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Ambiguities in interpreting functional neuroimaging studies of schizophrenia
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X. Functional Imaging A.229. AMBIGUITIES IN INTERPRETING FUNCTIONAL NEUROIMAGING STUDIES OF SCHIZOPHRENIA P.C. Fletcher, C.D. Frith, P.J. M c k e n n a , R.J. D o l a n
Corresponding author: P. C. Fletcher, Department of Psychiatry, Addenbrookes Hospital, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 2QQ; Institat far Hirnforschung, Heinrich-Heine Universitgit, D 40225 Dfisseldorf Germany Functional neuroimaging studies of schizophrenia have produced confusing results particularly with respect to function of prefrontal cortex (PFC). A fundamental source of this confusion concerns the unresolved question of whether it is better to evaluate brain activity in the context of a task in which subjects show impaired performance or one in which their performance is optimised to make it comparable with control subjects. Difficulties arise in both cases with respect to interpretations of findings whether these observations show apparently normal of abnormal physiological function. We carried out a study, using PET, in healthy controls and patients with schizophrenia. The effect of increasing memory load was observed in two contexts: normal and abnormal performance. It was found that left PFC response to increasing memory demands was measurably normal in the case when performance was unimpaired. However, as demands became greater, and performance across the two groups diverged, PFC activity showed a plateau in patients while it continued to climb in control subjects. These findings have implications for the understanding of both normal and abnormal findings in functional neuroimaging studies of mental illness. They indicate that findings must be interpreted within the context of how well or badly patients are able to perform a given task. Moreover, it may be the case that certain functional systems in schizophrenia may only be demonstrably abnormal under conditions of cognitive stress making it unlikely that any core trait abnormality will be elucidated by these techniques.
A.230. ALIEN VOICES: fMRI STUDIES OF OVERT VERBAL SELF-MONITORING IN SCHIZOPHRENIA C.H.Y. Fu*, F. A h m a d , E. A m a r o , M. B r a m m e r , C. Andrew, S.C.R. Williams, V. G i a m p i e t r o , P.K. M c G u i r e
*Department of Psychological Medicine, Institute of Psychiatry, London SE5 8AF, UK Introduction: Disordered verbal self-monitoring is characteristic of patients with schizophrenia with active auditory hallluc-
inations 1. However, functional magnetic resonance imaging (fMRI) of tasks that engage self-monitoring is potentially limited by the effects of scanner noise. We have developed fMRI acquisition sequences to overcome this limitation. Method: Subjects read aloud adjectives and heard their voices which were either: (i) undistorted; (ii) pitch distorted; (iii) replaced by an alien voice; (iv) replaced by a distorted alien voice. Subjects were matched groups of male patients with schizophrenia with active hallucinations, patients in remission, and controls. FMR images were acquired in a 1.5 Tesla GE Sigma System, and three designs were employed. All designs involved the presentation of words which were read and heard during silent portions of the acquisition sequence. In a blocked design, trials of a given condition were presented in 30 s epochs, alternating with another condition. In the first event-related design, single volumes were acquired at staggered intervals after each stimulus with a mean T R = I 0 s . In the second event-related design, 5 volumes were acquired following each stimulus with a TR = 3.25 s. Results: Comparison of blocked and event-related studies of the same conditions in the same subjects indicated that the event-related methods detected significantly more temporal activation. Results to-date indicate that patients with hallucinations and delusions are more likely than controls and patients in remission to misidentify their own distorted speech as alien. Conclusions: Investigation of overt verbal self-monitoring is feasible with fMRI. Event-related fMRI designs were superior to the blocked design as there was likely habituation of the neural response with repeated trials of the same condition.
Reference 1. Johns L.C., McGuire P.K. Verbal self-monitoring and auditory hallucinations in schizophrenia. Lancet 1999, Feb 6; 353(9151 ): 469-70.
