Does EEG predict response to valproate versus lithium in patients with mania?

A number of factors may suggest that a patient with mania may respond to valproate or to lithium. However, prediction of which patients will respond to either medication remains difficult. In this study nonepileptiform EEG abnormalities in responders to each medication were investigated. Six of 20 patients (30%) responsive to lithium but not to valproate had nonepileptiform EEG abnormalities while 14 of 20 patients (70%) responsive to valproate but not to lithium had nonepileptiform EEG abnormalities. Patients presenting with mania and EEG abnormalities, particularly sharp activity, are statistically more likely (chi2 = 4.9, df = 1, p = .027) to respond to valproate than to lithium. Whether such a finding will also hold true for other anticonvulsants used to treat mania remains to be seen.

Inadequacies of self-report data for exclusion criteria detection in marihuana research: an empirical case for multi-method direct examination screening.

Stringent exclusion criteria in drug abuse research are necessary to protect against methodological confounds compromising the interpretation of findings. However, reliance on self-report screening may fail to detect important exclusion variables. We compared three levels of exclusion criteria screening in a study of neurophysiological/neurocognitive sequelae of chronic marihuana use in normals. LEVEL 1 (self-report) consisted of telephone pre-screening. LEVEL 2 (also self-report) involved in-depth personal interviews. LEVEL 3 consisted of several direct examination assessments including a medical/psychiatric examination by a board certified psychiatrist, eight weeks of twice per week urine drug screens, an EEG exam and eight hours of neuropsychological testing. Results indicated that 39.0% of subjects passing self-report screening had significant exclusion criteria findings that were only detected through LEVEL 3 direct examination procedures. Of all subjects found to have exclusion criteria after being provisionally accepted following LEVEL 1 telephone pre-screening, 55.7% were detected only through more rigorous LEVEL 3 direct examination screening methods.

Topographic quantitative analysis of the intrinsic alpha rhythm in chronic obstructive pulmonary disease.

Twenty-two patients with documented COPD and no other significant illnesses were studied to assess the effect of varying degrees of COPD on the intrinsic alpha rhythm. The severity of COPD was determined by spirometry with assessment of FEV1, FVC, and FEV1/FVC. The alpha frequency for COPD patients was slower than that which characterizes age equated normals and averages 1.6 S.D. below normative data base mean values (range -0.43 S.D. to -1.85 S.D.). Impairment of pulmonary functioning significantly correlated with the degree of alpha frequency slowing over the posterior cortical regions, and the slowest alpha frequencies occurred in those COPD patients with the lowest FEV1/FVC ratios. Impairment of cognitive functioning is thus an important clinical consideration in treatment of patients with COPD but may go unrecognized until late in the course of the disease.

Reduction of auditory P50 gating response in marihuana users: further supporting data.

This report attempts to replicate our recent finding of a significantly reduced sensory gating response in medically and psychiatrically normal chronic marihuana users. After exclusions, 10 normal heavy marihuana users (> or = 3 times per week) and 10 normal non-user controls were tested with the paired auditory P50 sensory gating procedure. Sensory gating ratios were significantly higher (i.e., impaired suppression) for THC users as compared to controls. Using combined data from the current and previous report, the degree of sensory gating impairment among THC users was significantly correlated with the frequency of marihuana use per week. Suggestions for further research are offered.

Auditory and visual P300 cognitive evoked responses in patients with COPD: relationship to degree of pulmonary impairment.

Twenty-two subjects with documented COPD and no other significant illnesses were studied to assess the effect of varying degrees of COPD on cognitive P300 auditory and visual evoked potentials. The severity of COPD was determined by spirometry with assessment of FEV1, FVC, and FEV1/FVC. Auditory P300 latency was significantly correlated with the FEV1/FVC ratio (Pearson Product Moment correlations r = -.56, N = 20, probability level = 0.1), indicating that increasingly severe airflow impairment is associated with longer auditory P300 latencies. There was no significant association of FEV1/FVC with visual P300 latency or with auditory or visual evoked potential amplitude measures. Progressive impairment of the auditory P300 evoked potential latency occurs with increasing severity of COPD. This impairment is present even in patients with mild COPD, suggesting some degree of accompanying cognitive decline early in the course of COPD with worsening as the disease progresses.

Topographic quantitative EEG sequelae of chronic marihuana use: a replication using medically and psychiatrically screened normal subjects.

In two previous studies it was reported that chronic marihuana (THC) use was associated with unique quantitative EEG features which were present in the non-intoxicated state. THC users, as contrasted with controls, had significant elevations of Absolute Power, Relative Power, and Coherence of alpha activity over the bilateral frontal cortex. Furthermore, a quantitative EEG discriminant function analyses permitted a 95% correct user versus non-user classification. However, because all of the THC users and 58% of the non-user controls were psychiatric inpatients, diagnostic and medication effects, if any, were uncontrolled. In the present study the same quantitative EEG methods were used to study daily THC users and non-user controls who underwent a rigorous screening process to insure that they were medically and psychiatrically healthy. The results of previous studies were replicated and an additional EEG correlate of chronic THC exposure (reduced alpha frequency) was identified.

