Electrophysiological subtypes of psychotic states.

OBJECTIVE: This research sought neurobiological features common to psychotic states displayed by patients with different clinical diagnoses. METHOD: Cluster analysis with quantitative electroencephalographic (QEEG) variables was used to subtype drug-naïve, non-medicated, and medicated schizophrenic, depressed and alcoholic patients with psychotic symptoms, from the USA and Germany. QEEG source localization brain images were computed for each cluster. RESULTS: Psychotic patients with schizophrenia, depression and alcoholism, and drug- naïve schizophrenic patients, were distributed among six clusters. QEEG images revealed one set of brain regions differentially upregulated in each cluster and another group of structures downregulated in the same way in every cluster. CONCLUSION: Subtypes previously found among 94 schizophrenic patients were replicated in a sample of 390 non-schizophrenic as well as schizophrenic psychotics, and displayed common neurobiological abnormalities. Collaborative longitudinal studies using these economical methods might improve differential understanding and treatment of patients based upon these features rather than clinical symptoms.

Toward a better understanding of the pathophysiology of OCD SSRI responders: QEEG source localization.

OBJECTIVE: To demonstrate the utility of three-dimensional source localization of the scalp-recorded electroencephalogram (EEG) for the identification of the most probable underlying brain dysfunction in patients with obsessive-compulsive disorder (OCD). METHOD: Eyes-closed resting EEG data was recorded from the scalp locations of the International 10/20 System. Variable resolution electromagnetic tomography (VARETA) was applied to artifact-free EEG data. This mathematical algorithm estimates the source generators of EEG recorded from the scalp. RESULTS: An excess in the alpha range was found with sources in the corpus striatum, in the orbito-frontal and temporo-frontal regions in untreated OCD patients. This abnormality was seen to decrease following successful treatment with paroxetine. CONCLUSION: The VARETA findings of an activation/deactivation pattern in cortical and subcortical structures in paroxetine-responsive patients are in good accordance with data obtained in previously published positron emission tomography studies related to current hypotheses of a thalamo-striatal-frontal feedback loop being relevant for understanding the pathophysiology of OCD.

Prediction of longitudinal cognitive decline in normal elderly with subjective complaints using electrophysiological imaging.

An extensive literature reports changes in quantitative electroencephalogram (QEEG) with aging and a relationship between magnitude of changes and degree of clinical deterioration in progressive dementia. Longitudinal studies have demonstrated QEEG differences between mild cognitively impaired (MCI) elderly who go on to decline and those who do not. This study focuses on normal elderly with subjective cognitive complaints to assess the utility of QEEG in predicting future decline within 7 years. Forty-four normal elderly received extensive clinical, neurocognitive and QEEG examinations at baseline. All study subjects (N = 44) had only subjective complaints but no objective evidence of cognitive deficit (evaluated using the Global Deterioration Scale [GDS] score, GDS stage = 2) at baseline and were re-evaluated during 7-9 year follow-up. Baseline QEEGs of Decliners differed significantly (p < 0.0001, by MANOVA) from Non-Decliners, characterized by increases in theta power, slowing of mean frequency, and changes in covariance among regions, especially on the right hemisphere. Using logistic regression, an R2 of 0.93 (p < 0.001) was obtained between baseline QEEG features and probability of future decline, with an overall predictive accuracy of 90%. These data indicate high sensitivity and specificity for baseline QEEG as a differential predictor of future cognitive state in normal, subjectively impaired elderly.

The Patient State Index as an indicator of the level of hypnosis under general anaesthesia.

BACKGROUND: This retrospective study describes the performance of the Patient State Index (PSI), under standard clinical practice conditions. The PSI is comprised of quantitative features of the EEG (QEEG) that display clear differences between hypnotic states, but consistency across anaesthetic agents within the state. METHODS: The PSI was constructed from a systematic investigation of a database containing QEEG extracted from the analyses of continuous 19 channel EEG recordings obtained in 176 surgical patients. Induction was accomplished with etomidate, propofol, or thiopental. Anaesthesia was maintained by isoflurane, desflurane, or sevoflurane, total i.v. anaesthesia using propofol, or nitrous oxide/narcotics. It was hypothesized that a multivariate algorithm based on such measures of brain state, would vary significantly with changes in hypnotic state. RESULTS: Highly significant differences were found between mean PSI values obtained during the different anaesthetic states selected for study. The relationship between level of awareness and PSI value at different stages of anaesthetic delivery was also evaluated. Regression analysis for prediction of arousal level using PSI was found to be highly significant for the combination of all anaesthetics, and for the individual anaesthetics. CONCLUSIONS: The PSI, based upon derived features of brain electrical activity in the anterior/posterior dimension, significantly co-varies with changes in state under general anaesthesia and can significantly predict the level of arousal in varying stages of anaesthetic delivery.

