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BRAIN ACTIVATION PATTERNS DURING RTMS TREATMENT OF SCHIZOPHRENIA
466
Abstracts
for sex differences in human cognitive ability, lateralisation and brain development in a way that is relevant to the sex differences in psychosis as no other gene or genes are able to do. According to this view psychosis represents a deviation in the sex dependent dimension of variation by which the hominin lineage was established and within which lateralisation in the form of the cerebral torque developed as the species defining characteristic. doi:10.1016/j.schres.2010.02.872
Poster 112 BRAIN ACTIVATION PATTERNS DURING RTMS TREATMENT OF SCHIZOPHRENIA Radovan Prikryl1, Libor Ustohal1, Michal Mikl2, Tomas Kasparek1, Hana Prikrylova Kucerova1, Eva Ceskova1 1 Department of Psychiatry Masaryk University Brno Brno, CR, Czech Republic; 2Department of Neurology Masaryk University Brno Brno, CR, Czech Republic Background: Negative symptoms are regarded as the most persistent and disabling component of schizophrenia. The possibility of influencing them by means of antipsychotics remains problematic. Repetitive transcranial magnetic simulation (rTMS) presents a new opportunity for influencing negative schizophrenic symptoms. A theoretical justification of the effect of rTMS on negative schizophrenic symptoms can be seen in the fact that high-frequency rTMS has an activating impact on cortex neurons. The negative correlation between activity of the frontal cortex and severity of negative symptoms has been proved repeatedly. Another important fact is that dopamine can be released in the mesolimbic and mesostriatal brain systems by high-frequency stimulation of the frontal cortex. Methods: Twenty four schizophrenic patients on stable antipsychotic medication with prominent negative symptoms were included in the trial. They were divided into two groups: twelve of them were treated with effective rTMS and twelve with ineffective "sham" rTMS. The ineffectiveness of the sham rTMS was achieved through placebo coil. Stimulation was applied to the left dorsolateral prefrontal cortex. The stimulation frequency was 10 Hz. Stimulation intensity was 110% of the motor threshold intensity. Each patient received 15 rTMS sessions on 15 consecutive working days. Each daily session consisted of 15 applications of 10-second duration and 30-second intervals between sequences. There were 1500 stimuli per session. fMRI investigation was done before and after rTMS course with verbal fluency task as cognitive paradigm to assess brain activity changes. Results: During real rTMS treatment a statistical significant decrease of negative symptoms was determined. In sham rTMS treatment a decrease of negative symptoms was also identified, but to a lesser extent than in real rTMS. Mutual comparison revealed a greater decrease of negative symptoms in favor of real rTMS in contrast to sham rTMS. However there was no significant distinction between activated brain areas during VFT before and after rTMS as in real as in sham group. Discussion: The augmentation of antipsychotics with a highfrequency rTMS applied above the area of the left prefrontal cortex causes a significant reduction in the intensity of the negative symptoms of schizophrenia. The improvement of negative symptoms of schizophrenia and cognitive performance during VFT in real rTMS course was not followed by the increase of corresponding neuronal activation (DLPFC). This work was supported by the Internal Grant Agency of the Ministry of Health (Project No. 9890-4) and by the Ministry of Education, Youth and Sports of Czech Republic (Project MSM 0021622404).
