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To date, pain perception is thought to be a creative process of modulation carried out by an interplay of pro- and anti-nociceptive mechanisms. Recent research demonstrates that pain experience constitutes the result of top-down processes represented in cortical descending pain modulation. Cortical, mainly medial and frontal areas, as well as subcortical structures such as the brain stem, medulla and thalamus seem to be key players in pain modulation. An imbalance of pro- and anti-nociceptive mechanisms are assumed to cause chronic pain disorders, which are associated with spontaneous pain perception without physiologic scaffolding or exaggerated cortical activation in response to pain exposure. In contrast to recent investigations, the aim of the present study was to elucidate cortical activation of somatoform pain disorder patients during baseline condition. Scalp EEG, quantitative Fourier-spectral analyses and LORETA were employed to compare patient group (N = 15) to age- and sex-matched controls (N = 15) at rest. SI, SII, ACC, SMA, PFC, PPC, insular, amygdale and hippocampus displayed significant spectral power reductions within the beta band range (12-30 Hz). These results suggest decreased cortical baseline arousal in somatoform pain disorder patients. We finally conclude that obtained results may point to an altered baseline activity, maybe characteristic for chronic somatoform pain disorder.

Previous studies have shown abnormal electroencephalography (EEG) in Huntington's disease (HD). The aim of the present investigation was to compare quantitatively analyzed EEGs of HD patients and controls by means of low-resolution brain electromagnetic tomography (LORETA). Further aims were to delineate the sensitivity and utility of EEG LORETA in the progression of HD, and to correlate parameters of cognitive and motor impairment with neurophysiological variables. In 55 HD patients and 55 controls a 3-min vigilance-controlled EEG (V-EEG) was recorded during midmorning hours. Power spectra and intracortical tomography were computed by LORETA in seven frequency bands and compared between groups. Spearman rank correlations were based on V-EEG and psychometric data. Statistical overall analysis by means of the omnibus significance test demonstrated significant (p < 0.01) differences between HD patients and controls. LORETA theta, alpha and beta power were decreased from early to late stages of the disease. Only advanced disease stages showed a significant increase in delta power, mainly in the right orbitofrontal cortex. Correlation analyses revealed that a decrease of alpha and theta power correlated significantly with increasing cognitive and motor decline. LORETA proved to be a sensitive instrument for detecting progressive electrophysiological changes in HD. Reduced alpha power seems to be a trait marker of HD, whereas increased prefrontal delta power seems to reflect worsening of the disease. Motor function and cognitive function deteriorate together with a decrease in alpha and theta power. This data set, so far the largest in HD research, helps to elucidate remaining uncertainties about electrophysiological abnormalities in HD.

Huntington's disease (HD) is a devastating neurodegenerative disorder with prominent motor and cognitive decline. Previous studies with small sample sizes and methodological limitations have described abnormal electroencephalograms (EEG) in this cohort. The aim of the present study was to investigate objectively and quantitatively the neurophysiological basis of the disease in HD patients as compared to normal controls, utilizing EEG mapping. In 55 HD patients and 55 healthy controls, a 3-min vigilance-controlled EEG (V-EEG) was recorded during midmorning hours. Evaluation of 36 EEG variables was carried out by spectral analysis and visualized by EEG mapping techniques. To elucidate drug interference, the analysis was performed for the total group, unmedicated patients only and between treated and untreated patients. Statistical overall analysis by the omnibus significance test demonstrated significant (p < 0.01 and p < 0.05) EEG differences between HD patients and controls. Subsequent univariate analysis revealed a general decrease in total power and absolute alpha and beta power, an increase in delta/theta power, and a slowing of the centroids of delta/theta, beta and total power. The slowing of the EEG in HD reflects a disturbed brain function in the sense of a vigilance decrement, electrophysiologically characterized by inhibited cortical areas (increased delta/theta power) and a lack of normal routine and excitatory activity (decreased alpha and beta power). The results are similar to those found in other dementing disorders. Medication did not affect the overall interpretation of the quantitative EEG analysis, but certain differences might be due to drug interaction, predominantly with antipsychotics. Spearman rank correlations revealed significant correlations between EEG mapping and cognitive and motor impairment in HD patients.

Different psychiatric disorders, such as schizophrenia with predominantly positive and negative symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function, which in many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. This is supported by 3-dimensional low-resolution brain electromagnetic tomography (LORETA), which identifies regions within the brain that are affected by psychiatric disorders and psychopharmacological substances.

Rationale: Daytime fatigue, which at the neurophysiological level is due to vigilance decrements, is a frequent complaint in postmenopausal women., Objectives: In a three-arm, 2-month, parallel group-design study, vigilance-promoting effects of a novel continuous combination (=Climodien 2/3) of estradiol valerate (EV; 2 mg) and dienogest (DNG; 3 mg) were compared with the effects of both EV alone and placebo in 55 insomniac, postmenopausal syndrome patients., Methods: Low-resolution brain electromagnetic tomography (LORETA) was undertaken to identify the cerebral target regions of hormone replacement therapy., Results: An omnibus significance test revealed Climodien to increase activity in 882 of 2,394 voxels in the alpha-2 band, followed by 733, 706, and 664 voxels in the beta-2, beta-1, and beta-3 bands, and 509 voxels in the delta band, whereas 2 mg EV alone did not produce a significant suprathreshold activity. Current density increased predominantly in the right hemisphere, which had already been described in the literature as the center of the vigilance system. In the fast alpha range, which plays a major role in the context of vigilance, increased activity was found in the right prefrontal, temporal, and superior parietal cortices, i.e., those brain areas of the right-sided fronto-parietal neuronal network that are responsible for sustained attention. A further activity increase was seen in the anterior cingulate gyrus associated with attentional control and conflict monitoring. The right temporal lobe showed increased current density in all frequency bands., Conclusions: Electroencephalographic tomography (LORETA) identified the right-hemispheric vigilance system as the target region of Climodien.

The aim of the present study was to investigate the role of EEG mapping as an objective and quantitative measure of vigilance in untreated and modafinil-treated narcoleptics, and compare it with the conventional neurophysiological method of the Multiple Sleep Latency Test (MSLT) and the subjective Epworth Sleepiness Scale (ESS). In 16 drug-free narcoleptics and 16 normal controls a baseline 3-min vigilance-controlled EEG (V-EEG) and a 4-min resting EEG (R-EEG) were recorded during midmorning hours. Thereafter, in a double-blind, placebo-controlled crossover design, patients were treated with a 3-week fixed titration of modafinil (200, 300, 400 mg) and placebo. EEG-mapping, MSLT and ESS measures were obtained before and at the end of the third week of therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant EEG differences between untreated patients and controls in the resting condition only (R-EEG). Subsequent univariate analysis revealed an increase in absolute and relative theta power, a decrease in alpha-2 and beta power as well as a slowing of the dominant frequency and the centroids of the alpha, beta and total power spectrum and thus objectified a vigilance decrement in narcolepsy. Modafinil 400 mg/d significantly improved vigilance as compared with placebo (p < or = 0.01), inducing changes opposite to the aforementioned baseline differences (key-lock principle). The MSLT and the ESS also improved under modafinil as compared with placebo, but changes were less consistent. Spearman rank correlations revealed the highest correlations between EEG mapping and the ESS, followed by those between EEG mapping and the MSLT, while the lowest correlation was found between the MSLT and the ESS. In conclusion, EEG mapping is a valuable instrument for measuring vigilance decrements in narcolepsy and their improvement under psychostimulant treatment.

