Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naïve patients with schizophrenia: preliminary results.

We explored and refined the hypothesis that during a first episode of acute schizophrenia a disorganization of brain functioning is present. A novel EEG measure was introduced, Global Field Synchronization (GFS), that estimates functional connectivity of brain processes in different EEG frequency bands. The measure was applied to EEG's from 11 never-treated, first-episode, young patients with an acute, positive, schizophrenic symptomatology and from 19 controls, residing in Bern, Switzerland. In comparison to age- and sex- matched controls, patients had significantly decreased GFS in the theta EEG frequency band, indicating a loosened functional connectivity of processes in this frequency. The result was confirmed in an independent, comparable patient group from Osaka, Japan (9 patients and 9 controls), thus making a total of 20 analyzed patients. Previous EEG research in healthy, awake subjects indicated a positive correlation of theta activity with memory functions. Thus, our result suggests a loss of mutual interdependence of memory functions in patients with acute schizophrenia, which agrees well with previous reports of working memory dysfunction in schizophrenia.

An EEG approach to the neurodevelopmental hypothesis of schizophrenia studying schizophrenics, normal controls and adolescents.

Based on an integrative brain model which focuses on memory-driven and EEG state-dependent information processing for the organisation of behaviour, we used the developmental changes of the awake EEG to further investigate the hypothesis that neurodevelopmental abnormalities (deviations in organisation and reorganisation of cortico-cortical connectivity during development) are involved in the pathogenesis of schizophrenia. First-episode, neuroleptic-naive schizophrenics and their matched controls and three age groups of normal adolescents were studied (total: 70 subjects). 19-channel EEG delta-theta, alpha and beta spectral band centroid frequencies during resting (baseline) and after verbal stimuli were used as measure of the level of attained complexity and momentary excitability of the neuronal network (working memory). Schizophrenics compared with all control groups showed lower delta-theta activity centroids and higher alpha and beta activity centroids. Reactivity centroids (centroid after stimulus minus centroid during resting) were used as measure of update of working memory. Schizophrenics showed partial similarities in delta-theta and beta reactivity centroids with the 11-year olds and in alpha reactivity centroids with the 13-year olds. Within the framework of our model, the results suggest multifactorially elicited imbalances in the level of excitability of neuronal networks in schizophrenia, resulting in network activation at dissociated complexity levels, partially regressed and partially prematurely developed. It is hypothesised that activation of age- and/or state-inadequate representations for coping with realities becomes manifest as productive schizophrenic symptoms. Thus, the results support some aspects of the neurodevelopmental hypothesis.

Low resolution brain electromagnetic tomography (LORETA) functional imaging in acute, neuroleptic-naive, first-episode, productive schizophrenia.

Functional imaging of brain electrical activity was performed in nine acute, neuroleptic-naive, first-episode, productive patients with schizophrenia and 36 control subjects. Low-resolution electromagnetic tomography (LORETA, three-dimensional images of cortical current density) was computed from 19-channel electroencephalographic (EEG) activity obtained under resting conditions, separately for the different EEG frequencies. Three patterns of activity were evident in the patients: (1) an anterior, near-bilateral excess of delta frequency activity; (2) an anterior-inferior deficit of theta frequency activity coupled with an anterior-inferior left-sided deficit of alpha-1 and alpha-2 frequency activity; and (3) a posterior-superior right-sided excess of beta-1, beta-2 and beta-3 frequency activity. Patients showed deviations from normal brain activity as evidenced by LORETA along an anterior-left-to-posterior-right spatial axis. The high temporal resolution of EEG makes it possible to specify the deviations not only as excess or deficit, but also as inhibitory, normal and excitatory. The patients showed a dis-coordinated brain functional state consisting of inhibited prefrontal/frontal areas and simultaneously overexcited right parietal areas, while left anterior, left temporal and left central areas lacked normal routine activity. Since all information processing is brain-state dependent, this dis-coordinated state must result in inadequate treatment of (externally or internally generated) information.

A deviant EEG brain microstate in acute, neuroleptic-naive schizophrenics at rest.

