12.7 - Hallucinogen

Authors: Sadock, Benjamin James; Sadock, Virginia Alcott

Title: Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition

Copyright ©2007 Lippincott Williams & Wilkins

> Table of Contents > 3 - The Brain and Behavior > 3.4 - Electrophysiology

3.4

Electrophysiology

Electroencephalography (EEG) is the recording of the electrical activity of the brain. It is used in clinical psychiatry principally to evaluate the presence of seizures, particularly temporal lobe, frontal lobe, and petit mal seizures which can produce complex behaviors. The EEG is also used during electroconvulsive therapy (ECT) to monitor the success of the stimulus in producing seizure activity, and as a key component of the polysomnogram used in the evaluation of sleep disorders. Quantitative electroencephalography (QEEG) and cerebral evoked potentials (EP) represent newer EEG-based methods that provide improved research and clinical insights into brain functioning.

Electroencephalography

A brain wave is the transient difference in electrical potential (greatly amplified) between any two points on the scalp or between some electrode placed on the scalp and a reference electrode located elsewhere on the head (i.e., ear lobe or nose). The difference in electrical potential measured between any two EEG electrodes fluctuates or oscillates rapidly, usually many times per second. It is this oscillation that produces the characteristic “squiggly line” that is recognized as the appearance of “brain waves.”

Brain waves reflect change by becoming faster or slower in frequency or lower or higher in voltage, or perhaps some combination of these two responses. A normal EEG can never constitute positive proof of absence of brain dysfunction. Even in diseases with established brain pathophysiology, such as multiple sclerosis, deep subcortical neoplasm, some seizure disorders, and Parkinson's disease and other movement disorders, a substantial incidence of patients with normal EEGs may be encountered. Nonetheless, a normal EEG can often provide convincing evidence for excluding certain types of brain pathology that may present with behavioral or psychiatric symptoms. More often, information from the patient's symptoms, clinical course and history, and other laboratory results identifies a probable cause for the EEG findings. EEGs are often ordered when a pathophysiological process is already suspected or a patient experiences a sudden, unexplained change in mental status.

Electrode Placement

The electrodes normally used to record the EEG are attached to the scalp with a conductive paste. A standard array consists

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of 21 electrodes. Placement of the electrodes is based on the 10/20 International System of Electrode Placement. This system measures the distance between readily identifiable landmarks on the head and then locates electrode positions at 10 percent or 20 percent of that distance in an anterior-posterior or transverse direction. Electrodes are then designated by an uppercase letter denoting the brain region beneath that electrode and a number, with odd numbers used for the left hemisphere and with even numbers signifying the right hemisphere (the subscript Z denotes midline electrodes). Thus, the O2 electrode is placed over the right occipital region, and the P3 lead is found over the left parietal area.

In special circumstances, other electrodes may be used. Nasopharyngeal (NP) electrodes can be inserted into the NP space through the nostrils and can be closer to the temporal lobe than scalp electrodes. No actual penetration of tissue occurs. These electrodes may be contraindicated with many psychiatric patients displaying behaviors, such as confusion, agitation, or belligerence, which could pull the leads out, possibly lacerating the nasal passage. Sphenoidal electrodes use a hollow needle through which a fine electrode that is insulated, except at the tip, is inserted between the zygoma and the sigmoid notch in the mandible, until it is in contact with the base of the skull lateral to the foramen ovale.

Activated EEG

Certain activating procedures are used to increase the probability that abnormal discharges, particularly spike or spike-wave seizure discharges, will occur. Strenuous hyperventilation is one of the most frequently used activation procedures. While remaining reclined with the eyes closed, the patient is asked to overbreathe through the open mouth with deep breaths for 1 to 4 minutes, depending on the laboratory (3 minutes is common). In general, hyperventilation is one of the safest EEG activating procedures, and, for most of the population, it presents no physical risk. It can pose a risk for patients with cardiopulmonary disease or risk factors for cerebral vascular pathophysiology, however. Photic stimulation (PS) generally involves placing an intense strobe light approximately 12 inches in front of the subject's closed eyes and flashing at frequencies that can range from 1 to 50 Hz, depending on how the procedure is carried out. Retinal damage does not occur, because each strobe flash, although intense, is extremely brief in duration. 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. 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. It has been shown that the central nervous system (CNS) stress produced by 24 hours of sleep deprivation alone can lead to the activation of paroxysmal EEG discharges in some cases.