Recent studies have suggested an information-processing bias in social phobia (SP). Little is known about the electrophysiological correlates of anxiety in SP. The aim of the present study was to investigate the quantitative electroencephalogram (EEG) in 25 drug-free patients with SP as compared with age- and sex-matched normal controls and to correlate anxiety and depressive symptoms with EEG data. EEG was recorded under vigilance-controlled and resting conditions. The Spielberger State and Trait Anxiety Scale (STAI) and the Beck Depression Inventory (BDI) were administered to assess anxiety and depression levels. Multivariate analysis of variance revealed significant differences between patients and controls, specifically frontopolarly and right centrally. Statistical analysis demonstrated a decrease in absolute and relative delta, theta power, alpha-adjacent slow-beta and fast beta power and an increase in absolute and relative intermediate beta power, as well as an acceleration of the total centroid and a slowing in beta centroid and its variability. Trait anxiety and depression scores correlated positively with the dominant alpha frequency and the alpha centroid, and negatively with absolute theta and slow alpha power as well as with the centroid of the delta/theta frequency band. In conclusion, EEG mapping in patients with SP revealed significant differences from normal controls suggesting a hyperarousal as a pathogenetic factor of anxiety.

Aims: Early clinical electroencephalographers reported that low-voltage fast desynchronized patterns were frequently seen in chronic alcoholism, suggesting hyperarousal of the central nervous system (CNS). The aim of the present study was to investigate the brain function of drug-free, detoxified alcoholics, and compare this with that of normal controls, utilizing computerized quantitative EEG analysis and subsequent EEG mapping. Moreover, differences between patients relapsing or abstaining during 6 months of relapse prevention therapy, pharmacologically supported by either flupentixol decanoate 10 mg or placebo i.m. every 2 weeks, were determined., Methods: 22 drug-free, detoxified patients (15 men, seven women) aged between 27 and 58 (mean 41.5 +/- 8.1) years, diagnosed as alcohol-dependent (ICD-10: F10.23) were included in the study. They were subdivided into abstainers (n = 11) and relapsers (n = 11), and matched with normal healthy controls according to age (mean 41.5 +/- 8.4 years) and sex. A 3-min vigilance-controlled EEG (V-EEG) was obtained and analysed off-line by multi-lead EEG power spectral analysis and subsequent mapping methods., Results: The drug-free, detoxified, alcohol-dependent patients showed, as compared with controls, aberrant brain function characterized by a decrease in delta and slow alpha and an increase in beta activity as well as an acceleration of the total centroid. These findings were more pronounced in relapsing than in abstaining patients. After 6 months of treatment, abstaining patients showed an increase in slow activity, a decrease in fast alpha, an acceleration of the delta/theta centroid and a deceleration of the alpha centroid, reflecting a normalization of brain function., Conclusion: EEG maps of alcohol-dependent patients differ significantly from those of normal controls and patients suffering from other mental disorders and thus EEG mapping may be used for diagnostic purposes. Moreover, the quantitative EEG may also be of prognostic value as relapsing patients differ from abstaining ones, since they show a significantly more pronounced hyperarousal of the CNS.

Cognitive event-related potentials were recorded from 17 EEG leads in an auditory two-tone paradigm in 43 patients aged 51-79 years with the diagnosis of age-associated memory impairment (AAMI), in age-and sex-matched normal controls and in a control group 10 years older than the AAMI patients. In addition to P300 latencies, amplitudes and topographies, three-dimensional current density distribution utilizing low-resolution brain electromagnetic tomography (LORETA) was computed. P300 latency was delayed and P300 amplitude was reduced in both AAMI and older subjects. Topographically this amplitude reduction was most pronounced frontally. LORETA revealed medial (frontal and parietal) and lateral (dorso- and ventrolateral prefrontal, middle/superior temporal, posterior superior temporal/inferior parietal) sources. Significant reductions in LORETA source strength in normal aging and in AAMI were found mainly medially frontally, right dorsolaterally prefrontally and right inferiorly parietally. Since these anatomically highly interconnected brain regions in the right hemisphere are part of a network associated with sustained attention, the results speak for a decline in attentional resource capacity in AAMI patients and elderly subjects.

Background: S-Adenosyl-L-methionine (SAMe, or ademetionine) is a naturally occurring molecule used as both a nutraceutical and a pharmaceutical to treat depression., Objective: The central mode of action of SAMe was investigated in 20 healthy volunteers by mapping of electroencephalograms (EEGs) and event-related potentials (ERPs) and low-resolution brain electromagnetic tomography (LORETA)., Design: In an acute and subacute, double-blind, placebo-controlled, crossover study, subjects received in random order infusions of 800 mg SAMe and placebo for 7 d, with a washout period of 3 wk between the 2 treatment periods. EEG recordings were made 0, 1, 3, and 6 h after and ERP recordings were made 0 and 1 h after the drug infusions on days 1 and 7., Results: Multivariate analyses of variance and Hotelling T2 tests showed significant acute and subacute encephalotropic effects of SAMe compared with placebo. Acute pharmaco-EEG changes were typical of classic antidepressants of the thymoleptic type; subacute alterations were typical of cognition enhancers. Regarding ERPs, standard N1 and P2 latencies were shortened, and target P300 latencies were lengthened. N1 amplitudes increased after subacute treatment, and temporooccipital P300 amplitudes increased after the acute dose. Similar changes were described for antidepressants. LORETA showed that the N2 source strength increased in both the left and the right temporal lobes, whereas the P300 source strength increased in the dorsolateral prefrontal regions and decreased in the ventral limbic regions., Conclusion: EEG-ERP mapping identified SAMe as an antidepressant. LORETA targeted brain regions crucial in the therapeutic efficacy of antidepressants.

