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Regional cerebral blood flow abnormalities in posterior cingulate of psychotic temporal lobe epileptic patients
14. Neuroimaging, Functional DIFFERENTIAL ANTERIOR
219
ACTIVATION OF THE
CINGULATE
AND PREFRONTAL
CORTEX IN SCHIZOPHRENIC
AND BIPOLAR
PATIENTS: AN FMRI STUDY S. A. Gruber,* J. Rogowska, D. A. Yurgelun-Todd
Cognitive Neuroimaging Laboratory, McLean Hospital, Belmont, MA, USA Patients with schizophrenia have been shown to have deficits in attention, inhibition, and the ability to maintain cognitive set. Both the anterior cingulate and dorsolateral prefrontal cortices have been implicated in the pathophysiology of schizophrenia, and cognitive tasks mediated by these regions have been shown to be impaired in these patients. Neuroimaging studies have identified the anterior cingulate cortex as a site responsible for mediating selective attention and inhibition as measured by the Stroop task, and cytoarchitectural studies have suggested specific roles for subdivisions of this region, making their examination key to understanding changes in cortical activation. In a recent fMRI study, increased activation of the AAA and VOA subdivisions and a relative decrease within the DLPFC were found in healthy control subjects during the interference condition of the Stroop task. In comparison, schizophrenic patients demonstrated an altered pattern of activation during both the color naming and interference conditions. In order to address the specificity of these findings to schizophrenia, the current study examined patterns of cortical activation in schizophrenic patients, patients with bipolar disorder and control subjects. Eleven DSM-IV schizophrenic patients, 11 bipolar patients and 10 healthy control subjects were examined using the fMRI BOLD technique while subjects performed a modified version of the three conditions of the Stroop task. Compared to controls, schizophrenic patients produced significantly lower fight VOA activation (F=4.4; p=.04) and greater fight DLPFC activation (F=3.5; p=.07) during the interference condition. In contrast, no significant difference was detected between bipolar patients and control subjects within the right VOA subdivision (F=. 18;p=.67) during the interference condition, however, significantly greater activation within the right DLPFC (F=4.3; =.04) was detected in the bipolar patients. Comparison of patient groups indicated differences for the color naming condition in both the right VOA (F=4.2;p=.05) and the right DLPFC (F=3.9;p=.06), however, no between group differences were noted for the interference condition in either region. Results from this study indicate differential processing strategies of patients with schizophrenia and bipolar disorder and add additional support to the theory of altered frontal systems in psychiatric patients during the performance of cognitive tasks.
FAILURE OF PREFRONTAL
HABITUATION
NOVELTY IN SCHIZOPHRENIA:
TO
AN EVENT-
RELATED FMRI STUDY R. E. Gut,* B. I. Turetsky, L. Schroeder, J. D. Ragland, R. C. Gur
Psychiatry, University of Pennsylvania, Philadelphia, PA, USA While cognitive deficits in schizophrenia are pervasive, there is increased evidence that abnormalities occur at early stages of information processing and these may derail more complex elaborations. In particular, detection of salience and habituation to novel stimuli seem impaired. Advances in fMRI permit event-related paradigms that may help identify neural systems that are dysfunctional at specific information processing stages. We designed fMRI tasks to emulate ERP methods for salient target and novelty detection, and pro-
vide a measure of sensory habituation. The tasks were administered to a sample of 19 patients and 19 demographically balanced controls. Habituation was examined in patients and controls by averaging the signal for the first 10 and the last 10 presentations of unexpected fractal stimuli. We then obtained an unbiased estimate of the hemodynamic response in a frontal region found to show the most pronounced habituation effects (BA45) and in a primary sensory region (occipital). Coefficients were scaled to the multiple regression intercept term for each individual, and averaged across subjects within each group to obtain the mean (+SEM) response over 20 sec. The shape of the curves was nearly identical in patients and controls for the occipital region, but differed for the frontal. The occipital HDR was robust in both groups and showed no sign of habituation. In contrast, the smaller frontal HDR habituated in controls, but did not show an attenuation in patients. It is noteworthy that while the curves closely modeled the classic shape of the BOLD response, they could have assumed any shape because a predefined IRF was not used to fit the data. The results point to a fundamental deficit in schizophrenia in the ability of frontal brain regions to show diminished response with repetition of novel stimuli. This dysfunction could underlie learning and memory deficits strongly associated with schizophrenia.
