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Henri Gastaut observed that PMR occurs in 0.3 percent of normal subjects, 3 percent of epileptic patients, and 17 percent of patients with psychiatric disorders. The PMR is also enhanced in early stages of alcohol withdrawal in chronic alcoholics and after a sudden withdrawal from barbiturates and other sedatives. The clinical relevance of PMR is yet to be fully explored in systematic research.In terms of activating EEG abnormalities, one looks for a photoconvulsive response that consists of bilaterally synchronous, usually diffuse, spike-and-wave discharges of various frequencies or diffuse, multiple spike-wave complexes. When the resting EEG is normal, and a seizure disorder or behavior that is suspected to be a manifestation of a paroxysmal EEG dysrhythmia is suspected, PS can be a valuable activation to use. Its primary limitation, especially as a routine procedure, is the not insignificant false positive incidence of photoconvulsive EEG responses in individuals with no history of seizure disorder and no current symptoms suggestive of such. The persistence of the spike-wave discharges after the cessation of the PS may also be indicative of a photoconvulsive response. Moreover, the spread of the spike-wave activity to other leads besides the occipital leads may also be indicative of a pathological process.SleepLargely because of the pioneering studies and perseverance of Fred and Erna Gibbs, EEG recording during sleep, natural or sedated, is now widely accepted as an essential technique for eliciting a variety of paroxysmal discharges, when the wake tracing is normal, or for increasing the number of abnormal discharges to permit a more definitive interpretation to be made. A variety of focal and diffuse spike and spike-wave discharges, as well as several minor or controversial paroxysmal patterns, occurs much more often during drowsiness and light sleep than during the wake recording, and some of them are seen almost exclusively during the sleep recording. Paroxysmal patterns differ substantially among themselves in the degree to which their appearance in the tracing is sleep activation dependent (Fig. 1.14-13). Although most clinical EEGs should contain a drowsy- and light-sleep tracing to be complete, deep stages III and IV sleep with generalized high-voltage delta slowing has almost no activating property and is not clinically useful.

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FIGURE 1.14-13 Percent of various electroencephalography patterns detected only during drowsiness or sleep, or both. To be read as follows: Of all cases of multiple spike foci, 30 percent required a drowsy or sleep, or both, recording for their detection, and 70 percent were detected during a wake recording. RMTD, rhythmic mid-temporal discharges. (Data abridged from Gibbs FA, Gibbs EL: How much do sleep recordings contribute to the detection of seizure activity? Clin Electroencephalogr. 1971;2:169; and Struve FA, Pike LE: Routine admission electroencephalograms of adolescent and adult psychiatric patients awake and asleep. Clin Electroencephalogr. 1974;5:67. A greatly expanded graph with 27 electroencephalography patterns can be found in Struve FA. Clinical electroencephalography as an assessment method in psychiatric practice. In: Hall RCW, Beresford TP, eds. Handbook of Psychiatric Diagnostic Procedures. Vol 2. New York: Spectrum Publications, 1985.)

Sleep DeprivationIt has been shown that the CNS stress produced by 24 hours of sleep deprivation alone can lead to the activation of paroxysmal EEG discharges in some cases. This effect is presumably independent of the known activating properties of natural or sedated sleep itself. Sleep deprivation is without risk for the healthy patient but may be contraindicated for patients medically or physically compromised. The primary disadvantage is the tendency for sleep deprived individuals to enter into deep sleep (stages III and IV) immediately at the start of the recording, thus reducing the chances of detecting spike activity. The optimal method is to ensure that the subject stays awake until the recording begins and remains so for the initial recording period, after which a gradual transition into drowsy sleep can be observed.Miscellaneous Special ActivationsIt has long been recognized that seizure manifestations or aberrant behaviors that might rest on a seizure basis can be triggered by specific stimuli. In this regard, cases of audiogenic, musicogenic, photogenic, and reading epilepsy readily come to mind, even though such cases are rare, and most practitioners have never encountered them. Seizure phenomena related to other sensory system input (e.g., somatosensory and gustatory) are even more rare. Sometimes, it may be possible for laboratory personnel to duplicate or approximate sensory triggers in various modalities to determine if they activate EEG seizure discharges combined with overt symptoms. Psychiatrists evaluating a patient with an atypical behavioral reaction to a drug (for example, an unusually explosive reaction after a small amount of alcohol or other abused drug or some other highly idiosyncratic response) may want to consider a drug-activated EEG to determine if ingestion of the drug activates any type of seizure or other paroxysmal abnormality in the tracing that might have explanatory clinical value.NORMAL ANALOG EEG TRACINGAlthough the appearance of the EEG tracing may vary somewhat between individuals, the range of frequencies, voltages, and waveforms that characterize the normal EEG during wake and sleep has been well established. Nonetheless, there are certain waveforms that continue to engender disagreements regarding their place on the normal-abnormal continuum, and several of these controversial waveforms may have significant importance to psychiatry. Stated somewhat differently, the normal boundaries of the EEG, although well established for evaluating neurological or medical disorders, are not nearly as well established for psychiatric disorders. Furthermore, the dynamic nature of many psychiatric disorders, combined with the fact that many EEG findings and their associated symptoms are known to cut across specific psychiatric diagnostic categories, makes the electroclinical relationships between psychiatric syndromes and EEG more complex. Nonetheless, normative patterns that are not controversial are discussed in this section.Normal Intrinsic FrequenciesThe normal EEG tracing is composed of a complex mixture of many different frequencies. P.182