Restless legs syndrome (RLS) is a sensorimotor movement and sleep disorder with a high prevalence. While the sleep disturbance due to RLS has been studied quite well polysomnographically, little is known about the electrophysiological function during daytime. The aim of the present study was to investigate the diurnal quantitative EEG and clinical symptomatology in 33 drug-free RLS patients as compared with age- and sex-matched normal controls. Investigations comprised brain mapping of the vigilance-controlled EEG as well as completion of the Zung Self-Rating Depression Scale, the Zung Self-Rating Anxiety Scale, the Quality of Life Index, the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale for evaluation of clinical symptomatology. Statistical analysis demonstrated an increase in absolute delta and absolute and relative alpha-2 power, a decrease in absolute and relative alpha-1 power, an acceleration of the dominant frequency and the alpha centroid, and a slowing of the delta/theta centroid, as well as a non-significant attenuation in total power. These findings are characteristic of dissociated vigilance changes described in depression. Indeed, RLS patients demonstrated significantly higher depression and anxiety scores, lower quality of life and deteriorated sleep quality. The score of the Epworth Sleepiness Scale was not elevated, in contrast to the increased daytime sleepiness observed in other highly prevalent organic sleep disorders (e.g. sleep apnea). In conclusion, daytime EEG mapping revealed neurophysiological correlates of depression in RLS, which was confirmed by self-ratings at the symptomatological level.

Clinically well-defined diagnostic subgroups of mental disorders, such as schizophrenia with predominantly plus and minus symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multiinfarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show electroencephalogram (EEG) maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and nonsedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function compared with placebo, in which many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. This is supported by low-resolution brain electromagnetic tomography (LORETA), which identifies brain regions affected by psychiatric disorders and psychotropic drugs.

Middle latency and late components of event-related brain potential (ERPs) are closely related to perceptual and cognitive information processing, respectively. In a double-blind, placebo-controlled study, the acute effects of lorazepam (2 mg), haloperidol (3 mg), methylphenidate (20 mg) and citalopram (20 mg) on ERP latencies, amplitudes, topographies and tomographies were investigated in 20 healthy subjects of 23-34 years of age. After automatic artifact minimization and rejection, standard N1 and P2 and target N2 and P300 components were determined. The tranquilizer lorazepam prolonged P300 latency, which indicates an impairment of stimulus evaluation time. Low-resolution brain electromagnetic tomography (LORETA) revealed decreases in N1 and P300 source strength in those brain regions with relevant generators of these components, which reflects impairments of attentional and cognitive processing resources. The neuroleptic haloperidol decreased N1 and P300 source strength predominantly in those brain regions not involved in the generation of these components, suggesting a shift of resources. The psychostimulant methylphenidate increased P300 source strength in brain regions with major P3b generators, indicating increases in energetic resources associated with stimulus encoding. The antidepressant citalopram increased N1 and P3b source strength in multiple brain regions specifically in the left prefrontal cortex, a brain region in which reduced blood flow and metabolism was found in depressed patients.

Utilizing computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (EEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ: the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG profiles and maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described in this paper. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects, therapeutic efficacy and pharmacokinetic and pharmacodynamic data will be discussed. In recent times, imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be demonstrated for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently.

Daytime tiredness and daytime sleepiness are frequent complaints occurring in 29% and 14% of the Austrian population. Epidemiological studies demonstrate a high comorbidity between nonorganic hypersomnia and mental disorders. Especially comorbidity with affective disorders increases steadily from the general population over primary to tertiary care settings. Diagnostic criteria of nonorganic hypersomnia have been described in the International Classification of Diseases (ICD-10). Nonorganic hypersomnia can be primary or associated with a number of psychiatric disorders such as reaction to severe stress or adjustment disorders, affective disorders, other functional disorders, tolerance to or withdrawal of CNS-stimulating substances and chronic use of CNS-sedating substances. Diagnostic procedures comprise case history and symptom evaluation, sleep-specific and supplementary investigations. Concerning the latter, this article will focus on sleep questionnaires, vigilance and psychological tests as well as CNS investigations. Therapy of nonorganic hypersomnia rests on 3 pillars: psychological, somatic and pharmacological treatment. In view of the wide variety of psychiatric causes, resulting in a number of therapeutic options, it seems desirable that apart from subjective clinical assessment also objective methods be used in diagnosis and treatment. On the neurophysiological level objective measures can be obtained by means of EEG mapping during the day and polysomnography at night. Different mental disorder patients show different brain activity patterns as compared with normal controls and different classes of psychotropic substances cause different changes in neurophysiological variables. The fact that the changes in electrophysiological brain activity caused by mental disorders are exactly opposite to those induced by the psychotropic drugs used for their treatment suggests a key-lock principle in the diagnosis and treatment of nonorganic hypersomnia.

There is evidence that daytime tiredness is caused by apnea/hypopnea with oxygen desaturation and/or by sleep fragmentation due to arousals. The aim of this study was to investigate objective and subjective sleep and awakening quality and daytime vigilance--objectified by midmorning mapping of vigilance-controlled EEG (V-EEG)--in sleep apnea patients (N: 18), as compared with age- and sex-matched normal controls (N: 18) as well as to correlate nocturnal respiratory distress and arousals to daytime brain function. Statistical analyses demonstrated a deterioration in subjective and objective sleep and awakening quality in apnea patients. Midmorning V-EEG mapping in apnea patients exhibited less total power, more delta and theta, less alpha and beta activity, as well as a slower dominant frequency and centroid of the total activity compared to controls, which suggests a vigilance decrement. The Spearman rank correlation between 6 polysomnographically registered respiratory variables and 36 diurnal quantitative EEG measures demonstrated the following: the higher the apnea, apnea-hypopnea, snoring and desaturation indices and the lower the minimum and average low oxygen saturation, the more pronounced was diurnal tiredness. Eleven arousal measures based on ASDA criteria showed the following significant correlations: the higher the nocturnal arousal index and the more arousals due to hypopneas, the greater was daytime tiredness. On the other hand, the greater the average frequency change during arousals and the more spontaneous arousals, the better was daytime vigilance. Our findings show that, in contrast to the lengthy Multiple Sleep Latency (MSLT) and Maintenance of Wakefulness (MWT) tests which evaluate sleep pressure under resting conditions conducive to sleep, V-EEG mapping provides a brief objective measure of a sleep apnea patient's daytime tiredness under conditions of wakefulness more appropriate to reflect the patient's everyday life.

In Type I diabetic patients with history of recurrent severe hypoglycaemia, a more rapid decrease in vigilance (slowing of brain function) during hypoglycaemia in comparison to patients without history of such events was found. Our aims were: (1) to study EEG parameters of vigilance in non-hypoglycaemic state in representative groups of Type I diabetic patients with and without previous recurrent severe hypoglycaemia; and (2) to compare them with non-diabetic controls. A vigilance-controlled EEG mapping (10-20 system, significance probability maps) was performed in a non-hypoglycaemic state (blood glucose 4.0-10.0 mmol/l) in a group of 13 Type I diabetic patients with a history of recurrent severe hypoglycaemia and compared to that of 14 Type I diabetic patients without history of severe hypoglycaemia, matched for HbA1c, age and gender, and to age- and gender-matched non-diabetic controls. When compared to non-diabetic controls, hypoglycaemia patients demonstrated a reduction in absolute power in beta band (13-35 Hz) and slowing of centroid frequencies of beta and total frequency bands (1.3-35 Hz) (up to P < 0.01), whereas patients without history of severe hypoglycaemia showed only a borderline reduction of absolute power in delta (1.3-3.5 Hz) band. Deceleration in hypoglycaemia patients versus those without recurrent hypoglycaemia was most remarkable (P < .01) in centroid frequency of total frequency band. Patients with history of recurrent severe hypoglycaemia demonstrated in non-hypoglycaemic state significantly reduced vigilance when compared to the group without hypoglycaemia history and to the controls, as well. Lower vigilance may be at least in part responsible for impaired hypoglycaemia perception in these patients, but, as it resembles EEG patterns seen in pathologic ageing, it might also represent a consequence of recurrent episodes of severe hypoglycaemia.

