC
increasing pCO2, the EEG disappears even if the pO2 is above normal shift is observed, appropriately termed reactive positivity (3 in
levels. The disappearance of the EEG is associated with a positive DC Fig. 2.18A). According to the analysis of the experimental work,
shift and a hyperpolarization of most of the neurons. Simultaneously, the intermediate and the reactive types of positivity are due to
the amplitudes of stimulus (St) evoked EPSP are markedly reduced. an increase of CO2 tension in the brain tissue. With the resolu-
(From original tracings from Speckmann EJ, Caspers, H. The effect of tion of the reactive positivity, a restitution of the fast field
O2 and CO2 tensions in the nervous tissue on neuronal activity and DC potentials occurs that is also demonstrable with the conven-
potentials. In: Remond A, ed-in-chief. Handbook of Electroence- tional EEG. A comparison of the DC shifts and the alterations
phalography and Clinical Neurophysiology. Vol 2. Part C. Amsterdam: of the membrane potentials shows a parallelism of both events
Elsevier; 1974:7189.) (1,13,14,32,56,57).
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