- Email: [email protected]
The functional anatomy of language processing: Towards an understanding of schizophrenic thought disorder
168
4f7S normal volunteers (Krystal, 1996) and a short-lived exacerbation of psychotic symptoms in schizophrenic patients (Lahti, 1995). In a preliminary study, we showed that in schizophrenic patients, ketamine increased rCBF in anterior cingulate and decreased rCBF in hippocampal and primary visual cortex (Lahti, 1995). In this study, regional cerebral blood flow changes produced by ketamine using H 2 150 and PET were determined in 7 haloperidol-treated schizophrenic patients and 10 normal volunteers. In both populations, ketamine induced an rCBF increase in anterior cingulate and contiguous medial frontal regions and decreased rCBF in cerebellum. Because there was no significant difference in rCBF changes between the normals and the haloperidol-treated schizophrenics, we correlated the three post-ketamine scans for all 17 volunteers with behavioral ratings obtained at the time of PET scan. Positive symptoms as measured by the Psychosis subscale of the BPRS correlated with rCBF changes in left temporal lobe and left ventral basal ganglia. These regional correlations are consistent with imaging studies in schizophrenic population (Liddle, 1992;Siebersweig, 1995) showing association between positive symptoms and these brain areas.
4f7+
THE FUNCTIONAL ANATOMY OF LANGUAGE PROCESSING: TOWARDS AN UNDERSTANDING OF SCHIZOPHRENIC THOUGHT DISORDER Gina R. Kuperberg, Philip K. McGuire, Edward T. Bullmore, Michael J. Brammer, Ian C. Wright, Steven C.R. Williams, Andrew Simmons, Anthony S. David
Institute of Psychiatry. DeCrespigny Park. Denmark Hill. London SE58AP, UK Thought-disordered schizophrenics are less sensitive to linguistic incongruities than control subjects, suggesting that they have difficulty in using relevant context to process language. We conducted a pilot study of six right-handed males, using functional'magnetic resonance imaging to explore the brain regions activated as subjects listened to semantically-, pragmatically- and syntactically-anomalous sentences, contrasted with normal sentences using an alternating 'on-off' paradigm. An overall median image showed that the common areas involved in linguistic violation detection were left lateralized language areas (L. insula, L. superior temporal gyrus) and regions previously implicated in general monitoring/detection of anomalies (L and R. hippocampal gyri, L. retrosplenial cortex, subcortical areas). Interestingly, visual areas (L. lingual gyrus, R. cuneus) werealso activated, despite auditory presentation, perhaps reflecting the use of visual imagery by many of the subjects when listening to anomalous sentences. In addition, detecting semantically-violated sentences led to activation of the ventral temporal lobe (R fusiform gyrus, area 37), a region which may be involved in the integration of words into their surrounding context. We plan to apply this paradigm to the study of patients to gain insight into the functional anatomical deficits underlying thought disorder in schizophrenia.
FUNCTIONAL CONNECTIVITY DURING WORD GENERATION IN SCHIZOPHRENIA Peter F. Liddle, Michael Passmore, Karl J. Friston, Christopher D, Frith
DepartmentofPsychiatry. University ofBritish Columbia. 2255 Wesbrook Mall. Vancouver. British Columbia. V6T 2AI. Canada We compared the pattern of functional connectivity between frontal lobes and all other cerebral regions, in 17 schizophrenic patients, with that in 6 healthy controls, during word generation. We performed 6 PET scans per subject. During scanning, subjects performed tasks that varied in their demand for wordgeneration. We identified a cardinal site in left lateral frontal cortex that was activated in all subjects during the generation of words, by comparing rCBF during self-directedword generation with that during simple repetition of words. Functional connectivity between frontal cortex and other brain sites was quantified by determining the correlation of rCBF at the cardinal frontal site during the 6 conditions, with that at every other gray matter pixel. Using Statistical Parametric Mapping, we identified the pixels in which the correlation between rCBF in that pixel and rCBF at the cardinal frontal site diffe~ significantly between patients and controls. We found that. m schizophrenic patients the correlation of frontal cortex WIth temporal cortex was increased, while that with both thalamus and precuneus was decreased. Thus, schizophrenic patients exhibit a pattern of abnormal functional connectivity that embraces not only frontal and temporal lobes, but also other areas of association cortex and the thalamus.
41~ IMPAIRED SECONDARY AND TERTIARY OLFACTORY PROCESSING IN SCHIZOPHRENIA: A SPECT STUDY OF NEUROACTIVATION WITH THE UPSIT Dolores Malaspina, Angella Lignelli, Gerard Pererra, Randall Marshall, Jack Gorman, Ron Van Heerturn
Departmentsof Psychiatry, Columbia University. 722 West 168" Street NY, NY 10032 Olfactory discrimination deficits exist in schizophr~nia (S~) as well as in other neuropsychiatric diseases. The etiology IS not elucidated. We studied six male Sz and 7 age/sex matched controls with SPECT scans at baseline (matching pictures without delay) and activation by odor discrimination (UPS!!). Scans were done sequentially in a low dose/high dose ~eslgn with HMPAO. Images were read into an automated 3D una~ analysis software package (MEDX Sensor, Inc.) a~d sa~ed m ANALYZE format for SPM. After aligning, coregJstratlo~ to Talairach and Gaussian filtering of 12 mm FWHM; paired t-test statistical analysis data was displayed in Talairach space with rCBF changes given as Z-Scores. Activation differences between the tasks was contrasted among Sz and contr?ls revealed a contiguous cluster in the right cortical area WIth
4f7S normal volunteers (Krystal, 1996) and a short-lived exacerbation of psychotic symptoms in schizophrenic patients (Lahti, 1995). In a preliminary study, we showed that in schizophrenic patients, ketamine increased rCBF in anterior cingulate and decreased rCBF in hippocampal and primary visual cortex (Lahti, 1995). In this study, regional cerebral blood flow changes produced by ketamine using H 2 150 and PET were determined in 7 haloperidol-treated schizophrenic patients and 10 normal volunteers. In both populations, ketamine induced an rCBF increase in anterior cingulate and contiguous medial frontal regions and decreased rCBF in cerebellum. Because there was no significant difference in rCBF changes between the normals and the haloperidol-treated schizophrenics, we correlated the three post-ketamine scans for all 17 volunteers with behavioral ratings obtained at the time of PET scan. Positive symptoms as measured by the Psychosis subscale of the BPRS correlated with rCBF changes in left temporal lobe and left ventral basal ganglia. These regional correlations are consistent with imaging studies in schizophrenic population (Liddle, 1992;Siebersweig, 1995) showing association between positive symptoms and these brain areas.