doi:10.1016/j.schres.2010.02.873
Poster 113 INTERACTION BETWEEN DRD2 GENE AND PREFRONTAL CORTEX ACTIVITY DURING DIFFERENT WORKING MEMORY PHASES Tiziana Quarto, Leonardo Fazio, Raffaella Romano, Annabella Di Giorgio, Paolo Taurisano, Luciana Lo Bianco, Francesca Ferrante, Mariangela Martone, Apostolos Papazacharias, Grazia Caforio, Giuseppe Blasi, Marcello Nardini, Alessandro Bertolino Group of Psychiatric Neuroscience, Department of Neurology and Psychiatry, University of Bari, Bari, Italy Background: Dopamine D2 receptors are involved in modulation of the cortico-striato-thalamo-cortical circuit during working memory (WM) processing (Williams and Goldman-Rakic, 1995; Robbins, 2000). Consistently, recent studies have indicated that an intronic single nucleotide polymorphism in the D2 gene (DRD2 rs1076560, G > T) is associated with WM performance and differential cortical activity during WM tasks (Zhang, 2007; Bertolino, 2009). On the other hand, WM is not a unitary construct and involves distinct cognitive subprocesses, such as encoding, maintenance, and retrieval. In this fMRI study, we used an event-related design to investigate DRD2 rs1076560 association with prefrontal activity during these subprocesses within WM. Methods: 50 healthy subjects, genotyped for DRD2 rs1076560 (G/G = 39; G/T = 11, matched for a series of demographical variables) underwent BOLD-fMRI at 3 tesla while performing a modified version of the Sternberg Task implying different load of WM subprocesses. SPM5 random-effects models were used for statistical analysis (p< 0.05, small volume corrected). Results: ANOVA revealed an effect of WM subprocesses on prefrontal cortex activity, with greater involvement of the dorsolateral prefrontal cortex (DLPFC) during maintenance and of ventrolateral prefrontal regions (VLPFC) during encoding and retrieval. Furthermore, there was an effect of rs107560 genotype in both left DLPFC and bilateral VLPFC, with greater activity in GT relative to GG subjects. Moreover, there was an interaction between load, WM subprocesses and DRD2 genotype in a cluster in DLPFC. Inspection of signal change from this cluster suggested that GG subjects had greater activity during maintenance, while G/T individuals showed greater BOLD responses during retrieval. In addition, both genotype groups were associated with increasing DLPFC activity with greater cognitive load during maintenance and retrieval. However, during encoding, GT subjects had greater activity associated with the lower cognitive load. Discussion: This study suggests that the lateral PFC is differentially involved in WM subprocesses. Moreover, it may indicate that DRD2 rs1076560 differentially affects the WM prefrontal circuit as a function of the WM subprocess involved. These data suggest that genetically determined D2 signaling within the cortico-striatothalamo-cortical circuit affects prefrontal tuning efficiency in terms of regional activation and functional integration. doi:10.1016/j.schres.2010.02.874
Poster 114 POWER SPECTRUM SCALE INVARIANCE OF FMRI TIME SERIES IDENTIFIES PREFRONTAL DYSREGULATION IN SCHIZOPHRENIA Anca R. Radulescu, Denis Rubin, Lilianne R. Mujica-Parodi Stony Brook University Stony Brook, NY, USA Background: Both theory and experimental evidence suggest that complex living systems self-organize and function close to the boundary of chaos, with erroneous organization to an improper
Abstracts
for sex differences in human cognitive ability, lateralisation and brain development in a way that is relevant to the sex differences in psychosis as no other gene or genes are able to do. According to this view psychosis represents a deviation in the sex dependent dimension of variation by which the hominin lineage was established and within which lateralisation in the form of the cerebral torque developed as the species defining characteristic. doi:10.1016/j.schres.2010.02.872
Poster 112 BRAIN ACTIVATION PATTERNS DURING RTMS TREATMENT OF SCHIZOPHRENIA Radovan Prikryl1, Libor Ustohal1, Michal Mikl2, Tomas Kasparek1, Hana Prikrylova Kucerova1, Eva Ceskova1 1 Department of Psychiatry Masaryk University Brno Brno, CR, Czech Republic; 2Department of Neurology Masaryk University Brno Brno, CR, Czech Republic Background: Negative symptoms are regarded as the most persistent and disabling component of schizophrenia. The possibility of influencing them by means of antipsychotics remains problematic. Repetitive transcranial magnetic simulation (rTMS) presents a new opportunity for influencing negative schizophrenic symptoms. A theoretical justification of the effect of rTMS on negative schizophrenic symptoms can be seen in the fact that high-frequency rTMS has an activating impact on cortex neurons. The negative correlation between activity of the frontal cortex and severity of negative symptoms has been proved repeatedly. Another important fact is that dopamine can be released in the mesolimbic and mesostriatal brain systems by high-frequency stimulation of the frontal cortex. Methods: Twenty four schizophrenic patients on stable antipsychotic medication with prominent negative symptoms were included in the trial. They were divided into two groups: twelve of them were treated with effective rTMS and twelve with ineffective "sham" rTMS. The ineffectiveness of the sham rTMS was achieved through placebo coil. Stimulation was applied to the left dorsolateral prefrontal cortex. The stimulation frequency was 10 Hz. Stimulation intensity was 110% of the motor threshold intensity. Each patient received 15 rTMS sessions on 15 consecutive working days. Each daily session consisted of 15 applications of 10-second duration and 30-second intervals between sequences. There were 1500 stimuli per session. fMRI investigation was done before and after rTMS course with verbal fluency task as cognitive paradigm to assess brain activity changes. Results: During real rTMS treatment a statistical significant decrease of negative symptoms was determined. In sham rTMS treatment a decrease of negative symptoms was also identified, but to a lesser extent than in real rTMS. Mutual comparison revealed a greater decrease of negative symptoms in favor of real rTMS in contrast to sham rTMS. However there was no significant distinction between activated brain areas during VFT before and after rTMS as in real as in sham group. Discussion: The augmentation of antipsychotics with a highfrequency rTMS applied above the area of the left prefrontal cortex causes a significant reduction in the intensity of the negative symptoms of schizophrenia. The improvement of negative symptoms of schizophrenia and cognitive performance during VFT in real rTMS course was not followed by the increase of corresponding neuronal activation (DLPFC). This work was supported by the Internal Grant Agency of the Ministry of Health (Project No. 9890-4) and by the Ministry of Education, Youth and Sports of Czech Republic (Project MSM 0021622404).