FIGURE 3.4-1 Normal electroencephalogram (EEG) tracings in an awake 28-year-old man. (Reprinted from

Emerson RG, Walesak TS, Turner CA. EEG and evoked potentials. In: Rowland LP, ed. Merritt's Textbook of Neurology. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1995:68

, with permission.)

Normal EEG Tracing

The normal EEG tracing (Fig. 3.4-1) is composed of a complex mixture of many different frequencies. Discrete frequency bands within the broad EEG frequency spectrum are designated with Greek letters.

Awake EEG

The four basic wave forms are alpha, beta, delta, and theta. Highly 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. Alpha frequency can be increased or decreased by a wide variety of pharmacological, metabolic, or endocrine variables. Frequencies 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. Delta waves (≤ 3.5 Hz) are not present in the normal waking EEG but are a prominent feature of deeper stages of sleep. The presence of significant generalized or focal delta waves in the wake EEG is strongly indicative of a pathophysiological process. Waves with a frequency of 4.0 to

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7.5 Hz are collectively referred to as theta waves. 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.

With maturation, EEG activity gradually goes from a preponderance of irregular medium- to high-voltage delta activity in the tracing of the infant, to greater frequency and more rhythmic pattern. Rhythmic activity in the upper theta–lower 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.

Sleep EEG

The EEG patterns that characterize drowsy and sleep states are different from the patterns seen during wake state. 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 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.

EEG Abnormalities

Apart from some of the obvious indications for an EEG study (i.e., suspected seizures), EEGs are not routinely performed as part of a diagnostic work-up in psychiatry. EEG, however, is a valuable assessment tool in clinical situations in which the initial presentation or the clinical course appear to be unusual or atypical (Table 3.4-1). Table 3.4-2 summarizes some common types of EEG abnormalities.

Some psychotropic medications and recreational or abused drugs produce EEG changes, yet, with the exception of the benzodiazepines and some compounds with a propensity to induce paroxysmal EEG discharges, little, if any, clinically relevant effect is noted when the medication is not causing any toxicity. Benzodiazepines, which always generate a significant amount of diffuse beta activity, have EEG-protective effects, so that they can mask alterations caused by concomitant medications (Table 3.4-3).

Table 3.4-1 Warning Signs of the Presence of Covert Medical or Organic Factors Causing or Contributing to Psychiatric Presentation

Atypical age of onset (i.e., anorexia nervosa beginning at mid-adulthood)
Complete lack of positive family history of the disorder when a positive family history is expected
Any focal or localized symptoms (i.e., unilateral hallucinations)
Focal neurological abnormalities
Catatonia
Presence of any difficulty with orientation or memory (in general, Mini Mental State Examination should be normal)
Atypical response to treatment
Atypical clinical course
Note: Clinicians should have a high index of suspicion for underlying medical conditions and a low threshold for initiating appropriate workups.

Table 3.4-2 Common Electroencephalogram (EEG) Abnormalities

Diffuse slowing of background rhythms Most common EEG abnormality; nonspecific and is present in patients with diffuse encephalopathies of diverse causes
Focal slowing Suggests localized parenchymal dysfunction and focal seizure disorder; seen with focal fluid collection, such hematomas
Triphasic waves Typically consist of generalized synchronous waves occurring in brief runs; approximately one half the patients with triphasic waves have hepatic encephalopathy, and the remainder have other toxic-metabolic encephalopathies
Epileptiform discharges Interictal hallmark of epilepsy; strongly associated with seizure disorders
Periodic lateralizing epilptiform discharges Suggest the presence of an acute destructive cerebral lesion; associated with seizures, obtundation, and focal neurological signs
Generalized periodic sharp waves Most commonly seen following cerebral anoxia; recorded in about 90% of patients with Creutzfeldt- Jakob disease

Medical and neurological conditions produce a wide range of abnormal EEG findings. EEGs, thus, can contribute to the detection of unsuspected organic pathophysiology influencing a psychiatric presentation (Fig. 3.4-2). Table 3.4-4 lists EEG

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alterations in medical disorders and Table 3.4-5 lists EEG alterations associated with psychiatric disorders.

