- Email: [email protected]
Frontal and thalamic hypometabolism in schizophrenia
216
14. Neuroimaging, Functional
was used to compute average coordinates (x, y, z) and to test for significant differences in the location of LIFG activation between phonological vs. semantic tasks in healthy individuals, visually vs. verbally presented stimulus, and overt vs. covert responses. Results Phonological activation coordinates (-47.3,21.3,13.0) were different to those of semantic activation (-40.2,22.7,6.5) with a statistically significant inferior site of activation in the z-axis for the semantic task. There were no significant differences between visually (46.2,18.2,7.2) vs. verbally (-44.6,22.9,12.4) presented stimuli, nor between covert (-44.3,22.7,11.3) vs. overt (-47.9,22.7,11.3) responses. Furthermore, the activation for the schizophrenic patients (52,6,31) lay outside the confidence intervals along the x, y, and z axes obtained in healthy subjects. Conclusion These results are consistent with previous data that suggest a functional independence of phonological vs. semantic tasks and with reports of heterogeneity within Broca's area. This method can be used to test formally whether different mental operations imply segregation of brain activation. An abnormal regional activation with the LIFG in schizophrenia is suggested. The functional and possible structural significance of this difference in schizophrenia requires further investigation.
FRONTAL
AND THALAMIC
HYPOMETABOLISM
IN SCHIZOPHRENIA
T. Cullen,* L. B e a s o n - H e l d , M. Tagamets, C. T a m m i n g a , H. H o l c o m b
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA Some functional imaging studies show a relative hypometabolism of the prefrontal cortex (PFC), thalamus and cerebellum in schizophrenia. In this study we used functional Magnetic Resonance Imaging (fMRI) to compare the neural activity of 10 healthy volunteers (3 men, 7 women, mean age 28 years); and 9 clinically stable outpatients diagnosed with schizophrenia (7 men, 2 women, mean age 35 years, mean age of onset 23 years, all medicated, with a mean BPRS of 29) during the performance of a delayed match to sample task. The task required subjects to decide whether two sequentially presented rectangles were the same or different from one another in height. There were two levels of task difficulty: easy and hard, reflecting either a substantial or a minimal difference in height between the two rectangles. Height disparity was adjusted to ensure similar levels of performance, as determined by error rates, in the two groups. Subjects underwent fMRI scanning as they performed this task using a Philips 1.5Tesla magnet and a single-shot gradient echo, echoplanar pulse sequence. The cerebral activity of the two groups was directly compared using a random effects model implemented in SPM 99. During the easy runs the control condition was associated with thalamic hypometabolism in the schizophrenic subjects relative to the healthy volunteers, Talaireach coordinates (4, -8, 12), cluster level significance, p=0.005 corrected. The difference in signal between the task minus the control conditions gives some indication of the brain circuitry involved in perceptual discrimination and retention over the delay period; comparing the activity in the two groups during the easy task minus the control condition reveals relative hypometabolism in medial frontal regions in the schizophrenic group, coordinates (-6, 28, 30) and (6, 24, 34), cluster level significance, p<0.001 corrected. A similar group difference was observed during the hard task which also involvced the anterior insula and dorsal prefrontal cortex, discrete clusters at coordinates (-34, 18, -12), (38, 28, 4), (-22, 4, 18) and (18, 26, 28), cluster level significance p<0.001 corrected. We conclude that subjects with schizophrenia
demonstrate abnormal neuronal activity in several disparate though interconnected areas of the brain including thalamus and PFC. Results are unlikely to reflect poor task performance in the disease group. Supported by the William K Warren Foundation
VARIABILITY
OF SPEECH HEMISPHERIC
SPECIALIZATION
IN SCHIZOPHRENIA
S. Dollfus,* A. R a z a f i m a n d i m b y , G. Josse, R Delamillieure, M. Joliot, R Brazo, B. Mazoyer, N. T z o u r i o - M a z o y e r