doi:10.1016/j.schres.2010.02.873
Poster 113 INTERACTION BETWEEN DRD2 GENE AND PREFRONTAL CORTEX ACTIVITY DURING DIFFERENT WORKING MEMORY PHASES Tiziana Quarto, Leonardo Fazio, Raffaella Romano, Annabella Di Giorgio, Paolo Taurisano, Luciana Lo Bianco, Francesca Ferrante, Mariangela Martone, Apostolos Papazacharias, Grazia Caforio, Giuseppe Blasi, Marcello Nardini, Alessandro Bertolino Group of Psychiatric Neuroscience, Department of Neurology and Psychiatry, University of Bari, Bari, Italy Background: Dopamine D2 receptors are involved in modulation of the cortico-striato-thalamo-cortical circuit during working memory (WM) processing (Williams and Goldman-Rakic, 1995; Robbins, 2000). Consistently, recent studies have indicated that an intronic single nucleotide polymorphism in the D2 gene (DRD2 rs1076560, G > T) is associated with WM performance and differential cortical activity during WM tasks (Zhang, 2007; Bertolino, 2009). On the other hand, WM is not a unitary construct and involves distinct cognitive subprocesses, such as encoding, maintenance, and retrieval. In this fMRI study, we used an event-related design to investigate DRD2 rs1076560 association with prefrontal activity during these subprocesses within WM. Methods: 50 healthy subjects, genotyped for DRD2 rs1076560 (G/G = 39; G/T = 11, matched for a series of demographical variables) underwent BOLD-fMRI at 3 tesla while performing a modified version of the Sternberg Task implying different load of WM subprocesses. SPM5 random-effects models were used for statistical analysis (p< 0.05, small volume corrected). Results: ANOVA revealed an effect of WM subprocesses on prefrontal cortex activity, with greater involvement of the dorsolateral prefrontal cortex (DLPFC) during maintenance and of ventrolateral prefrontal regions (VLPFC) during encoding and retrieval. Furthermore, there was an effect of rs107560 genotype in both left DLPFC and bilateral VLPFC, with greater activity in GT relative to GG subjects. Moreover, there was an interaction between load, WM subprocesses and DRD2 genotype in a cluster in DLPFC. Inspection of signal change from this cluster suggested that GG subjects had greater activity during maintenance, while G/T individuals showed greater BOLD responses during retrieval. In addition, both genotype groups were associated with increasing DLPFC activity with greater cognitive load during maintenance and retrieval. However, during encoding, GT subjects had greater activity associated with the lower cognitive load. Discussion: This study suggests that the lateral PFC is differentially involved in WM subprocesses. Moreover, it may indicate that DRD2 rs1076560 differentially affects the WM prefrontal circuit as a function of the WM subprocess involved. These data suggest that genetically determined D2 signaling within the cortico-striatothalamo-cortical circuit affects prefrontal tuning efficiency in terms of regional activation and functional integration. doi:10.1016/j.schres.2010.02.874
Poster 114 POWER SPECTRUM SCALE INVARIANCE OF FMRI TIME SERIES IDENTIFIES PREFRONTAL DYSREGULATION IN SCHIZOPHRENIA Anca R. Radulescu, Denis Rubin, Lilianne R. Mujica-Parodi Stony Brook University Stony Brook, NY, USA Background: Both theory and experimental evidence suggest that complex living systems self-organize and function close to the boundary of chaos, with erroneous organization to an improper