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rCBF pattern differences in trained normal volunteers and schizophrenic patients performing effortful tone recognition tasks
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chronic medicated (n= 13) schizophrenic patients and normal volunteers (n= 18). After correcting for age, height, weight, sex, education and parental education, there were no differences between subject groups on volume measures of total brain, total frontal lobe, frontal white matter, frontal grey matter or hippocampus. Significant correlations between total brain volumes and the frontal and hippocampal volumes (up to r=0.9, p<0.02) were observed in the schizophrenic groups but not the normal volunteers. Never treated and chronic medicated patients had lower phosphomonoesters (p < 0.001 ) and higher calculated intracellular magnesium levels (p < 0.001 ) compared to normal volunteers. These findings suggest membrane phospholipid abnormalities in schizophrenia. As no differences were seen between patients and normals on frontal grey or white matter, 31p MRS abnormalities cannot be accounted for by tissue loss. The presence of a correlation between total brain volumes and the frontal and hippocampal volumes only in patients may suggest increased brain symmetry associated with abnormal brain development. Further subjects and regions of interest are being analyzed. This work was supported by the Canadian Psychiatric Research Foundation, the Medical Research Council of Canada, Grant No. MT-12078 and the National Institute of Mental Health, Grant No. 1R01 MH 50768-01.
were 676.3+119.3msec, NV; and 745.7+118.1msec, SZ. Groups did not differ significantly from one another on either measure. Statistical Parametric Maps (MRC Cyclotron Unit, Hammersmith Hospital, London) were created to contrast rCBF activity patterns in NV and SZ. A group by condition comparison (2 × 2 ANOVA) revealed the NV having greater rCBF activity in left inferior frontal (z = - 8 nun), left superior frontal (z = - 8 mm), and right middle temporal (z = - 12 mm); cluster volumes averaged 3.5 cubic cm. SZ exhibited greater rCBF clusters in the left inferior temporal gyrus (z = 0 mm), left thalamus (z = + 8 mm), and right superior temporal gyrus (z= +20 mm); cluster volumes averaged 5.0 cubic cm. At this preliminary stage of analysis there appear to be differences in functional auditory circuitry associated with these two groups in spite of their similar performance levels.
THE APPLICATION OF A FINITE NORMAL MIXTURE MODEL TO MR IMAGE SEGMENTATION AND SUBSEQUENT STEREOTAXIC NORMALIZATION Z. Z h a o , H.H. H o l c o m b
Maryland Psychiatric Research Center, Univ. Maryland, Baltimore, MD 21228, USA rCBF PATTERN DIFFERENCES IN TRAINED NORMAL VOLUNTEERS AND SCHIZOPHRENIC PATIENTS PERFORMING EFFORTFUL TONE RECOGNITION TASKS H.H. Holcomb*, P.J. Caudill, Z. Z h a o , D. Medoff, A. Lahti, H.T. Ravert, R.F. D a n n a l s , C.A. T a m m i n g a
Maryland Psych. Res. Cntr. and Johns Hopkins Medical Institutes, Baltimore, MD 21228, USA Brain activity patterns measured by blood flow (rCBF) and electrophysiology are modulated by task novelty and difficulty. Individual variations in task performance, floor and ceiling effects make it difficult to interpret rCBF patterns obtained from diverse diagnostic groups. Large performance differences are particularly important in studies comparing normal volunteers (NV) with schizophrenics (SZ). We report rCBF pattern differences associated with tone frequency recognition, made by trained NV and SZ during multiple 150 labeled water PET studies. Eight NV and four SZ were trained (2400-3200 trials) to recognize high frequency vs low frequency tones (avg. difference= 18 Hz, NV; 47 Hz, SZ; reference tone= 1500 Hz). This was a forced choice recognition task with a fixed intertrial interval of 2 s. Twelve rCBF scans were obtained from each subject, 4 resting with eyes and ears open without tones, 4 sensory-motor control scans in which the subjects alternated button responses between right and left hands in time to tones, and 4 tone recognition scans. Only the recognition and rest scan analyses are reported here. The average accuracy for the 60 trials presented during each decision scan was 79.4%+9.1, NV; and 76.9%+13.7, SZ. Median accurate response times
Whereas positron emission tomography (PET) provides physiological maps of regional cerebral blood flow (rCBF), magnetic resonance imaging (MRI) represents the anatomical structure of the brain. Optimal fusion of these modalities requires multiple corrections for resolution, registration, and segmentation. This protocol describes a rigorous, but approximate solution to that problem. PET image data from eight normal volunteers performing an auditory tone recognition task, were analyzed using Statistical Parametric Mapping (MRC Cyclotron Unit, Hammersmith Hospital). PET rCBF data were stereotaxically normalized to match data in the coordinate space of Talairach and Tournoux (1988). High resolution MRI data (SPGR acquisition, 1.5 mm 3D) were initially registered manually (MIRA, Loats Associations, Inc.) and then algorithmically with corresponding PET volumes (Woods et al., JCAT 16: 620-633, 1993). To reconcile differences in smoothness between MR and PET data the full width half maximal signal distribution (FWHM) was measured from the normalized PET image of each subject (Worsley et al., J. Cereb. Blood Flow Metabol. 12: 900-918, 1992). Each subject's MRI was then convolved with a 3D Gaussian filter to match its smoothness with that of its companion PET. The MR data were then segmented according to a finite normal mixture model. This stochastic procedure allowed us to transform the MR image into a pattern similar to that of the PET. Gray matter was assigned the highest gray scale values, white matter intermediate, and cerebrospinal fluid the lowest. Stereotaxic normalization was then applied to each modified MRI (Friston et al., JCAT 15: 634-639, 1991). Averaged group anatomical MRI templates were then generated to match the normalized PET data sets. The average MRI/PET template fit was then measured using the root mean square error method.