The application of an automatic sleep spindle detection procedure allowed the documentation of the topographic distribution of spindle characteristics, such as number, amplitude, frequency and duration, as a function of sleep depth and of recording time. Multichannel all-night EEG recordings were performed in 10 normal healthy subjects aged 20-35 years. Although the interindividual variability in the number of sleep spindles was very high (2.7 +/- 2.1 spindles per minute stage 2 sleep), all but two subjects showed maximal spindle activity in centro-parietal midline leads. Moreover, this topography was seen in all sleep stages and changed only slightly--to a more central distribution--towards the end of the night. On the other hand, slow (11.5-14 Hz) and fast (14-16 Hz) spindles showed a completely different topography, with slow spindles distributed anteriorly and fast spindles centro-parietally. The number of sleep spindles per min was significant depending on sleep stages, with the expected highest occurrence in stage 2, and on recording time, with a decrease in spindle density from the beginning towards the end of the night. However, spindle amplitude, frequency and individual duration was not influenced by sleep depth or time of the night.

Objective and subjective sleep and awakening quality as well as daytime vigilance of insomniac patients with generalized anxiety disorder (GAD) were investigated, as compared with normal controls. Forty-four outpatients (25 females, 19 males), aged 24-65 (mean 43) years, diagnosed with non-organic insomnia (ICD-10: F 51.0), related to mild GAD (F 41.1), with a Hamilton anxiety (HAMA) score of 22 +/- 6 and a Zung self-rating anxiety (SAS) score of 37 +/- 6 were included. After 1 adaptation night, sleep induction, maintainance and architecture were measured objectively by polysomnography, subjective sleep and awakening quality were assessed by self-rating scales and visual analog scales, objective awakening quality was measured by a psychometric test battery, and diurnal tiredness was measured by a 3-min vigilance-controlled EEG (V-EEG) and a 4-min resting EEG mapping. In polysomnography patients demonstrated-as compared with normals-significantly increased wake time during the total sleep period and more early-morning awakening, decreased total sleep and sleep efficiency. Subjective sleep quality was deteriorated as well, as were well-being, drive, mood, and wakefulness in the morning. In noopsychic performance, GAD patients did rather well in attention, concentration, attention variability, and numerical memory, while fine-motor activity and reaction time were deteriorated. In psychophysiology, critical flicker frequency was decreased in the morning, while muscle strength, blood pressure and pulse rate showed no differences. EEG mapping during the late morning hours (10.00-12.00 h) demonstrated hypervigilance in the V-EEG, while in the resting recording an increased sleep pressure was detected. The latter was correlated significantly to the SAS score, but less so to the observer-rated Hamilton anxiety score. Our findings suggest that CNS hypervigilance and hyperarousal, as actual symptoms of GAD, lead to nocturnal insomnia, which in turn may cause-as a consequence of sleep pressure not slept off-diurnal tiredness.

In a double-blind, placebo-controlled, crossover study, the encephalotropic and psychotropic properties of single oral doses of the novel neuroprotective agent, riluzole, were investigated utilizing EEG mapping and psychometry. Twenty healthy young volunteers received randomly at weekly intervals, placebo, 50, 100 and 200 mg riluzole. EEG recordings and evaluation of 9 noopsychic and 5 thymopsychic variables were carried out at 0, 2, 4, 6 and 8 h after oral drug administration. EEG maps on the multivariate analysis demonstrated that all three doses induced significant changes in human brain function, as compared with placebo, between 2 and 8 h, with effect only increasing slightly with dose. EEG maps on univariate analysis demonstrated generally an increase of delta/theta, decrease of alpha and beta power, as well as a slowing of the centroid of the total power spectrum, which suggests sedative properties of the drug. Only after the two highest doses at 6 h were some different findings observed. Multivariate statistics on psychometry failed to show any significant effects on the noopsyche, while for the thymopsyche, all three doses of riluzole produced a deterioration. The latter was characterized by a decrease in drive and wakefulness as well as deterioration in well-being, mood and affectivity. Thus, under normoxia, in all three doses riluzole produced neurophysiologically a sedative effect, accompanied at the behavioral level by a deterioration in the thymopsyche, which may be expected from a drug with antiglutamatergic effects in normals.

In a double-blind, placebo-controlled study, the antihypoxidotic properties of the novel neuroprotective agent, riluzole, were investigated utilizing blood gas analysis, EEG mapping and psychometry under a transient, reversible, hypoxic hypoxidosis. The latter was induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found at 6000 m altitude), which was inhaled for 23 min under normobaric conditions by 20 healthy, young volunteers. They randomly received, after an adaptation session, single oral doses of placebo, and 50, 100 and 200 mg riluzole. Evaluation of blood gases, EEG mapping and psychometry were carried out 0, 2, 4, 6 and 8 h postdrug, each time under the 23-min hypoxia. Blood gas analysis demonstrated a drop in PO2 from 106 to 37 and 36 mmHg, in PCO2 from 35 to 31 and 31 mmHg at 14 and 23 min of inhalation, respectively, while pH increased from 7.43 to 7.48 and 7.48. Base excess and standard bicarbonate remained stable. EEG mapping exhibited under hypoxia a marked increase of delta/theta, decrease of alpha and an increase of superimposed beta activity, as well as a slowing of the centroid of the total activity, which reflects deterioration of vigilance. Riluzole in lower doses and at early hours after higher doses did not attenuate this hypoxia-induced vigilance decrement, while with higher doses (100-200 mg) in later recording periods (6-8 h) brain protection occurred. As compared with placebo, delta/theta power increased at 2-8 h after 50 mg riluzole and up to 4 h after 100 mg riluzole, while a decrease occurred at 4 and 8 h after 100 mg and at 6-8 h after 200 mg. Alpha power showed no changes after 50 mg, an increase at 2 and 8 h after 100 mg and a decrease at 4 h after 200 mg, with no changes thereafter. Beta power decreased at various times after all three doses. At the behavioral level, hypoxic hypoxidosis induced a deterioration of the noopsyche, which was not mitigated by riluzole. In regard to the thymopsyche, there was even a slight deterioration after all three doses, as compared with placebo.