Centre EsqubvI, Centre Hospitalier Universitaire, Caen, France Aim : Functional imaging offers the opportunity to test the hypothesis that schizophrenia is a failure of left hemispheric dominance for language as suggested by Crow (1997). In order to do so, we investigated left /right functional asymmetries related to speech comprehension in right-handed (RH) schizophrenic patients and matched healthy subjects with functional magnetic resonance imaging. Methods : Nine pairs of schizophrenic and healthy subjects, all RH and matched on sex, age and education levels, were submitted to both 3D high resolution T1 and BOLD acquisitions (1.5-T GE Signa). A block design alternating 30-s duration periods of either auditory French (4 blocks) or Tamil stories (4 blocks) was used as previously (Mazoyer et al., 1993). We computed on the French-Tamil contrast a group conjunction analysis (to uncover activations present in both kinds of subjects) and individual analyses (to investigate inter-individual variability). Results : Conjunction analysis unveiled activations along the left superior temporal sulcus and the presence of homologous, although of smaller amplitude, right hemisphere clusters in both population. These results highlight the existence of an invariant network for language comprehension in both population that predominates in the left temporal lobe. More importantly, individual analysis evidenced a rightward hemispheric speech specialization in 3 schizophrenic patients (33%), characterized by strong right temporal activations, while 100% of the healthy subjects presented a leftward dominance during this task. Conclusion : These preliminary results show that, although a common network is implicated during speech processing in RH patients and their controls, an important inter-individual variability of hemispheric specialization for speech processing occurs in schizophrenic patients. They support the hypothesis of an abnormal developmental setting up of the left hemisphere specialization for language comprehension, which appears to be independent of handedness.
CROSS-MODAL DEFICIT
GENERALITY
OF THE GATING
IN SCHIZOPHRENIA
C. J. Edgar,* S. M o s e s , R. J. T h o m a , M. H u a n g , F. Hanlon, M. R Weisend, J. Bustillo, G. A. Miller, L. E. Adler, J. M. C a n i v e
Department of Psychology and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA Auditory paired-click studies have established a clear relationship between schizophrenia (Sz) and impaired sensory gating using the P50 component of the event-related brain potential. The response to the second click ($2) is not as reduced relative to the response to the first click (S 1) in patients as it is in controls. However, the presumed cross-modal generality of the gating deficit has not been systematically tested. The current study did so by investigating the M20 component of the somatosensory response. Patients were expected to
International Congress on Schizophrenia Research 2003
14. Neuroimaging, Functional
was used to compute average coordinates (x, y, z) and to test for significant differences in the location of LIFG activation between phonological vs. semantic tasks in healthy individuals, visually vs. verbally presented stimulus, and overt vs. covert responses. Results Phonological activation coordinates (-47.3,21.3,13.0) were different to those of semantic activation (-40.2,22.7,6.5) with a statistically significant inferior site of activation in the z-axis for the semantic task. There were no significant differences between visually (46.2,18.2,7.2) vs. verbally (-44.6,22.9,12.4) presented stimuli, nor between covert (-44.3,22.7,11.3) vs. overt (-47.9,22.7,11.3) responses. Furthermore, the activation for the schizophrenic patients (52,6,31) lay outside the confidence intervals along the x, y, and z axes obtained in healthy subjects. Conclusion These results are consistent with previous data that suggest a functional independence of phonological vs. semantic tasks and with reports of heterogeneity within Broca's area. This method can be used to test formally whether different mental operations imply segregation of brain activation. An abnormal regional activation with the LIFG in schizophrenia is suggested. The functional and possible structural significance of this difference in schizophrenia requires further investigation.
