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Functional MRI assessment of atypical and conventional antipsychotic effects on cognitive function in schizophrenia patients
14. Neuroimaging, Functional
229
pathway. A systems approach to functional brain analysis allows movement beyond the static regional activation analysis of the schizophrenic - normal brain differences to a circuit analysis that more closely models the brain at work and possibly more closely models the brain as it may malfunction in schizophrenia.
FUNCTIONAL
MRI ASSESSMENT
OF
ATYPICAL AND CONVENTIONAL ANTIPSYCHOTIC FUNCTION
EFFECTS ON COGNITIVE
IN SCHIZOPHRENIA
PATIENTS
R. A. Morey,* K. Emberger, S. Inan, R. McClure, J. Lieberman, R. Keefe, G. McCarthy, A. Belger
Brain Imaging and Analysis Center, Duke University, Durham, NC, USA Atypical autipsychotic medications are purported to ameliorate the cognitive deficits associated with schizophrenia. Deficits in attention, processing of visual and auditory information, and executive function are prominent features. The frontal-limbic brain circuits, and in particular the dorsolateral prefrontal and superior temporal cortical regions, have been implicated in these deficits. Early reports suggest a selective improvement of frontal executive functions and related cortical activation as measured by fMRI following treatment with atypical antipsychotics. We sought to further characterize the effects of atypical antipsychotics on frontal and temporal neurocognitive functions and the associated dynamics of cortical response. Thirty schizophrenia patients and 15 healthy control subjects will be studied. Patients receive treatment with thiothixene for four weeks, and then undergo a blind crossover to treatment with either risperidone or olanzapine for eight weeks. Patients undergo a battery of neurocognitive tests and fMRI investigation while performing auditory and visual oddball tasks both prior to, and following an eightweek treatment course of atypical antipsychotic medication. Healthy control subjects undergo identical fMRI investigations eight weeks apart. The primary analyses aim to compare prefrontal and temporal cortical activation and neurocognitive outcome measures under the two treatment conditions for patients, to the cortical activation patterns at two time points in control subjects. Preliminary analyses indicate that intensity (percent signal change) and extent of cortical activation in prefrontal and temporal regions appears to be differentially sensitive to treatment with typical and atypical and antipsychotics. Specifically, atypical antipsychotics reduced aberrant prefrontal activation, whereas conventional antipsychotic treatment reduced aberrant temporal cortical activation, with little effects on prefrontal cortex. The results suggest that treatment with atypical antipsychotics may improve function in the prefrontal cortex treatment with conventional antipsychotics may improve temporal lobe function. Research supported by a grant from Janssen Research Foundation and Lilly Laboratories.
AN ASSESSMENT EQUIVALENT
OF THE AUDITORY P300
WITH SPARSE FMRI IMAGING
B. W. Miiller,* R Stude, M. Ladd, K, Nebel, H. Wiese, M. Forsting, M. Jiiptner
Clinicjor Psychiatry and Psychotherapy, University Clinics Essen, Essen, NRW, Germany The auditory P300 ERP component emerges in response to rare target stimuli and has been used widely in the assessment of patients with schizophrenia. However, little is known about cortical genera-
tors contributing to the scalp recorded P300 ERP component thereby limiting the impact of experimental results on theoretical concepts of disturbed information processing. A major problem in the assessment of the auditory P300 equivalent within the MRI-context emerges from interference between experimental stimuli and scanner noise. The aim of our study was to assess the auditory P300 without auditory interference by means of sparse imaging. Within sparse imaging experiments an increased time between the acquisition of successive EPI volumes creates periods of silence which can be used for auditory stimulation. The sparse imaging technique has been introduced recently in the assessment of primary auditory cortex function. Sixteen healthy subjects were presented frequent standard stimuli (1000Hz, 80ms, 80dB, 800ms ISI) and rare target stimuli (500Hz, 80ms, 80dB) and subjects had to press a button upon the emergence of the rare target stimulus. Imaging data were acquired in 6 runs of 30 trials. Each trial started with a train of standard stimuli followed either by the target stimulus or an additional nontarget standard Stimulus. The BOLD response to 90 target and 90 standard stimuli was assessed with a delay of 4 seconds (TR 1.8 sec, TE 60 ms, Flip Angle 90 deg, 18 Slices, 1.8 sek / Volume, 1.5 T Siemens Sonata). Functional imaging data were analysed with SPM99. The contrast of the BOLD responses to target vs. standard stimuli revealed bilateral activation within the insula and the inferior frontal gyms, the superior temporal and cingulate gyms, the left middle frontal and middle temporal gyms, the left inferior parietal lobule, the cuneus and precuneus, the right thalamus and the cerebellum bilaterally. Our results further support recent evidence on inferior frontal, superior temporal and parietal contributions to a network of auditory deviance processing. In contrast to previous imaging studies on the P300 we found only minor activation within the DLPC. In summary, our results demonstrate that the equivalent of the P300 ERP cornponent can be assessed with sparse imaging and thereby provide an experimental method to further study the P300 component with EEG / fMRI coregistration in patients with schizophrenia.