Changes in cortical electrical activity during induction of anaesthesia with thiopental/fentanyl and tracheal intubation: a quantitative electroencephalographic analysis.

BACKGROUND: There are regional differences in the effects of anaesthetics agents and perioperative stimuli on the EEG. We studied the topography of the EEG during induction of anaesthesia and intubation in patients receiving thiopental and fentanyl to document regional electrical brain activity. METHODS: EEG was recorded in 25 patients in the awake state, after pre-medication, during induction, at loss of consciousness and after intubation. Eight bipolar recordings were made and the relative power of the frequency bands delta, theta, alpha, and beta were used (after z-score transformation for age) to measure changes in regional EEG activity. RESULTS: Noxious stimulation during tracheal intubation partially reversed the slowing of the EEG caused by anaesthesia. During induction of anaesthesia alpha activity was most reduced in temporal and occipital regions. The most prominent EEG changes after intubation were an increase in alpha and a decrease in delta power (P<0.001). The largest changes were in the frontal and temporal leads for alpha and in the frontal and central leads for delta. Heart rate and arterial pressure remained constant during intubation. CONCLUSIONS: Changes in alpha and delta power were identified as the most sensitive EEG measures of regional changes in electrical brain activity during anaesthesia and noxious stimulation.

Quantitative EEG changes associated with loss and return of consciousness in healthy adult volunteers anaesthetized with propofol or sevoflurane.

Significant changes in topographic quantitative EEG (QEEG) features were documented during induction and emergence from anaesthesia induced by the systematic administration of sevoflurane and propofol in combination with remifentanil. The goal was to identify those changes that were sensitive to alterations in the state of consciousness but independent of anaesthetic protocol. Healthy paid volunteers were anaesthetized and reawakened using propofol/remifentanil and sevoflurane/remifentanil, administered in graded steps while the level of arousal was measured. Alterations in the level of arousal were accompanied by significant QEEG changes, many of which were consistent across anaesthetic protocols. Light sedation was accompanied by decreased posterior alpha and increased frontal/central beta power. Frontal power predominance increased with deeper sedation, involving alpha and, to a lesser extent, delta and theta power. With loss of consciousness, delta and theta power increased further in anterior regions and also spread to posterior regions. These changes reversed with return to consciousness.

Invariant reversible QEEG effects of anesthetics.

Continuous recordings of brain electrical activity were obtained from a group of 176 patients throughout surgical procedures using general anesthesia. Artifact-free data from the 19 electrodes of the International 10/20 System were subjected to quantitative analysis of the electroencephalogram (QEEG). Induction was variously accomplished with etomidate, propofol or thiopental. Anesthesia was maintained throughout the procedures by isoflurane, desflurane or sevoflurane (N = 68), total intravenous anesthesia using propofol (N = 49), or nitrous oxide plus narcotics (N = 59). A set of QEEG measures were found which reversibly displayed high heterogeneity of variance between four states as follows: (1) during induction; (2) just after loss of consciousness (LOC); (3) just before return of consciousness (ROC); (4) just after ROC. Homogeneity of variance across all agents within states was found. Topographic statistical probability images were compared between states. At LOC, power increased in all frequency bands in the power spectrum with the exception of a decrease in gamma activity, and there was a marked anteriorization of power. Additionally, a significant change occurred in hemispheric relationships, with prefrontal and frontal regions of each hemisphere becoming more closely coupled, and anterior and posterior regions on each hemisphere, as well as homologous regions between the two hemispheres, uncoupling. All of these changes reversed upon ROC. Variable resolution electromagnetic tomography (VARETA) was performed to localize salient features of power anteriorization in three dimensions. A common set of neuroanatomical regions appeared to be the locus of the most probable generators of the observed EEG changes.

Localization of deep white matter lymphoma using VARETA: a case study.

