Elsevier

Biological Psychiatry

Volume 51, Issue 12, 15 June 2002, Pages 1008-1011
Biological Psychiatry

Brief report
Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations

https://doi.org/10.1016/S0006-3223(02)01316-1Get rights and content

Abstract

Background: We used functional magnetic resonance imaging (fMRI) to investigate the frontotemporal disconnection hypothesis of schizophrenia.

Methods: Eight DSM-IV schizophrenia patients and 10 control subjects were studied with fMRI while they thought of the missing last word in 128 visually presented sentences. The fMRI data were analyzed comparing the effect of sentence completion (vs. rest) using a random effects analysis.

Results: There were no significant group differences in regional brain responses. Correlation coefficients between left temporal cortex (x = −54, y = −42, z = 3) and left dorsolateral prefrontal cortex (x = −39, y = 12, z = 24) were significantly lower in the schizophrenic group and were negatively correlated with the severity of auditory hallucinations.

Conclusions: Previous demonstrations of hypofrontality in schizophrenia may reflect particular task requirements. Frontotemporal functional connectivity is reduced in schizophrenia and may be associated with auditory hallucinations.

Introduction

Hypofrontality, particularly in dorsolateral prefrontal cortex (DLPFC), has been commonly but inconsistently found in schizophrenia Ebmeier et al 1995, Lawrie 1999, Weinberger and Berman 1996. Superior temporal gyrus (STG) abnormalities have been associated with auditory hallucinations (e.g., Shergill et al 2000), and some studies have suggested abnormal frontotemporal connectivity Fletcher et al 1996, Frith et al 1995, Yurgelun-Todd et al 1996. We have used fMRI to study schizophrenia patients and healthy control subjects while they completed a version of the Hayling Sentence Completion Task (Burgess and Shallice 1997). This task is sensitive to lesions of the frontal lobe (Burgess and Shallice 1996) and activates frontal and temporal regions (Nathaniel-James et al 1997). We tested the hypotheses that patients with schizophrenia would show less frontal activity and reduced frontotemporal connectivity, specifically between the left DLPFC and STG, compared with control subjects, and that reduced connectivity would be associated with auditory hallucinations.

Section snippets

Participants

The eight patients were clinically stable outpatients in Edinburgh, diagnosed with schizophrenia but no other major disorders according to DSM-IV criteria (American Psychiatric Association 1994) by two experienced clinicians (SML, ECJ). Three were men, and five were women; mean age was 28.6 years (SD 5.8), mean illness duration was 8 years (SD 6), and mean premorbid IQ (Nelson 1982) was 107.0 (SD 8.8). All patients were Caucasian and right-handed. All were medicated: three received clozapine,

Behavioral measures

The mean reaction times and word appropriateness scores for schizophrenia patients and control subjects are shown in Table 1. Both groups showed the expected increasing reaction times and word appropriateness scores with reduced constraint. Both measures showed group effects (p < .05 and p < .01 respectively) and condition (constraint) effects (both p < .01), but a nonsignificant interaction (both .05 <p < .1).

Sentence completion versus rest

Both groups showed activations of the bilateral DLPFC and the left middle/superior

Discussion

These schizophrenia patients were able to do the task, although they took longer and seemed to produce fewer appropriate words than did control subjects. We did not find hypofrontality while they performed this task nor any differential effect of varying constraint. Rather, we report direct evidence of reduced frontotemporal functional connectivity in schizophrenia, associated with auditory hallucinations but not delusions. We did, however, study a small group of high-functioning patients, only

Acknowledgements

The authors thank Majella Byrne, Richard Cosway, Julia Kestelman, and Robby Steel for help in recruiting the patients and control subjects, the MR physics and radiographer team at the Functional Imaging Laboratory in London, and the participating subjects. We also thank Norma Brearley for the careful preparation of the manuscript.

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