In a double-blind, placebo-controlled, cross-over trial, the antihypoxidotic properties of BMS-181168 (previously BMY 21502)--a 1-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4-piperidinyl]methyl]-2- pyrrolidinone alleviating impairment of learning and memory in the animal--were studied utilizing EEG mapping under an experimental hypoxic hypoxidosis. The latter was induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found at 6000 m altitude), which was inhaled for 23 minutes under normobaric conditions by 16 healthy male volunteers (aged 23-35 years, mean 27.2 years). After an adaptation session, they received in randomized order at weekly intervals oral single doses of placebo, or of 100 mg, 200 mg, and 400 mg BMS-181168. Evaluation of blood gases (PO2, PCO2, SO2), adverse events, and EEG mapping was carried out prior to drug administration and 2, 4, 6 and 8 hours post-drug, on each occasion under normoxic and transient hypoxic conditions. Hypoxemia was controlled by drawing arterialized capillary blood samples from the earlobes after hyperemization of the latter (after 0, 14, and 23 minutes of hypoxic gas inhalation) and by oximetry. After 23 minutes of inhalation, analysis showed a drop in PO2 from 98 to 48 mm Hg, in PCO2 from 41 to 31 mm Hg, and in SO2 from 97 to 80%. Descriptive statistical analyses of EEG mapping data demonstrated under hypoxia/placebo conditions an increase in delta/theta activity and a decrease in alpha activity as well as a slowing of the delta/theta centroid and an increase in the alpha and beta centroid, which suggests a marked deterioration in physiological vigilance.(ABSTRACT TRUNCATED AT 250 WORDS)

The topographic distributions of absolute delta and theta powers were used to classify demented patients and normals by means of z statistics, discriminant analysis and artificial neural networks (NN). The data were taken from two psychopharmacological studies in mildly to moderately demented patients (111 and 96 patients for studies I and II, respectively) and from 56 normal healthy controls. All patients were diagnosed according to DSM-III criteria and were free of medication for at least 2 weeks. The NN used was a strictly layered feed-forward network with complete connections. The z-transformed absolute power values in the combined delta and theta frequency range at 17 electrodes, recorded in a 3 min vigilance-controlled EEG with eyes closed, were used as input. After having trained the NN successfully by backpropagating of errors, the generalization test with independent data results in a classification performance of 90% determined by "relative operating characteristic" analysis. The NN out-performed z statistics and discriminant analysis. This high percentage of correct classifications may justify the development of further application of NNs based on topographic EEG data.

Topographic aspects of all night sleep EEG were investigated in 10 healthy volunteers (age 20-35 years). EEG brain maps showed an increase of delta power from stage 1 to 4, a decrease of alpha power most pronounced parieto-occipitally and a slowing of the dominant alpha frequency. Differences of EEG power in different sleep stages (as compared to wakefulness) are displayed topographically. Analysis of the course of stage 2 showed an increase of delta power and a decrease of theta power in the first sections of the night, and an increase of beta power later in the night.

In a double-blind, placebo-controlled, crossover study, the blood levels and pharmacodynamic properties of single oral doses of 15 and 30 mg d-fenfluramine (d-FEN) and 30 mg l-fenfluramine (l-FEN) were investigated as compared with 50 mg chlorpromazine (CPZ) and 20 mg d-amphetamine (AMPH) utilizing pharmaco-electroencephalogram (EEG) mapping as well as prolactin and safety assessments. Eighteen healthy young volunteers randomly (Latin square) received at weekly intervals the different treatments. Blood sampling to determine AMPH, FEN and its main metabolite norFEN, as well as plasma prolactic levels, EEG recordings and evaluation of hemodynamics and spontaneous side effects were carried out at 0, 2, 4, 6 and 8 h after drug administration. Before and 24 h after drug intake morning subjective sleep quality was also assessed. Blood level investigations after d-FEN demonstrated dose-dependent blood concentrations peaking after 2-4 h and slowly declining thereafter. NorFEN, the main metabolite, exhibited a steady increase in plasma concentrations up to the 8th h. After l-FEN a similar time course was obtained but the concentrations of the parent compound were higher and those of the metabolite lower in comparison with the d-isomer, suggesting stereoselective kinetics. d-FEN induced significant and dose-dependent pharmaco-EEG changes characterized by a decrease in total power and combined delta/theta activity and by an increase in beta activity and an acceleration of the centroid of the total activity with no changes in alpha power, which were quite different from those of the reference drugs. l-FEN produced only minimal changes (of the same type as d-FEN). 50 mg CPZ and 20 mg d-AMPH produced significant changes as compared to placebo but with quite opposite patterns, the former exhibiting the typical sedative-neuroleptic profile and the latter that typical of psychostimulants. Dose/treatment- and time-efficacy calculations based on all variables showed in the V-EEG that only 30 mg d-FEN and 50 mg CPZ were different from placebo (with peak effects in the 8th and 4th h, respectively), while in the resting condition (R-EEG) all drugs/dosages but 30 mg l-FEN differed from placebo (with the peak effect occurring in the 4th-6th h after d-FEN and l-FEN, in the 2nd h after CPZ and in the 4th-6th h after AMPH). Plasma prolactin levels were only modified by CPZ (maximal increase in the 2nd h).(ABSTRACT TRUNCATED AT 400 WORDS)

Computed tomography (CT), electroencephalograms (EEG), clinical and psychometric data were obtained in 96 mildly to moderately demented patients (72 women, 24 men), aged 61-96 years (mean 82), diagnosed according to DSM-III criteria. Patients were off drugs for at least 2 weeks and subdiagnosed according to the modified Marshall-Hachinski ischemic score and CT in 45 senile dementia of the Alzheimer type (SDAT) and 51 multiinfarct dementia (MID) patients. Evaluations were carried out before and 12 weeks after treatment with either 100 mg denbufylline BID or placebo and included EEG mapping, the Sandoz Clinical Assessment Geriatric (SCAG) score/factors, the Clinical Global Impression (CGI), the Digit Symbol Substitution Test (DSST), the Trail-Making Test (TMT) and the Digit Span Test (DS). Descriptive data analysis including confirmatory statements found delta/theta activity enhanced, alpha and beta activity reduced, total power augmented, and the centroid slowed down over various brain regions in patients as compared with controls. The two subtypes of dementia could be differentiated in some conventional EEG variables but mostly by means of power asymmetry indices. Denbufylline induced a statistically significant and clinically relevant improvement in both SDAT and MID patients, whereas after placebo this was not the case in CGI, the TMT, and the DS, with interdrug differences being significant in all primary target variables such as the CGI, MMS, SCAG, and DSST. Thus, both the degenerative and vascular type of dementia exhibited a therapeutic benefit that could be objectified at the neurophysiological level by EEG mapping in an improvement of vigilance.