Methods have recently been proposed for localization of multiple brain sources of particular EEG frequencies recorded from the scalp, to identify their most probable neuroanatomical generators. This paper reports the accurate localization of a deep white matter lymphoma, using Variable Resolution Electromagnetic Tomography (VARETA). The accuracy of this localization was confirmed by MRI studies. The patient was referred for a quantitative EEG evaluation, two weeks following an automobile accident, with no known loss of consciousness. There was marked excess and asymmetry of frontal slow wave activity, with highly significant hypocoherence. Significant gradient shifts within the left hemisphere were also seen. Visual inspection of the EEG tracings revealed theta paroxysms in left dorsolateral and mesial frontal regions. The MRI revealed a large space-occupying lesion deep within the white matter of the left frontal lobe, with evidence of subependymal spread and significant surrounding vasogenic edema. Localization of the sources of the maximal QEEG abnormalities using VARETA was consistent with the lesion location seen in the MRI images. This case demonstrates that VARETA can achieve highly sensitive and accurate localization of sources of QEEG abnormalities which lie in the deepest brain regions.

Prediction of treatment outcome in cocaine dependent males using quantitative EEG.

This study investigates the existence of outcome related neurophysiological subtypes within a population of abstinent cocaine dependent adults. We have previously reported and replicated the existence of a distinctive quantitative EEG (QEEG) profile in such a population, and demonstrated the persistence of this pattern at one and six month follow-up evaluations. This profile is characterized by significant deficits of absolute and relative delta and theta power, and excess of relative alpha power, as compared with age expected normal values. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. In the current study, 35 adult males with DSM-III-R cocaine dependence, were evaluated while residents of a drug-free residential therapeutic community, 5-15 days after last use of crack cocaine. Using multivariate cluster analysis, two neurophysiological subtypes were identified from the baseline QEEGs; Cluster 1 characterized by significant deficits of delta and theta activity, significant excess of alpha activity and more normal amounts of beta activity (alpha CLUS) and Cluster 2 characterized by deficits of delta, more normal amounts of theta and anterior excess of alpha and beta activity beta CLUS). No significant relationships were found between QEEG subtype membership and length of exposure to cocaine, time since last use of cocaine or any demographic characteristics. Further, no significant relationships were found between the commonly reported comorbid clinical features of depression and anxiety and subtype membership. However, a significant relationship was found between QEEG subtype membership and length of stay in treatment, with members of the alpha CLUS retained in treatment significantly longer than members of the beta CLUS.

Correlation of qEEG with PET in schizophrenia.

PET relative metabolism was correlated with quantitative EEG in 9 schizophrenic patients. The PET metabolic regions of interest were the frontal lobes, thalamus and basal ganglia, and right and left temporal lobes. Significant positive correlations were seen for the frontal lobes and delta EEG power, and alpha power with subcortical metabolism. The physiologic plausibility of those correlations is discussed with reference to the possible effect of neuroleptic medication.

Persistent QEEG abnormality in crack cocaine users at 6 months of drug abstinence.

The major objective of this study was to examine the persistence of abnormal quantitative EEG (qEEG) measures over a six month time interval in subjects in strictly supervised drug free residential treatment for crack cocaine dependence. Seventeen subjects were assessed with qEEG at five to 10 days, one month and six months following their last use of cocaine. No significant changes were noted over time in abnormal qEEG measures, which included deficits of absolute and relative power in the delta band and increased relative alpha power. The persistence of qEEG abnormality in crack cocaine withdrawal suggests a persistent neurobiologic alteration resulting from chronic cocaine exposure. The specificity of the qEEG findings is discussed, and an interpretation is suggested with reference to the hypothesis of neural sensitization in cocaine dependence.

Quantitative electroencephalographic characteristics of crack cocaine dependence.

This study replicates preliminary findings reporting a quantitative electroencephalographic (QEEG) profile of crack cocaine dependence in abstinence. All subjects (n = 52) met criteria for DMS-III-R cocaine dependence (in the form of crack), and were residing in a drug-free therapeutic community. Baseline QEEG evaluations were conducted at intake (5-10 days after last use of crack, and at follow-up (1 month after last reported use). Previous findings of significant excess of relative alpha power and deficit of absolute and relative delta and theta power were replicated in this expanded group. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. Further, QEEG showed little change in the interval between the first and second evaluations. This QEEG profile may reflect persistent alterations in neurotransmission as a possible consequence of chronic cocaine exposure.

Neurometric QEEG studies of crack cocaine dependence and treatment outcome.

