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Prospective longitudinal FMRI study of prefrontal cortex based context processing in never medicated first-episode schizophrenia
214 and velocity scaling (VS - a measure of parkinsonian bradykinesia in which subjects flex their thumb to reach targets located at different angels of flexion, presumably with different velocities). Preliminary results from a region of interest analysis indicate that schizophrenia subjects with FS impairment exhibited reduced activity within the external globus pallidus and increased activity within the primary motor cortex (M1) and supplementary motor area, (SMA) relative to subjects with nomlal FS performance. Results fxom theVS task indicate that schizophrenia subjects with VS impairment exhibit decreased activity within the internal globus pallidus and decreased activity within the SMA, but not M1. These findings are discussed as they pertain to theoretical models of abnormal basal ganglia function in schizophrenia and how functional neuroimaging of the frontal-subcortical motor circuit can inform us about neural mechanisms underlying psychopathology.
ALTERED PHYSIOLOGIC ACTIVITY IN A DISTRIBUTED NEURAL SYSTEM DURING WORKING MEMORY PROCESSING IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA T. D. Cannon,* D. C. Glahn, J. Kim, D. Shirinyan, K. H. Nuechterlein
Department of Psychology, UCLA, Los Angeles, CA, USA Patients with schizophrenia perform more poorly than healthy subjects on working memory tasks, but the nature of these deficits remains poorly understood at both the cognitve and neural systems levels. Here we utilized functional magnetic resonance imaging to contrast physiological activity in 12 first-episode schizophrenia patients, clinically stablized on a standard dose of rispiridone, with that in 12 demographically matched healthy subjects during performance of a spatial working memory task. The task utilized a block design allowing for contrasts among three conditions: rest, maintenance only, and maintenance plus manipulation. The latter condition required a mental transformation of the working memory store in addition to maintenance over a 6 sec delay. Both groups performed more poorly in the maintenance plus manipulation compared with maintenance only condition; this condition effect was significantly more pronounced in the patients. Scanning was performed on a 3 Telsa MRI scanner (General Electric), and imaging data were processed and analyzed using AIR, FSL, and AFNI. In both groups, both working memory conditions were associated with significant activity in a distributed system including dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, frontal eye fields, supplementary motor cortex, anterior cingulate, thalamus, and superior and inferior parietal cortex. In both groups, the maintenance plus manipulation condition was associated with significantly greater activation in all of these regions compared with the maintenance only condition. Patients showed significantly less activation than controls in small subregions within DLPFC, thalamus, and superior parietal cortex. These effects persisted even when task performance was equated across groups. These findings support the view that storage and executive processes in working memory utilize largely the same distributed circuitry and that patients with schizophrenia manifest altered physiologic activity in a number of specific components of this circuitry, including prefrontal, parietal, and subcortical sites.
14. Neuroimaging, Functional PROSPECTIVE LONGITUDINAL FMRI STUDY OF PREFRONTAL CORTEX BASED CONTEXT PROCESSING IN NEVER MEDICATED FIRSTEPISODE SCHIZOPHRENIA C. S. Carter,* A. MacDonald, A. Holmes, V. A. Stenger Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA To evaluate changes in prefrontal cortical activity over the course of an acute episode, we used event-related fMRI and a novel context processing task (the Arrow Task) in first-episode schizophrenia patients. Subjects were studied initally in the unmedicated state and at a 4-week follow-up after initial treatment with atypical antipsychotics during which they showed moderate improvement in their symptoms. All schizophrenia diagnoses were confirmed at 6 month follow up. Ten schizophrenia patients were compared with 20 demographically matched healthy subjects who were also studied twice using fMRI. Patients showed a significant deficit in context processing relative to controls at both baseline and at follow-up. Preliminary fMRI data at baseline indicated that even when controlling tbr on-task performance, patients did not activate left dorsolateral prefrontal cortex (DLPFC, BA 9) when required to maintain and represent context information over a brief delay. These data suggest that context processing is 1) a trait-like deficit in schizophrenia 2) observable at the very beginning of the illness, and is 3) associated with a reduction in DLPFC (functional hypofrontality). This deficit was not affected by the use of antipsychotic medication. Further analyses examining the specificity of this finding to schizophrenia (vs a group of first episode patients with non-schizophrenia related psychosis), the relationship of prefrontal based cognition to the symptoms of schizophrenia, and the effects of treatment on the function of other brain regions implicated in impaired cognition in schizophrenia, such as the anterior cingulate cortex, will be presented.
