Cortical hypoactivation during resting EEG in schizophrenics but not in depressives and schizotypal subjects as revealed by low resolution electromagnetic tomography (LORETA)
Introduction
Hypofrontality has been one of the most prominent and consistent findings in schizophrenia since the advent of functional neuroimaging (Ingvar and Franzén, 1974, Weinberger, 1987, Goldman-Rakic and Friedman, 1991, Andreasen et al., 1992, Weinberger and Berman, 1996). Various sets of independent PET and fMRI data have indicated that hypofrontality reflects a dysfunction in the schizophrenic prefrontal cortex. The physiological dysfunction of the prefrontal lobe in schizophrenics was psychometrically associated with deficits in attention, planning and working memory (Goldberg and Gold, 1995). In line with these findings, numerous quantitative electroencephalographic studies also have described—though not entirely consistently—hypofrontality, defined as frontally pronounced slowing of EEG activity (Coger et al., 1979, Etevenon et al., 1979, Guich et al., 1989, John et al., 1994, Pascual-Marqui et al., 1999, Wuebben and Winterer, 2001) or a reduced amplitude of the contingent negative variation (CNV) (Van der Bosch, 1983, Verhey et al., 1984, Abraham et al., 1986, Heimberg et al., 1999). As slowing of EEG activity correlates with reduced blood flow and glucose utilisation—especially when the latter is measured during cognitive task performance—this finding has been regarded as the electrophysiological equivalent of hypofrontality (Ingvar et al., 1976, Guich et al., 1989). Indeed, long before the concept of hypofrontality became popular, Lemere (1941) described a slowing of EEG activity in schizophrenic patients, especially those with a deteriorating course of illness. Since then, many electroencephalograph have stressed the relation between a slowing of EEG activity and an unfavourable course of the illness and/or negative symptoms (Fenton et al., 1980, Dierks et al., 1989, Guich et al., 1989).
Several studies have described increased alpha and/or theta power in a high percentage of depressive patients, especially on the left anterior side (frontal alpha asymmetry) (Monakhov and Perris, 1980, Nyström et al., 1986, Knott and Lapierre, 1987; John et al., 1988; Henriques and Davidson, 1991, Alper, 1995, Debener et al., 2000), although there are also contradictory findings (Pollock and Schneider, 1990, Reid et al., 1998). Generally, this finding was interpreted as evidence for left frontal hypoactivation since alpha activity is considered as an inverse correlate of cerebral activation (Shagass, 1972, Cook et al., 1998). However, decreased alpha activity also has been reported, especially in bipolar depressive patients (Knott and Lapierre, 1987, Clementz et al., 1994). In line with the hypofrontality concept, a reduced amplitude of the contingent negative variation (CNV) has been described in depressive patients (Timsit-Bertier et al., 1973, Thier et al., 1986, Heimberg et al., 1999), though others have not found a decreased amplitude (Bolz and Giedke, 1981, Elton, 1984). Neuroimaging studies are only partially in accordance with the electrophysiological findings. George et al. (1994) and Ho et al. (1996) also described reduced glucose utilisation in unipolar depressive patients. However, Buchsbaum et al. (1986) described a reduced frontal-to-occipital glucose utilisation (FDG-PET) in bipolar patients, whereas the opposite was found in unipolar patients. Kling et al. (1986) and Berman et al. (1993) did not find reduced glucose utilisation. Ebert et al. (1993), applying Tc-99m HMPAO SPECT, described reduced blood flow in both schizophrenics and patients with major depression. Galynker et al. (1998), applying the same methodology, also found reduced blood flow in depressive patients, which was negatively correlated with negative symptoms but not depressive symptoms in this patient group. Together, these findings suggest that hypofrontality might be found in a subgroup of depressive patients but not necessarily in all patients.
Subjects, who are considered to be potentially at increased risk for schizophrenia, such as individuals with schizotypal personality or unaffected relatives of schizophrenics, also were shown to demonstrate lower performance on psychological tasks that are linked to the function of the prefrontal cortex (Lyons et al., 1991, Raine et al., 1992, DeVegar et al., 1993, Keefe et al., 1994). However, neuroimaging studies in high-risk subjects, measuring regional cerebral blood flow in the prefrontal cortex with PET or SPECT, are less unequivocal and either described negative results (Berman et al., 1991) or inconclusive results (Buchsbaum et al., 1997). Even more, Siever et al. (1995) suggested from a preliminary analysis of SPECT data that this group of high-risk subjects might possibly display cortical over-activation that is not restricted to the frontal lobe. In line with the negative result in respect to hypofrontality, Stassen et al. (1999) found no evidence for an increase of slow EEG activity in discordant twins of schizophrenic patients. Quite similarly, our own group did not find electrophysiological changes in schizotypal subjects that were compatible with the notion of hypofrontality (Wuebben and Winterer, 2001). However, Clementz et al. (1994) described a reduced alpha peak frequency in relatives of schizophrenic patients.
To assess whether the new imaging tool, low resolution electromagnetic tomography (LORETA) (Pascual-Marqui et al., 1994, Pascual-Marqui et al., 1999), can detect hypofrontality in schizophrenic subjects, we investigated unmedicated schizophrenic patients and compared them with normal control subjects. We also investigated unmedicated depressive patients and subjects with schizotypal personality since there is some evidence that these subjects also may exhibit hypofrontality.
Section snippets
Subjects
The samples, which were investigated in the present study with LORETA, were drawn from a large database. This database was previously analysed with conventional EEG methodology (factor analyses, EEG mapping) and published elsewhere (Wuebben and Winterer, 2001). Now, we investigated 10 healthy male and 10 healthy female volunteers (36.15±10.09 years) randomly selected and age-matched to the schizophrenic patients from an EEG database of 254 healthy control subjects, who were recruited by a
Results
There were no significant age differences between healthy subjects (HS) and unmedicated schizophrenic patients (US) (Z=−0.15; P=0.99), healthy subjects and schizotypal subjects (SS) (Z=−1.67; P=0.94), and healthy subjects and unmedicated depressive patients (UD) (Z=−1.35; P=1.78).
Group comparison of unmedicated schizophrenic and healthy subjects revealed a significant increase of delta activity in the US group (Fig. 1, Table 1). Roughly, this difference in the delta frequency band was found all
Discussion
In this study, we investigated whether low resolution electromagnetic tomography (LORETA) (Pascual-Marqui et al., 1994, Pascual-Marqui et al., 1999) can detect hypofrontality in schizophrenic patients as well as depressive patients and potentially high-risk subjects for schizophrenia (schizotypal subjects).
In line with numerous relatively consistent reports in the literature and our own previous study with conventional EEG methodology (Coger et al., 1979, Etevenon et al., 1979, Guich et al.,
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft (Wi 1316/2-1; Wi 1316/3-2).
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