REGIONAL
CEREBRAL
ABNORMALITIES OF PSYCHOTIC
BLOOD FLOW
IN POSTERIOR TEMPORAL
CINGULATE
LOBE EPILEPTIC
PATIENTS J. E. Hallak,* R. Guarnieri, L. Wichert-Ana, R. Walz, K. O. Rezek, E. R. Coimbra, A. C. Sakamoto, A. W. Zuardi, J. E Deakin
Neuroscience and Psychiatry Unit, University of Manchester, Manchester, Lancashire, United Kingdom Interictal psychosis occurs in up to 15% of patients with epilepsy. In patients referred to epilepsy surgery centres this prevalence is much higher, reaching up to 28.5%. Patients with temporal lobe epilepsy (TLE) are particularly susceptible to psychotic symptoms. The association of psychosis with TLE provides one clue to the pathogenesis of schizophrenia. We have used SPECT (Single Photon Emission Computed Tomography) to determine what pattern of regional cerebral blood flow (rCBF) distinguishes TLE with psychosis from TLE without. We compared 21 TLE patients with schizophrenia with 23 non-psychotic TLE patients. All had been psychiatrically evaluated and were diagnosed according DSM-IV. Subjects with other psychiatric disorders, mental retardation, history of abuse or illicit drug or alcohol dependence, presence of structural lesions (tumours, map formations) were excluded. Neurological evaluation included videoEEG monitoring, neuropsychological testing, structural and functional imaging. SPECT scans were carried out with 99Technetium and the images normalised to average uptake in cerebellum. Bilateral regions of interest (ROIs) were drawn: frontal pole (in two levels), prefrontal lobe, anterior and posterior cingulate, basal ganglia, thalamus, temporal lobe (anterior, lateral, posterior and mesial), superior parietal lobe, occipital pole and cerebellum. The groups were compared with a t-test and ANOVA. The psychotic group had greater right posterior cingulate rCBF (p=0.034, t-test). No other statistical significant differences were observed. Increased rCBF in right posterior cingulate in the psychotic TLE group is intriguing because: i) imaging studies in schizophrenia have also reported similar abnormalities; ii) has been reported that phencyclidine (PCP) pre-treatment in rats is associated with cytotoxicity, specifically in posterior
International Congress on Schizophrenia Research 2003
220 cingutate, which reinforces the idea that the posterior cingulate may play a role in the pathogenesis of schizophrenia; iii) the hippocampus has strong monosynaptic interconnections with posterior cingulate but for almost all the subjects the TLE loci were on the left side. This suggests that for TLE to cause psychosis, spread of some neuropathic process to the right cingulate may be necessary.
SELECTIVE ANTERIOR CINGULATE DYSFUNCTION DURING COGNITIVE INTERFERENCE IN SCHIZOPHRENIA S. Heckers,* A. Weiss, D. Golf, T. Deckersbach, G. B u s h
Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Previous studies have provided evidence that the structure and function of anterior cingulate cortex (ACC) are abnormal in schizophrenia. We studied 20 male patients with chronic schizophrenia and 15 male healthy subjects with the novel Multi-Source Interference Task (MSIT) [1], designed to elicit robust dorsal ACC (dACC) activation in individual subjects. After a brief training session, subjects performed three runs of the MSIT while being scanned in a 1.5 T Siemens Sonata scanner. We studied brain activation during the performance of the control and the interference trials in individual subjects and tested for group-by-condition interactions using a mixed effects model in SPM99. The control and schizophrenia groups performed similarly with respect to 1) accuracy during neutral (control: 99.4% and schizophrenia: 98.0%) and interference blocks (93.4% and 92.4%) and 2) reaction time during neutral (603 ms and 649 ms) and interference blocks (883 ms and 938 ms). Comparison of interference and neutral blocks revealed robust activation of a dACC region (BA 24'/32') in healthy subjects (peak activation at 0,18,46, z=4.86, p=0.026, corrected for multiple comparisons) and schizophrenic subjects (peak activation at 2,16,50, z=4.81, p=0.031, corrected for multiple comparisons). Analysis of the ACC anatomy revealed that 6/15 healthy and 7/20 schizophrenic subjects displayed a paracingulate gyrus. Each healthy subject demonstrated activation in cingulate gyrus, paracingulate gyrus, or the adjacent prefrontal gyrus, whereas 3 of the schizophrenic subjects did not. Finally, only 1/15 healthy subjects (compared to 7/20 schizophrenic subjects) did not show activation in either cingulate or paracingulate gyrus. The MSIT revealed robust activation in dACC. Group analysis revealed no significant difference when comparing mean activation between interference and control trials. However, detailed analysis of ACC activation in each individual subject revealed that most healthy subjects activated dorsal and ventral aspects of the ACC, whereas more than 1/3 of schizophrenic subjects failed to activate the ventral aspects of ACC. This provides support for the hypothesis of abnormal ventral (limbic) ACC function in the context of normal dorsal (cognitive-motor) ACC function in schizophrenia. [1] Bush Get al., Molecular Psychiatry, 2002 (in press)