Furthermore, some frequency bands are expressed more strongly over some cortical regions than others, and, in addition, the frequency profile varies considerably as the recording moves from alert wakefulness into sleep. Following the lead of Berger, discrete frequency bands within the broad EEG frequency spectrum are designated with Greek letters.AlphaHighly rhythmic alpha waves with a frequency range of 8 to 13 Hz constitute the dominant brain wave frequency of the normal eyes-closed wake EEG. Through middle age, the vast majority of normal adults have an alpha frequency at, or close to, 10 Hz, whereas, with normal geriatric populations, a slower alpha frequency of 8 to 9 Hz is not uncommon. Alpha activity is also most prominent over the posterior cortex, particularly the parietal, posterior temporal, and occipital cortex, with the occipital region being best suited to show this activity. The registration of alpha activity diminishes as one records from more anterior locations, and this frequency is rare at prefrontal electrode sites. Alpha activity is abolished, or at least severely attenuated, by eye opening, and alpha activity also disappears with drowsiness and sleep. It is often not appreciated that alpha activity can be highly responsive to cognitive activity, such as focused attention or concentration. For example, under eyes-closed recording conditions, alpha can be blocked or attenuated by engaging in visual imagery, numeric calculation, or almost anything requiring significant concentration (Fig. 1.14-14). Alpha frequency can be increased or decreased by a wide variety of pharmacological, metabolic, or endocrine variables

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FIGURE 1.14-14 Resting, eyes-closed, awake electroencephalography recording. Effect of mental concentration on alpha activity. While instructed to keep the eyes closed, at the heavy vertical line, the patient is asked to divide 389 by 7. Note the immediate blocking of alpha activity.

ThetaWaves with a frequency of 4.0 to 7.5 Hz are collectively referred to as theta activity. A small amount of sporadic, arrhythmic, and isolated theta activity can be seen in many normal waking EEGs, particularly in frontal-temporal regions. Although theta activity is limited in the waking EEG, it is a prominent feature of the drowsy and sleep tracing. Excessive theta in wake, generalized or focal in nature, suggests the operation of a pathological process.DeltaDelta activity (equal to or less than 3.5 Hz) is not present in the normal waking EEG but is a prominent feature of deeper stages of sleep. The presence of significant generalized or focal delta in the wake EEG is strongly indicative of a pathophysiological process.BetaFrequencies that are faster than the upper 13 Hz limit of the alpha rhythm are termed beta waves, and they are not uncommon in normal adult waking EEGs, particularly over frontal-central regions. It is also not uncommon for beta to appear as runs of rhythmic activity as opposed to sporadic isolated waves. Although there is no real upper limit designation for beta activity, the practical constraints of recording apparatus and filtering requirements tend to restrict beta activity to less than 40 or 50 Hz. The voltage of beta activity is also almost always lower than that of activity in the other frequency bands described previously. Researchers sometimes divide beta activity into low and high beta frequencies, and some have even specified the higher frequencies by using designations, such as gamma 1 (25 to 35 Hz), gamma 2 (35 to 50 Hz), and gamma 3 (50 to 100 Hz).Changes with AgeThe appearance of the EEG tracing changes dramatically from birth to advanced age. From a preponderance of irregular medium- to high-voltage delta activity in the tracing of the infant, EEG activity gradually increases in frequency and becomes more rhythmic with increasing age. Rhythmic activity in the upper thetalower alpha range (7 to 8 Hz) can be seen in posterior areas by early childhood, and, by the time mid-adolescence is reached, the EEG essentially has the appearance of an adult tracing. The interpretation of EEGs secured from children demands a solid grounding in the age-related changes during this period and is best performed by one specializing in pediatric EEG.Sleep PatternsThe EEG patterns that characterize drowsy and sleep states are different from the patterns seen during wake state. A detailed accounting of the nuances of sleep patterns would exceed the scope of this chapter. In simplistic terms, the rhythmic posterior alpha activity of the waking state subsides during drowsiness and is replaced by irregular low-voltage theta activity. As drowsiness deepens, slower frequencies emerge, and sporadic vertex P.183