Momentary brain electric field configurations are manifestations of momentary global functional states of the brain. Field configurations tend to persist over some time in the sub-second range ("microstates") and concentrate within few classes of configurations. Accordingly, brain field data can be reduced efficiently into sequences of re-occurring classes of brain microstates, not overlapping in time. Different configurations must have been caused by different active neural ensembles, and thus different microstates assumably implement different functions. The question arises whether the aberrant schizophrenic mentation is associated with specific changes in the repertory of microstates. Continuous sequences of brain electric field maps (multichannel EEG resting data) from 9 neuroleptic-naive, first-episode, acute schizophrenics and from 18 matched controls were analyzed. The map series were assigned to four individual microstate classes; these were tested for differences between groups. One microstate class displayed significantly different field configurations and shorter durations in patients than controls; degree of shortening correlated with severity of paranoid symptomatology. The three other microstate classes showed no group differences related to psychopathology. Schizophrenic thinking apparently is not a continuous bias in brain functions, but consists of intermittent occurrences of inappropriate brain microstates that open access to inadequate processing strategies and context information

Brain electric microstates and momentary conscious mind states as building blocks of spontaneous thinking: I. Visual imagery and abstract thoughts.

Prompted reports of recall of spontaneous, conscious experiences were collected in a no-input, no-task, no-response paradigm (30 random prompts to each of 13 healthy volunteers). The mentation reports were classified into visual imagery and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was continuously recorded, viewed as series of momentary spatial distributions (maps) of the brain electric field and segmented into microstates, i.e. into time segments characterized by quasi-stable landscapes of potential distribution maps which showed varying durations in the sub-second range. Microstate segmentation used a data-driven strategy. Different microstates, i.e. different brain electric landscapes must have been generated by activity of different neural assemblies and therefore are hypothesized to constitute different functions. The two types of reported experiences were associated with significantly different microstates (mean duration 121 ms) immediately preceding the prompts; these microstates showed, across subjects, for abstract thought (compared to visual imagery) a shift of the electric gravity center to the left and a clockwise rotation of the field axis. Contrariwise, the microstates 2 s before the prompt did not differ between the two types of experiences. The results support the hypothesis that different microstates of the brain as recognized in its electric field implement different conscious, reportable mind states, i.e. different classes (types) of thoughts (mentations); thus, the microstates might be candidates for the 'atoms of thought'.

Differences in the EEG profiles of early and late responders to antipsychotic treatment in first-episode, drug-naive psychotic patients.

The aim of this study was to search for differences in the EEG of first-episode, drug-naive patients having a schizophrenic syndrome which presented different time courses in response to antipsychotic treatment. Thirteen patients who fulfilled DSM-IV diagnosis for schizophrenia or schizophreniform disorder participated in this study. Before beginning antipsychotic treatment, the EEG was recorded. On the same day psychopathological ratings were assessed using the ADMDP system, and again after 7 and 28 days of treatment. The resting EEG (19 leads) was subject to spectral analysis involving power values for six frequency bands. The score for the schizophrenic syndrome was used to divide the patients into two groups: those who displayed a clinically meaningful improvement of this syndrome (reduction of more than 30%) after 7 days of treatment (early responders, ER) and those who showed this improvement after 28 days (late responders. LR). Analysis of variance for repeated measures between ER, LR and their matched controls with the 19 EEG leads yielded highly significant differences for the factor group in the alpha2 and beta2 frequency band. No difference was found between the slow-wave frequency bands. Compared to controls the LR group showed significantly higher alpha2 and beta2 power and, in comparison to the ER group, significantly higher alpha2 power. There were no significant differences between the ER and the control group. These findings point to differences in brain physiology between ER and LR. The implications for diagnosis and treatment are discussed.

EEG reactivity and EEG activity in never-treated acute schizophrenics, measured with spectral parameters and dimensional complexity.

Our approaches to the use of EEG studies for the understanding of the pathogenesis of schizophrenic symptoms are presented. The basic assumptions of a heuristic and multifactorial model of the psychobiological brain mechanisms underlying the organization of normal behavior is described and used in order to formulate and test hypotheses about the pathogenesis of schizophrenic behavior using EEG measures. Results from our studies on EEG activity and EEG reactivity (= EEG components of a memory-driven, adaptive, non-unitary orienting response) as analyzed with spectral parameters and "chaotic" dimensionality (correlation dimension) are summarized. Both analysis procedures showed a deviant brain functional organization in never-treated first-episode schizophrenia which, within the framework of the model, suggests as common denominator for the pathogenesis of the symptoms a deviation of working memory, the nature of which is functional and not structural.

Source localization of brain electric field frequency bands during conscious, spontaneous, visual imagery and abstract thought.

