CHA PTER

75

Clinical Neurophysiology and Electroencephalography

Jong Woo Lee, MD, PhD, and Shahram Khoshbin, MD

KEY POINTS
The electroencephalogram (EEG) records low-voltage electrical activity from the scalp and offers excellent temporal, but poor spatial, resolution. The EEG is most often used to detect epileptic activity, but it is also a sensitive detector of encephalopathy and other types of brain dysfunction. Use of medications and state changes frequently affect the EEG. Evoked potentials can be used to test the integrity of sensory pathways in the nervous system. Nerve conduction studies and electromyography are used to assess abnormalities of the peripheral nervous system.

OVERVIEW
The history of the encephalogram (EEG) may be traced back to the 1700s when Luigi Galvani demonstrated that electrical stimulation of a peripheral nerve in a frog caused contraction. In the mid-nineteenth century, Carlo Matteucci and Emil DuBoid-Reymond established the eld of electrophysiology. In 1929, the German neuropsychiatrist Hans Berger demonstrated the Elektrenkephalogramm as a graphical representation of electrical activity in the human brain. In 1935, Frederic and Erna Gibbs with William Lennox recorded the EEG in patients in epilepsy and demonstrated its clinical utility.1 The synaptic origin of the EEG was demonstrated by Renshaw in the 1940.2 Starting in the 1950s, intracranial implantation of EEG electrodes was used for evaluation of epilepsy surgery. During this period, systematic description of sleep architecture with the EEG was also described. Computerized EEG acquisition and analysis have been possible since the 1970s.3 Long-term recording of simultaneous video and EEG tracings revolutionized the evaluation of epilepsy on many fronts. The EEG records low-voltage electrical activity produced by the brain. Recordings are often characteristic of certain ages and states of consciousness. Although primarily used to detect epileptic abnormalities, it is possible to recognize

generalized malfunction of the brain, sleep disturbances, and other localized or paroxysmal abnormalities. The EEG has excellent temporal resolution but relatively poor spatial resolution; it can detect rapid changes in function, but it has difculty localizing abnormalities. Most commonly, the EEG is recorded from the scalp with small surface electrodes. However, other electrodes are sometimes used under special circumstances. Intracranial electrodes may be placed in the subdural or epidural space, or deep in the brain (as depth electrodes in patients with epilepsy). These are used to record electrical signals with much greater spatial resolution and sensitivity than can be achieved with surface electrodes; in addition, electrical signals may be applied to the electrodes to perform brain mapping. Although the precise origin of the electrical activity is unknown, EEG activity recorded from the scalp is believed to originate from the postsynaptic potential of the neurons of the cortical pyramidal layer of the cortex. These charges form an electrical dipole, with a positive charge on one end and a negative charge on the other; this creates an electrical eld. The summation of the electrical elds may be recorded by surface electrodes.4 The EEG records differences in electric elds, rather than a single action potential. As such, the voltage difference between two electrodes is measured by an amplier; it is impossible to record from a single electrode. Each pair of electrodes outputs the difference between their potentials through a single channel, which may be graphically displayed on paper or on a computer monitor. The typical EEG machine connects a minimum of 21 electrodes and can display 16 (or more) channels. Electrical activity is recorded from a variety of standard sites on the scalp, according to a standard layout scheme (called the 10-20 International System of Electrode Placement) that can be easily replicated in all laboratories.5 Careful calibration of the signal intensity needs to be performed before each recording. Because of the low amplitude of electrical signals from the brain, artifacts frequently contaminate the EEG. These may include eye movements, muscle movements, electrode noise, and sweating, as well as others. A major challenge in the interpretation of EEGs is to distinguish artifact from brain signals. Filters are routinely used to reduce noise, in both the high- and low-frequency domains. A special 60-Hz lter may be used to attenuate artifacts from electrical devices that use alternating current.

1031

MASSACHUSETTS GENERAL HOSPITAL COMPREHENSIVE CLINICAL PSYCHIATRY

Considerable attention must be given to the selection of montages (or derivations), for example, determining the combination of pairs of electrodes to be recorded. Two different montages are currently in use. In the referential (or monopolar) montage, each of the electrodes is measured against the same reference electrode, which is presumed to be relatively electrically inactive. Commonly used reference points are the ears, other noncephalic regions, or the average of all other electrodes. In bipolar montages, electrodes in a line along an anatomical region are recorded serially as successive pairs. The rst channel would be from the rst and second electrodes, the second channel would be from the second and third electrodes, and so forth. The most popular bipolar montage is the anteroposterior double banana montage. Creation of different montages gives various views of the electrical activity at different parts of the brain. All EEGs are analyzed using multiple montages over the same recording, including both referential and bipolar montages. A routine EEG is recorded for at least 20 minutes. However, it is possible to record from electrodes that are glued onto the scalp; these will record the patients EEG for hours, days, and even weeks, if clinically necessary. Before the 1980s, the EEG was recorded on paper through an analog system. Today, nearly all EEGs are recorded digitally and displayed on a computer monitor. The major advantage of digital recording is that the EEG can be reformatted and exibly reviewed in any montage, allowing the development of automated seizure detection algorithms. Benets of other quantitative tools remain to be realized (see Quantitative EEG, later in this chapter).6