sharp waves may appear at central electrode sites, particularly among younger persons. Finally, the progression into sleep is marked by the appearance of 14-Hz sleep spindles (also called sigma waves), which, in turn, gradually become replaced by high-voltage delta waves as deep sleep stages are reached.ArtifactsArtifacts are electric potentials of nonbrain origin that are in the frequency and voltage range of EEG signals and that are detected by scalp electrodes. Most EEGs contain some artifacts, and the electroencephalographer must identify them, particularly those that can closely mimic real brain waves, before making an interpretation. Common artifacts include eye blinks, vertical or lateral eye movements, frontalis EMG, muscle potentials from jaw clenching, perspiration artifact (galvanic skin response), and head movement. Less frequently seen are artifacts from electrocardiogram (ECG) (especially in heavy barrel-chested subjects recorded with a monopolar EEG montage), lateral rectus eye muscle spikes, lingual movements, and a variety of electrode and amplifier problems. The competent technologist is capable of modifying recording conditions and patient instructions to distinguish artifact from brain waves when necessary, and, when this competence is not available, the quality of the EEG may become compromised. Automatic artifact rejection programs exist for some computerized research applications, but they have not strongly entered the clinical arena.EEG ALTERATIONS FROM MEDICATIONS AND DRUGSA great many medications, as well as substances consumed for recreational or abuse purposes, can produce some degree of alteration in the EEG. This section attempts to highlight those compounds most relevant to clinical and research psychiatry.Psychotrophic Medications (General Considerations)It is well known that psychotropic agents can affect the EEG. For the routine EEG, with the exception of the benzodiazepines and some compounds with a propensity to induce paroxysmal EEG discharges, there is little, if any, clinically relevant effect when the medication is not causing any toxicity. Benzodiazepines, even in small doses, always generate a significant amount of beta activity that is seen diffusely. This response is so universal that it has been suggested that, if a particular brain region fails to exhibit the expected benzodiazepine-induced beta activity, that area may be dysfunctional.Psychotropic Medications (Toxic Effects)For a long time, it has been accepted that the EEG is sensitive to the neurotoxic effects of psychotropic medications, and clinical vignettes illustrating the value of EEG in detecting a neurotoxic reaction to medications when a clinical deterioration was evident have been reported. It is P.184

often specifically stressed that such a scenario could occur at any time during the course of treatment, because many factors impact the patient, and the symptoms could be subtle. An EEG investigation may be useful when patients undergoing long-term therapy present with clinical deterioration, particularly if the patient is known to be taking the medication, and the serum plasma levels are within the therapeutic range. Such clinical situations may also highlight the need for having baseline EEGs available for comparison when a patient presents with clinical exacerbation. EEG norms currently available are based on cross sectional evaluations and do not take into account the dynamic nature of psychiatric disorders or the constantly changing medication status. Thus, in terms of possible toxicity, the effects of medications on the routine (visually inspected) EEG remain of immediate significance and of relevance to the everyday management of patients. The appearance of significant diffuse EEG slowing in a patient who is receiving psychotropic medications and whose clinical condition is not stable (particularly the elderly) should prompt the clinician to consider medication toxicity, as well as other causes of encephalopathy (e.g., electrolyte imbalance and thyroid problems, to name only two).Psychotropic DrugInduced EEG Abnormality (Nonparoxysmal and Paroxysmal)Almost from the time psychotropic medications were introduced, it was known that some of these compounds could precipitate EEG abnormalities, including paroxysmal EEG discharges (spike and spike-wave activity) in some individuals. Usually, medication-induced paroxysmal EEG activity remains behaviorally silent and is not accompanied by iatrogenic overt seizure manifestations. A little more than 20 years ago, a team of investigators from the Psychiatry Department at the University of Munich led by J. Kuglar conducted an exceptionally large retrospective study (680 EEGs obtained from 593 patients) of the effects of psychotropic agents on the EEG and reported that the highest proportion of abnormal EEGs occurred in clozapine (Clozaril)treated patients (59 percent), followed by lithium (Eskalith, Lithobid) (50 percent). The overall proportion of paroxysmal EEG discharges was 13 percent, and actual seizures were witnessed with treatment with clozapine, lithium, and maprotiline (Ludiomil). Lithium continues to be widely used in the treatment of bipolar disorder, as well as other episodic behavioral syndromes, including aggressive tendencies. This compound is capable of causing abnormal generalized slowing or paroxysmal activity, or both, including a 10 percent incidence of toxic delirium, in normal research volunteers and patients undergoing lithium treatment.Recent times have seen the emergence of several new atypical antipsychotic compounds. Although clozapine has received extensive EEG study and is now recognized as a compound highly associated with risk of induced EEG abnormality, information regarding the other new compounds remains sparse. A research team led by Franca Centorrino recently made a substantial effort to fill this knowledge gap. In their study, the effects of typical and atypical antipsychotic medications were compared using EEG recordings from 323 hospitalized psychiatric patients (293 on antipsychotic medications and 30 not receiving antipsychotic drugs) who were graded blind to diagnosis and treatment for type and severity of EEG abnormalities. Abnormal EEGs occurred in 19 percent of treated patients and 4 percent of untreated patients; however, the risk for EEG abnormality varied widely among the different types of medication (Fig. 1.14-15). The highest incidence of EEG abnormalities was associated with clozapine (47 percent) and was somewhat lower with olanzapine (Zyprexa) (38.5 percent) and risperidone (Risperdal) (28 percent). There were no EEG abnormalities seen in association with quetiapine (Seroquel). The incidence of EEG abnormalities in association with typical neuroleptics was lower, in general, than with atypical antipsychotics. The clinical significance of EEG abnormalities associated with the therapeutic use of antipsychotic agents, particularly in the absence of any indications of seizures or encephalopathic effects, remains an open research question.