Table 3.4-3 Electroencephalogram (EEG) Alterations Associated with Medication and Drugs

Drug Alterations
Benzodiazepines Increased beta activity
Clozapine (Clozaril) Nonspecific change
Olanzapine (Zyprexa) Nonspecific change
Risperidone (Risperdal) Nonspecific change
Quetiapine (Seroquel) No significant changes
Aripiprazole (Abilify) No significant changes
Lithium Slowing or paroxysmal activity
Alcohol Decreased alpha activity; increased theta activity
Opioids Decreased alpha activity; increased voltage of theta and delta waves; in overdose, slow waves
Barbiturates Increased beta activity; in withdrawal states, generalized paroxysmal activity and spike discharges
Marijuana Increased alpha activity in frontal area of brain; overall slow alpha activity
Cocaine Similar to marijuana
Inhalants Diffuse slowing of delta and theta waves
Nicotine Increased alpha activity; in withdrawal, marked decrease in alpha activity
Caffeine In withdrawal, increase in amplitude or voltage of theta activity

FIGURE 3.4-2 Diffuse slowing in a 67-year-old patient with dementia. Six- to seven-cps activity predominates over the parieto-occipital regions. Although reactive to eye closure, the frequency of this rhythm is abnormally slow. (Reprinted from

Emerson RG, Walesak TS, Turner CA. EEG and evoked potentials. In: Rowland LP, ed. Merritt's Textbook of Neurology. 9th ed. Baltimore: Lippincott Williams & Wilkins. 1995:68

, with permission.)

Topographic Quantitative Electroencephalography (QEEG)

Unlike standard EEG interpretation, which relies on waveform recognition, QEEG involves a computer analysis of data extracted from the EEG. Findings are compared with a large population database of subjects without any known neurological or psychiatric disorder as well as QEEG profiles that may be characteristic of some defined diagnostic group. In QEEG, the analogue-based electrical signals are processed digitally and converted to graphic, colored topographical displays. These images are sometimes called “brain maps.” Figure 3.4-3 illustrates topographic QEEG images of patients with psychiatric disorders (see Color Plate 3.4-3 on p. 84).

Table 3.4-4 Electroencephalogram (EEG) Alterations Associated with Medical Disorders

Seizures Generalized, hemispheric, or focal spike, spike-wave discharge, or both
Structural lesions Focal slowing, with possible focal spike activity
Closed head injuries Focal slowing (sharply focal head trauma)
Focal delta slowing or more widespread slowing (subdural hematomas)
Infectious disorders Diffuse, often synchronous, high voltage slowing (acute phase of encephalitis)
Metabolic and endocrine disorders Diffuse generalized slowing of wake frequencies
Triphasic waves: 1.5 to 3.0 per second high-voltage slow-waves, with each slow wave initiated by a blunt or rounded spike-like transient (hepatic encephalopathy)
Vascular pathophysiology Slowed alpha frequency and increased generalized theta slowing (diffuse atherosclerosis)
Focal or regional delta activity (cerebrovascular accidents)

QEEG remains primarily a research method, but it holds considerable clinical potential for psychiatry, mainly in establishing

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neurophysiological subtypes of specific disorders and for identifying electrophysiological predictors of response. Examples of some of the more promising results of QEEG research include the identification of subtypes of cocaine dependence and the subtype most likely to be associated with sustained abstinence; identification of subtypes of obsessive–compulsive disorder (OCD) that predict clinical responsiveness or lack of responsiveness to selective serotonin reuptake inhibitors (SSRIs); and the differentiation between normals, attention–deficit disorder and attention-deficit/hyperactivity disorder (ADHD), and learning disability subpopulations. QEEG findings in ADHD show that increased theta abnormality frontally may be a strong predictor of response to methylphenidate and other psychostimulants and that favorable clinical responses may be associated with a normalization of the EEG abnormality.