THE NORMAL EEG

The electrical activity from any electrode pair can be described in terms of amplitude and frequency (Figure 75-1). Ampli-

tude ranges from 5 V to 200 V. The frequency of EEG activity ranges from 0 Hz to about 20 Hz. The frequencies are described by Greek letters: delta (0 to 3 Hz), theta (4 to 7 Hz), alpha (8 to 13 Hz), and beta (more than 13 Hz). In the normal awake adult (with eyes closed), alpha rhythm predominates in the posterior part of the head. The amplitude of the alpha waves falls off anteriorly, and it is often replaced by low-voltage beta activity. Often, some lowvoltage theta activity can be seen in frontocentral or temporal regions. The alpha rhythm, which is prominent posteriorly, disappears (or is blocked) when the eyes open. This reactivity to eye opening/closure is an important aspect of a normal EEG, and is often attenuated with many pathologies. When a normal adult becomes drowsy, the alpha rhythm gradually disappears, frontocentral beta activity may become more prominent, and frontocentrotemporal theta activity becomes predominant. Drowsiness is stage I sleep. As sleep becomes deeper, high-voltage single or complex theta or delta waves, called vertex sharp waves, appear centrally. Stage II sleep is characterized by increased numbers of vertex sharp waves, and runs of sinusoidal 12- to 14-Hz beta activity, called sleep spindles, occur. Deeper sleep (Stage III, slow wave sleep), characterized by progressively more and higher-voltage delta activity, is not usually seen in routine EEG recordings. In routine EEG studies, some activation procedures are carried out to enhance or elicit normal or abnormal EEG activity. These procedures, such as hyperventilation, photic stimulation, sleep, sleep deprivation, and, rarely, the use of drugs, are useful in bringing out epileptic activity.7 The most common activation procedures are 3 minutes of hyperventilation and a ashing strobe light (at frequencies between 5 and 30 Hz). The normal response to hyperventilation ranges from no change from baseline to a buildup of high-amplitude delta waves. A hyperventilation response is particularly marked in children and young adults. The most specic abnormal

Figure 75-1 A normal EEG in an anterior-posterior bipolar montage. Each dark line represents 1 second. An eye closure is present during the rst second, which results in a resting background alpha rhythm.

1032

Clinical Neurophysiology and Electroencephalography

response to hyperventilation is the production of generalized spike-wave discharges of a typical absence seizure. Photic stimulation with a stroboscope may produce a driving response, or occipital discharges at a frequency that is a harmonic multiple of the ash frequency. In a small number of epileptic patients, photic stimulation may elicit electrographic epileptiform activity, or even frank seizures.8 The use of an activating procedure in patients monitored on video-EEG for nonepileptic psychogenic seizures is controversial. On the one hand, procedures (such as saline injection or placement of a vibrating tuning fork on the patient) to elicit psychogenic seizures are easy, safe, and potentially diagnostic. However, others believe that the deception involved undermines the care of the patient. Some have proposed using only standard activating procedures (e.g., hyperventilation and photic stimulation) to elicit psychogenic seizures.9

tent. An abnormality that appears and disappears suddenly is called paroxysmal.

Nonepileptic EEG Abnormalities

The most common focal EEG abnormality consists of slow wave activity. Increased slow activity (i.e., theta and delta activity in a waking record) is virtually always abnormal. Almost all conditions that diffusely affect the brain increase slow activity. In particular, focal delta activity is usually irregular in conguration and is termed polymorphic delta activity (PDA) (Figure 75-2). PDA is usually indicative of a focal brain lesion (such as tumor, stroke, hemorrhage, or abscess).13 Before the advent of modern neuroimaging, focal delta abnormalities were used to localize cerebral lesions. Focal cerebral lesions may also cause asymmetric slowing of the background alpha waves or asymmetric beta activity. The EEG may also show generalized abnormalities, particularly in encephalopathies. As a general rule, the EEG is a sensitive, though nonspecic, test for encephalopathies. The most common pattern with metabolic encephalopathies is generalized moderate- to high-amplitude theta and delta activity without an alpha resting background.14 Another common pattern observed with hepatic and renal encephalopathies is the presence of triphasic delta waves.15 These are high-voltage, diffuse periodic discharges, and are at times difcult to differentiate from epileptiform generalized spike/ sharp-slow wave discharges.16 In infectious encephalopathies, particularly in encephalitides, an admixture of slow activity and epileptogenic activity is often seen. Intermittent rhythmic delta activity may be seen focally or diffusely. Such activity is frequently conned to the frontal region in adults, and is called frontal intermittent rhythmic delta activity (FIRDA); in children, this pattern is most often located posteriorly. Although initially believed to have been

EEG AND AGE

The EEG background is dramatically different in neonates, infants, and children. The EEG plays an important role in the evaluation of preterm infants, as stereotyped EEG changes are seen in the maturing brain.10 The EEG may be discontinuous and asynchronous in premature infants. Sharp activity, not indicative of epileptic activity, may be seen up to age 1 month. Posterior background rhythms increase from 5 to 6 Hz at age 1 to the normal 9 to 11 Hz by age 15.11 Alpha background decreases with age, but should not drop below 8 Hz.12

EEG ABNORMALITIES
Abnormalities of the EEG are either focal (involving only one area of the brain) or generalized (involving the entire brain). Additionally, abnormalities are either continuous or intermit-

Figure 75-2 Polymorphic delta activity in the left hemisphere in a patient with a brain tumor.