The effects of donepezil on the P300 auditory and visual cognitive evoked potentials of patients with Alzheimer's disease.

Donepezil is a cholinesterase inhibitor used for the treatment of patients with mild to moderately severe Alzheimer's disease (AD). The purpose of this study was to determine the effect of treatment with donepezil 5 mg qd on cognitive evoked potentials (EPs) of patients with AD. Although treatment with donepezil did not normalize EP latencies, treatment was associated with a significant decrease in the auditory P300 latency (mean latency pretreatment=401. 5 msec; posttreatment=392.7 msec.; P=0.04), and the visual P300 latency (mean latency pretreatment=605.7 msec; posttreatment=580.3 msec; P=0.04). Treatment with donepezil had no discernible effect on auditory or visual P300 EP amplitudes.

Reduced P50 auditory gating response in psychiatrically normal chronic marihuana users: a pilot study.

BACKGROUND: Neurophysiological studies of marihuana (THC) often contain uncontrolled confounds [psychiatric diagnoses, polydrug use, central nervous system (CNS)-relevant injury, etc.] that can alter electrophysiological measures. This P50 sensory gating report is part of a larger neurophysiological and neurocognitive investigation of chronic THC exposure using rigorously screened medically and psychiatrically normal individuals without concurrent use of non-THC substances. METHODS: Following medical and psychiatric screening, including serial urine drug screens, technically adequate P50 paired auditory recovery tests were obtained on 19 chronic THC users and 14 control subjects. Fifty pairs of 80-dB auditory clicks (1 pair per 10 sec, 500-msec interclick separation) were delivered through earphones. The sensory gating measure was the ratio between the P50 amplitudes at the vertex elicited by the conditioning (first) and test (second) click. RESULTS: THC subjects had significantly higher sensory gating ratios (i.e., reduced suppression) than did control subjects. Among THC users, sensory gating ratios did not correlate with duration or frequency of THC use, although subjects with ratios above 40 had nearly twice the number of "joint-years" of THC exposure than did those with lower ratios. CONCLUSIONS: Reduced P50 suppression in the sensory gating paradigm may be a possible neurophysiological CNS sequela of long-term cumulative exposure to THC.

Carisoprodol (soma): abuse potential and physician unawareness.

Carisoprodol is a noncontrolled skeletal muscle relaxant whose active metabolite is meprobamate, a Schedule IV controlled substance. Although several case reports have shown that carisoprodol has abuse potential, it continues to be widely prescribed. The usage patterns of 40 patients who had taken carisoprodol for three or more months (20 of whom had no history of substance abuse and 20 of whom carried a diagnosis of substance abuse or dependence) were reviewed and compared and a survey was conducted to assess physician awareness of the abuse potential of the drug. Findings showed that some patients using carisoprodol for over three months may abuse the medication, especially those individuals with a history of substance abuse. A significant percentage of the physician population is unaware of the potential of carisoprodol for abuse and of its metabolism to meprobamate, a controlled substance. Physicians should exercise caution when prescribing carisoprodol, especially if the patient has a history of substance abuse.

The effects of caffeine withdrawal on cognitive P300 auditory and visual evoked potentials.

Auditory and visual P300 cognitive evoked potentials were obtained in 13 individuals who regularly consumed caffeine prior to and during a 4 day period of abstinence from caffeine. During the period of caffeine abstinence auditory P300 evoked potentials showed significant decreases in amplitude measures but no significant changes in latency, while the visual P300 evoked potentials showed significant latency decreases but no significant changes in amplitude. The reason for these opposite effects is unclear and further research in this area is needed.

Possible EEG sequelae of very long duration marihuana use: pilot findings from topographic quantitative EEG analyses of subjects with 15 to 24 years of cumulative daily exposure to THC.

In previous work we demonstrated and replicated a significant association between increased absolute and relative power and interhemispheric coherence of EEG alpha activity over the bilateral frontal-central cortex ("alpha hyperfrontality") in daily marihuana users as contrasted with nonusers. In this report we focused our analyses on subjects who reported smoking marihuana on a daily basis for 15 to 24 consecutive years. Compared to nonuser controls and subjects who had used marihuana on a daily basis for shorter periods of time, subjects with excessively long cumulative exposures to THC were found to have significantly elevated absolute power of theta activity over bilateral frontal-central cortex, as well as significantly increased interhemispheric coherence of theta activity across central and posterior regions. Concurrent reaction time studies conducted in our laboratory suggest that very long duration cumulative marihuana exposure might be associated with slowed cognitive processing.

Somatic dysfunction increase during caffeine withdrawal.

The authors studied the effects of caffeine withdrawal on 14 subjects at baseline and during a 4-day period of abstinence from caffeine. They studied the results from quantitative electroencephalograms performed on these subjects and gauged any changes that may have been evoked during this withdrawal period. The participants were also evaluated for the occurrence of somatic dysfunctions. Examinations for the presence of somatic dysfunctions were performed on the participants before caffeine cessation and on Days 1, 2 and 4 of abstinence. Results showed that the number of somatic dysfunctions increased significantly during the process of caffeine withdrawal.

