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

Abstract

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.

Introduction

Research on structural and functional brain abnormalities in schizophrenic patients has suggested a series of brain regions that might be involved in the disorder. However, the locations of these regions vary considerably depending on factors such as medication and experimental tasks (Chua and McKenna, 1995) so that there is no convergent evidence for a localized brain dysfunction. Recent reports on functional brain imaging in schizophrenia therefore suggested that the observed psychopathology might be related to a functional disconnection of various large-scale neural networks (Friston and Frith, 1995, Andreasen, 1997) and an imbalance of neural activity (Liddle, 1996) rather than abnormal functions in delimited anatomical regions. This is supported by reports of increased EEG dimensionality and complexity that imply increased independence of brain processes in the resting EEG of never-medicated, first-episode, acute schizophrenic patients (Koukkou et al., 1993, Saito et al., 1998).

The aim of the present study was to explore and extend this hypothesis of functional disconnection, using EEG frequency domain analysis. As there is a large knowledge base about frequency-dependent functional significance of oscillatory brain activity, a frequency domain approach should elucidate which types of brain functions are most affected by the hypothesized disorganization of neuronal activity. We are introducing here a novel method of multichannel EEG analysis that yields a single measure of global functional connectivity as a function of EEG frequency bands. This measure is called Global Field Synchronization (GFS). Using a single, global measure of functional connectivity does not imply that any particular brain region must be involved in the process to be studied, which is in agreement with the pursued hypothesis of functional disconnection of large-scale, distributed neural systems. In addition, and contrary to previous EEG studies on functional connectivity which typically used EEG coherence between different scalp sites, our method is reference-independent, the problem of repeated testing is avoided, and no implicit or explicit source model is needed for the interpretation of the results.

The analysis used EEG data from never-medicated, young patients recorded at the acute onset of their first episode of positive schizophrenic symptomatology. This study thus includes patients with a common, initial, positive symptomatology rather than heterogeneous symptoms present after a common long-term psychiatric diagnosis. Thereby, confounding variables, such as duration of illness (DeLisi et al., 1997), medication and task execution were avoided. The results were confirmed in a second, comparable data set from patients with schizophrenic symptomatology from an independent laboratory. In earlier analyses, these data had shown increased complexity and dimensionality in the time domain EEG (Saito et al., 1998).