1033

MASSACHUSETTS GENERAL HOSPITAL COMPREHENSIVE CLINICAL PSYCHIATRY

a sign of increased intracranial pressure in young people, these monomorphic high-amplitude waves are most often seen in diffuse encephalopathies.17 In hypoxic encephalopathies, low-amplitude slow waves are typically observed.18 In more severe cases, one may observe a burst-suppression pattern, in which a voltagesuppressed background is interrupted by generalized highamplitude sharp activity. In most severe cases of coma, generalized suppression of amplitude (i.e., electrocerebral silence) on the EEG in the absence of possible modifying factors (e.g., medications and hypothermia) is an ancillary test to conrm brain death.19

EEG Abnormalities in Seizure Disorders

The EEG has been particularly useful in the analysis of patients with seizure disorders. Paroxysmal abnormalities are common between overt seizures (i.e., interictally), as well as during seizures (ictally). Paroxysmal abnormalities include the spike and the sharp wave. A spike is a single wave that stands out from the background activity and has a duration of less than 70 ms. A sharp wave is similar with a duration between 70 and 200 ms. A spike or sharp wave has an asymmetric up-phase and down-phase and is often followed by a slow wave. The existence of a spike or sharp wave is highly specic; a single sharp wave in the proper clinical context may be sufcient to conrm a seizure disorder. However, such ndings are insensitive; the EEG is frequently normal and devoid of such discharges even in patients known to have epilepsy. Multiple recordings may be required to capture an abnormality and to make a diagnosis.20 Epileptic paroxysmal abnormalities can be either generalized or focal. The classic generalized abnormality is the 3-Hz spike and wave pattern that underlies the petit mal absence attack (Figure 75-3). A typical focal abnormality is a focal

single spike followed by a slow wave. This abnormality can be seen interictally in focal epilepsy, such as temporal lobe epilepsy (TLE). EEG recorded during a seizure may show a variety of patterns, including repetitive spikes/sharp waves, spikeslow wave complexes, rhythmic theta activity, and others. After a seizure (postictally), the EEG most frequently shows pronounced slow waves. Scalp EEGs are notoriously unreliable for the detection of simple partial seizures. The relationship of any of these abnormalities to the particular patient is complex. For example, paroxysmal activity on an EEG may (or may not) mean that the patients problem is related to epilepsy; the nal determination typically rests on the overall clinical picture and on the results of a therapeutic trial. One should resist the temptation to consider the EEG independently. In particular, a normal EEG does not exclude epilepsy, since the EEG may be normal during a focal seizure that is observed clinically.

THE EEG AS IT RELATES TO PSYCHIATRY

Medication Effects
Benzodiazepines are well known to increase the beta frequency and mild background slowing in EEG recordings.21 Barbituates, in small doses, increase the beta activity, predominantly in the frontal leads. With increasing doses, there is increased slow activity and attenuation of alpha activity, indicative of increasing drowsiness. With sufciently high doses, a burst suppression pattern and eventually electrocerebral silence ensues.22 Withdrawal will result in generalized sharp activity and may be accompanied by withdrawal seizures. General anesthetics will induce fast frontal activity and attenuation of alpha, and, with deeper coma, a burst suppression pattern.23 Conventional antiepileptic medications have not been associated with denite EEG changes at therapeutic levels.22

Figure 75-3 Generalized spike-wave discharges in absence seizures.

1034

Clinical Neurophysiology and Electroencephalography

Few denite electrographic changes have been reported with most typical antipsychotic drugs at therapeutic doses; background slowing and even epileptic activity may be seen at higher doses. Clozapine induces abnormalities (such as slowing and spikes) in more than half of patients.24 Lithium may produce diffuse slowing and enhance preexisting epileptiform activity on the EEG.22 No specic EEG changes are seen with use of antidepressants.

Alcohol and Other Recreational Drugs

Patients with alcoholism are vulnerable to falls and to other head trauma. In these patients, focal EEG abnormalities and partial seizures may be seen. During acute intoxication, slowing is seen on the EEG, but it diminishes with tolerance. Alcohol withdrawal seizures are generalized, even in patients with focal injuries. The EEG in chronic alcoholism is associated with a greater incidence of low-voltage (less than 25 V) recordings with little slowing in more than half the patients (56%) as compared to control subjects without a history of alcoholism (13.9%).25 This can be helpful in distinguishing delirium tremens (DTs) from other toxic metabolic encephalopathies that are associated with diffuse theta and delta slow waves. An increase in beta activity is seen on the EEG with use of cocaine and other central nervous system (CNS) stimulants.22,26 No clinically useful changes on the EEG are seen with other recreational drugs.