BRAIN ACTIVATION DURING VERBAL ENCODING S. Heinze,* G. Sartory, B. W. Mueller, M. Forsting, M. Jueptner
Clinicjbr Psychiatry and Psychotherapy, University of Ess'en, Essen, NRW, Germany Studies of cognitive dysfunction in patients with schizophrenia revealed evidence for deficits of verbal memory. Neural generators
14. Neuroimaging, Functional contributing to verbal memory performance are still under discussion. The aim our study was to investigate brain activation during verbal encoding by means of event-related functional MRI in a sample of healthy control subjects. Fifteen healthy controls (8 female, 7 male) took part in the fMRI scanning procedure. Nine runs were administered; each consisting of 22 words interleaved with 22 fixation crosses. All stimuli were presented visually for 2,4 sec each. During seven of these runs the instruction was to learn the words without using a memolizing strategy. During the remaining two runs, words should be read only. These runs were then utilized as baseline condition. After presentation of each list subjects were asked to reproduce all the words they remembered. Functional imaging data were acquired on a 1.5 T Siemens Sonata scanner and Statistical Parametric Mapping SPM99 was used for the analysis of the data. Encoding related activation was compared between words that were reproduced and that were not and reproduced words were also compared to the baseline condition, Successful verbal encoding (reproduced versus forgotten words) was related to greater activity in bilateral middle and superior frontal gyrus (BA 6), left inferior frontal gyrus (BA 9), left inferior and superior parietal lobule (BA 7) and left fusiform gyrus (BA 37). Greater activity for reproduced versus baseline words was found in left middle and superior frontal gyrus (BA 6 and cingulate BA 32), bilateral inferior and superior parietal lobule (BA 7, BA 19, BA 40), left fusiform gyrus (BA 20) and bilateral cerebellum. Results of the two analyses differed with regard to greater activation in left inferior frontal gyrus (BA 9) and left fusiform gyrus (BA 37) in case of reproduced versus forgotten words compared to reproduced versus baseline words. Our results are in keeping with previous studies on verbal encoding (Wagner et al., 1998) and will provide a tool for the assessment of memory deficits in patients with schizophrenia.
AMELIORATION OF HYPOFRONTALITY IN SCHIZOPHRENIA DURING COGNITIVE TRAINING A. Hempel,* E Giesel, T. Wuestenberg, M. Amann, M. Essig, C. Bottmer, J. Schroeder Psychiatry, University of HeMelberg, Heidelberg, Germany It is generally accepted that the majority of patients with schizophrenia show a reduced activation of the frontal cortices (hypofrontality). In healthy volunteers, an optimization of frontal lobe function with a reduced activation and increased performance in corresponding neuropsychological tests was recently described [1]. Hence, one may hypothesize that hypofrontality in schizophrenia may be ameliorated by cognitive training. Up to now, 8 patients with schizophrenia and 10 healthy controls were included. Patients were in a clinically stable condition after remission of an acute episode and received constant dosages of atypical neuroleptics as medication. Functional magnetic resonance hnaging (fMRI) was performed prior to and following a standardized training of a visual spatial n-back task over a 2 week period. At baseline, patients showed pronounced decreases of fronto-parietal activation when compared with the controls. Training led to an increased working memory performance in all patients. These performance gains corresponded to increases in activation of the right inferior and medial frontal gyrus, the right parietal lobe, and the anterior cingulate. In contrast, lower activation levels were found occipitally in the lingual gyrus after training. Additionally, three patients demonstrated further activation in the left medial frontal gyrus. Despite these changes in working memory functioning and fMRI the patients did not reach normalization of task-related cerebral activation patterns. Our preliminary
International Congress on Schizophrenia Research 2003
219
ACTIVATION OF THE
CINGULATE
AND PREFRONTAL
CORTEX IN SCHIZOPHRENIC
AND BIPOLAR
