Working memory related gamma oscillations in schizophrenia patients
Introduction
One of the crucial cognitive processes which are affected in schizophrenia are processes related to working memory (WM). WM refers to a limited, attention-demanding capacity to hold and manipulate information in the mind for several seconds in the context of cognitive activity (Baddeley and Hitch, 1974). Evidence from human lesion studies suggests that WM depends on the activity of a number of cortical regions, primarily the prefrontal and parietal regions (Petrides and Milner, 1982, Frisk and Milner, 1990, Owen et al., 1996). Neuroimaging studies have also confirmed that the prefrontal regions, as well as other areas of association cortex, are active during WM tasks (Smith et al., 1996, Braver et al., 1997, Cohen et al., 1997, Courtney et al., 1998, Romanski, 2004). Event-related potential (ERP) studies suggest that WM is a function of a distributed system with both task specific and task independent components (Gevins et al., 1997, Kusak et al., 2000, Halgren et al., 2002, Herrmann et al., 2004a, Herrmann et al., 2004b). It appears that abnormalities in such a distributed system, especially the abnormal temporal integration of brain networks, may account for the core disturbance in schizophrenia (Lee et al., 2001, Lee et al., 2003). Many other studies support this hypothesis and show abnormalities in neural circuitry, especially in functional gamma activity in schizophrenia (Haig et al., 2000, Spencer et al., 2003, Spencer et al., 2004, Herrmann and Demiralp, 2005). It has been suggested that the impaired functional (inter- and intra-hemispheric) neuronal connectivity is reflected in reduced phase synchrony as well as reduced and delayed evoked and induced amplitudes in the gamma frequency range during initial attention and preparatory phases of information processing in schizophrenia (Haig et al., 2000, Lee et al., 2001, Slewa-Younan et al., 2004, Symond et al., 2005).
In the last decade many studies have implied that the event-related oscillations in the delta, theta, alpha and gamma frequency range may contribute to functional integration in the brain (for review see Basar et al., 2001, Basar, 2004). The results of our previous studies suggest that oscillatory networks are selectively distributed, working in parallel and functionally related to sensory as well as cognitive processes (Basar, 1999, Basar, 2004). Synchrony of gamma oscillations has been suggested to be related to attentional processing (Basar-Eroglu et al., 1996, Fell et al., 2003, Herrmann et al., 2004a, Tiitinen et al., 1993, Strüber et al., 2000, Yordanova et al., 1997, Karakas et al., 2001), which has been proposed to be inseparably associated with mnemonic processing (Fuster, 2000, Basar et al., 2000, Basar, 2004, Fell et al., 2002). Furthermore, gamma activity appears to have the universal role for sensory and cognitive processing and this activity can be described as selectively distributed (for review see Basar et al., 2000, Basar, 1999, Demiralp et al., 1996, Karakas and Basar, 1998).
Since the impairments in WM have been proposed to account for the core cognitive deficits in schizophrenia patients (Green, 1998), it is expected that such patients compared to healthy controls would have different responses in the oscillatory activity during WM tasks. Indeed, in our recent study, we reported reduced modulation of fronto-central late theta oscillations in schizophrenia patients, which seemed to be associated with WM memory formation and strategy adjustment during WM tasks (Schmiedt et al., 2005). These results support the notion that theta oscillations are involved in mediating frontal lobe activity associated with enhanced executive control and integrative processing. Furthermore, schizophrenia patients showed deficits in acquiring a mental task set which appeared to be associated with impairments in action monitoring and task specific regulation of executive control (Schmiedt et al., 2005).
In the current study, we reanalyzed the data presented in the former study (Schmiedt et al., 2005) to further characterize the disrupted oscillatory activity during WM processing in schizophrenia. Specifically, the aim of the present study was to investigate the event-related gamma activity during incrementally increasing WM load in healthy controls and schizophrenia patients. It was hypothesized that, similar to our previous findings in late theta, the event-related gamma oscillations would differ between healthy controls and schizophrenia patients. We expected that deficits in integrative processes in schizophrenia would be reflected by altered evoked or induced gamma amplitude during simple and higher cognitive processing. The above mentioned evidence, which documents the relationship between gamma activity and attentional processes, led to the hypothesis that increasing task-related cognitive load should be related to an increase in gamma activity in healthy subjects. However, it can be assumed that this process requires higher executive control, which has been reported to be deficient in schizophrenia due to attenuated allocation of attention. Therefore, we expected that the patients would show either reduced gamma activity during increasing WM task difficulty or no alterations between the tasks regardless of task difficulty.
Section snippets
Subjects
The study was approved by the research ethics committee at the University of Bremen. The participant characteristics are reported elsewhere (Schmiedt et al., 2005). Briefly, ten healthy controls (mean age 24 ± 4 years) and ten schizophrenia patients (mean age 34 ± 6 years) participated in this study following written informed consent. They were all right-handed, had normal or corrected to normal vision and no neurological and mental disorders. The patients were diagnosed according to the DSM-IV
Behavioral data
In Fig. 2 error rates and reaction times (RTs) are presented for each group, stimulus and task. In controls, there was a significant difference in RTs between the control and both WM tasks (main effect of TASK, F(1,18) = 5.58, p < .02). There was also a significant main effect of STIMULUS and an interaction between TASK and STIMULI suggesting that in controls the stimuli with higher cognitive demand (S2 and S3) lead to prolonged RTs under higher overall cognitive demand (STIMULUS, F(2,36) = 68.01, p <
Discussion
The results of the event-related oscillations (EROs) analysis showed a gradual increase of gamma amplitudes in controls during the retention interval (pre-stimulus) and after the stimulus onset with increases in WM load. In contrast, in schizophrenia patients high pre- and post-stimulus gamma amplitudes remained constant regardless of task demand throughout all three tasks. Additionally, there were no significant topographical differences in both groups during the WM tasks.
To our knowledge,
Acknowledgements
We are thankful to Prof. Dr. Erol Basar, Prof. Dr. Tamer Demiralp (University of Istanbul), and Prof. Dr. Christoph Herrmann (University of Magdeburg) for many valuable discussions and to Wilfried Alexander (University of Bremen) for the technical support.
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