Mapping of the electroencephalogram (EEG) has been found to be a valuable method in clinical neuropsychopharmacology. It is evident that careful treatment of artifacts is of utmost importance for EEG data processing, as artifacts that contaminate the EEG data can lead to spurious results. The artifact-processing method described in this article splits signal analysis into a preprocessing step, yielding individual electro-oculographic (EOG) regression factors for EOG minimization, and into a processing step, yielding target variables. The combination of avoiding, minimizing, and identifying artifacts, as well as visual checking of face validity, will help remove artifactual effects from the EEG.

In a double-blind, placebo-controlled trial, human brain function and mental performance were studied under two different degrees of hypoxia after administration of two different doses (6 mg and 9 mg) of co-dergocrine mesylate (CDM) utilizing blood gas analysis, EEG mapping and psychometry. Hypoxic hypoxidosis (i.e. impairment of cerebral metabolism due to hypoxia) was experimentally induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found in 6000 m altitude), and of 8.6% O2, 91.4% N2 (found in 7000 m altitude), which was inhaled for 23 min under normobaric conditions by 18 healthy volunteers. They received randomized after an adaptation session placebo, 6 mg and 9 mg co-dergocrine mesylate (CDM). Evaluation of blood gases, brain mapping and psychometry was carried out at 0, 2, 4, 6, 8 h after oral drug administration. Blood gas analysis demonstrated a drop in PO2 to 42 and 32 mm Hg 23 min after inhalation of the 9.8% and 8.6% gas mixture, respectively, PCO2 decreased to 32 and 31 mm Hg, pH increased to 7.46 and 7.47 and base excess increased to 0.50 and 0.90 nmol/l, respectively. EEG mapping demonstrated an increase in delta and decrease of alpha power and a slowing of the centroid over almost the whole brain. 6 mg and slightly less so 9 mg CDM attenuated this deterioration of vigilance (i.e. dynamic state of the neuronal network determining adaptive behavior). At the behavioral level, moderate hypoxia induced a deterioration of noopsychic performance, which was mitigated by 6 mg, but not by 9 mg CDM. A deepening of the hypoxia resulted in a loss of these brain protective effects of both doses. Decrement of the thymopsyche increased after both doses in the moderate hypoxic condition, while under marked hypoxia 6 mg CDM attenuated and 9 mg aggravated this deterioration. Time-wise, brain protective effects reached the level of statistical difference between the 2nd and the 6th hour. Somatic complaints like feeling dazed, giddiness and headache were mitigated dose dependently by CDM in the moderate, but not in the marked hypoxic hypoxidosis.

Amantadine is generally used in the prophylaxis of infection with influenza A, in the treatment of Parkinson's disease and in the treatment of neuroleptic side effects. In this study acute effects of amantadine infusions on event-related potentials (ERP) were studied in 20 mildly demented patients diagnosed according to DSM-III-R criteria. Each patient was treated, in randomized order, with 0.2 g amantadine-sulfate in 500 ml NaCl and 500 ml NaCl placebo, i.v. over one hour with an interval of two weeks in-between. ERPs were investigated in an auditory odd-ball paradigm before as well as 5 hours after the infusion. In addition to 17 EEG records, vertical and horizontal EOGs were recorded. After EOG-minimization and visual artifact rejection the peak latencies of the spatial average were determined by an automatic procedure. There was no effect of amantadine on ERP latencies. N1 of the non-target showed a trend towards amplitude augmentation, P2 amplitude was reduced. As compared to placebo, P300 amplitude of targets was significantly augmented by 3.1 microV (30% of pre-treatment value), confirming the hypothesis that amantadine may influence the P 300 amplitude in the sense of an improved availability of cognitive processing resources.

EEG brain mapping has been proven to be a valuable method in diagnostic and therapeutic assessment in dementia trials, because it is a readily available, inexpensive, high time-resolution method for objective and quantitative evaluation of the neurophysiological aspects of dementias. In 111 mildly to moderately demented patients diagnosed according to DSM-III as both degenerative [senile dementia of the Alzheimer type (SDAT)] and vascular [multi-infarct dementia (MID) type], we were interested in showing not only differences between SDAT and MID patients and normal controls but also the relationship between CT scans, EEG maps, clinical ratings and psychometric tests. CT measures included 10 cerebrospinal fluid (CSF) space variables as well as 17 cortical density measures (1.7 mm3 cubes, Hounsfield units). Clinical investigations consisted of the SCAG score/factors, the digit symbol substitution test, the trailmaking test and the digit span forward test. In brain maps, SDAT patients showed slightly to moderately more slow and less alpha and beta activity as well as a slowing of the dominant frequency (DF) and the centroid (C) than did normal controls. These findings were most prominent in parietal and temporal regions. MID patients exhibited markedly augmented delta/theta and attenuated alpha and beta activity and a slowing of the DF and C. These neurophysiological findings suggest a deterioration of vigilance. Differences between SDAT and MID patients were found mostly in measures concerning differences in the maps. Brain maps of correlation coefficients between CT and EEG variables demonstrated: the greater the anterior horn distance, lateral ventricle distance, and Evan's index, as well as the less cortical density, the more delta/theta and the less alpha and beta activity in the EEG. Moreover, the higher the delta/theta, the less alpha and beta activity, the higher the SCAG scores, and the worse the psychometric performance. From the pharmacological point of view, we observed a significant improvement in vigilance after administration of several nootropic drugs both in normal and pathologically aging subjects, which was associated also with improvement of psychopathometric scores. Based on multi-variante analysis of variance (MANOVA)/Hotlelling T2 we observed a drug's effect in different brain regions of MID and SDAT patients. Thus, pharmaco-EEG mapping mediates valuable information regarding if, how, when, in which dosage, and where a nootropic drug acts on its target organ--the aging human brain.

EEG brain maps obtained in 48 drug-free hospitalized schizophrenics diagnosed according to DSMIII demonstrated significant differences as compared with normal controls characterized by a decrease of alpha-1 activity, increase of beta activity and acceleration of the centroid. These findings suggest a state of sustained hyperarousal in schizophrenia. While the patients with negative schizophrenia showed a bi-temporal and frontal augmentation of delta/theta activity, patients with florid symptomatology exhibited just the opposite findings. Alpha-1 activity was attenuated, beta activity augmented in both groups with the findings more pronounced in the positive schizophrenia group. The increase of slow activity suggests an organic factor in the pathogenesis of the negative syndrome, which was supported by correlation maps between EEG measures and the apathy syndrome as measured by the AMDP system. Treatment of schizophrenics with predominantly positive symptoms with 2 different neuroleptics such as remoxipride and haloperidol resulted also in differential effects on brain activity: while haloperidol augmented delta/theta and alpha activity and decreased beta activity, remoxipride produced a decrease of slow and increase of beta activity as well as an acceleration of the centroid suggesting vigilance-promoting properties of the drug. These differential effects on the neurophysiological level were also reflected at the behavioural one evaluated by psychometry, while global clinical evaluation showed, as expected, similar improvement with both drugs (apart from extrapyramidal side effects being significantly more pronounced after haloperidol than remoxipride). Our findings suggest that brain electrical signal topography is a promising method in regard to a better understanding of pathogenesis and treatment in schizophrenia.