This paper presents an overview of the quantitative electrophysiological (QEEC) research on cocaine dependence conducted at Brain Research Laboratories of New York University Medical Center. These studies have demonstrated that subjects with DSM-III-R cocaine dependence (without dependence on any other substance) evaluated in the withdrawal state, have replicable abnormalities in brain function when evaluated at baseline (approximately 5 to 10 days after last crack cocaine use), which are still seen at one and six month follow-up evaluations. These abnormalities were characterized by significant excess of relative alpha power and deficit of absolute and relative delta and theta power. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. In addition, QEEC subtypes were identified within the population of cocaine dependent subjects at baseline, and these subtypes were found to be significantly related to subsequent length of stay in treatment. The relationship between these QEEG findings and the neuropharmacology of cocaine dependence is discussed.

Quantitative EEG characteristics of children exposed in utero to cocaine.

Quantitative EEGs (QEEGs) were evaluated in a group of 6 school age children with in utero cocaine exposure. Their QEEGs showed significant deviations from age expected normal values. Further, the QEEG profile of brain dysfunction seen in these children was extremely similar to that previously reported in a large population of crack cocaine dependent adults. These abnormalities were characterized by significant excess of relative power in the alpha frequency band, and deficits of absolute and relative power in the delta and theta bands. Characteristic disturbances in interhemispheric relationships were also present. The similarities between the QEEG profiles of those adults with chronic exposure and children with prenatal exposure suggests that the brain dysfunction reflected in the QEEG is not a result of a transient change in neurotransmission, but a more profound alteration which persists in these children at school age. Further study is required to extend these findings to a larger group of children, and to investigate the potential relationship between these neurophysiological abnormalities and the developmental, behavioral and co-morbid features observed in such children.

Quantitative electrophysiological characteristics and subtyping of schizophrenia.

Quantitative descriptors of resting electroencephalogram (EEG) (QEEG) and event-related potentials (QERP) to visual and auditory stimuli were obtained from normal subjects and 94 chronic schizophrenic patients on medication, 25 chronic schizophrenics off medication, and 15 schizophrenics with no history of medication. These schizophrenic groups showed a high incidence of neurometric features that were significantly deviant from normative values. Multivariate discriminant analysis using these features successfully separated the schizophrenic patients from normals with high accuracy in independent replication. The data from the medicated group were subjected to cluster analysis. Newly developed algorithms were used for objective selection of the most effective set of variables for clustering and the optimum number of clusters to be sought. Five clusters were obtained, containing roughly equivalent proportions of the sample with markedly different QEEG profiles. The whole sample was then classified into these clusters. Each cluster contained patients both on and off medication, but patients who had never been medicated were classified into only three of these clusters. No significant clinical or demographic differences were found between members of the five clusters; however, clear differences in QERP profiles were seen. These results are described in detail and possible physiological and pharmacological implications are discussed.

Standardized varimax descriptors of event related potentials: evaluation of psychiatric patients.

A large normative data base of visual and auditory event related potentials (ERPs) was collected. Factor analysis (PCVA) was used to extract factor wave shapes that accurately reconstructed these normal ERPs with appropriate "factor scores." The mean value and standard deviation (SD) of the normative factor score distribution were computed separately for each stimulus, factor, and electrode. This enabled reconstruction of any individual ERP as a combination of these standardized Varimax descriptors, with z-transformation of the required factor scores giving objective statistical assessment of ERP wave shape. Statistical probability factor z-score topographic maps were constructed, color coded in SDs from the normative means. The incidence of significant individual deviations from these normative mean values was at or near chance levels in test groups of normal subjects. For many of these new ERP descriptors, significant deviations from the norms were found for single features in from 20% to as much as 63% of the patients in particular diagnostic categories. Factor z-scores were used to construct multivariate discriminant functions that accurately and replicably separated (1) normal from schizophrenic from demented subjects and (2) schizophrenic from bipolar depressed subjects.

Quantitative EEG correlates of cognitive deterioration in the elderly.

We report on the quantitative analysis of the EEG (QEEG), using the Neurometric method, in large samples of normal elderly; normal subjectively impaired elderly; patients with mild cognitive impairment; patients presenting with a continuum of primary cognitive deterioration from mild to moderately severe as measured by the Global Deterioration Scale (GDS), compatible with dementia of the Alzheimer's type (DAT). Neurometric QEEG measures were found to be a sensitive index of degree of cognitive impairment, especially reflected in increased absolute and relative power in the theta band, with delta increasing in later stages of deterioration. While these abnormalities were widespread, neither localized or lateralized, MANOVA's for GDS and relative power in theta reached highest significance in a bilateral temporo-parietal arc. A possible relationship between hippocampal dysfunction, cognitive deterioration, and theta abnormalities is discussed in relation to these findings. The results suggest that Neurometric QEEG features are sensitive to the earliest presence of subjective cognitive dysfunction and might be useful in the initial evaluation of patients with suspected dementia, as well as in estimating the degree of cognitive deterioration in DAT patients.

