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399. A PET study of brain activation in response to auditory hallucinations and external speech in schizophrenic patients
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BIOL PSYCHIATRY 2000;47:1S–173S
398. FUNCTIONAL MRI STUDIES OF AUDITORY HALLUCINATIONS P.K. McGuire, S. Shergill, M. Brammer, S. Williams, R.M. Murray Institute of Psychiatry & GKT School of Medicine, London We used functional MRI to examine the neural correlates of 1) cognitive processes putatively relevant to auditory hallucinations, and 2) auditory hallucinations themselves. Images were acquired on a 1.5T system and analysed using nonparametric methods. In study 1, patients with schizophrenia who had a history of frequent hallucinations were compared with volunteers. Images were acquired while subjects imagined another person’s speech, which entails the implicit generation and monitoring of inner speech. Volunteers engaged a network of areas including the inferior frontal and temporal cortex bilaterally, the SMA, cingulate cortex, and the cerebellar cortex. Patients prone to hallucinations differed from controls in showing attenuated activation in the lateral temporal cortex and fusiform gyrus/cerebellum. Study 2 employed a within-subject event related design, comparing activity in patients with schizophrenia when they were and were not experiencing auditory hallucinations. Hallucinations were associated with activation in a network that resembled that engaged during imagining speech, except that there was an absence of activation in the SMA and cerebellum, but additional activation in the left parahippocampal cortex, and in the right thalamus and inferior colliculus. These data suggest there is a close relationship between auditory hallucinations and inner speech, and are consistent with the notion that hallucinations represent inner speech which has been misidentified as “alien” due to defective verbal self-monitoring.
399. A PET STUDY OF BRAIN ACTIVATION IN RESPONSE TO AUDITORY HALLUCINATIONS AND EXTERNAL SPEECH IN SCHIZOPHRENIC PATIENTS D.L. Copolov (1), M.L. Seal (1,3), P. Maruff (1,3), M. Waite (1), M.T.H. Wong (1), R. Ulusoy (1,2,4), G.F. Egan (1,4) (1) Mental Health Research Institute of Victoria, Parkville, Australia; (2) Swinburne University of Technology, Hawthorn, Australia; (3) La Trobe University, Bundoora, Australia; (4) Howard Florey Institute, University of Melbourne, Australia Imaging neuroanatomical correlates of auditory hallucinations using positron emission tomography (PET) techniques is difficult, due mainly to their unpredictable nature. This study identified brain activations associated with self-reports of auditory perception using a PET correlation analysis method (after Silbersweig et al., 1995) in hallucinating (n ⫽ 9) and non-hallucinating (n ⫽ 7) schizophrenic patients. Analyses involved relating the timing and duration of patient-reported auditory perception to the injection and uptake of a radiotracer (H2[15O]). Hallucinating and non-hallucinating patients were asked to report the onset and duration of auditory hallucinations or auditory stimuli (of varying duration), respectively, from which a standard score was computed. All hallucinating patients reported experiencing auditory hallucinations during scans and results indicated between-subject variability in the duration of auditory hallucinatory experience (mean ⫽ 27.7 secs, sd ⫽ 23.7). To undertake correlational analyses, reconstructed images for each participant were aligned, normalised to a Talairach space, spatially smoothed, and
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analysed using SPM99. Both groups demonstrated significant temporal cortex activation (z ⫽ 3.5, p ⬍ 0.001). Both individually and as a group, non-hallucinating patients demonstrated robust bilateral auditory cortex activation (BA 22, 40/42). The group of hallucinating patients demonstrated right medial and inferior frontal activations (BA 45/46), focal bilateral temporal lobe activations (BA 22, 37), and a left parahippocampal gyral activation. These findings expand upon previous observations (McGuire et al, 1996) that the perception of self- and externally-generated speech are processed in similar regions of temporal cortex and that hallucinating subjects have a reduced capacity to monitor self-generated verbal mental imagery.