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FIGURE 1.14-15 Risk of electroencephalography (EEG) abnormalities with specific antipsychotic agents among 293 hospitalized psychiatric patients. (From Centorrino F et al.: EEG abnormalities during treatment with typical and atypical antipsychotics. Am J Psychiatry. 2002;159:109, with permission.)

Pharmaco-EEGThe effects of psychotropic drugs on the frequency and power distribution of the different EEG spectra, using topographic QEEG methods, is the subject of a vast and growing field entitled pharmacoelectroencephalography (pharmaco-EEG). The focus of this field is to be able to predict the likely psychotropic effect of newly developed agents (i.e., antipsychotic vs. antidepressant vs. anxiolytic). Researchers in this field are also developing methods to predict the responsiveness of a particular patient to a particular compound by using test doses with the hopes of avoiding having to subject patients to 3 to 6 weeks of a medication trial before realizing that this agent is not helpful.Drugs of AbuseRecreational and addictive involvement with abuse drugs is a significant phenomenon in society today, and it is becoming of increasing concern for those involved in the assessment and treatment of psychiatric disorders. Nearly all abuse drugs are capable of altering the frequency spectrum of the EEG, and the degree of alteration varies with recreational versus heavy use and whether the EEG was secured during or close to acute exposure (intoxication), during intervening nonintoxication states, or during clinical withdrawal in the addicted individual.With only infrequent exceptions, the use of an abuse drug does not introduce frank clinical abnormalities into the visually analyzed EEG tracing. This is especially true for recreational drug use and is even largely true for dependent and addictive use, as well, and, for this reason, drug abuse alone is not a sufficient reason for EEG referral. Although the alterations of EEG frequency and voltage in the visually analyzed EEG produced by many abuse drugs are often unimpressive, topographic QEEG analyses often reveal marked alterations of the EEG