domain through Fourier transformation, thus allowing the assessment of the power of a frequency over a given recording; source analysis, a technique used to back-project EEG signals to derive localization of a dipole; and electromagnetic tomography, a method of graphing statistical results onto the patients structural neuroimaging scan (such as a magnetic resonance imaging [MRI] scan) to create a map of these results. Because of difculty in replicating studies, overenthusiastic usage of statistical manipulation, and aggressive marketing of qEEG devices in the 1980s, the role of qEEG in a wide range of neuropsychiatric disorders has been cast into doubt by the neurological community.32 The American Neuropsychiatric Association recommends cautious use of qEEG in attentional and learning disabilities of childhood, and in mood and dementing disorders.32

EVOKED POTENTIALS
Evoked potentials (EPs) can be used to test the integrity of a pathway in the CNS. A sensory stimulus in any modality (e.g., visual, auditory, or somatosensory) will produce a change in the EEG. The change is usually small compared with the background EEG; the exact conguration of the change depends on the nature of the stimulus and the site of the recording on the scalp. The evoked potential is the change in the EEG that is dependent on, and time-locked to, the stimulus; to see it, the stimulus must be repeated many times and the EEG averaged.33-35 The most common use of evoked potentials is to test the speed of conduction in a particular pathway. Multiple sclerosis is a disease of central myelin; if myelin is damaged, conduction is slowed and the evoked potentials will be delayed. Although many multiple sclerosis plaques are clinically silent they often show themselves with this electrical test. Hence, evoked potentials are quite useful in making the diagnosis of multiple sclerosis.36 Visual evoked potentials (VEPs) were the rst to become popular. They are ordinarily obtained with a checkerboard stimulus that alternates black and white squares repetitively. Each eye is stimulated individually and then responses are measured from the occipital area of the scalp. The major wave measured is a large positive wave at a latency of about 100 ms (P100). In multiple sclerosis or optic neuritis, the wave is delayed.36 Delayed or absent VEPs can be seen in many other conditions, including ocular conditions (e.g., glaucoma), compressive lesions of the optic nerve (e.g., pituitary lesions), and pathological conditions of the optic radiations or the occipital cortex. Auditory stimulation produces complex waveforms. Stimulation with brief clicks produces six small waves in the rst 10 ms. Surprisingly, the sources of this electrical activity are in serial ascending structures in the brainstem. It becomes possible to study the integrity of the brainstem with these waves, and the test has also been used to assess brainstem death in cases suspected of brain death.37 The waves are also delayed in multiple sclerosis. Somatosensory evoked potentials (SEPs) are the averaged electrical responses in the CNS to somatosensory stimulation.

Dementia and Pseudodementia

Obtaining an EEG may be helpful in the process of differentiating dementia with secondary depression from depressive pseudodementia. In patients with either depression or depressive pseudodementia, the EEG has been shown to be either normal or mildly slowed. In contrast, in patients with dementia with secondary depression, the majority have abnormal EEGs; in up to one-third of patients, there may be moderate or severe abnormalities.27

Schizophrenia
Studies have demonstrated that patients who demonstrate normal EEG ndings with decreased reactivity to stimuli, deemed to be hypernormal, had an unfavorable prognosis.28 Increased delta and beta activity, as well as decreased alpha frequencies, have been reported in patients with schizophrenia.29 Electroencephalography has been used to evaluate the theory that schizophrenia is the result of functional disconnections in cerebral networks. Decreased intrahemispheric coherence in the EEG has been demonstrated in patients with schizophrenia.30 In general, EEG studies in schizophrenic patients have produced inconsistent results, and it has been debated whether EEG abnormalities in these patients are due to the state of the patient or due to the trait of the disease.31

QUANTITATIVE EEG
Quantitative EEG (qEEG) involves the use of computerized statistical analysis and graphical representation of EEG data. Common manipulations include spectral analysis, which involves conversion of the time domain into a frequency

1035

MASSACHUSETTS GENERAL HOSPITAL COMPREHENSIVE CLINICAL PSYCHIATRY

Like sensory nerve action potentials (SNAPS) in the peripheral nervous system, most components of SEPs represent activity carried in the large sensory bers of the dorsal column (medial lemniscus primary sensorimotor cortex pathway). SEPs can be used to test the integrity of the pathway and to test the speed of conduction in the pathway. SEPs from the upper extremity are commonly produced by stimulation of the median nerve at the wrist. The cerebral SEP to this type of stimulation was the rst EP to be discovered. The cerebral SEP to median nerve stimulation is best recorded from a site approximately 2 cm posterior to the contralateral central electrode. SEPs from the lower extremity are produced by stimulation of the posterior tibia1 nerve at the ankle or the peroneal nerve at the bular head and are recorded best at the vertex of the head. It is possible to localize a lesion in the somatosensory pathway by using short latency SEPs from subcortical structures. Several systems of electrode placement can be used, but the one that seems to produce potentials of greatest amplitude is where the active electrode is placed over the cervical spine and referred to an inactive site such as the vertex of the head. Four components can be identied.38 By stimulating leg nerves, it is possible to obtain EPs at all levels of the neuraxis, including over the spinal cord. SEPs are particularly useful in evaluation of a comatose patient. Bilaterally absent SEPs are highly predictive of poor outcome.39