In a double-blind placebo-controlled study, the effects of Actovegin on cognitive event-related potentials were studied in 18 age-associated memory impairment (AAMI) patients. Actovegin is a protein-free metabolically active hemoderivative improving oxygen and glucose utilization. Each patient was treated, in randomized order, for 2 weeks with 250 ml 20% Actovegin and 250 ml placebo daily with an interval of 3 weeks in between. Psychophysiological tests were carried out by means of the Viennese Psychophysiological Test System (VPTS) before as well as 5 h after the administration of one single infusion on day 1 (acute effect), before (subacute effect) as well as after one additional superimposed infusion on day 15 (superimposed effect). There was no effect on earlier stages of information processing measured by N1 and P2 component of nontarget ERP nor on ERP latencies. However, P300 amplitude increased after acute, subacute as well as superimposed infusion of Actovegin as compared to placebo, confirming the hypothesis that nootropic drugs may influence the P300 amplitude in the sense of an improved availability of cognitive processing resources. This increase of P300 amplitude (up to 4.8 microV), seen specifically in central and parietal regions, proved to be significant in a confirmatory test.

In a double-blind, placebo-controlled parallel group trial, the therapeutic efficacy and central effects of propentofylline (HWA 285) - a xanthine derivative with neuroprotective, metabolic, hemorheologic and antithrombotic action - were studied in 190 elderly outpatients with mild to moderate chronic cognitive disturbances (mild dementia, DSM-III-R). They received after a 2-week run-in period (placebo) for 12 weeks either 3 x 300 mg propentofylline or 3 x 1 tablet placebo (given at least 1 h before meals). The verum group (n = 96, age 68 +/- 9) was comparable to the placebo group (n = 94, age 69 +/- 8) in regard to age, height, smoking, consumption of stimulating alcoholic drinks, family and living status. Clinical evaluation by the Gottfries-Brane-Steen (GBS) scale demonstrated a significant superiority of propentofylline over placebo in the total score and the four GBS factors (motor, intellectual, emotional functions and other symptoms) as well as in the clinical global impression and Mini-Mental State. Psychometric measures showed slight and significant improvement in both groups but no intergroup differences. EEG brain mapping was carried out before and after 12 weeks' treatment in the Viennese subsample involving 24 propentofylline and 24 placebo patients. Propentofylline-treated patients exhibited, as compared with placebo-treated ones, a trend towards augmentation of total power, furthermore an increase in relative delta and beta and a decrease in alpha power, an acceleration of the dominant frequency as well as a slowing of the centroid of the combined delta/theta band. The total centroid tended towards acceleration, while the centroid deviation increased significantly. These alterations reflect vigilance changes of the dissociative type and differ from those of the classical nootropics. Clinical and psychometric evaluations demonstrated changes in the same direction as in the total sample, but interdrug differences were not significant. Thus, EEG brain mapping seems to be more sensitive in objectivating central drug effects.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic effects of Actovegin--a protein-free metabolically active hemoderivative improving oxygen and glucose utilization--were investigated in age-associated memory impairment (AAMI) patients, utilizing EEG brain mapping, psychometric and psychophysiological analyses. Each patient had a treatment of 2 weeks with 250 ml 20% Actovegin and 250 ml placebo daily with an interval of 3 weeks in between (the order of drugs sequence was randomized). Pharmacodynamic evaluations were carried out 0, 2, 4, 6 and 8 h after the administration of one single infusion on day 1 (acute effect), at 0 h on day 15 (subacute effect) as well as 2, 4, 6 and 8 h after one additional superimposed infusion on day 15 (superimposed effect). EEG brain mapping demonstrated that Actovegin exerted a significant action on the human brain function as compared with placebo characterized by a decrease of delta and theta, an increase of alpha-adjacent slow beta, a decrease of fast beta, an acceleration of the centroid of the delta/theta and alpha activity, a slowing of the beta centroid and an increase of the centroid of the total activity. Topographically the encephalotropic effects were mostly pronounced in the parietal, frontocentral and temporooccipital regions. These changes are indicative of an improvement of vigilance which was proven also by psychometric investigations at the behavioral level. Actovegin improved the noopsyche mostly in regard to attention, memory and rigidity/perseveration measures. In regard to the thymopsyche an improvement was noted in mood, affectivity, well-being and sedation. Psychophysiological evaluations demonstrated an increase in CFF, skin conductance, pupillary diameter and shortening of the latency and augmentation of the amplitude of the pupillary response. Time-efficacy calculations exhibited more effect after subacute than acute administration with the pharmacodynamic maximum in the 4th h after the superimposed dose. Evaluations of pulse, blood pressure and side effects demonstrated a very good tolerability of the drug. Our present neurophysiological, psychometric and psychophysiological findings confirm earlier results obtained in elderlies with similar methodology.

The brain function of 60 patients undergoing open-heart surgery (36 patients receiving coronary artery bypass, 21 patients valve replacements, 3 both) was investigated before and 10 days after the operation utilizing topographic brain mapping of the electroencephalogram (EEG). The postoperative EEG changes were characterized by a slight delta-theta increase, an alpha decrease [especially in the fast alpha (10.5-13 Hz) band] and a beta increase in the relative power. The total power and the absolute power of the delta-theta, alpha and beta showed a decrease, the dominant frequency a significant slowing from 9.7 to 9.3 Hz. The centroid of alpha and beta activity decreased as well. These results are similar to findings obtained in patients with organic brain syndrome. The EEG changes were prominent over the left hemisphere, which may be of particular clinical relevance.

Multi-lead analysis of drug-induced changes in human brain function as monitored by the scalp-recorded electroencephalogram (EEG) and subsequent imaging of topographic pharmaco-EEG maps has become possible and practical with the advent of modern mini- and micro-computers. The present paper gives a survey about topographic analyses of pharmaco-EEG data obtained in systematic double-blind, placebo-controlled studies in normal healthy volunteers involving representative drugs of 5 different psychopharmacological classes, such as neuroleptics (chlorprothixene), antidepressants (imipramine), tranquilizers (diazepam), psychostimulants (caffeine), and antihypoxidotics/nootropics (pyritinol). The determination of cerebral bioavailability utilizing time- and dose-efficacy relations, as well as the evaluation of bioequipotency of different formulations of compounds is shown. Topographic pharmaco-EEG seems not only to confirm our previous knowledge that quantitative analysis of the human EEG in combination with certain statistical procedures ("quantitative pharmaco-EEG") is a valuable method to determine if, how, when and at which dosage a drug will be centrally effective, but also to have the potential to show effects of psychotropic drugs on the target organ--the human brain--which could not be previously picked up by single lead recordings. Topographic pharmaco-EEG imaging can be viewed as an enlargement of our armamentarium to better understand the mode of action of psychotropic drugs in human neuropsychopharmacology, as well as to monitor and (eventually) predict therapeutic efficacy in patients.