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spectrum that constitute significant deviations from population norms, even though the clinical implications may not be clear. Because of this, they constitute significant problems for researchers using topographic QEEG measures in their work. For example, if one wants to establish a QEEG profile for a particular diagnostic group or a particular psychotropic medication (i.e., as in pharmaco-EEG research), the QEEG effects of certain abuse drugs may constitute serious methodological confounds, rendering any results scientifically uninterpretable.AlcoholThere is considerable consensus that an increase in the amount of alpha activity and a slight slowing of alpha frequency typically accompany alcohol consumption and that higher blood alcohol levels increase the amount of theta in the tracing. Some reports have indicated that chronic alcohol consumption may be associated with a lower voltage and slightly faster resting EEG, although the clinical relevance of this remains obscure. Higher-frequency beta activity may be substantially increased in the addicted alcoholic undergoing withdrawal, and, if delirium tremens complicates the clinical picture, excessive fast activity may dominate the EEG tracing (whereas delirium from other causes is associated with generalized slowing).OpiatesOpiate effects on the EEG are similar to those of alcohol and involve slight reductions in alpha frequency. They may also increase the voltage of the EEG, particularly the power of theta and delta activity. However, when an opiate overdose produces a comatose clinical presentation, the EEG usually consists of clinically abnormal diffuse slowing.BarbituratesWhen barbiturates are taken for medical purposes or for recreational or habitual abuse, beta activity is introduced into the EEG, particularly over frontal regions. The barbiturate effect on the EEG is thus opposite to that of alcohol. However, sudden, abrupt withdrawal from barbiturates after long-term dependence can produce EEGs containing generalized paroxysmal activity and spike discharges, which are often not associated with overt motor seizure manifestations, and these effects may be seen for days or even a few weeks after last drug exposure.MarijuanaUse of marijuana (tetrahydrocannabinol [THC]) is widespread in society and not infrequently constitutes a comorbid feature of psychiatric conditions. Exposure to THC produces highly characteristic alterations of the waking EEG that can be appreciated visually but are best documented through use of topographic QEEG study. The EEG response to smoking THC is rapid. The voltage, amount, and interhemispheric coherence of alpha activity increases dramatically over the bilateral frontal cortex (areas in which alpha activity normally is only rarely seen) within 2 minutes of the first THC inhalation. The frequency of the alpha activity also slows by as much as 0.5 Hz. Some studies have shown that increases in frontal alpha are accompanied by subjective feelings of euphoria. With the chronic user, the EEG always shows increased frontal alpha and slowed alpha frequency, even when THC urine levels are absent, to the degree that a suspicion of THC use from mere inspection of the tracing would not be unreasonable.CocaineChronic cocaine exposure produces topographic QEEG changes similar (but not identical) to those seen with marijuana abuse, and the EEG effects can last throughout 6 or more months of abstinence. Primary effects are reported to consist of increased relative power (i.e., amount, abundance) of alpha activity seen maximally over the frontal cortex combined with a deficit of the amount and voltage of theta and delta frequencies.InhalantsInhalation abuse of volatile substances (e.g., airplane glue, cleaning fluid, paint thinner, and gasoline) can produce a nearly instantaneous sensation of euphoria, and, in the early period of use, there may be no obvious residuals after the acute response subsides. However, with continued inhalant abuse, neurological and neurocognitive deficits, which are often quite serious, can emerge, and they are not always completely reversible with abstinence. The immediate effects of inhalation of volatiles on the human EEG appear not to have been well studied. Where persistent neurological or neurocognitive sequelae follow chronic inhalant abuse, clinically abnormal diffuse EEG slowing in the lower theta to upper delta range may be seen.HallucinogensDrugs, such as lysergic acid diethylamide (LSD) and mescaline, appear to have only minor effects on the visualized EEG and do not produce clinically relevant changes.TobaccoLike many of the drugs reviewed previously, tobacco does not appear to produce dramatic alterations in the analog EEG. However, topographic QEEG analyses reveal striking EEG changes with acute exposure to, as well as withdrawal from, tobacco. The immediate effects of smoking include a decrease in slower frequencies (especially theta), increased power of frequencies in the upper one-half of the alpha frequency band, and beta activity. Twenty-four hours of tobacco deprivation produce a marked decrease in alpha frequency, with a corresponding marked increase in the relative power (amount) of theta activity. The effects of acute smoking and abstinence are essentially opposite to one another.CaffeineCoffee and products containing caffeine are also ubiquitous in this culture. The use of caffeine is of little concern to the electroencephalographer interpreting the visually analyzed EEG. Withdrawal from caffeine in the caffeine-dependent individual, however, produces a markedly significant increase in the amplitude, or voltage, of theta activityan effect that is reversible within 15 minutes of consuming one cup of coffee.CLINICAL INTERPRETATION OF THE EEGThe interpretation of the standard or analog EEG tracing is essentially a problem of learning to recognize all of the myriad intrinsic waveforms, their expected distributions over the various cortical regions, and their range of variation in amplitude and degree of symmetry. Although there is little doubt that 16, 32, or even 64 channels of oscillating waves appear quite confusing to the beginner, there is an inherent regularity to the brain's electrical output that the experienced electroencephalographer comes to recognize. Because of this inherent regularity, the intrinsic EEG rhythms and their range of variation that characterizes the wake, drowsy, and various sleep states become easily recognized through practice and experience. Furthermore, various artifacts (electrical potentials of nonbrain origin) produce localized or regional waveforms of distinctive shapes, allowing for their identification. The primary job of the interpreter is to identify those EEG waveforms that appear to fall outside of what one might call the normal range of variation of the intrinsic background activity and that are therefore (1) frankly abnormal with known pathophysiological correlates or (2) controversial abnormal waveforms of potential clinical relevance, pending the results of further continuing clinical investigation. The number of accepted and still controversial EEG abnormalities is quite large and well beyond the scope of this chapter. For the purpose of illustration only, four classic abnormal EEG patterns are shown (Figs. 1.14-16, 1.14-17, 1.14-18, and 1.14-19).

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FIGURE 1.14-16 Diffuse three-per-second spike-and-wave discharge of the petit mal type with a multiple spike component. Female patient, 16 years of age. Previous history of petit mal seizures and rare grand mal attacks. At a previous psychiatric facility, the diagnosis was changed to hysterical seizures after a psychological evaluation.

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FIGURE 1.14-17 Focal slow (delta), right prefrontal spreading with reduced voltage to right anterior and mid-temporal and right central. During the sleep recording (not shown), sleep spindles were absent in the right hemisphere. Female patient, 49 years of age. No prior psychiatric history. Recent emergence (over 6 months) of depression, mild episodic confusion, symptoms of hyperthyroidism, and pathological crying. Glioblastoma found at surgery.