A.231. DO PATIENTS WITH SCHIZOPHRENIA OVER-MONITOR PROSODIC ASPECTS OF SPEECH? AN fMRI STUDY R. Mitchell, M. Barry, R. Elliott, A. C r u t t e n d e n , J.F.W. Deakin, P.W.R. W o o d r u f f
G907, Neuroseience and Psychiatry Unit, Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK Evidence suggests that the normal left-lateralised response to speech is reversed in patients with schizophrenia 1. Both structural and functional hypotheses can be proposed to account for this phenomenon: (i) processing of language is performed by right hemisphere structures because of left hemisphere damage, or (ii) processing of prosodic aspects of language is performed by right hemisphere structures. Reversal could be due to over-attention to prosody. To examine these competing hypotheses we performed an fMRI study of 12 healthy controls, and 12 schizophrenic patients. In three A/B
X. Functional Imaging A.229. AMBIGUITIES IN INTERPRETING FUNCTIONAL NEUROIMAGING STUDIES OF SCHIZOPHRENIA P.C. Fletcher, C.D. Frith, P.J. M c k e n n a , R.J. D o l a n
Corresponding author: P. C. Fletcher, Department of Psychiatry, Addenbrookes Hospital, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 2QQ; Institat far Hirnforschung, Heinrich-Heine Universitgit, D 40225 Dfisseldorf Germany Functional neuroimaging studies of schizophrenia have produced confusing results particularly with respect to function of prefrontal cortex (PFC). A fundamental source of this confusion concerns the unresolved question of whether it is better to evaluate brain activity in the context of a task in which subjects show impaired performance or one in which their performance is optimised to make it comparable with control subjects. Difficulties arise in both cases with respect to interpretations of findings whether these observations show apparently normal of abnormal physiological function. We carried out a study, using PET, in healthy controls and patients with schizophrenia. The effect of increasing memory load was observed in two contexts: normal and abnormal performance. It was found that left PFC response to increasing memory demands was measurably normal in the case when performance was unimpaired. However, as demands became greater, and performance across the two groups diverged, PFC activity showed a plateau in patients while it continued to climb in control subjects. These findings have implications for the understanding of both normal and abnormal findings in functional neuroimaging studies of mental illness. They indicate that findings must be interpreted within the context of how well or badly patients are able to perform a given task. Moreover, it may be the case that certain functional systems in schizophrenia may only be demonstrably abnormal under conditions of cognitive stress making it unlikely that any core trait abnormality will be elucidated by these techniques.
A.230. ALIEN VOICES: fMRI STUDIES OF OVERT VERBAL SELF-MONITORING IN SCHIZOPHRENIA C.H.Y. Fu*, F. A h m a d , E. A m a r o , M. B r a m m e r , C. Andrew, S.C.R. Williams, V. G i a m p i e t r o , P.K. M c G u i r e
*Department of Psychological Medicine, Institute of Psychiatry, London SE5 8AF, UK Introduction: Disordered verbal self-monitoring is characteristic of patients with schizophrenia with active auditory hallluc-
inations 1. However, functional magnetic resonance imaging (fMRI) of tasks that engage self-monitoring is potentially limited by the effects of scanner noise. We have developed fMRI acquisition sequences to overcome this limitation. Method: Subjects read aloud adjectives and heard their voices which were either: (i) undistorted; (ii) pitch distorted; (iii) replaced by an alien voice; (iv) replaced by a distorted alien voice. Subjects were matched groups of male patients with schizophrenia with active hallucinations, patients in remission, and controls. FMR images were acquired in a 1.5 Tesla GE Sigma System, and three designs were employed. All designs involved the presentation of words which were read and heard during silent portions of the acquisition sequence. In a blocked design, trials of a given condition were presented in 30 s epochs, alternating with another condition. In the first event-related design, single volumes were acquired at staggered intervals after each stimulus with a mean T R = I 0 s . In the second event-related design, 5 volumes were acquired following each stimulus with a TR = 3.25 s. Results: Comparison of blocked and event-related studies of the same conditions in the same subjects indicated that the event-related methods detected significantly more temporal activation. Results to-date indicate that patients with hallucinations and delusions are more likely than controls and patients in remission to misidentify their own distorted speech as alien. Conclusions: Investigation of overt verbal self-monitoring is feasible with fMRI. Event-related fMRI designs were superior to the blocked design as there was likely habituation of the neural response with repeated trials of the same condition.
Reference 1. Johns L.C., McGuire P.K. Verbal self-monitoring and auditory hallucinations in schizophrenia. Lancet 1999, Feb 6; 353(9151 ): 469-70.
A.231. DO PATIENTS WITH SCHIZOPHRENIA OVER-MONITOR PROSODIC ASPECTS OF SPEECH? AN fMRI STUDY R. Mitchell, M. Barry, R. Elliott, A. C r u t t e n d e n , J.F.W. Deakin, P.W.R. W o o d r u f f
G907, Neuroseience and Psychiatry Unit, Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK Evidence suggests that the normal left-lateralised response to speech is reversed in patients with schizophrenia 1. Both structural and functional hypotheses can be proposed to account for this phenomenon: (i) processing of language is performed by right hemisphere structures because of left hemisphere damage, or (ii) processing of prosodic aspects of language is performed by right hemisphere structures. Reversal could be due to over-attention to prosody. To examine these competing hypotheses we performed an fMRI study of 12 healthy controls, and 12 schizophrenic patients. In three A/B