eld, and thus the amplitude of the recorded sensory action potential is a measure of the number of functioning axons. Using the distance between the site of stimulation and the site of recording and the time between stimulation and the arrival of the action potentials at the recording site, it is possible to calculate the conduction velocity, which reects the quality of myelin of the axons. In axonal degeneration neuropathies, the primary feature is reduced sensory action potential amplitudes. The conduction velocity may be slightly slowed, but only to the extent that the normally largest axons are gone and the measured conduction velocity reects the velocity of the largest remaining axons. In demyelinating neuropathies, the primary feature is slowing of conduction. In radiculopathies, sensory action potential amplitudes and conduction velocities are fully normal. This is because the lesion is virtually always proximal to the dorsal root ganglion and the cell body and its peripheral process remain normal. Sensory action potentials similarly remain normal with lesions of the CNS.

Motor Nerve Conduction

There are signicant differences between sensory and motor nerve conduction that depend in large part on the differences of their anatomy. Motor neurons have cell bodies in the anterior horn of the spinal cord and send their axons to innervate muscle bers. Motor axons are always intertwined with sensory axons; there are no nerves that are pure motor nerves. Hence, the electrically stimulated compound action potential of any nerve with motor bers in it is really a mixed nerve action potential. Consequently, it is not possible to deduce the number of functioning motor axons by looking at the amplitude of a nerve action potential. It is possible to study motor nerve axons separately from sensory axons by electrically stimulating a nerve and by recording from the muscle bers innervated by the motor axons in that nerve. Since each motor axon typically innervates hundreds of muscle bers, the compound muscle action potential is much larger than the nerve action potential. The number of axons can be diminished and the action potential normal if the process of collateral reinnervation by the remaining axons has been complete. The number of axons can be normal and the action potential diminished if there is a neuromuscular junction decit or if there is loss of muscle bers. As a neuropathy progresses and collateral reinnervation fails to keep pace, the muscle action potential will decline. The interval between delivery of the electrical stimulus and the onset of the muscle action potential may be difcult to interpret. This period is composed of the time it takes for the motor nerve action potential to travel down the terminal branches of the axon, the time for the release of acetylcholine into the neuromuscular junction, the time for the acetylcholine to produce an endplate potential, the time for generation of a muscle action potential, and, depending on the position of the recording electrodes, the time for the muscle action potential to propagate to the recording electrodes. Calculation of a conduction velocity for these neurons is not as straightforward as it is for the sensory nerve. The interval

NERVE CONDUCTION
Peripheral Nerve Conduction Studies Sensory Nerve Conduction
The cell bodies of sensory neurons are located in the dorsal root ganglia. Each neuron has a central process entering the spinal cord through the dorsal horn and a peripheral process connecting to a sensory receptor in the skin or deep tissues of the limb. The receptors transduce somatosensory stimuli into electrical potentials, which eventually give rise to action potentials in the axons that are transmitted along the peripheral process to the central process. This is termed the sensory nerve action potential (SNAP). There are a variety of sensory neurons, each with a characteristic spectrum of axonal diameters. Some neurons are myelinated and others are unmyelinated; in routine studies the unmyelinated bers cannot be measured. Many sensory axons with differing function and size run together with motor axons. The goals of sensory nerve conduction studies are to assess the number of functioning axons and to assess the state of the myelin of these axons. In the usual sensory nerve conduction study, all of the axons in a sensory nerve are activated with a pulse of electric current. The nerve is stimulated at one location while the transmitted signal is recorded at another location. Electrical stimulation of these nerves can be performed, either orthodromically (along the direction of physiological nerve conduction) or antidromically (along the opposite direction). Action potentials travel along the nerve, and the electric eld produced by these action potentials is recorded at a site distant from the site of stimulation. Each axon makes a contribution to the magnitude of the electrical

1036

Clinical Neurophysiology and Electroencephalography

itself, if obtained under standard conditions, can be a useful measure of the conduction time in the terminal part of the axon; it is termed the distal motor latency. The conduction velocity of motor axons can be determined for parts of the axon proximal to the distal portion. If the nerve is stimulated supramaximally in two places, virtually identical muscle action potentials will result; the major difference will be the different latencies from the time of stimulation. The difference in the latencies is due to the difference in the distances from the sites of stimulation to the muscle. Dividing the difference in the distances by the difference in the times produces a conduction velocity for the segment of nerve between the two sites of stimulation. Similar to the measurement of the sensory action potential, measurements of the muscle action potential are ordinarily made to the time of onset; hence, the calculated conduction velocity refers to the fastest (and largest) axons in the nerve. In axonal degeneration neuropathies, motor nerve conduction studies are not signicantly abnormal until the process is moderately advanced. Total reliance on motor nerve conduction would result in failure to detect many signicant neuropathies. Typically, there will be a slight slowing of conduction velocity and prolongation of the distal motor latency since the largest axons are lost. There may be loss of action potential amplitude when the process is advanced. In demyelinating neuropathies, there will be slowing of conduction velocity and prolongation of distal motor latency. A focal lesion of a nerve will lead to slowing of conduction and to a decrement of amplitude across the segment, including the area of the lesion, but studies of the nerve distal to the lesion will be fully normal. Studies of nerve segments proximal to the lesion will show normal conduction velocity with an unchanging and reduced action potential amplitude. Quite dramatic nerve conduction ndings are seen with a focal, total lesion. The nerve is fully normal below the lesion, but electrical stimulation proximal to the lesion produces no response (similar to the patients attempts to activate the muscle).40 In radiculopathy (lesion of the nerve roots), motor nerve conduction studies will ordinarily be normal. There may be slight slowing of conduction velocity in direct relation to the amount of loss of large bers. In CNS disease, there will ordinarily be no change in motor nerve conduction unless there is involvement of anterior horn cells.