Topographic brain mapping of the electroencephalogram (EEG) is a promising new method in neuropsychiatry and neuropsychopharmacology. Rapid advances in computer technology allow on-line analysis by means of micro-computers. This paper describes an acquisition and signal analysis system for studying neurophysiological and neuropsychopharmacological aspects of human brain function. It consists of a server micro-computer functioning as an acquisition unit which is connected to a workstation micro-computer for statistical analysis and subsequent documentation of data on a printer and color plotter. According to the recommendations for standardization of data acquisition and signal analysis in pharmaco-electroencephalography, the paper mediates detailed information concerning recording and analysis equipment with special emphasis on the treatment of artifacts. Since up to now there is no normative consensus on the choice of reference conventions and interpolation algorithms, the system is designed for high flexibility to enable empirical comparisons between different methods.

In a double-blind, placebo-controlled study the pharmacokinetic and pharmacodynamic properties of a standard solution of diazepam (DZ) (ValiumR) were compared with those of a novel diazepam mixed-micelles solution (DZ MM) (Valium MMR) both after i.v. and i.m. application utilizing radioreceptor assay, quantitative pharmaco-EEG and brain mapping techniques as well as psychometric and psychophysiological methods. The local tolerance was studied as well. The subjects received randomized and, in weekly intervals, following injections: (1) 10 mg DZ i.v. + placebo i.m.; (2) 10 mg DZ MM i.v. + placebo i.m.; (3) placebo i.v. + 10 mg DZ i.m.; (4) placebo i.v. + 10 mg DZ MM i.m.; (5) placebo i.v. + placebo i.m. Blood sampling, EEG-recordings, psychometric and psychophysiological tests as well as tolerance evaluations were carried out at 0, 1/2, 1, 2, 4, 6 and 8 h. Blood level evaluation demonstrated after i.m. application a significantly shortened tmax, a higher Cmax and generally higher plasma concentrations in the first and second hour following the mixed-micelles solution than the standard formulation, which suggests better absorption of the former than the latter in the muscle. Subsequent to i.v. administration, lower blood levels were observed between 30 min and 2 h after DZ MM than DZ. Power spectral density analysis of the EEG resulted in typical anxiolytic-sedative pharmaco-EEG profiles after all 4 active substances as compared with placebo. However, there were significant inter-drug differences as far as topographic aspects (pharmaco-EEG maps) were concerned. DZ MM i.v. induced significantly more initial but also late delta augmentation, alpha attenuation and centroid slowing than DZ i.v. which suggests more sedative effects at those times. Following i.m. application, a significantly more pronounced delta/theta attenuation, beta augmentation and centroid acceleration after DZ MM than DZ suggested more anxiolytic effects of the novel than the standard formulation. Discriminant analysis of changes in 6 thymopsychic, 12 noopsychic and 17 psychophysiological variables demonstrated the best discrimination of the 4 substances based on thymopsychic effects. Considering the latter, all 4 active compounds differed significantly from placebo, with no inter-drug differences after i.v. application but a marked superiority of the novel mixed-micelles solution over the standard solution after i.m. application. Specifically, DZ MM i.m. induced more desactivation and affect-attenuation than DZ i.m.(ABSTRACT TRUNCATED AT 400 WORDS)

In a double-blind, placebo-controlled parallel group study, the encephalatropic effects of multiple doses of linopirine (I)VP P16), a novel phenylindolinone derivative enhancing the stimulated release of acetylcholine in cholinergic nerve terminals, hut also increasing concentrations of dopamine and serotonin, were investigated in 30 elderly. healthy volunteers. Fifteen subjects were randomly assigned to receive 20 mg DUP 996 b.i.d. and 15 were assigned It' receive placebo The doses were given at 12-h intervals for 10 days with an additional morning dose on day II Multi-lead LEG recordings were obtained alter an adaptation session on day - 1. as well as on days 2, 5 and 1(1 prior to and in the second hour after the morning dose. Computer-assisted spectral analysis of the EEC and subsequent topographic brain mapping of the drug-induced EEC changes demonstrated significant central effects of DUP 996,characterized h) art augmentation of total power, decrease of delta and theta activity, increase in alpha and beta activity and an acceleration of the centroid. These findings are opposite to those seen in dementias and indicative of an improvement in vigilance, and lime also been described with other cognition-enhancing drugs. Time-course investigations demonstrated more CNS changes 2 hours after than before morning oral dosing on days 2 and 5. The pharmacodynamic peak was observed in the 2 hour after dosing on day 2, topographically, the drug-induced changes over time were most pronounced over frontal-temporal. temporal-occipital, parietal and frontal regions. e.g. over brain areas afflicted most by Alzheimer's disease. [ABSTRACT FROM AUTHOR]

In a double-bind, placebo-controlled study the encephalotropic and psychotropic effects of kavain-a synthetic kava psychopysiogical analyses. 15 normal volunteers received randomized in weekly intervals single oral doses of placebo, 200 mg, 400 mg and 600 mg kavain as well as 30 mg clobazam as reference compound. EEG recordings, psychometric tests, evaluations of pulse, blood pressure and side effects were carried out at the hours 0, 1, 2, 4, 6 and 8. Brain maps of drug induced pharmaco-EEG changes (pharmaco-EEG maps) demonstrated that kavain exerted a significant action on the human brain function as compared with placebo characterized by a dose-dependent increase of delta, theta and alpha I activity while alpha 2, beta activity and the centroid of the total activity decreased. These findings are indicative of a sedative effect which was, however, in type quite different from that of the 1·5 benzodiazepine. The latter produced a decrease of delta, theta, alpha I and alpha 2 and an increase of beta activity while the total centroid was accelerated. Interestingly, 200 mg kavain induced with a decrease of delta and beta activity and an increase of alpha activity and of total power also vigilance promoting effects. Psychometric investigations demonstrated also clear differences between the two compounds at the behavioural level. Kavain improved the noopsyche as compared with placebo in all 3 doses as there was a significant improvement in intellectual performance (Pauli test), attention, concentration, reaction time and motor speed (rigidity test), while opposite findings were observed after 30 mg clobazam. In regard to thymopsychic variables such as drive, wakefulness, affectivity, mood, well-being, 200 mg kavain produced an improvement as compared with palcebo while 600 mg kavain produced sedation as did 30 mg clobazam. Psychophysiological evaluations resulted in only minimal findings. [ABSTRACT FROM AUTHOR]