Gamma activity in schizophrenia: evidence of impaired network binding?

Abstract

Objectives: Gamma (‘40 Hz’) rhythms may play a role in the integration of sensory processing activity. Impaired temporal integration may be a key feature of the associated disturbances in schizophrenia. This is the first study to examine the time course of Gamma activity induced in response to stimuli in this disorder.

Methods: Gamma activity induced in response to task-relevant and irrelevant auditory oddball stimuli was examined in 35 medicated schizophrenics and 35 age- and gender-matched normal controls. We employed a moving Welch window with short time FFT to examine the time course of Gamma amplitude. The amplitude spectrum for each time point was de-trended to eliminate any contribution of broad spectrum activity (EEG or EMG) to Gamma amplitude.

Results: For targets, schizophrenics showed a significant decrease in post-stimulus Gamma response amplitude in left hemisphere and frontal sites and an increase in right hemisphere and parieto-occipital sites (P<0.0009). The abnormalities correlated with PANSS general symptom scores. In the non-targets (at a different latency), schizophrenics showed a widespread Gamma decrease (P<0.0005).

Conclusions: The Gamma findings in non-targets may reflect an abnormality in appropriately processing irrelevant stimuli. This could result in defective processing of the context (integration) of relevant target information.

Introduction

A fundamental unsolved process in neuroscience concerns the manner in which, amongst the vast array of parallel processes occurring in the brain at any given time, the diverse neuronal activities relating to a single stimulus are bound together or integrated. For instance, a visual image of an object contains a collection of features which must be identified and segregated from those comprising other objects. However, different features of the image are processed by different regions of the brain. The issue arises how this spatially distributed processing relating to the one object is integrated. This is known as the binding problem (Singer and Gray, 1995, Robinson et al., 1998). It has been suggested that synchronous activity in specific narrow band frequency ranges may be a mechanism involved in distributed network binding, and there is evidence that the Gamma band may be of particular importance in this regard (Joliot et al., 1994, Basar-Eroglu et al., 1996). There is still some controversy concerning the precise functional significance of these findings in animal research, including whether this entrained frequency would be sufficiently rapid to solve the binding problem (Barinaga, 1998).

It has been hypothesized that an impairment in the integration, association, timing, coupling or binding of spatially diffuse cerebral activity related to specific cognitive tasks may be a key feature of the pathophysiology of schizophrenia (Johannisson, 1993, Hook et al., 1995). From the earliest descriptions of schizophrenia (Stransky, 1914, Bleuler, 1950, Berze, 1960), disordered association (thought disorder) has been recognized as a major feature of this illness. Many (if not all) other features of schizophrenia may be derived from a cognitive impairment primarily affecting association mechanisms, which itself may be consequent to a disorder of cerebral control mechanisms, and thus of cerebral stability (Wright and Kydd, 1986). If Gamma activity has a role in mediating binding of brain activity, then it is possible that abnormalities of Gamma in schizophrenia might be expected in relation to the failure of integrative processing in this disorder. Previous studies testing temporal coupling dysfunction have, however, focussed on measures with relatively low temporal resolution such as RCBF (Hook et al., 1995) and PET (Andreason, 1997). Analysis of induced Gamma therefore constitutes a logical step in the further exploration of brain dysfunction in schizophrenia as a means of further exploring the coupling impairment hypothesis. It is not yet definitely proven that Gamma activity plays a role in binding, and therefore interpretation of any Gamma abnormalities in schizophrenia in these terms must be tentative. However, the fact that impaired integration of processing seems to be a crucial disturbance in schizophrenia justifies an examination of Gamma activity in this disorder, since it suggests the possibility that Gamma abnormalities might be an important feature of the illness.

Previously, studies of induced Gamma activity have primarily been undertaken in normal subjects (Pantev et al., 1991, Goertz et al., 1994, Jokeit and Makeig, 1994). Some power spectral analysis of event-related potentials has been undertaken in schizophrenia (Roschke and Fell, 1997), but no previous study has examined the time course of Gamma activity induced in response to stimuli in schizophrenia. Since Gamma activity fluctuates fairly rapidly as a function of time in relation to cognitive processes (Basar-Eroglu et al., 1996), some form of time-frequency analysis is required, as power spectral analysis per se does not provide any temporal information.

In a recent study, we showed that the latency of the main component of the induced Gamma response to targets in a conventional auditory oddball paradigm in 40 normal subjects was strongly positively correlated with reaction time, and that this response was not due to EMG contamination (Haig et al., 1999). We also demonstrated that this activity was confined to a narrow frequency band between 37 and 41 Hz, and that adjacent bands showed no reaction time-related response. In the present study, we examined induced activity in this 37–41 Hz range in response to task-relevant (target) and task-irrelevant (background) auditory stimuli in the oddball paradigm in 35 patients with schizophrenia and 35 age- and sex-matched controls.