FRONTAL
AND THALAMIC
HYPOMETABOLISM
IN SCHIZOPHRENIA
T. Cullen,* L. B e a s o n - H e l d , M. Tagamets, C. T a m m i n g a , H. H o l c o m b
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA Some functional imaging studies show a relative hypometabolism of the prefrontal cortex (PFC), thalamus and cerebellum in schizophrenia. In this study we used functional Magnetic Resonance Imaging (fMRI) to compare the neural activity of 10 healthy volunteers (3 men, 7 women, mean age 28 years); and 9 clinically stable outpatients diagnosed with schizophrenia (7 men, 2 women, mean age 35 years, mean age of onset 23 years, all medicated, with a mean BPRS of 29) during the performance of a delayed match to sample task. The task required subjects to decide whether two sequentially presented rectangles were the same or different from one another in height. There were two levels of task difficulty: easy and hard, reflecting either a substantial or a minimal difference in height between the two rectangles. Height disparity was adjusted to ensure similar levels of performance, as determined by error rates, in the two groups. Subjects underwent fMRI scanning as they performed this task using a Philips 1.5Tesla magnet and a single-shot gradient echo, echoplanar pulse sequence. The cerebral activity of the two groups was directly compared using a random effects model implemented in SPM 99. During the easy runs the control condition was associated with thalamic hypometabolism in the schizophrenic subjects relative to the healthy volunteers, Talaireach coordinates (4, -8, 12), cluster level significance, p=0.005 corrected. The difference in signal between the task minus the control conditions gives some indication of the brain circuitry involved in perceptual discrimination and retention over the delay period; comparing the activity in the two groups during the easy task minus the control condition reveals relative hypometabolism in medial frontal regions in the schizophrenic group, coordinates (-6, 28, 30) and (6, 24, 34), cluster level significance, p<0.001 corrected. A similar group difference was observed during the hard task which also involvced the anterior insula and dorsal prefrontal cortex, discrete clusters at coordinates (-34, 18, -12), (38, 28, 4), (-22, 4, 18) and (18, 26, 28), cluster level significance p<0.001 corrected. We conclude that subjects with schizophrenia
demonstrate abnormal neuronal activity in several disparate though interconnected areas of the brain including thalamus and PFC. Results are unlikely to reflect poor task performance in the disease group. Supported by the William K Warren Foundation
VARIABILITY
OF SPEECH HEMISPHERIC
SPECIALIZATION
IN SCHIZOPHRENIA
S. Dollfus,* A. R a z a f i m a n d i m b y , G. Josse, R Delamillieure, M. Joliot, R Brazo, B. Mazoyer, N. T z o u r i o - M a z o y e r
Centre EsqubvI, Centre Hospitalier Universitaire, Caen, France Aim : Functional imaging offers the opportunity to test the hypothesis that schizophrenia is a failure of left hemispheric dominance for language as suggested by Crow (1997). In order to do so, we investigated left /right functional asymmetries related to speech comprehension in right-handed (RH) schizophrenic patients and matched healthy subjects with functional magnetic resonance imaging. Methods : Nine pairs of schizophrenic and healthy subjects, all RH and matched on sex, age and education levels, were submitted to both 3D high resolution T1 and BOLD acquisitions (1.5-T GE Signa). A block design alternating 30-s duration periods of either auditory French (4 blocks) or Tamil stories (4 blocks) was used as previously (Mazoyer et al., 1993). We computed on the French-Tamil contrast a group conjunction analysis (to uncover activations present in both kinds of subjects) and individual analyses (to investigate inter-individual variability). Results : Conjunction analysis unveiled activations along the left superior temporal sulcus and the presence of homologous, although of smaller amplitude, right hemisphere clusters in both population. These results highlight the existence of an invariant network for language comprehension in both population that predominates in the left temporal lobe. More importantly, individual analysis evidenced a rightward hemispheric speech specialization in 3 schizophrenic patients (33%), characterized by strong right temporal activations, while 100% of the healthy subjects presented a leftward dominance during this task. Conclusion : These preliminary results show that, although a common network is implicated during speech processing in RH patients and their controls, an important inter-individual variability of hemispheric specialization for speech processing occurs in schizophrenic patients. They support the hypothesis of an abnormal developmental setting up of the left hemisphere specialization for language comprehension, which appears to be independent of handedness.
CROSS-MODAL DEFICIT
GENERALITY
OF THE GATING
IN SCHIZOPHRENIA
C. J. Edgar,* S. M o s e s , R. J. T h o m a , M. H u a n g , F. Hanlon, M. R Weisend, J. Bustillo, G. A. Miller, L. E. Adler, J. M. C a n i v e
Department of Psychology and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA Auditory paired-click studies have established a clear relationship between schizophrenia (Sz) and impaired sensory gating using the P50 component of the event-related brain potential. The response to the second click ($2) is not as reduced relative to the response to the first click (S 1) in patients as it is in controls. However, the presumed cross-modal generality of the gating deficit has not been systematically tested. The current study did so by investigating the M20 component of the somatosensory response. Patients were expected to
International Congress on Schizophrenia Research 2003