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FIGURE 1.14-18 Focal negative spike and spike-wave discharges in the right anterior temporal cortex and often spreading with reduced voltage throughout the right hemisphere. Adult male patient. Complex partial seizures (psychomotor). Psychiatric outpatient with infrequent periods of sudden unresponsiveness during which time he would make grunting and guttural sounds and speak with incoherent words and syllables with amnesia for these events. (His girlfriend, who was involved in New Age phenomena, was convinced that he was communicating with spirits during these unresponsive spells and did not want him to be medicated.)

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FIGURE 1.14-19 Diffuse spike-and-wave discharges during the sleep recording. The waking electroencephalography (EEG) was within normal limits. Female patient, 15 years of age. Admitted to inpatient adolescent psychiatric unit with the complaint of serious temper dyscontrol and episodic dizzy spells.

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Interpreter ReliabilityBecause the EEG record is obtained by precisely measuring the microvolt fluctuations of electrical potentials over the scalp, a misconception often emerges that EEG interpretation is purely objective in the sense that measurements of temperature, weight, length, and volume are objective. In truth, there is a large, subjective element of judgment in EEG interpretation, and the achievement of skill in this area only follows a period of thorough training and the guiding hand of clinical experience. Accepted EEG abnormalities do not always appear in the EEG tracing in clear-cut textbook form, and there is always a gray area in which EEG activity that is clearly normal becomes blurred and shades off into waveforms that are unequivocally abnormal. P.187

Although the important area of reliability of clinical EEG interpretation has not enjoyed extensive study over the years, the balance of available evidence suggests that high levels of statistically (and clinically) significant interpretation reliability can be obtained. The two methods for assessing reliability involve comparing the independent readings of two or more EEG interpreters (interjudge reliability) and asking one electroencephalographer to blindly reinterpret a sample of EEGs after an elapsed time (intrajudge reliability). A review of interjudge and intrajudge interpretative comparisons involving 1,567 clinical standard EEGs revealed a weighted average of 91 percent interpretive agreement over 11 separate studies (see the 1985 article by Frederick Struve). It should be noted that interpretive differences usually involve disagreements over gray areas in which alterations in the frequency, symmetry, or amplitude of the intrinsic EEG activity begin to shade off into what, by consensus, would be considered outside of normal limits. In such transition areas in which the dividing line is not sharply precise, statements such as borderline slowing are sometimes used to denote the understandable uncertainty that is involved. When disagreements in this borderline region are removed from consideration, interpretive agreements ranging from 95 to 98 percent are not uncommon.P.188

Normal versus Abnormal: General ConsiderationsOne of the factors that may have limited the perception of clinical EEG as a useful assessment tool in psychiatry is the simplistic attempt to conceptualize EEG findings as a normal-versus-abnormal dichotomy. Psychiatric practitioners commonly ask if their patient's EEG is abnormal and seem content with an affirmative or negative answer. Furthermore, much of the published research literature reports the percentage of abnormal EEGs in this or that study population without much in the way of clarifying discussion. In actuality, the simple normalabnormal dichotomy has little to recommend it, and, for the practicing psychiatrist, it may lead to conceptual confusion. Rather than being considered as a dichotomy, the range of EEG findings exists on a broad continuum anchored on one end by unequivocally normal EEGs and extending in the other direction through a long parade of findings from those with unclear yet potential clinical relevance all the way to findings that correlate with life-threatening pathology. Some EEG patterns that are correctly classified as abnormal are on the low end of the continuum of clinical expressivity and may not always contribute strongly to diagnostic decisions. The psychiatrist receiving a report (without clarification) of a minor finding of limited clinical relevance may understandably begin to question the value of EEG when no current or past history organic signs are detected. The bottom line is that one should not ask simply if an EEG is abnormal, as if it were one side of a dichotomy, but instead should ask what specific kind of finding was present and what is the range of possible clinical correlates associated with it.An additional confusion caused by unwise reliance on the normal-abnormal dichotomy involves reports in review articles and book chapters stating that 10 percent, 15 percent, or even 20 percent of the normal population have abnormal EEGs. Because such statements are almost never properly clarified, they tend to be terribly misleading. Clearly, there can be an understandable reluctance to follow up an abnormal EEG report if one has read in a presumably authoritative source that 20 percent of the normal population have abnormal EEGs. More importantly, there may also be an equally understandable reluctance to refer a patient for EEG study for the same reason. To place the issue in proper perspective, the reports of substantial percentages of abnormal EEGs within the normal population are heavily skewed by the inclusion of minor EEG findings which often have low levels of clinical or diagnostic relevance. Furthermore, Nashaat Boutros, Hugh Mirolo, and Struve provided a comprehensive review of the literature on EEG findings in normal control populations that highlights the fact that most control studies have been seriously compromised by failure to screen subjects for a variety of medical and psychiatric variables that can impact on the EEG results. One of the authors (see the 1985 article by Struve) previously reanalyzed data from numerous published EEG-control population studies. When borderline EEG findings were removed from the data, the incidence of EEG abnormality dropped to 3.2 percent of 6,182 adult control subjects and 3.5 percent of 1,450 children control subjects, and the prevalence of accepted paroxysmal EEG abnormalities dropped to only 1.14 percent of a sample of 11,560 mixed-age control subjects.Topographic Quantitative Electroencephalography (QEEG)In QEEG analyses, raw analog waveforms are replaced by quantitative estimates of absolute power (V2), the percentage of relative power and mean frequency at all electrode locations for all four standard EEG frequency bands (alpha, theta, delta, and beta). In addition, estimates of power asymmetry and interhemispheric coherence between homologous regions can be obtained, and some systems permit estimates of intrahemispheric coherence values as well. It has been demonstrated that many QEEG measures show considerable variation with age or are not distributed normally, or both. Recognizing these constraints, E. Roy John has developed a sophisticated topographic QEEG method of analyses (termed neurometrics) in which raw quantitative measures extracted from the artifact-free analog EEG are age regressed and transformed to achieve a gaussian curve (e.g., a normal, bell-shaped curve). The neurometric normative database spans the age range and is comprised of large numbers of well-screened subjects free of significant medical or psychiatric complaint. Because all of the QEEG variables are z-transformed, it becomes possible to express, in standard deviation units, the degree to which any of a given patient's QEEG values deviate above or below the mean for the normal population for their age. Thus, unlike standard EEG interpretation, which relies on waveform recognition, interpretation of the QEEG involves an assessment of the statistical degree of congruence or lack of congruence between a patient and the normal population or the degree of similarity between a given patient and a QEEG profile that may be characteristic of some defined clinical group. Typically, the interpretive results can be displayed numerically or with topographic color-graphic brain maps. Among many other things, the quantitative approach can display variations in QEEG profiles (which presumably reflect variations in neurophysiological function) across primary diagnostic groups (Fig. 1.14-20). It can also display progressive change in neurophysiological function over time.