Table 3.4-5 Electroencephalogram (EEG) Alterations Associated with Psychiatric Disorders

Panic disorder Paroxysmal EEG changes consistent with partial seizure activity during attack in one third of patients; focal slowing in about 25% of patients
Catatonia Usually normal, but EEG indicated in new patient presenting with catatonia to rule out other causes
Attention-deficit/hyperactivity disorder (ADHD) High prevalence (up to 60%) of EEG abnormalities versus normal controls; spike or spike-wave discharges
Antisocial personality disorder Increased incidence of EEG abnormalities in those with aggressive behavior
Borderline personality disorder Positive spikes: 14- and 6 per second seen in 25% of patients
Chronic alcoholism Prominent slowing and periodic lateralized paroxysmal discharges
Alcohol withdrawal May be normal in patients who are not delirious; excessive fast activity in patients with delirium
Dementia Rarely normal in advanced dementia; may be helpful in differentiating pseudodementia from dementia

Cerebral Evoked Potentials

Cerebral EPs are a series of surface (scalp) recordable waves that result from brain visual, auditory, somatosensory, and cognitive stimulation. They have been shown to be abnormal in many psychiatric conditions, including schizophrenia and Alzheimer's disease, thus creating difficulty in using cerebral EPs for differential diagnosis purposes.

References

Boutros NN, Mirolo HA, Struve FA. Normal analog EEG in neuropsychiatry: Examination of adequacy for neuropsychiatric research. J Neuropsychiatry Clin Neurosci. 2005;17:84.

Boutros NN, Struve FA. Applied electrophysiology. In: Sadock BJ, Sadock VA, eds. Kaplan & Sadock's Comprehensive Textbook of Psychiatry. 8th ed. Vol. 1. Baltimore: Lippincott Williams & Wilkins; 2005:171.

Hanson ES, Prichep LS, Bolwig TG, John ER. Quantitative electroencephalography in OCD patients treated with Paroxetine. Clin Electroencephalogr. 2003; 34:70.

Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, Olney JW, Wozniak DW. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci. 2003;23:876–882.

Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, MacKinnon R. X-ray structure of a voltage-dependent K+ channel. Nature. 2003;423:33–41.

Jiang Y, Ruta V, Chen J, Lee A, MacKinnon R. The principle of gating charge movement in a voltage-dependent K+ channel. Nature. 2003;423:42–48.

Jorgensen PL, Hakansson KO, Karlish SJD. Structure and mechanism of Na, K-ATPase: functional sites and their interactions. Annu Rev Physiol. 2003;65:817–849.

Karlin A. Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci. 2002;3:102–114.

Noebels JL. The biology of epilepsy genes. Annu Rev Neurosci. 2003;26:599–625.

Reid MS, Prichep LS, Ciplet D, O'Leary S, Tom ML, Howard B, Rotrosen J, John ER. Quantitative electroencephalographic studies of cue-induced cocaine craving. Clin Electroencephalogr. 2003;34:110.

Sadja R, Alagem N, Reuveny E. Gating of GIRK channels: Details of an intricate, membrane-delimited signaling complex. Neuron. 2003;39:9–12.

Sather WA, McClesky EW. Permeation and selectivity in calcium channels. Annu Rev Physiol. 2003;65:133–159.

Smirnow BW, Holloway HC. The neuroscience of psychotherapy: Building and rebuilding the human brain. Psychiatry. 2005;68(2):187–192.

Struve FA, Manno BR, Kemp P, Patrick G, Manno JE. Acute marijuana (THC) exposure produces a “transient” topographic quantitative EEG profile identical to the “persistent” profile seen in chronic heavy users. Clin Electroencephalogr. 2003;34:75.

Umbricht D, Koller R, Schmid L, Skrabo A, Grubel C, Huber T, Stassen H. How specific are deficits in mismatch negativity generation to schizophrenia? Biol Psychiatry. 2003;53:1120.

Yang-Whan J, Polich J. Meta-analysis of P300 and schizophrenia: Patients, paradigms, and practical implications. Psychophysiology. 2003;40:684.

Zorumski CF, Isenberg KE, Mennerick SJ. Basic electrophysiology. In: Sadock BJ, Sadock VA, eds. Kaplan & Sadock's Comprehensive Textbook of Psychiatry. 8th ed. Vol. 1. Baltimore: Lippincott Williams & Wilkins; 2005:99.