The H-reex is a monosynaptic reex response similar in its pathway to that of the tendon jerk. The electrical stimulus activates the I-a afferents (coming from the muscle spindles) and action potentials travel orthodromically to the spinal cord. In the cord, the I-a afferents make excitatory monosynaptic connections to the alpha motor neurons; a volley of action potentials is set up in the motor nerve, which runs orthodromically the entire length of the nerve from the cell bodies to the muscle. Hence, action potentials travel through the proximal segment of the nerve twice during the production of the H-reex (once in the sensory portion of the nerve and once in the motor portion). Obtaining an H-reex depends on the ability to stimulate the I-a afferents. If a motor axon is electrically stimulated, an action potential will travel along the axon antidromically toward the spinal cord, as well as orthodromically toward the muscle. The antidromic action potential will collide either in the proximal motor axon or in the cell body with the developing H-reex in that axon and nullify it. In routine clinical practice, it is possible to get this differential stimulation and to produce E-reexes only in the posterior tibia1 division of the sciatic nerve while recording from the triceps surae. The F-response or F-wave has an advantage over the Hreex in that it can be found in most muscles. It is a manifestation of recurrent ring of an anterior horn cell after it has been invaded by an antidromic action potential. After a motor nerve is stimulated, an action potential runs antidromically as well as orthodromically; a small percentage of anterior horn cells that have been invaded antidromically will produce an orthodromic action potential that is responsible for the F-response. Thus, to produce an F-response, action potentials must travel twice through the proximal segment of the motor nerve.41

ELECTROMYOGRAPHY
The Physiology Underlying Electromyography
Understanding the concept of the motor unit is central to the understanding of the physiology of electromyography (EMG). A motor unit is composed of all the muscle bers innervated by a single anterior horn cell. In most proximal limb muscles, there are hundreds of bers in each motor unit. In the normal situation, the muscle bers from the same unit are not clumped together, but are intermingled with bers from other motor units. When a motor axon res, each muscle ber in its motor unit is activated in a constant time relationship to the other bers in the unit. EMG activity is ordinarily recorded with a needle placed into the muscle. Because the muscle bers of a single motor unit are not packed closely together, the EMG needle records from only about 10 bers from each motor unit. The amplitude, duration, and conguration of the electrical activity recorded from a motor unit vary as the needle changes its orientation to the muscle bers. Despite its variability it is possible to specify a normal range for the amplitude, duration, and conguration of motor unit action potentials (MUAPs) for each muscle and each age.

Late Responses
Studying the most proximal segments of nerves is difcult, because they are deep and not easily accessible as they leave the spinal column. However, it is useful to study the proximal segments of nerves since processes such as radiculopathies from disc protrusion and certain neuropathies (e.g., GuillainBarr) predominantly affect this segment. The so-called late responses (the H-reex and the F-response) provide a relatively easy technique for study of the proximal segments of nerves. These responses are produced in certain circumstances after an electrical stimulus to a peripheral nerve, and are late with respect to the muscle response (the M-response) produced by the orthodromic volley of action potentials traveling to the muscle directly from the electrical stimulus.

1037

MASSACHUSETTS GENERAL HOSPITAL COMPREHENSIVE CLINICAL PSYCHIATRY

When an EMG needle is placed in a normal muscle at rest, there is no electrical activity. With weak effort, rst one and then several motor units are activated. At this low level of activation, it is possible to see the individual MUAPs and evaluate their parameters. With maximal effort so many units are brought into action that individual MUAPs cannot be discerned; all that can be seen is a dense electrical pattern, called an interference pattern, which can be characterized by its density and peak-to-peak amplitude. The normal density would be either full, if there are no gaps, or highly mixed, if there are a few, short gaps. Some people are not willing or able to exert a maximal effort and the pattern will be less dense as a result. Hence, the degree of effort has to be taken into account when assessing the interference pattern.

Complete Injury
In this circumstance no voluntarily initiated motor nerve action potentials can reach the muscle due to a focal demyelinating injury. Muscle bers will not be denervated so they will not brillate. EMG examination will reveal no spontaneous activity, no MUAPs, and no interference pattern. This is no different from the rst few days of a total injury; after these rst days the denervated muscle bers begin to brillate.