Treatment resistant depression in a case of minor head injury: an electrophysiological hypothesis.

A relatively small but highly concordant literature suggests that manic depressive psychoses may include familial as well as nonfamilial subtypes. The latter, which appears to be an acquired form, follows brain injury of various etiology, displays EEG abnormalities and tends to respond well to anticonvulsant therapy. In this study we postulate an extension of this dichotomy to a larger spectrum of affective disorder, including milder but "treatment resistant" forms often associated with a high degree of dysfunction. Central to this hypothesis is information gathered from the longitudinal study of a well defined case in which precise clinical and electrophysiological data have been obtained at critical junctures. This data also leads us to suggest the existence of a latent vulnerability to psychosocial stressors in a subgroup of minor head injured patients. Once triggered, the resulting psychopathological state may be clinically indistinguishable from similar but etiologically distinct conditions. However, they respond poorly, if at all, to the treatments usually effective for mood disorders, often causing puzzlement and frustration among clinicians as well as mounting hopelessness in patients. This organic mood disorder subtype, which can be described as "neuro-sensitization mood disorder," may be identified by combining a thorough history, including perinatal events and putative brain injury, with electrophysiological data consisting of quantitative EEG (QEEG) in association with evoked potentials. In cases with positive findings, anticonvulsants such as carbamazepine, clonazepam and valproic acid can be a treatment of choice.

Quantitative electroencephalographic subtyping of obsessive-compulsive disorder.

Current neuropsychological, electrophysiological, and other imaging data strongly suggest the existence of a neurobiological basis for obsessive-compulsive disorder (OCD), which was long considered to be exclusively of psychogenic origin. The positive response of some OCD patients to neurosurgery, as well as the efficacy of agents that selectively block serotonin reuptake, lends further support to a biological involvement. However, a survey of the treatment literature reveals that only 45-62% of OCD patients improve with these specific medications. In a pilot study using a quantitative electroencephalographic (QEEG) method known as neurometrics, in which QEEG data from OCD patients were compared statistically with those from an age-appropriate normative population, we previously reported the existence of two subtypes of OCD patients within a clinically homogeneous group of patients who met DSM-III-R criteria for OCD. Following pharmacological treatment, a clear relationship was found between treatment response and neurometric cluster membership. In this study, we have expanded the OCD population, adding patients from a second site, and have replicated the existence of two clusters of patients in an enlarged, statistically more robust population. Cluster 1 was characterized by excess relative power in theta, especially in the frontal and frontotemporal regions; cluster 2 was characterized by increased relative power in alpha. Further, 80.0% of the members of cluster 1 were found to be nonresponders to drug treatment, while 82.4% of the members of cluster 2 were found to be treatment responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Standardized varimax descriptors of event related potentials: basic considerations.

This paper describes a set of proposed standardized quantitative descriptors of event-related potentials, based upon principal component varimax analysis (PCVA). No claim is made that these mathematical descriptors correspond to discrete neurophysiological processes which generate the ERP. However, adoption and prospective evaluation of such a set of precise, standardized descriptors of the quantitative ERP may eventually result in advances like those which resulted from adoption of equally arbitrary standardized descriptors for QEEG. PCVA was performed on data from normal subjects and from groups of patients with a wide variety of psychiatric disorders ("Abnormals"). This yielded two sets of factor waveshapes, Normal and Abnormal, which were closely similar. Reconstruction of the normal and abnormal ERP data with either set of factors yielded almost identical allocation of variance. These results gave acceptable reassurance that factors derived from normal population could reasonably be used to describe ERP waveshapes from patients. The ERPs at each electrode of the 10/20 System in a "training group" of normal subjects were then reconstructed. The resulting distributions of factor scores were transformed to achieve Gaussianity. Mean values and standard deviations were obtained for the normative distribution of each factor score, the root mean square deviation, the residual and the absolute ERP power at each electrode. Individual ERPs could then be reconstructed with the normal factors, and the resulting factor scores rescaled to "probability of abnormal morphology" by Z-transformation. Statistical probability maps could be generated by using a color scale in standard deviation units. These methods were used to evaluate visual and auditory ERPs from an independent normal "test group" and the patients in the Abnormal sample. High specificity and sensitivity were obtained for many factor Z- scores. Multiple discriminant functions were constructed which separated normal from abnormal patients with high, replicable accuracy. Further development and testing of these descriptors may make them clinically useful.