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FIGURE 1.14-20 Baseline group average topographic images of z scores for selected quantitative electroencephalography (QEEG) features in different Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision, psychiatric populations. Successive columns in the left and right panels include absolute (Abs.) power delta, relative (Rel.) power theta, interhemispheric coherence (Coh.) alpha, interhemispheric power asymmetry (Asy.) beta, and total power mean frequency (Freq.). Populations include normal adults; unipolar depressions; bipolar depressions; alcoholics (in withdrawal); cocaine-dependent subjects (5 to 14 days after last drug use); obsessive-compulsive disorder (OCD); global deterioration scale (GDS) 2, which are normal elderly with only subjective cognitive complaints; GDS 3, which meet criteria for mild cognitive impairment; GDS 4 through 6, which meet criteria for dementia; first-break schizophrenics (Sz FB); schizophrenics off medication (Sz NoMed); and schizophrenics on medication (Sz Med). The color scale of each z image is in standard deviation units, with a range of +0.75, indicated with a diamond, or +1.25, indicated with a club. To estimate the significance of any regional z score for this group average data, the z score should be multiplied by the square root of the number of patients in the group. For a group with 100 subjects, the z value imaged should be multiplied by 10 to get the estimate of the significance of that z. (See Color Plate.) (Courtesy of Dr. E. Roy John, Director, Brain Research Laboratories, Department of Psychiatry, New York University School of Medicine, New York, NY and Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY.)

Recent years have seen a substantial growth in research and attempted clinical applications involving topographic QEEG. Such methods hold considerable promise for psychiatry, particularly in terms of possibly establishing neurophysiological subtypes of certain psychiatric disorders and in seeking electrophysiological indicators of clinical outcome. For example, in papers published in 1999 and 2002, Leslie Prichep, Kenneth Alper, and their colleagues successfully used topographic QEEG methods to derive three distinct electrophysiological subtypes of cocaine dependence. They were able to show that electrophysiological subtype membership significantly predicted outcome retention in treatment, defined as ability to maintain abstinence for 6 months or longer. In 2003, this same team also demonstrated distinct topographic quantitative QEEG correlates of cue-induced cocaine craving. Beginning in 1993, a team led by Prichep developed a topographic QEEG electrophysiological subtyping of obsessive-compulsive disorder (OCD) that predicted clinical responsiveness versus lack of responsiveness to treatment with selective serotonin uptake inhibitors (SSRIs), and Elsebet Hanson, Prichep, and associates confirmed those results in 2003. Topographic QEEG also appears to be superior to standard visually analyzed EEG in documenting electrophysiological sequelae of both chronic and acute exposure to abuse drugs.Because the waveforms of artifacts of nonbrain origin are quantified by the computer program as if they were real brain waves, it is extremely important to remove artifacts from the analog EEG signals one is submitting for quantification. Furthermore, QEEG is usually based on the waking EEG, and, if drowsy or sleep segments are allowed to inadvertently enter the quantification process, serious distortions of the QEEG profile or topographic brain map, or both, occur, and the distortions may not be easily recognized as such. On numerous occasions, the authors have seen color graphic topographic displays of pronounced frontal delta activity that probably represented vertical eye movement, as well as maps showing widespread theta that may have been based on drowsy segments entered into quantification in error. The identification and rejection of artifacts is an involved task and can only be done with visual inspection of the analog tracing by experienced electroencephalographers or P.189

