Are oscillatory brain responses generally reduced in schizophrenia during long sustained attentional processing?

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Abstract

Deficits in sustained attention and vigilance were assessed for oscillatory delta, theta, alpha, and gamma EEG activity during an auditory continuous performance task in patients with schizophrenia and healthy controls by quantifying peak-to-peak amplitudes of averaged and single-trial data. Averaged data indicated significantly reduced amplitudes in schizophrenia patients in all analyzed frequency bands, mainly at anterior locations. Single-trial analysis suggested that the amplitude reductions observed in the averaged delta, theta, and alpha response in patients originated from increased inter-trial phase variability. Gamma activity maximum amplitudes were reduced at the single-trial level. The findings imply that EEG activity in patients with schizophrenia can be characterized by multiple deficits in oscillatory networks, which indicates a disturbance in the temporal integration and interaction of all frequency components and their inter-trial variability.

Introduction

Attentional deficits are common and wide ranging in patients with schizophrenia, who perform poorly on tests of vigilance or sustained attention. Some of these attentional deficits may be markers of vulnerability to the illness, as they are seen before, during, and after episodes of psychotic symptoms. Andreasen et al. (1999) proposed that a core cognitive deficit, neurodevelopmental in origin and referred to as cognitive dysmetria, is hypothesized to occur as a result of a disruption of the feedback mechanism within the cortico-cerebellar-thalamo-cortical circuit (CCTCC). This abnormality is caused by dysfunctional control and coordination processes and cognitive impairment because the inter-regional connectivity within the CCTCC is altered. fMRI findings from a continuous performance test (CPT) support this view, showing functional abnormal inter-regional connectivity in patients with negative symptoms (Honey et al., 2005). Indeed, as task attentional load increased, cognitive impairments were increased by the mediation of further abnormalities in the underlying neurophysiological systems subserving attentional processing with impaired behavioral performance and abnormal task-related connectivity between anterior cingulate and supplementary motor area. These findings implied a disconnection within the CCTCC that was independent of diagnostic subtype.

These functional disconnectivities have also been studied by assessing neuroelectric oscillatory activity to understand the neural basis of schizophrenia, as it has been suggested that investigating oscillations across the frequencies could be extensively useful (Ford et al., 2007, van der Stelt and Belger, 2007). The electrophysiological findings suggest abnormal temporal integration of brain networks as a core disturbance in schizophrenia (Andreasen et al., 1999, Lee et al., 2003), especially as reflected by functional gamma activity (Basar-Eroglu et al., 2007, Gallinat et al., 2004, Haig et al., 2000, Herrmann and Demiralp, 2005, Spencer et al., 2003, Spencer et al., 2004). These processes may reflect deficits in the neural mechanism underlying the integration or binding of brain functions across diverse networks that provide a temporal coherence to perceptions and actions (Basar et al., 2001, Haig et al., 2000, Herrmann and Demiralp, 2005, Kaiser et al., 2004, Sannita et al., 2001, Singer and Gray, 1995, Tallon-Baudry et al., 1996, Varela et al., 2001). Consonant with the cognitive dysmetria model of schizophrenia not only are decreased frequency magnitude but also decreased phase synchrony observed, which appear to index binding errors in the integration of cognitive activities across variegated brain regions (Haig et al., 2000, Lee et al., 2003, van der Stelt and Belger, 2007). However, deficits in temporal integration may not just be localizable to one altered frequency but may reflect a dysfunctional interplay of different frequencies, such as a coupling between gamma amplitude and theta oscillations (Demiralp et al., 2007a), or delta and gamma oscillations that are functionally related and concurrently increased during attention (Basar-Eroglu and Basar, 1991, Mathes et al., 2006). Thus, the interplay of all frequency components may be disturbed in schizophrenia.

Evidence for this view is beginning to accumulate. During a complex visual working memory n-back task patients with schizophrenia did not demonstrate modulations of frontal theta and gamma oscillations by increases in task difficulty as was the case in controls (Basar-Eroglu et al., 2007, Schmiedt et al., 2005). Furthermore, we have recently shown that the deficit of temporal and regional integration of neural networks in schizophrenia is reflected in the alpha and theta band during simple sensory processing and in the alpha, theta and delta band during target detection (Basar-Eroglu and Demiralp, 2001, Ergen et al., 2008).

As patients with negative symptoms show attentional impairments for Continuous Performance Test (CPT), this task has been used to quantify treatment efficacy on attention (Hain et al., 1993, Liu et al., 1997). Indeed, the CPT is used to measure sustained focused attention (Gur et al., 2007), since subjects only need to concentrate on a single simple task but for a long time period (Riccio et al., 2001). The present study therefore employed the CPT to assay oscillatory activities during sustained attention in distributed neural networks. First, gamma as well as delta, theta, and alpha frequencies were assessed to characterize and specify deficits in the interplay of all frequency components in schizophrenia. Second, single-trial amplitudes were also measured to determine whether amplitude reductions observed typically in averages was associated with inter-trial latency jitter or reduced amplitude of individual trials. Third, trials from the first and second half of the recording session were differentiated to determine how sustained attention might affect development of oscillatory activity in the patients.

Section snippets

Subjects

A total of 17 in-patients and 14 healthy controls gave informed consent and participated in the study. Due to artifacts and technical problems only ten (1F, 9M) schizophrenic in-patients (M = 36, ± 8 years) and ten healthy (7F, 3M) subjects (M = 32 ± 4) were included in the EEG data analysis. All patients were interviewed using a structured diagnostic interview and were required to meet DSM-IV criteria for schizophrenia (APA, 1994). Mean illness duration was 5 ± 3 years. All patients were recruited as

Behavioral data

The control and patient groups did not differ on response time (591 ± 35 vs. 577 ± 79 ms), overall error rate (5.86 ± 3.9% vs. 10.48 ± 8.04%), commission error rate (3.09 ± 4.46% vs. 4.62 ± 5.11%), or omission error rate (10.00 ± 7.71% vs. 8.48 ± 9.51%). Patients and controls did not differ between the first and second half of the trials for RT or error rates. Although very infrequent, controls made fewer errors than patients defined as pressing too early or late (< 200 ms or > 930 ms) after stimulus onset (1.82

Discussion

Brain oscillations from sustained attentional processing in a continuous performance task were assessed in patients with schizophrenia compared to healthy controls. Whether or not altered oscillations were found consistently in patients was specifically addressed. The findings indicate that reduced amplitudes in schizophrenia may originate in some cases from increased inter-trial processing jitter instead of single-trial reduced amplitudes.

The behavioral results demonstrated no significant

Conclusion

That schizophrenia is a complex disorder is reflected by complex changes in oscillatory responses: increased inter-trial jitter in slow frequencies during target-detection and generally reduced early gamma in schizophrenia patients. These alterations in oscillatory responses may reflect multifunctional impairments or disorders, possibly an imbalance of sensory and cognitive processing, which may be related to a dysfunctional mechanism of temporal integration. It should be therefore emphasized

Acknowledgements

We thank Edwin Hoff and Claudia Schieber for data recording and valuable critiques. Thanks also are due to Jens Behnen for assistance in the statistical analysis. Part of this research was supported by a special research grant (“Zentrale Forschungsförderung” 11/854/05) from the University of Bremen, Germany.

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