Elsevier

Schizophrenia Research

Volume 59, Issues 2–3, 1 February 2003, Pages 253-260
Schizophrenia Research

Altered hemispheric asymmetry and positive symptoms in schizophrenia: equivalent current dipole of auditory mismatch negativity

https://doi.org/10.1016/S0920-9964(02)00154-8Get rights and content

Abstract

The abnormality of mismatch negativity (MMN) in schizophrenia is thought to be associated with perceptional disturbance and cognitive dysfunction. The purpose of the present study was to investigate the change of the normal functional hemispheric lateralization in schizophrenia by employing the equivalent current dipole (ECD) model of auditory MMN with individual MRI and high-density electroencephalography (EEG). The MMNs resulting from auditory stimuli with passive oddball paradigm in a group of schizophrenics (n=15), and also a group of age-, sex-, and handedness-matched normal controls, were recorded by 128 channel EEG. The location and power of ECD sources at the peak point were calculated. Individual 3-D brain magnetic resonance images (MRI) were used for realistic head modeling and for source localization. For both groups, the MMN source was determined to be located in the superior temporal gyrus (STG). However, the normal functional hemispheric asymmetry of ECD power was significantly altered in the schizophrenics (χ2 test=16.13, p<0.001). Left MMN ECD power and the asymmetry coefficient (AC) were negatively correlated with the positive scores from Positive and Negative Syndrome Scale (PANSS) (r=−0.673, p=0.008), especially with the hallucinatory behavior subscale (r=−0.677, p=0.008). These findings support the deficits in preattentive automatic processing of auditory stimuli, especially in the left hemisphere, and indicate the correlation between positive symptoms, especially auditory hallucination, and left temporal lobe dysfunction in schizophrenia.

Introduction

Mismatch negativity (MMN) is an event-related potential (ERP) elicited when a sequence of unattended repetitive sounds is interrupted by a deviant stimulus (Näätänen et al., 1978). MMN is elicited by any change in frequency, intensity or duration of tone stimuli, as well as by changes in complex stimuli such as phonetic stimuli (Näätänen, 1992). Since MMN occurs irrespective of whether or not stimuli are being attended, MMN is thought to be an automatic cerebral process for detecting change and an index for automatic process involved in sensory or echoic memory. MMN abnormalities have been found consistently in schizophrenics and interpreted as reflecting the impairment of early preattentive auditory processing in schizophrenia Shelley et al., 1991, Hirayasu et al., 1998, Javitt, 2000. Studies have further suggested that the main cortical source of MMN is localized within the superior temporal plane Scherg et al., 1989, Alho, 1995, Wible et al., 2001. Meanwhile, morphometric studies have also proposed abnormalities of the superior temporal gyrus in schizophrenia Barta et al., 1990, Shenton et al., 1992, Kwon et al., 1999, Gur et al., 2000. However, limits remain in attempts to localize the MMN generator, because most previous electrophysiological studies used a small number of electrodes to record ERP and few studies have used a realistic head model for localization Buchner et al., 1995, Waberski et al., 1998. Therefore, studies using high-density electroencephalography (EEG) recording and a realistic head model are needed for the precise localization of the MMN generator.

In the human brain, many structures are normally lateralized which is consistently larger in one of the hemispheres, occasionally in conjunction with lateralized functions such as language (reviewed in Pearlson and Marsh, 1999). In schizophrenia, many studies have demonstrated a reduced or reversed hemispheric asymmetry, particularly of temporal lobe structures (i.e., planum temporale (PT)) Barta et al., 1997, Kwon et al., 1999. Because it has been suggested that the source of the MMN generator is located in the superior temporal gyrus (STG), an investigation of the hemispheric asymmetry of MMN ECD power in both schizophrenics and controls will be helpful for understanding the pathophysiology of schizophrenia.

With this background, we investigated the location and power of the MMN generator in schizophrenia compared with those in normal volunteers using the equivalent current dipole (ECD) model with high-density EEG acquisition and the subjects' own high-resolution 3-D magnetic resonance images (MRI) for a realistic head model. We also explored the functional hemispheric asymmetry in schizophrenia and its correlation with clinical symptoms to understand the pathophysiology of schizophrenia.

Section snippets

Subjects

Fifteen right-handed schizophrenic patients (male: nine, female: six; mean age 27.8±5.6 years) were recruited from Seoul National University Hospital, Seoul, Korea. All patients met the DSM-IV criteria based on both SCID-IV and information from psychiatric records. Exclusion criteria included a history of auditory dysfunction, electroconvulsive therapy, neurologic illness, major head trauma, or alcohol and drug abuse or dependence. All patients were receiving neuroleptic medication, with a mean

Results

There was no significant difference in MMN generator location between groups (Table 1). The MMN sources of most subjects of both groups (12 subjects in schizophrenia, 13 subjects in comparison group) were clearly localized in the superior temporal gyri (STG), mainly in the HG according to each individual's structural MRI (Fig. 1). The MMN sources of the rest of subjects were located in insula and subgyral space by using individual MRI.

The left MMN ECD power of the schizophrenic patients was

Discussion

Our results suggest that normal functional hemispheric asymmetry is altered in schizophrenia. In the control group, MMN ECD power of the left STG was greater than the right one, but in the schizophrenic patients, a reversal of MMN ECD powers was observed, as was that of normal functional asymmetry. With respect to AC, 86.7% of control subjects (13/15) showed normal functional left hemispherical dominance in contrast with only 13.3% of schizophrenics (2/15). Therefore, it is suggested that

Acknowledgements

This work was supported by the grant No. 04-2001-036 from Seoul National University Hospital.

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