PATIENTS: AN FMRI STUDY S. A. Gruber,* J. Rogowska, D. A. Yurgelun-Todd
Cognitive Neuroimaging Laboratory, McLean Hospital, Belmont, MA, USA Patients with schizophrenia have been shown to have deficits in attention, inhibition, and the ability to maintain cognitive set. Both the anterior cingulate and dorsolateral prefrontal cortices have been implicated in the pathophysiology of schizophrenia, and cognitive tasks mediated by these regions have been shown to be impaired in these patients. Neuroimaging studies have identified the anterior cingulate cortex as a site responsible for mediating selective attention and inhibition as measured by the Stroop task, and cytoarchitectural studies have suggested specific roles for subdivisions of this region, making their examination key to understanding changes in cortical activation. In a recent fMRI study, increased activation of the AAA and VOA subdivisions and a relative decrease within the DLPFC were found in healthy control subjects during the interference condition of the Stroop task. In comparison, schizophrenic patients demonstrated an altered pattern of activation during both the color naming and interference conditions. In order to address the specificity of these findings to schizophrenia, the current study examined patterns of cortical activation in schizophrenic patients, patients with bipolar disorder and control subjects. Eleven DSM-IV schizophrenic patients, 11 bipolar patients and 10 healthy control subjects were examined using the fMRI BOLD technique while subjects performed a modified version of the three conditions of the Stroop task. Compared to controls, schizophrenic patients produced significantly lower fight VOA activation (F=4.4; p=.04) and greater fight DLPFC activation (F=3.5; p=.07) during the interference condition. In contrast, no significant difference was detected between bipolar patients and control subjects within the right VOA subdivision (F=. 18;p=.67) during the interference condition, however, significantly greater activation within the right DLPFC (F=4.3; =.04) was detected in the bipolar patients. Comparison of patient groups indicated differences for the color naming condition in both the right VOA (F=4.2;p=.05) and the right DLPFC (F=3.9;p=.06), however, no between group differences were noted for the interference condition in either region. Results from this study indicate differential processing strategies of patients with schizophrenia and bipolar disorder and add additional support to the theory of altered frontal systems in psychiatric patients during the performance of cognitive tasks.
FAILURE OF PREFRONTAL
HABITUATION
NOVELTY IN SCHIZOPHRENIA:
TO
AN EVENT-
RELATED FMRI STUDY R. E. Gut,* B. I. Turetsky, L. Schroeder, J. D. Ragland, R. C. Gur
Psychiatry, University of Pennsylvania, Philadelphia, PA, USA While cognitive deficits in schizophrenia are pervasive, there is increased evidence that abnormalities occur at early stages of information processing and these may derail more complex elaborations. In particular, detection of salience and habituation to novel stimuli seem impaired. Advances in fMRI permit event-related paradigms that may help identify neural systems that are dysfunctional at specific information processing stages. We designed fMRI tasks to emulate ERP methods for salient target and novelty detection, and pro-
vide a measure of sensory habituation. The tasks were administered to a sample of 19 patients and 19 demographically balanced controls. Habituation was examined in patients and controls by averaging the signal for the first 10 and the last 10 presentations of unexpected fractal stimuli. We then obtained an unbiased estimate of the hemodynamic response in a frontal region found to show the most pronounced habituation effects (BA45) and in a primary sensory region (occipital). Coefficients were scaled to the multiple regression intercept term for each individual, and averaged across subjects within each group to obtain the mean (+SEM) response over 20 sec. The shape of the curves was nearly identical in patients and controls for the occipital region, but differed for the frontal. The occipital HDR was robust in both groups and showed no sign of habituation. In contrast, the smaller frontal HDR habituated in controls, but did not show an attenuation in patients. It is noteworthy that while the curves closely modeled the classic shape of the BOLD response, they could have assumed any shape because a predefined IRF was not used to fit the data. The results point to a fundamental deficit in schizophrenia in the ability of frontal brain regions to show diminished response with repetition of novel stimuli. This dysfunction could underlie learning and memory deficits strongly associated with schizophrenia.