Decreased multi-band posterior interhemispheric coherence with a lipoma on the corpus callosum: a case report of a possible association.

The corpus callosum plays a role in mediating interhemisphere communication. Coherence may be a quantitative EEG-based measure of this communication. The present report is of a female schizophrenic patient with a marked coherence deficit in the temporal-parietal-occipital region involving multiple frequency bands. An MRI scan of her brain revealed a lipoma involving the splenium of the corpus callosum. It is speculated that this lipoma may have caused a physical impingment on or developmental aberration of adjacent callosal fibers, resulting in the observed coherence deficit. Further studies of coherence measures in patients with collosal lipomas are proposed.

Early and middle latency evoked potentials in medically and psychiatrically normal daily marihuana users: a paucity of significant findings.

The use of evoked potentials to study CNS effects of marihuana (THC) have produced inconsistent findings. Our previous pilot studies suggested that auditory P300 latencies and amplitudes, auditory P50 and somatosensory P30 amplitudes and brainstem auditory evoked potential latencies were altered in THC users. Because these findings were flawed by uncontrolled psychiatric diagnostic and medication variables, we undertook a controlled investigation of screened medically and psychiatrically normal THC users and controls. When age effects were controlled, THC related alterations of brain stem and both auditory and visual P300 responses could not be seen. This report extends our analyses to other auditory, somatosensory and visual evoked potentials. With the possible exception of an elevated auditory P50 amplitude, significant evoked potential correlates to daily THC use were not seen when normals were studied and age effects controlled.

Does caffeine cessation increase firing rates of diffuse paroxysmal slowing dysrhythmia? A serendipitous observation.

As part of a quantitative EEG study of caffeine withdrawal a serendipitous observation suggested that individuals with Diffuse Paroxysmal Slowing (a minor EEG dysrhythmia) in their baseline resting EEGs had an increased firing rate of this pattern while undergoing a period of caffeine abstinence. For all EEGs, individual bursts of Diffuse Paroxysmal Slowing were identified by consensus rating and the firing rate for this pattern expressed as the number of bursts per 10 minutes of alert waking activity. The firing rate of this pattern was seen to increase markedly during 4 days of verified abstinence and to return to baseline or lower than baseline levels following reintroduction of caffeine. Some possible implications of this phenomenon are discussed.

Topographic quantitative EEG measures of alpha and theta power changes during caffeine withdrawal: preliminary findings from normal subjects.

Neurophysiological consequences of withdrawal from caffeine are poorly understood. In particular, quantitative studies of EEG changes that may occur during the period of caffeine abstinence in caffeine dependent individuals have not been reported. In this pilot study, 13 physically- and psychiatrically-normal caffeine users were asked to abstain from caffeine for a period of 4 days. Quantitative EEGs were obtained prior to stopping caffeine and on Days 1, 2, and 4 of the caffeine abstinence period. Results indicated that significant increases in alpha and theta absolute power accompany the caffeine withdrawal process with return to the pre-abstinent EEG levels when caffeine usage is resumed. The implications of these findings are discussed with special reference to the possible need to control for the variable of caffeine usage in quantitative EEG studies of other phenomena.

Auditory and visual P300 event related potentials are not altered in medically and psychiatrically normal chronic marihuana users.

Attempts to use Event Related Potentials, particularly the cognitive or P300 evoked potential, as measures of CNS effects of THC use have been infrequent and have produced inconsistent results. We published a pilot study in which psychiatric patient THC users had significantly prolonged auditory P300 latencies and reduced amplitudes as contrasted with non-users. Because psychiatric diagnoses and medication effects could not be controlled, we repeated the study with medically and psychiatrically normal subjects selected with extremely stringent exclusion criteria and screening procedures. P300 latency differences between THC users and controls were not detected. Using all subjects, THC users displayed reduced auditory and visual P300 amplitudes. However, when age differences between THC users and controls were removed, all significant P300 amplitude differences were removed as well. The contaminating effect of using psychiatric patients in THC research is discussed and the importance of using carefully screened normal subjects in studies of neurophysiological abuse drug effects is stressed.

Habituation and motion sickness.

The vestibular, cerebellar, and reticular systems are central in importance, in motion sickness and habituation, to the effects of motion. Nuclear medicine single photon emission computed tomography (SPECT) studies of cerebral blood flow and power spectral electroencephalographic recordings during motion sickness were used to determine alterations in the central nervous system. The rotating chair with and without visual stimulation was used to study the rate of habituation and the effect of antimotion sickness medications on this rate. An increase of theta waves over the frontal cortex indicated a decreased activation of the higher centers during motion sickness. Motion sickness also produces an increase of blood flow in the central cerebellum that has connections to the reticular system. This increase in cerebellar activity is relayed to the reticular system whereby neural recruitment builds up to trigger the vomiting center, producing motion sickness. Habituation may be a conditioned compensatory activation of the reticular neurons that prevents this disruption of normal activation. The rate of habituation when motion sickness was prevented by scopolamine was slowed, indicating that, if the central nervous system is not challenged by disruption of normal activation, it does not produce the compensatory reactions that result in habituation.