Myopathy
The simple model of myopathy is characterized by dropout of individual muscle bers from their motor units. In active myopathies, especially polymyositis, there may be some segmental muscle necrosis. This process divides a muscle ber into an innervated segment and an uninnervated segment. The uninnervated segment might brillate and, hence, result in active myopathies, some brillation, and positive sharp waves; most commonly spontaneous activity is lacking.

Findings on the Electromyogram Acute Partial Injury (e.g., Partial Laceration of a Nerve)
Motor axons that are injured undergo Wallerian degeneration over the course of about 5 days, leaving muscle bers previously innervated by those axons in a denervated state. Within approximately 10 to 14 days, denervated muscle ber action potentials are recorded by the EMG needle as brillations and positive sharp waves. There is nothing different about brillations and positive sharp waves other than a slight difference in the particulars of the recording; both are simply small, diphasic potentials beginning with a positive phase. The motor units that can be activated will be normal; it will not be possible to voluntarily activate the denervated muscle bers. Descriptive terminology for these patterns is high mixed, mixed, low mixed, and single unit, in order of decreasing density.

Neuromuscular Junction Studies

The most common abnormality at the neuromuscular junction is myasthenia gravis. The standard neurophysiological studies for myasthenia gravis are the repetitive nerve stimulation test and the single-ber EMG. During the repetitive stimulation test, the nerve is stimulated with rates of stimulation of 2 to 10 Hz. In normal patients, the action potential is the same, but in those with myasthenia gravis, the amplitude of the action potentials might decline on successive stimulations. In the inverse myasthenic syndromeEatonLambert syndromethe repetitive stimulation test shows a progressive increase in amplitude of the muscle action potential. Single-ber EMG is highly sensitive for the diagnosis of myasthenia gravis. In this test, a small needle is used that can detect the action potentials from single muscle bers. The time between the ring of two muscle bers from the same motor unit should be very stable. In myasthenia gravis, due to the slow and uncertain function of the neuromuscular junction, there may be an increase in the variability of the time between ring of these two muscle bers; this is called increased jitter.42

Chronic Partial Injury

After weeks to months, there will be collateral sprouting from surviving motor axons to innervate denervated muscle bers. Spontaneous activity will cease. Motor units will now contain more muscle bers than normal; hence, MUAPs will be long-lasting, high, and more complex in shape or polyphasic. The density of the interference pattern may improve, but will probably remain less than full although the amplitude will increase.

REFERENCES
1. Gibbs F, Davis H, Lennox W: The electro-encephalogram in epilepsy and in conditions of impaired consciousness, Arch Neurol Psychiatr 34:1133-1148, 1935. 2. Gloldensohn ES: Animal electricity from Bologna to Boston, Electroencephalogr Clin Neurophysiol 106(2):94-100, 1998. 3. Niedermeyer E: Historical aspects. In Niedermeyer E, da Silva F, editors: Electroencephalography: basic principles, clinical applications, and related elds, ed 5, Philadelphia, 2005, Lippincott Williams & Wilkins. 4. Schaul N: The fundamental neural mechanisms of electroencephalography, Electroencephalogr Clin Neurophysiol 106(2):101-107, 1998. 5. Jasper H: Report of committee on methods of clinical exam in EEG, Electroencephalogr Clin Neurophysiol 10:370-375, 1958. 6. Krauss G, Webber W: Digital EEG. In Niedermeyer E, da Silva F, editors: Electroencephalography: basic principles, clinical applications, and related elds, ed 5, Philadelphia, 2005, Lippincott Williams & Wilkins. 7. Leach J, Stephen L, Salveta C, et al: Which electroencephalography (EEG) for epilepsy? The relative usefulness of different EEG protocols in patients with possible epilepsy, J Neurol Neurosurg Psychiatry 77(9):1040-1042, 2006. 8. Fisch B, So E: Activation methods. In Ebersole JS, Pedley TA, editors: Current practice of clinical encephalography, ed 3, Philadelphia, 2003, Lippincott Williams & Wilkins. 9. Iriarte J, Parra J, Urrestarazu E, et al: Controversies in the diagnosis and management of psychogenic pseudoseizures, Epilepsy Behav 4(3):354-359, 2003.