REGIONAL
CEREBRAL
ABNORMALITIES OF PSYCHOTIC
BLOOD FLOW
IN POSTERIOR TEMPORAL
CINGULATE
LOBE EPILEPTIC
PATIENTS J. E. Hallak,* R. Guarnieri, L. Wichert-Ana, R. Walz, K. O. Rezek, E. R. Coimbra, A. C. Sakamoto, A. W. Zuardi, J. E Deakin
Neuroscience and Psychiatry Unit, University of Manchester, Manchester, Lancashire, United Kingdom Interictal psychosis occurs in up to 15% of patients with epilepsy. In patients referred to epilepsy surgery centres this prevalence is much higher, reaching up to 28.5%. Patients with temporal lobe epilepsy (TLE) are particularly susceptible to psychotic symptoms. The association of psychosis with TLE provides one clue to the pathogenesis of schizophrenia. We have used SPECT (Single Photon Emission Computed Tomography) to determine what pattern of regional cerebral blood flow (rCBF) distinguishes TLE with psychosis from TLE without. We compared 21 TLE patients with schizophrenia with 23 non-psychotic TLE patients. All had been psychiatrically evaluated and were diagnosed according DSM-IV. Subjects with other psychiatric disorders, mental retardation, history of abuse or illicit drug or alcohol dependence, presence of structural lesions (tumours, map formations) were excluded. Neurological evaluation included videoEEG monitoring, neuropsychological testing, structural and functional imaging. SPECT scans were carried out with 99Technetium and the images normalised to average uptake in cerebellum. Bilateral regions of interest (ROIs) were drawn: frontal pole (in two levels), prefrontal lobe, anterior and posterior cingulate, basal ganglia, thalamus, temporal lobe (anterior, lateral, posterior and mesial), superior parietal lobe, occipital pole and cerebellum. The groups were compared with a t-test and ANOVA. The psychotic group had greater right posterior cingulate rCBF (p=0.034, t-test). No other statistical significant differences were observed. Increased rCBF in right posterior cingulate in the psychotic TLE group is intriguing because: i) imaging studies in schizophrenia have also reported similar abnormalities; ii) has been reported that phencyclidine (PCP) pre-treatment in rats is associated with cytotoxicity, specifically in posterior
International Congress on Schizophrenia Research 2003
220 cingutate, which reinforces the idea that the posterior cingulate may play a role in the pathogenesis of schizophrenia; iii) the hippocampus has strong monosynaptic interconnections with posterior cingulate but for almost all the subjects the TLE loci were on the left side. This suggests that for TLE to cause psychosis, spread of some neuropathic process to the right cingulate may be necessary.
SELECTIVE ANTERIOR CINGULATE DYSFUNCTION DURING COGNITIVE INTERFERENCE IN SCHIZOPHRENIA S. Heckers,* A. Weiss, D. Golf, T. Deckersbach, G. B u s h
Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Previous studies have provided evidence that the structure and function of anterior cingulate cortex (ACC) are abnormal in schizophrenia. We studied 20 male patients with chronic schizophrenia and 15 male healthy subjects with the novel Multi-Source Interference Task (MSIT) [1], designed to elicit robust dorsal ACC (dACC) activation in individual subjects. After a brief training session, subjects performed three runs of the MSIT while being scanned in a 1.5 T Siemens Sonata scanner. We studied brain activation during the performance of the control and the interference trials in individual subjects and tested for group-by-condition interactions using a mixed effects model in SPM99. The control and schizophrenia groups performed similarly with respect to 1) accuracy during neutral (control: 99.4% and schizophrenia: 98.0%) and interference blocks (93.4% and 92.4%) and 2) reaction time during neutral (603 ms and 649 ms) and interference blocks (883 ms and 938 ms). Comparison of interference and neutral blocks revealed robust activation of a dACC region (BA 24'/32') in healthy subjects (peak activation at 0,18,46, z=4.86, p=0.026, corrected for multiple comparisons) and schizophrenic subjects (peak activation at 2,16,50, z=4.81, p=0.031, corrected for multiple comparisons). Analysis of the ACC anatomy revealed that 6/15 healthy and 7/20 schizophrenic subjects displayed a paracingulate gyrus. Each healthy subject demonstrated activation in cingulate gyrus, paracingulate gyrus, or the adjacent prefrontal gyrus, whereas 3 of the schizophrenic subjects did not. Finally, only 1/15 healthy subjects (compared to 7/20 schizophrenic subjects) did not show activation in either cingulate or paracingulate gyrus. The MSIT revealed robust activation in dACC. Group analysis revealed no significant difference when comparing mean activation between interference and control trials. However, detailed analysis of ACC activation in each individual subject revealed that most healthy subjects activated dorsal and ventral aspects of the ACC, whereas more than 1/3 of schizophrenic subjects failed to activate the ventral aspects of ACC. This provides support for the hypothesis of abnormal ventral (limbic) ACC function in the context of normal dorsal (cognitive-motor) ACC function in schizophrenia. [1] Bush Get al., Molecular Psychiatry, 2002 (in press)