THE SPET METHOD AS A MEANS OF STUDYING BIPOLAR DISORDER AND SCHIZOPHRENIA
(PRELIMINARY
RESULTS)
A. Norsa,* F. Bilone, C. A. Robotti, M. C. Nicotra, R G. Giorgetti
Psychiatry, Azienda Ospedaliera, Verona, Italy This study was carried out by the First Psychiatric Departement of the Ospedale Civile Maggiore in Verona. 45 patients of both sexes and aged between 35 and 56 inclusive were examined. 23 were affected with Bipolar Disorder and 22 with Schizo- affective Disorder. Diagnosis was made according to DSM- 1V criteria. The SPET method was used and the radio- tracer was a 99m Tc HMPAO, 99m Te ECD. All patients were examined using a double head rotating y. No other psychological tests were carried out at the same time. A degree of hypo- frontality may be associated with Bipolar Disorder in the depressive phase, as noted in 83% of the patients examined. The results were less conclusive in the case of Bipolar patients in the maniacal period, were both left/fight asymmetry and the focal deficits in the frontal, temporal and ganglia areas were noted. Despite the lack of data to confirm this, a change of metabolic flow in the temporal area in bipolar patients may often be associated with a decrease in the ability to interact positively with reality (as noted in 76% of cases) and with hallucinations (in 33% of cases). The fact that the data regarding the cerebral area in patients in maniacal phase is not consistent and the lack of clear evidence of perfusional deficits may be due to the pharmacological treatment the patient is undergoing. In
International Congress on Schizophrenia Research 2003
229
pathway. A systems approach to functional brain analysis allows movement beyond the static regional activation analysis of the schizophrenic - normal brain differences to a circuit analysis that more closely models the brain at work and possibly more closely models the brain as it may malfunction in schizophrenia.
FUNCTIONAL
MRI ASSESSMENT
OF
ATYPICAL AND CONVENTIONAL ANTIPSYCHOTIC FUNCTION
EFFECTS ON COGNITIVE
IN SCHIZOPHRENIA
PATIENTS
R. A. Morey,* K. Emberger, S. Inan, R. McClure, J. Lieberman, R. Keefe, G. McCarthy, A. Belger
Brain Imaging and Analysis Center, Duke University, Durham, NC, USA Atypical autipsychotic medications are purported to ameliorate the cognitive deficits associated with schizophrenia. Deficits in attention, processing of visual and auditory information, and executive function are prominent features. The frontal-limbic brain circuits, and in particular the dorsolateral prefrontal and superior temporal cortical regions, have been implicated in these deficits. Early reports suggest a selective improvement of frontal executive functions and related cortical activation as measured by fMRI following treatment with atypical antipsychotics. We sought to further characterize the effects of atypical antipsychotics on frontal and temporal neurocognitive functions and the associated dynamics of cortical response. Thirty schizophrenia patients and 15 healthy control subjects will be studied. Patients receive treatment with thiothixene for four weeks, and then undergo a blind crossover to treatment with either risperidone or olanzapine for eight weeks. Patients undergo a battery of neurocognitive tests and fMRI investigation while performing auditory and visual oddball tasks both prior to, and following an eightweek treatment course of atypical antipsychotic medication. Healthy control subjects undergo identical fMRI investigations eight weeks apart. The primary analyses aim to compare prefrontal and temporal cortical activation and neurocognitive outcome measures under the two treatment conditions for patients, to the cortical activation patterns at two time points in control subjects. Preliminary analyses indicate that intensity (percent signal change) and extent of cortical activation in prefrontal and temporal regions appears to be differentially sensitive to treatment with typical and atypical and antipsychotics. Specifically, atypical antipsychotics reduced aberrant prefrontal activation, whereas conventional antipsychotic treatment reduced aberrant temporal cortical activation, with little effects on prefrontal cortex. The results suggest that treatment with atypical antipsychotics may improve function in the prefrontal cortex treatment with conventional antipsychotics may improve temporal lobe function. Research supported by a grant from Janssen Research Foundation and Lilly Laboratories.