chronic medicated (n= 13) schizophrenic patients and normal volunteers (n= 18). After correcting for age, height, weight, sex, education and parental education, there were no differences between subject groups on volume measures of total brain, total frontal lobe, frontal white matter, frontal grey matter or hippocampus. Significant correlations between total brain volumes and the frontal and hippocampal volumes (up to r=0.9, p<0.02) were observed in the schizophrenic groups but not the normal volunteers. Never treated and chronic medicated patients had lower phosphomonoesters (p < 0.001 ) and higher calculated intracellular magnesium levels (p < 0.001 ) compared to normal volunteers. These findings suggest membrane phospholipid abnormalities in schizophrenia. As no differences were seen between patients and normals on frontal grey or white matter, 31p MRS abnormalities cannot be accounted for by tissue loss. The presence of a correlation between total brain volumes and the frontal and hippocampal volumes only in patients may suggest increased brain symmetry associated with abnormal brain development. Further subjects and regions of interest are being analyzed. This work was supported by the Canadian Psychiatric Research Foundation, the Medical Research Council of Canada, Grant No. MT-12078 and the National Institute of Mental Health, Grant No. 1R01 MH 50768-01.
were 676.3+119.3msec, NV; and 745.7+118.1msec, SZ. Groups did not differ significantly from one another on either measure. Statistical Parametric Maps (MRC Cyclotron Unit, Hammersmith Hospital, London) were created to contrast rCBF activity patterns in NV and SZ. A group by condition comparison (2 × 2 ANOVA) revealed the NV having greater rCBF activity in left inferior frontal (z = - 8 nun), left superior frontal (z = - 8 mm), and right middle temporal (z = - 12 mm); cluster volumes averaged 3.5 cubic cm. SZ exhibited greater rCBF clusters in the left inferior temporal gyrus (z = 0 mm), left thalamus (z = + 8 mm), and right superior temporal gyrus (z= +20 mm); cluster volumes averaged 5.0 cubic cm. At this preliminary stage of analysis there appear to be differences in functional auditory circuitry associated with these two groups in spite of their similar performance levels.
THE APPLICATION OF A FINITE NORMAL MIXTURE MODEL TO MR IMAGE SEGMENTATION AND SUBSEQUENT STEREOTAXIC NORMALIZATION Z. Z h a o , H.H. H o l c o m b
Maryland Psychiatric Research Center, Univ. Maryland, Baltimore, MD 21228, USA rCBF PATTERN DIFFERENCES IN TRAINED NORMAL VOLUNTEERS AND SCHIZOPHRENIC PATIENTS PERFORMING EFFORTFUL TONE RECOGNITION TASKS H.H. Holcomb*, P.J. Caudill, Z. Z h a o , D. Medoff, A. Lahti, H.T. Ravert, R.F. D a n n a l s , C.A. T a m m i n g a
Maryland Psych. Res. Cntr. and Johns Hopkins Medical Institutes, Baltimore, MD 21228, USA Brain activity patterns measured by blood flow (rCBF) and electrophysiology are modulated by task novelty and difficulty. Individual variations in task performance, floor and ceiling effects make it difficult to interpret rCBF patterns obtained from diverse diagnostic groups. Large performance differences are particularly important in studies comparing normal volunteers (NV) with schizophrenics (SZ). We report rCBF pattern differences associated with tone frequency recognition, made by trained NV and SZ during multiple 150 labeled water PET studies. Eight NV and four SZ were trained (2400-3200 trials) to recognize high frequency vs low frequency tones (avg. difference= 18 Hz, NV; 47 Hz, SZ; reference tone= 1500 Hz). This was a forced choice recognition task with a fixed intertrial interval of 2 s. Twelve rCBF scans were obtained from each subject, 4 resting with eyes and ears open without tones, 4 sensory-motor control scans in which the subjects alternated button responses between right and left hands in time to tones, and 4 tone recognition scans. Only the recognition and rest scan analyses are reported here. The average accuracy for the 60 trials presented during each decision scan was 79.4%+9.1, NV; and 76.9%+13.7, SZ. Median accurate response times
Whereas positron emission tomography (PET) provides physiological maps of regional cerebral blood flow (rCBF), magnetic resonance imaging (MRI) represents the anatomical structure of the brain. Optimal fusion of these modalities requires multiple corrections for resolution, registration, and segmentation. This protocol describes a rigorous, but approximate solution to that problem. PET image data from eight normal volunteers performing an auditory tone recognition task, were analyzed using Statistical Parametric Mapping (MRC Cyclotron Unit, Hammersmith Hospital). PET rCBF data were stereotaxically normalized to match data in the coordinate space of Talairach and Tournoux (1988). High resolution MRI data (SPGR acquisition, 1.5 mm 3D) were initially registered manually (MIRA, Loats Associations, Inc.) and then algorithmically with corresponding PET volumes (Woods et al., JCAT 16: 620-633, 1993). To reconcile differences in smoothness between MR and PET data the full width half maximal signal distribution (FWHM) was measured from the normalized PET image of each subject (Worsley et al., J. Cereb. Blood Flow Metabol. 12: 900-918, 1992). Each subject's MRI was then convolved with a 3D Gaussian filter to match its smoothness with that of its companion PET. The MR data were then segmented according to a finite normal mixture model. This stochastic procedure allowed us to transform the MR image into a pattern similar to that of the PET. Gray matter was assigned the highest gray scale values, white matter intermediate, and cerebrospinal fluid the lowest. Stereotaxic normalization was then applied to each modified MRI (Friston et al., JCAT 15: 634-639, 1991). Averaged group anatomical MRI templates were then generated to match the normalized PET data sets. The average MRI/PET template fit was then measured using the root mean square error method.