400. TEMPORAL LOBE RESPONSES TO SPEECH PROBES IN SCHIZOPHRENIA J.M. Ford (1,2), D.H. Mathalon (3), Susan L. Whitfield (1,2), W.O. Faustman (1,2) (1) Department of Psychiatry & Behavioral Science, Stanford University School of Medicine, Stanford, CA; (2) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; (3) SRI International, Menlo Park, CA Hemodynamic brain imaging studies implicate temporal lobe dysfunction in auditory hallucinations. When asked to engage in inner speech, controls and patients with schizophrenia showed similar patterns of brain activation, but when imagining speech in someone else’s voice (auditory imagery), patients showed less activation in left middle temporal gryus and more in right superior temporal gyrus than control subjects (McGuire et al, 1996). We used event-related brain potential (ERPs), a temporally sensitive brain imaging method, to assess responses to speech probes during inner speech and auditory imagery in 11 patients with schizophrenia, 9 of whom suffered from chronic auditory hallucinations, and 7 ageand sex-matched normal controls. The early (⬃100 msec) negative component of the ERP (N1) recorded over left and right temporal lobe sites to speech probes (syllable /ba/) showed a significantly different pattern in controls and schizophrenic patients. In controls, N1 was reduced over left relative to right temporal lobe sites during inner speech and was further reduced during auditory imagery, with no change in N1 on the right, suggesting preferential involvement of the left temporal lobe in distinguishing inner speech from auditory imagery. In schizophrenic patients, although the N1 was reduced over left relative to right temporal sites during inner speech (similar to the controls), auditory imagery led to a reduction of N1 over the right, with no change in N1 over the left temporal site. This is consistent with brain imaging data of McGuire et al., showing abnormal involvement of the right temporal lobe during auditory imagery, perhaps akin to hallucinations. Furthermore, abnormal effects are seen as early as 100 msec after stimulus onset. Supported by DVA and NIMH (MH40052, MH58262).
401. ONE HERTZ rTMS OF LEFT TEMPOROPARIETAL CORTEX IN SCHIZOPHRENIC PATIENTS REPORTING AUDITORY HALLUCINATIONS R.E. Hoffman, N.N. Boutros, R.M. Berman, S. Hu, F. Rachid, N.A. Schaffer, J.H. Krystal, D.S. Charney Department of Psychiatry, Yale University School of Medicine Studies suggest that auditory hallucinations (AHs) of spoken speech arise partly from brain regions responsible for speech processing. One
BIOL PSYCHIATRY 2000;47:1S–173S
398. FUNCTIONAL MRI STUDIES OF AUDITORY HALLUCINATIONS P.K. McGuire, S. Shergill, M. Brammer, S. Williams, R.M. Murray Institute of Psychiatry & GKT School of Medicine, London We used functional MRI to examine the neural correlates of 1) cognitive processes putatively relevant to auditory hallucinations, and 2) auditory hallucinations themselves. Images were acquired on a 1.5T system and analysed using nonparametric methods. In study 1, patients with schizophrenia who had a history of frequent hallucinations were compared with volunteers. Images were acquired while subjects imagined another person’s speech, which entails the implicit generation and monitoring of inner speech. Volunteers engaged a network of areas including the inferior frontal and temporal cortex bilaterally, the SMA, cingulate cortex, and the cerebellar cortex. Patients prone to hallucinations differed from controls in showing attenuated activation in the lateral temporal cortex and fusiform gyrus/cerebellum. Study 2 employed a within-subject event related design, comparing activity in patients with schizophrenia when they were and were not experiencing auditory hallucinations. Hallucinations were associated with activation in a network that resembled that engaged during imagining speech, except that there was an absence of activation in the SMA and cerebellum, but additional activation in the left parahippocampal cortex, and in the right thalamus and inferior colliculus. These data suggest there is a close relationship between auditory hallucinations and inner speech, and are consistent with the notion that hallucinations represent inner speech which has been misidentified as “alien” due to defective verbal self-monitoring.