1038

Clinical Neurophysiology and Electroencephalography

10. Scher MS: Neurophysiological assessment of brain function and maturation: I. A measure of brain adaptation in high risk infants, Pediatr Neurol 16(3):191-198, 1997. 11. Clancy R, Berquvist A, Dlugos DJ: Neonatal electroencephalography. In Ebersole JS, Pedley TA, editors: Current practice of clinical encephalography, ed 3, Philadelphia, 2003, Lippincott Williams & Wilkins. 12. Brenner RP, Ulrich RF, Spiker DG, et al: Computerized EEG spectral analysis in elderly normal, demented and depressed subjects, Electroencephalogr Clin Neurophysiol 64(6):483-492, 1986. 13. Bazil C, Herman S, Pedley TA: Focal electroencephalographic abnormalities. In Ebersole JS, Pedley TA, editors: Current practice of clinical encephalography, ed 3, Philadelphia, 2003, Lippincott Williams & Wilkins. 14. Markand O: Electroencephalography in diffuse encephalopathies, J Clin Neurophysiol 1(4):357-407, 1984. 15. Fisch B, Klass D: The diagnostic specicity of triphasic patterns, Electroencephalogr Clin Neurophysiol 70(1):1-8, 1988. 16. Boulanger JM, Deacon C, Lecuyer D, et al: Triphasic waves versus nonconvulsive status epilepticus: EEG distinction, Can J Neurol Sci 33(2):175-180, 2006. 17. Hooshmand H: The clinical signicance of frontal intermittent rhythmic delta activity (FIRDA), Clin Electroencephalogr 14(3):135137, 1983. 18. Synek V: Prognostically important EEG coma patterns in diffuse anoxic and traumatic encephalopathies in adults, J Clin Neurophysiol 5(2):161-174, 1988. 19. Wijdicks EF: The diagnosis of brain death, N Engl J Med 344(16):1215-1221, 2001. 20. Gilbert D, Sethuraman G, Kotagal U, et al: Meta-analysis of EEG test performance shows wide variation among studies, Neurology 60(4):564-570, 2003. 21. Browne TR, Penry JK: Benzodiazepines in the treatment of epilepsy. A review, Epilepsia 14(3):277-310, 1973. 22. Van Cott AC, Brenner RP: Drug effects and toxic encephalopathies. In Ebersole JS, Pedley TA, editors: Current practice of clinical encephalography, ed 3, Philadelphia, 2003, Lippincott Williams & Wilkins. 23. Bauer G, Bauer R: EEG, drug effects, and central nervous system poisoning. In Niedermeyer E, da Silva F, editors: Electroencephalography: basic principles, clinical applications, and related elds, ed 5, Philadelphia, 2005, Lippincott Williams & Wilkins. 24. Spatz R, Kugler J: Abnormal EEG activities induced by psychotropic drugs, Electroencephalogr Clin Neurophysiol Suppl 36:549-558, 1982. 25. Krauss G, Niedermeyer E: Electroencephalogram and seizures in chronic alcoholism, Electroencephalogr Clin Neurophysiol 78(2):97104, 1991.

26. Herning RI, Jones RT, Hooker WD, et al: Cocaine increases EEG beta: a replication and extension of Hans Bergers historic experiments, Electroencephalogr Clin Neurophysiol 60(6):470-477, 1985. 27. Brenner RP, Reynolds CF 3rd, Ulrich RF: EEG ndings in depressive pseudodementia and dementia with secondary depression, Electroencephalogr Clin Neurophysiol 72(4):298-304, 1989. 28. Shagass C: An electrophysiological view of schizophrenia, Biol Psychiatry 11(1):3-30, 1976. 29. Kemali D, Galderisi S, Maj M, et al: Computerized EEG topography ndings in schizophrenic patients before and after haloperidol treatment, Int J Psychophysiol 13(3):283-290, 1992. 30. Tauscher J, Fischer P, Neumeister A, et al: Low frontal electroencephalographic coherence in neuroleptic-free schizophrenic patients, Biol Psychiatry 44(6):438-447, 1998. 31. Sengoku A, Takagi S: Electroencephalographic ndings in functional psychoses: state or trait indicators? Psychiatry Clin Neurosci 52(4):375-381, 1998. 32. Nuwer M: Assessment of digital EEG, quantitative EEG, and EEG brain mapping: report of the American Academy of Neurology and the American Clinical Neurophysiology Society, Neurology 49(1):277-292, 1997. 33. Chiappa KH: Evoked potentials in clinical medicine, ed 3, New York, 1997, Lippincott Williams & Wilkins. 34. Nuwer M: Fundamentals of evoked potentials and common clinical applications today, Electroencephalogr Clin Neurophysiol 106(2):142148, 1998. 35. American Electroencephalographic Society: Guidelines in electroencephalography, evoked potentials, and polysomnography, J Clin Neurophysiol 11(1):1-147, 1994. 36. Khoshbin S, Hallet M: Multimodality evoked potentials and blink reex in multiple sclerosis, Neurology 31(2):138-144, 1981. 37. Stockard J, Pope-Stockard J, Sharbrough F: Brainstem auditory evoked potentials in neurology: methodology, interpretation and clinical applications. In Aminoff AM, editor: Electrodiagnosis in clinical neurology, ed 3, New York, 1992, Churchill-Livingstone. 38. Jones SJ: Short latency potentials recorded from the neck and scalp following median nerve stimulation in man, Electroencephalogr Clin Neurophysiol 43(6):853-863, 1977. 39. Facco E, Munari M, Gallo F, et al: Role of short latency evoked potentials in the diagnosis of brain death, Clin Neurophysiol 113(11):1855-1866, 2002. 40. Cornblath DR, Sumner AJ, Daube J, et al: Conduction block in clinical practice, Muscle Nerve 14(9):869-871, discussion 867-868, 1991. 41. Andersen H, Stalberg E, Falck B: F-wave latency, the most sensitive conduction parameter in patients with diabetes mellitus, Muscle Nerve 20(10):1296-1302, 1997. 42. Stalberg E, Tronteli J: Single ber electromyography: studies in healthy and diseased muscle, New York, 1994, Raven Press.

1039