technologists skilled in EEG interpretation. When the issue of artifact contamination of the QEEG is not properly addressed, one has a situation described a generation ago by computer programmers, namely, garbage ingarbage out. Several commercial QEEG instruments also have programs for automatic artifact rejection. Although some of these may be useful to some degree for major high-voltage artifacts, such as vertical eye blinks, seldom are they completely effective with all sources of contamination.CLINICAL FINDINGS (GENERAL OVERVIEW)The routine EEG is a completely noninvasive test that is even available in out-of-the-way rural areas. It is a relatively inexpensive test, with charges of $200 for the test and $100 for the interpretation being common (in some instances a range of $500 to $600). Furthermore, any psychiatrist can be fully trained to interpret EEGs, and, with skill, useful EEG data can often be obtained from agitated and psychotic patients.Brief Synopsis of EEG Findings in Organic PathophysiologyThe standard clinical EEG has a high degree of sensitivity to a wide variety of medical conditions and events that impinge on CNS function. For this reason, EEGs have sometimes contributed to the detection of unsuspected organic pathophysiologies influencing the psychiatric presentation. However, the range of EEG findings in medical disease is enormous and far beyond the scope of this chapter. The reader is referred to the large edited volume by Ernst Niedermeyer and Fernando Lopes da Silva for more in-depth coverage.P.190

Findings with SeizuresThe hallmark EEG finding for a seizure disorder is the generalized, hemispheric, or focal spike or spike-wave discharge, or both (Figs. 1.14-16, 1.14-18, and 1.14-19). However, this statement constitutes a large oversimplification, because many types of EEG abnormalities have been associated with seizures at one time or another, and some patients with a bona fide seizure disorder have been known to have normal interictal EEG tracings. Furthermore, seizure disorders can be associated with an extremely wide range of etiologies (idiopathic or genetic, closed or open head trauma, cerebrovascular pathophysiology, metabolic disorders, structural brain lesions, infectious or toxic encephalopathies, certain drug-abuse withdrawal states, iatrogenic causes, to name only a few), and these considerations may modify the nature of the EEG-seizure disorder association.The classification of seizure types is also wide, and the majority of specific seizure manifestations may be of little concern to the practicing psychiatrist. One of the exceptions may be petit mal status, which can last from less than 1 hour to longer than 1 day, during which time the patient presents with grossly impaired consciousness marked by pronounced confusion, greatly slowed mental processes, or stuporous or somnolent behavior, or both. The psychiatrist is most likely to encounter this clinical presentation in the emergency room, where it is often confused with other functional or organic syndromes or intoxicant states. If suspected, the status can be confirmed quickly by an EEG demonstration of continuous, diffuse spike-wave activity. Typical petit mal seizures (i.e., nonstatus) may also be of relevance to the child psychiatrist, because this type of epilepsy has a peak age distribution during childhood and early adolescence, and, in some cases, the absence attack may be mistaken for inattention or other functional behavioral reactions. Spike foci, usually anterior temporal, associated with CPSs (psychomotor) should also interest the psychiatrist, because the wide range of possible seizure manifestations is truly amazing, and almost any combination of automatic motor movements, sensory disturbances, seemingly psychiatric symptoms, or autonomic signs may be seen. The symptom cluster almost always remains the same from one attack to another, and the automatic behavior during the ictal event may, at times, be bizarre, with the patient undressing, picking at clothing and lip smacking, walking in circles and yelling, trying to climb on a table while making guttural noises, experiencing hallucinatory symptoms, or almost any other action. When continuous or closely spaced CPS attacks (complex partial status) lasting hours or longer than a day occur, they may mimic hysterical dissociative states.Spike activity of various kinds and locations is sometimes found in the EEGs of psychiatric patients with no obvious seizure manifestations. In such cases, one might consider possible relationships to episodic aberrant behavior (particularly explosive aggressiveness), if present, followed by an empirical trial with an anticonvulsant. Sometimes, such spike discharges in the nonseizure psychiatric patient may indicate an elevated risk for iatrogenic seizures after treatment with neuroleptic medication (Fig. 1.14-21).Gambar 9

FIGURE 1.14-21 Routine admission electroencephalography (EEG). Diffuse spike and wave with multiple spike component during drowsy recording (the wake EEG was normal). Male patient, 16 years of age. No present or past history of seizures. No history of head trauma, encephalitis, or other plausible cause for the spiking. Patient later developed iatrogenic grand mal seizures during treatment with neuroleptics.