399. A PET STUDY OF BRAIN ACTIVATION IN RESPONSE TO AUDITORY HALLUCINATIONS AND EXTERNAL SPEECH IN SCHIZOPHRENIC PATIENTS D.L. Copolov (1), M.L. Seal (1,3), P. Maruff (1,3), M. Waite (1), M.T.H. Wong (1), R. Ulusoy (1,2,4), G.F. Egan (1,4) (1) Mental Health Research Institute of Victoria, Parkville, Australia; (2) Swinburne University of Technology, Hawthorn, Australia; (3) La Trobe University, Bundoora, Australia; (4) Howard Florey Institute, University of Melbourne, Australia Imaging neuroanatomical correlates of auditory hallucinations using positron emission tomography (PET) techniques is difficult, due mainly to their unpredictable nature. This study identified brain activations associated with self-reports of auditory perception using a PET correlation analysis method (after Silbersweig et al., 1995) in hallucinating (n ⫽ 9) and non-hallucinating (n ⫽ 7) schizophrenic patients. Analyses involved relating the timing and duration of patient-reported auditory perception to the injection and uptake of a radiotracer (H2[15O]). Hallucinating and non-hallucinating patients were asked to report the onset and duration of auditory hallucinations or auditory stimuli (of varying duration), respectively, from which a standard score was computed. All hallucinating patients reported experiencing auditory hallucinations during scans and results indicated between-subject variability in the duration of auditory hallucinatory experience (mean ⫽ 27.7 secs, sd ⫽ 23.7). To undertake correlational analyses, reconstructed images for each participant were aligned, normalised to a Talairach space, spatially smoothed, and
Saturday Abstracts
analysed using SPM99. Both groups demonstrated significant temporal cortex activation (z ⫽ 3.5, p ⬍ 0.001). Both individually and as a group, non-hallucinating patients demonstrated robust bilateral auditory cortex activation (BA 22, 40/42). The group of hallucinating patients demonstrated right medial and inferior frontal activations (BA 45/46), focal bilateral temporal lobe activations (BA 22, 37), and a left parahippocampal gyral activation. These findings expand upon previous observations (McGuire et al, 1996) that the perception of self- and externally-generated speech are processed in similar regions of temporal cortex and that hallucinating subjects have a reduced capacity to monitor self-generated verbal mental imagery.
400. TEMPORAL LOBE RESPONSES TO SPEECH PROBES IN SCHIZOPHRENIA J.M. Ford (1,2), D.H. Mathalon (3), Susan L. Whitfield (1,2), W.O. Faustman (1,2) (1) Department of Psychiatry & Behavioral Science, Stanford University School of Medicine, Stanford, CA; (2) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; (3) SRI International, Menlo Park, CA Hemodynamic brain imaging studies implicate temporal lobe dysfunction in auditory hallucinations. When asked to engage in inner speech, controls and patients with schizophrenia showed similar patterns of brain activation, but when imagining speech in someone else’s voice (auditory imagery), patients showed less activation in left middle temporal gryus and more in right superior temporal gyrus than control subjects (McGuire et al, 1996). We used event-related brain potential (ERPs), a temporally sensitive brain imaging method, to assess responses to speech probes during inner speech and auditory imagery in 11 patients with schizophrenia, 9 of whom suffered from chronic auditory hallucinations, and 7 ageand sex-matched normal controls. The early (⬃100 msec) negative component of the ERP (N1) recorded over left and right temporal lobe sites to speech probes (syllable /ba/) showed a significantly different pattern in controls and schizophrenic patients. In controls, N1 was reduced over left relative to right temporal lobe sites during inner speech and was further reduced during auditory imagery, with no change in N1 on the right, suggesting preferential involvement of the left temporal lobe in distinguishing inner speech from auditory imagery. In schizophrenic patients, although the N1 was reduced over left relative to right temporal sites during inner speech (similar to the controls), auditory imagery led to a reduction of N1 over the right, with no change in N1 over the left temporal site. This is consistent with brain imaging data of McGuire et al., showing abnormal involvement of the right temporal lobe during auditory imagery, perhaps akin to hallucinations. Furthermore, abnormal effects are seen as early as 100 msec after stimulus onset. Supported by DVA and NIMH (MH40052, MH58262).
401. ONE HERTZ rTMS OF LEFT TEMPOROPARIETAL CORTEX IN SCHIZOPHRENIC PATIENTS REPORTING AUDITORY HALLUCINATIONS R.E. Hoffman, N.N. Boutros, R.M. Berman, S. Hu, F. Rachid, N.A. Schaffer, J.H. Krystal, D.S. Charney Department of Psychiatry, Yale University School of Medicine Studies suggest that auditory hallucinations (AHs) of spoken speech arise partly from brain regions responsible for speech processing. One