BRAIN ACTIVATION DURING VERBAL ENCODING S. Heinze,* G. Sartory, B. W. Mueller, M. Forsting, M. Jueptner
Clinicjbr Psychiatry and Psychotherapy, University of Ess'en, Essen, NRW, Germany Studies of cognitive dysfunction in patients with schizophrenia revealed evidence for deficits of verbal memory. Neural generators
14. Neuroimaging, Functional contributing to verbal memory performance are still under discussion. The aim our study was to investigate brain activation during verbal encoding by means of event-related functional MRI in a sample of healthy control subjects. Fifteen healthy controls (8 female, 7 male) took part in the fMRI scanning procedure. Nine runs were administered; each consisting of 22 words interleaved with 22 fixation crosses. All stimuli were presented visually for 2,4 sec each. During seven of these runs the instruction was to learn the words without using a memolizing strategy. During the remaining two runs, words should be read only. These runs were then utilized as baseline condition. After presentation of each list subjects were asked to reproduce all the words they remembered. Functional imaging data were acquired on a 1.5 T Siemens Sonata scanner and Statistical Parametric Mapping SPM99 was used for the analysis of the data. Encoding related activation was compared between words that were reproduced and that were not and reproduced words were also compared to the baseline condition, Successful verbal encoding (reproduced versus forgotten words) was related to greater activity in bilateral middle and superior frontal gyrus (BA 6), left inferior frontal gyrus (BA 9), left inferior and superior parietal lobule (BA 7) and left fusiform gyrus (BA 37). Greater activity for reproduced versus baseline words was found in left middle and superior frontal gyrus (BA 6 and cingulate BA 32), bilateral inferior and superior parietal lobule (BA 7, BA 19, BA 40), left fusiform gyrus (BA 20) and bilateral cerebellum. Results of the two analyses differed with regard to greater activation in left inferior frontal gyrus (BA 9) and left fusiform gyrus (BA 37) in case of reproduced versus forgotten words compared to reproduced versus baseline words. Our results are in keeping with previous studies on verbal encoding (Wagner et al., 1998) and will provide a tool for the assessment of memory deficits in patients with schizophrenia.
AMELIORATION OF HYPOFRONTALITY IN SCHIZOPHRENIA DURING COGNITIVE TRAINING A. Hempel,* E Giesel, T. Wuestenberg, M. Amann, M. Essig, C. Bottmer, J. Schroeder Psychiatry, University of HeMelberg, Heidelberg, Germany It is generally accepted that the majority of patients with schizophrenia show a reduced activation of the frontal cortices (hypofrontality). In healthy volunteers, an optimization of frontal lobe function with a reduced activation and increased performance in corresponding neuropsychological tests was recently described [1]. Hence, one may hypothesize that hypofrontality in schizophrenia may be ameliorated by cognitive training. Up to now, 8 patients with schizophrenia and 10 healthy controls were included. Patients were in a clinically stable condition after remission of an acute episode and received constant dosages of atypical neuroleptics as medication. Functional magnetic resonance hnaging (fMRI) was performed prior to and following a standardized training of a visual spatial n-back task over a 2 week period. At baseline, patients showed pronounced decreases of fronto-parietal activation when compared with the controls. Training led to an increased working memory performance in all patients. These performance gains corresponded to increases in activation of the right inferior and medial frontal gyrus, the right parietal lobe, and the anterior cingulate. In contrast, lower activation levels were found occipitally in the lingual gyrus after training. Additionally, three patients demonstrated further activation in the left medial frontal gyrus. Despite these changes in working memory functioning and fMRI the patients did not reach normalization of task-related cerebral activation patterns. Our preliminary
International Congress on Schizophrenia Research 2003