This paper addresses the issue of mind-brain correspondence, using a novel way to reduce brain electric field data in the frequency domain to estimates of intracerebral model source locations, and applying this method to brain electric data collected during the 2-s epochs immediately before the randomly solicited reports of spontaneous, conscious, covert experiences from 12 normal volunteers. The mentation reports were classified into visual imagery and abstract thought. The mean locations of the EEG model sources associated with abstract thoughts were generally more anterior and deeper than those of visual imagery, particularly significant for the delta/theta band; the finding was common across subjects. Thus, different brain functional states involving different geometries of activated neural populations exist during conscious, spontaneous, task-free mentations of the visual imagery type and of the abstract thought type.

Dimensional complexity of EEG brain mechanisms in untreated schizophrenia.

The dimensional complexity of left temporal-parietal and parietal-occipital electroencephalographic (EEG) recordings was assessed by computing the correlation dimension during 20 sec in six recording conditions from 15 first-episode acute schizophrenics before medication, 12 other medication-free individuals clinically and socially remitted after a first schizophrenic episode, 17 medication-free neurotics and 17 controls. The correlation dimension of the temporal-parietal EEG differed between groups [analysis of variance (ANOVA)] (p < 0.004), whereas neurotics (different from schizophrenics at p < 0.002) and remitted schizophrenics showed intermediate values. There was no overall significant difference between groups in the parietal-occipital EEG. Differences of the correlation dimension of the temporal-parietal versus the parietal-occipital EEG were significant between groups (ANOVA p < 0.05); first-episode schizophrenics differed from controls (p < 0.002) and remitted patients (p < 0.08). Increased dimensional complexity of schizophrenic EEG was found in one of two examined brain regions. The higher dimensional complexity of functional brain mechanisms in schizophrenics versus normals is reminiscent of the loosened organization of thought, and of suggestions of certain superior abilities in the patients.

EEG reactivity in high and low symptomatic schizophrenics, using source modelling in the frequency domain.

A dipole localization method in the frequency domain was used (FFT Dipole Approximation) to assess spatial differences in the spectral EEG reactivity (orienting response) between high and low symptomatic schizophrenics. Frequency bands of interest were determined empirically by comparing the two dichotomized patient groups with two matched control groups. Evidence for a correlation between EEG reactivity and severity of schizophrenic symptomatology was found, especially in the higher beta frequency range (16-25.5 Hz). Opposite effects were found in the two beta ranges of 20.5-22.5 Hz and 23.0-25.5 Hz, supporting the hypothesis that different EEG frequency bands have specific functional significances and that these bands are not necessarily those that are conventionally selected.

A psychobiological model of the pathogenesis of schizophrenic symptoms.

Schizophrenic symptoms are non-specific and are modifiable by unspecific drugs, by environmental input and 'spontaneously'. An information-theory-based model of their pathogenesis is presented. The model is based on data and theories which suggest memory-driven and state-dependent brain operations for the organization of human behavior in normal or in psychopathological states. The data are integrated in the concept of EEG-defined functional states of the brain with state-dependent information processing. The brain's functional state is multifactorially defined, reflects at each moment the memory storages accessible to the operations of information processing and is continuously readjusted to the demands made on the organism by current received information as estimated by the cerebral mechanisms of initiation of the orienting reaction and of its 'habituation'. Major conclusions of evoked potentials and of EEG-reactivity studies on information processing anomalies in schizophrenia integrated into the model suggest the following: schizophrenic symptoms reflect the behavioral manifestations of brain's information processes which have access to memory storages which contain mnemonic representations of skills and of cognitive-emotional coping strategies which are inadequate to recognize the age- and state-corresponding significance of the current information for the organism.

[A communications theory approach to the mechanisms of development of psychiatric disorders exemplified by foreign workers]. / Ein kommunikationstheoretischer Ansatz der Entstehungsmechanismen psychischer Störungen am Beispiel von ausländischen Arbeitnehmern.

This article is intended as a contribution towards interpreting the development of psychiatric symptoms as a final result of disturbed processes of communication. We should like to point out that the importance of communication for normal and abnormal behaviour has been established both from the viewpoints of sociopsychology and family therapy as well as of cognition psychology and psychophysiology. The present study is limited to the presentation of clinical aspects, but it should be pointed out that a systematic phase concept of treatment can be developed via an integration of psychophysiological research studies on this subject; however, we have not gone into this possibility in detail in the present study.

[EEG correlates of information processing in acute and remittent schizophrenic patients]. / EEG-Korrelate der Informationsverarbeitung bei akuten und remittierten Schizophrenen.