AN ASSESSMENT EQUIVALENT
OF THE AUDITORY P300
WITH SPARSE FMRI IMAGING
B. W. Miiller,* R Stude, M. Ladd, K, Nebel, H. Wiese, M. Forsting, M. Jiiptner
Clinicjor Psychiatry and Psychotherapy, University Clinics Essen, Essen, NRW, Germany The auditory P300 ERP component emerges in response to rare target stimuli and has been used widely in the assessment of patients with schizophrenia. However, little is known about cortical genera-
tors contributing to the scalp recorded P300 ERP component thereby limiting the impact of experimental results on theoretical concepts of disturbed information processing. A major problem in the assessment of the auditory P300 equivalent within the MRI-context emerges from interference between experimental stimuli and scanner noise. The aim of our study was to assess the auditory P300 without auditory interference by means of sparse imaging. Within sparse imaging experiments an increased time between the acquisition of successive EPI volumes creates periods of silence which can be used for auditory stimulation. The sparse imaging technique has been introduced recently in the assessment of primary auditory cortex function. Sixteen healthy subjects were presented frequent standard stimuli (1000Hz, 80ms, 80dB, 800ms ISI) and rare target stimuli (500Hz, 80ms, 80dB) and subjects had to press a button upon the emergence of the rare target stimulus. Imaging data were acquired in 6 runs of 30 trials. Each trial started with a train of standard stimuli followed either by the target stimulus or an additional nontarget standard Stimulus. The BOLD response to 90 target and 90 standard stimuli was assessed with a delay of 4 seconds (TR 1.8 sec, TE 60 ms, Flip Angle 90 deg, 18 Slices, 1.8 sek / Volume, 1.5 T Siemens Sonata). Functional imaging data were analysed with SPM99. The contrast of the BOLD responses to target vs. standard stimuli revealed bilateral activation within the insula and the inferior frontal gyms, the superior temporal and cingulate gyms, the left middle frontal and middle temporal gyms, the left inferior parietal lobule, the cuneus and precuneus, the right thalamus and the cerebellum bilaterally. Our results further support recent evidence on inferior frontal, superior temporal and parietal contributions to a network of auditory deviance processing. In contrast to previous imaging studies on the P300 we found only minor activation within the DLPC. In summary, our results demonstrate that the equivalent of the P300 ERP cornponent can be assessed with sparse imaging and thereby provide an experimental method to further study the P300 component with EEG / fMRI coregistration in patients with schizophrenia.
THE SPET METHOD AS A MEANS OF STUDYING BIPOLAR DISORDER AND SCHIZOPHRENIA
(PRELIMINARY
RESULTS)
A. Norsa,* F. Bilone, C. A. Robotti, M. C. Nicotra, R G. Giorgetti
Psychiatry, Azienda Ospedaliera, Verona, Italy This study was carried out by the First Psychiatric Departement of the Ospedale Civile Maggiore in Verona. 45 patients of both sexes and aged between 35 and 56 inclusive were examined. 23 were affected with Bipolar Disorder and 22 with Schizo- affective Disorder. Diagnosis was made according to DSM- 1V criteria. The SPET method was used and the radio- tracer was a 99m Tc HMPAO, 99m Te ECD. All patients were examined using a double head rotating y. No other psychological tests were carried out at the same time. A degree of hypo- frontality may be associated with Bipolar Disorder in the depressive phase, as noted in 83% of the patients examined. The results were less conclusive in the case of Bipolar patients in the maniacal period, were both left/fight asymmetry and the focal deficits in the frontal, temporal and ganglia areas were noted. Despite the lack of data to confirm this, a change of metabolic flow in the temporal area in bipolar patients may often be associated with a decrease in the ability to interact positively with reality (as noted in 76% of cases) and with hallucinations (in 33% of cases). The fact that the data regarding the cerebral area in patients in maniacal phase is not consistent and the lack of clear evidence of perfusional deficits may be due to the pharmacological treatment the patient is undergoing. In
International Congress on Schizophrenia Research 2003