4f7+
THE FUNCTIONAL ANATOMY OF LANGUAGE PROCESSING: TOWARDS AN UNDERSTANDING OF SCHIZOPHRENIC THOUGHT DISORDER Gina R. Kuperberg, Philip K. McGuire, Edward T. Bullmore, Michael J. Brammer, Ian C. Wright, Steven C.R. Williams, Andrew Simmons, Anthony S. David
Institute of Psychiatry. DeCrespigny Park. Denmark Hill. London SE58AP, UK Thought-disordered schizophrenics are less sensitive to linguistic incongruities than control subjects, suggesting that they have difficulty in using relevant context to process language. We conducted a pilot study of six right-handed males, using functional'magnetic resonance imaging to explore the brain regions activated as subjects listened to semantically-, pragmatically- and syntactically-anomalous sentences, contrasted with normal sentences using an alternating 'on-off' paradigm. An overall median image showed that the common areas involved in linguistic violation detection were left lateralized language areas (L. insula, L. superior temporal gyrus) and regions previously implicated in general monitoring/detection of anomalies (L and R. hippocampal gyri, L. retrosplenial cortex, subcortical areas). Interestingly, visual areas (L. lingual gyrus, R. cuneus) werealso activated, despite auditory presentation, perhaps reflecting the use of visual imagery by many of the subjects when listening to anomalous sentences. In addition, detecting semantically-violated sentences led to activation of the ventral temporal lobe (R fusiform gyrus, area 37), a region which may be involved in the integration of words into their surrounding context. We plan to apply this paradigm to the study of patients to gain insight into the functional anatomical deficits underlying thought disorder in schizophrenia.
FUNCTIONAL CONNECTIVITY DURING WORD GENERATION IN SCHIZOPHRENIA Peter F. Liddle, Michael Passmore, Karl J. Friston, Christopher D, Frith
DepartmentofPsychiatry. University ofBritish Columbia. 2255 Wesbrook Mall. Vancouver. British Columbia. V6T 2AI. Canada We compared the pattern of functional connectivity between frontal lobes and all other cerebral regions, in 17 schizophrenic patients, with that in 6 healthy controls, during word generation. We performed 6 PET scans per subject. During scanning, subjects performed tasks that varied in their demand for wordgeneration. We identified a cardinal site in left lateral frontal cortex that was activated in all subjects during the generation of words, by comparing rCBF during self-directedword generation with that during simple repetition of words. Functional connectivity between frontal cortex and other brain sites was quantified by determining the correlation of rCBF at the cardinal frontal site during the 6 conditions, with that at every other gray matter pixel. Using Statistical Parametric Mapping, we identified the pixels in which the correlation between rCBF in that pixel and rCBF at the cardinal frontal site diffe~ significantly between patients and controls. We found that. m schizophrenic patients the correlation of frontal cortex WIth temporal cortex was increased, while that with both thalamus and precuneus was decreased. Thus, schizophrenic patients exhibit a pattern of abnormal functional connectivity that embraces not only frontal and temporal lobes, but also other areas of association cortex and the thalamus.
41~ IMPAIRED SECONDARY AND TERTIARY OLFACTORY PROCESSING IN SCHIZOPHRENIA: A SPECT STUDY OF NEUROACTIVATION WITH THE UPSIT Dolores Malaspina, Angella Lignelli, Gerard Pererra, Randall Marshall, Jack Gorman, Ron Van Heerturn
Departmentsof Psychiatry, Columbia University. 722 West 168" Street NY, NY 10032 Olfactory discrimination deficits exist in schizophr~nia (S~) as well as in other neuropsychiatric diseases. The etiology IS not elucidated. We studied six male Sz and 7 age/sex matched controls with SPECT scans at baseline (matching pictures without delay) and activation by odor discrimination (UPS!!). Scans were done sequentially in a low dose/high dose ~eslgn with HMPAO. Images were read into an automated 3D una~ analysis software package (MEDX Sensor, Inc.) a~d sa~ed m ANALYZE format for SPM. After aligning, coregJstratlo~ to Talairach and Gaussian filtering of 12 mm FWHM; paired t-test statistical analysis data was displayed in Talairach space with rCBF changes given as Z-Scores. Activation differences between the tasks was contrasted among Sz and contr?ls revealed a contiguous cluster in the right cortical area WIth