Studies of the EEG correlates of information processing in normals indicate that different cognitive processing of information is correlated with different functional brain states. Studies in experimental psychology have demonstrated a communication and performance deficit in schizophrenics which indicates a deviation in one or more stages of information processing. Accordingly it can be hypothesized that the functional brain states as manifested in the EEG during information processing in schizophrenics are different from these states in normals or former schizophrenics. The paper tested this hypothesis in drug-free acute and former schizophrenics, neurotics and normals. The results indicate 1) that acute schizophrenics show a deviant electrical brain state during information processing; 2) former schizophrenics in a good clinical remission have electrical brain states during information processing which in some aspects are normalised, and in other aspects still differ from these states in normals and neurotics. The importance of these physiological findings for the assessment of the efficacy of the biological and psychological treatments in schizophrenia is discussed.

Antipsychotic efficacy of fluperlapine. An open multicenter trial.

In an open multicenter trial 46 schizophrenic patients were treated with fluperlapine for 20 days. A mean daily dosage of 300-400 mg appeared to be an effective antipsychotic treatment in most cases. The marked antipsychotic effect was accompanied by a good improvement of depressive symptoms. Extrapyramidal side effects were extremely rare.

Dreaming: The functional state-shift hypothesis. A neuropsychophysiological model.

The different brain functional states during sleep and wakefulness are associated with differences in processing strategies, memory stores, and EEG patterns. Shifts of functional state occur spontaneously or as orienting reactions to processed information, and cause the formal characteristics of dreams. Forgetting of dreams is a function of the magnitude of the difference between states during storage and recall. Based on EEG similarities between sleep stages and developmental stages, brain states during sleep in adults are proposed to correspond functionally with waking states during childhood. Repeated functional regressions occur during sleep, with access to earlier memory material and cognitive strategies unavailable during waking life, so that earlier experiences can be used for current problems. This dream work constitutes the biological significance of sleep.

EEG states of the brain, information processing, and schizophrenic primary symptoms.

The electroencephalographic (EEG) reactivity to auditory information (the central component of the orienting reaction) was used to examine brain states underlying information processing in acute and recovered medication-free schizophrenics and matched controls. EEG reactivity was assessed as information-induced changes of parameters extracted from power spectral frequency analysis of the ongoing EEG. EEG reactivity in controls and schizophrenics in remission was largely similar. Acute schizophrenics showed a deviant (ectropic) reactivity, which consisted of changes within the 2-8 Hz band, and of either severely reduced or absent response in the 8-13 Hz (alpha) band. These results indicate an ectropic brain state during cognitive processing of received information during the period of acute schizophrenic symptomatology.

Correlations between cannabis-induced psychopathology and EEG before and after drug ingestion.

The study investigates EEG characteristics in relation to psychopathology. Tetrahydro-Cannabinol (THC) was taken orally by 12 volunteers. The EEG was recorded continuously, and THC-induced psychopathology was assessed by pre- and post-experiment questionnaires. Subjects had to signal THC experiences. EEG measurements (distribution means of frequency bands derived from EEG frequency analysis) before and after THC were correlated with THC induced psychopathology. High correlations were found before THC ingestion, and after THC during periods without experiences. Thus, the pre-drug EEG indicates predisposition to THC induced body image disturbances and euphoria, and the drug-influenced EEG in periods without experiences indicates the tendency to drug-induced experiences. The predicting EEG parameters were different for THC induced visual experiences and for body image disturbances.

Human EEG spectra before and during cannabis hallucinations.

EEG correlates of subjective experiences induced by delta9-trans-tetrahydrocannabinol (THC) and EEG correlates of individual disposition to such experiences were investigated. Twelve normal volunteers took 200 mug/kg THC orally. The subjects were asked to signal subjective experiences. The EEG was analyzed (period analysis) before and repeatedly after THC injestion, during resting, attention, eye closure, visual hallucinations, and body image disturbances. EEG frequency spectra differed significantly between resting and visual hallucinations and body image disturbances. The differences included slower alpha and more theta during THC experiences, reminiscent of initial drowsiness EEG, and of some results in schizophrenia. The differences between spectra during visual hallucinations and during body image disturbances indicate different functional brain states. Subjects with a high tendency to cannabinol induced experiences exhibited resting spectra before and after THC with higher modal alpha frequences (reminiscent of subjects with high neuroticism scores) than subjects with a low tendency.