M E A S U R I N G PREPULSE INHIBITION A N D
FACILITATION OF THE EYEBLINK RESPONSE TO ACOUSTIC STARTLE DURING CONTINUOUS ACQUISITION WITH ER-FMRI A. S. Chien,* L. Heidinger, K. Kulkarni, M. Goldman Psychiatry, University of Chicago, Chicago, IL, USA Impaired prepulse inhibition of the eyeblit~k response to acoustic startle (PPI) is one of the most reliable findings in schizophrenia. Because PPI 1) has been linked to brain structures and functions implicated in the disorder, and 2) is a relatively straightforward measure of brain activity whose components (e.g. prepulse and pulse intensity and the time interval between them) can be manipulated and presented multiple times in the same session, it lends itself to study with event-related functional magnetic resonance imaging (ER-fMRI). Several methodological issues, however, appear to hinder the development of" this methodology. Previously we demonstrated the adequate extent and stability of PPI in a mock scanner under conditions replicating a typical ER-iMRI scan, and showed that startle-induced movement does not prevent the detection of the ER-fMRI generated neural correlates of PPI. We now report our initial efforts to measure PPI in the scanner using an event-related design (i.e. during active scanning). Two normal subjects were studied in a 3T LX GE scanner using a reverse spiral sequence to image the entire brain at 2 second intervals. Subjects heard 42 trials during each of three 10 minute runs. Trials were presented through MR1compatible air conduction headphones and were equally divided between four types: pulse alone (107db fbr 40 ms); prepulse alone
International Congress on Schizophrenia Research 2003
ALTERED PHYSIOLOGIC ACTIVITY IN A DISTRIBUTED NEURAL SYSTEM DURING WORKING MEMORY PROCESSING IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA T. D. Cannon,* D. C. Glahn, J. Kim, D. Shirinyan, K. H. Nuechterlein
Department of Psychology, UCLA, Los Angeles, CA, USA Patients with schizophrenia perform more poorly than healthy subjects on working memory tasks, but the nature of these deficits remains poorly understood at both the cognitve and neural systems levels. Here we utilized functional magnetic resonance imaging to contrast physiological activity in 12 first-episode schizophrenia patients, clinically stablized on a standard dose of rispiridone, with that in 12 demographically matched healthy subjects during performance of a spatial working memory task. The task utilized a block design allowing for contrasts among three conditions: rest, maintenance only, and maintenance plus manipulation. The latter condition required a mental transformation of the working memory store in addition to maintenance over a 6 sec delay. Both groups performed more poorly in the maintenance plus manipulation compared with maintenance only condition; this condition effect was significantly more pronounced in the patients. Scanning was performed on a 3 Telsa MRI scanner (General Electric), and imaging data were processed and analyzed using AIR, FSL, and AFNI. In both groups, both working memory conditions were associated with significant activity in a distributed system including dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, frontal eye fields, supplementary motor cortex, anterior cingulate, thalamus, and superior and inferior parietal cortex. In both groups, the maintenance plus manipulation condition was associated with significantly greater activation in all of these regions compared with the maintenance only condition. Patients showed significantly less activation than controls in small subregions within DLPFC, thalamus, and superior parietal cortex. These effects persisted even when task performance was equated across groups. These findings support the view that storage and executive processes in working memory utilize largely the same distributed circuitry and that patients with schizophrenia manifest altered physiologic activity in a number of specific components of this circuitry, including prefrontal, parietal, and subcortical sites.
14. Neuroimaging, Functional PROSPECTIVE LONGITUDINAL FMRI STUDY OF PREFRONTAL CORTEX BASED CONTEXT PROCESSING IN NEVER MEDICATED FIRSTEPISODE SCHIZOPHRENIA C. S. Carter,* A. MacDonald, A. Holmes, V. A. Stenger Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA To evaluate changes in prefrontal cortical activity over the course of an acute episode, we used event-related fMRI and a novel context processing task (the Arrow Task) in first-episode schizophrenia patients. Subjects were studied initally in the unmedicated state and at a 4-week follow-up after initial treatment with atypical antipsychotics during which they showed moderate improvement in their symptoms. All schizophrenia diagnoses were confirmed at 6 month follow up. Ten schizophrenia patients were compared with 20 demographically matched healthy subjects who were also studied twice using fMRI. Patients showed a significant deficit in context processing relative to controls at both baseline and at follow-up. Preliminary fMRI data at baseline indicated that even when controlling tbr on-task performance, patients did not activate left dorsolateral prefrontal cortex (DLPFC, BA 9) when required to maintain and represent context information over a brief delay. These data suggest that context processing is 1) a trait-like deficit in schizophrenia 2) observable at the very beginning of the illness, and is 3) associated with a reduction in DLPFC (functional hypofrontality). This deficit was not affected by the use of antipsychotic medication. Further analyses examining the specificity of this finding to schizophrenia (vs a group of first episode patients with non-schizophrenia related psychosis), the relationship of prefrontal based cognition to the symptoms of schizophrenia, and the effects of treatment on the function of other brain regions implicated in impaired cognition in schizophrenia, such as the anterior cingulate cortex, will be presented.
M E A S U R I N G PREPULSE INHIBITION A N D
FACILITATION OF THE EYEBLINK RESPONSE TO ACOUSTIC STARTLE DURING CONTINUOUS ACQUISITION WITH ER-FMRI A. S. Chien,* L. Heidinger, K. Kulkarni, M. Goldman Psychiatry, University of Chicago, Chicago, IL, USA Impaired prepulse inhibition of the eyeblit~k response to acoustic startle (PPI) is one of the most reliable findings in schizophrenia. Because PPI 1) has been linked to brain structures and functions implicated in the disorder, and 2) is a relatively straightforward measure of brain activity whose components (e.g. prepulse and pulse intensity and the time interval between them) can be manipulated and presented multiple times in the same session, it lends itself to study with event-related functional magnetic resonance imaging (ER-fMRI). Several methodological issues, however, appear to hinder the development of" this methodology. Previously we demonstrated the adequate extent and stability of PPI in a mock scanner under conditions replicating a typical ER-iMRI scan, and showed that startle-induced movement does not prevent the detection of the ER-fMRI generated neural correlates of PPI. We now report our initial efforts to measure PPI in the scanner using an event-related design (i.e. during active scanning). Two normal subjects were studied in a 3T LX GE scanner using a reverse spiral sequence to image the entire brain at 2 second intervals. Subjects heard 42 trials during each of three 10 minute runs. Trials were presented through MR1compatible air conduction headphones and were equally divided between four types: pulse alone (107db fbr 40 ms); prepulse alone
International Congress on Schizophrenia Research 2003