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Poster #27 NEURAL CORRELATES OF REALITY JUDGMENT ABNORMALITY IN PATIENTS WITH SCHIZOPHRENIA
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Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
to search for compromise alternatives. Also, as patients with schizophrenia experience high emotional arousal when positivity and negativity was co-activated, patients seem to activate emotional regulation function over-excessively.
Poster #26 ATTENUATED FRONTAL ACTIVATIONS AND REDUCED FUNCTIONAL CONNECTIVITY ELICITED BY AN OVERT SEMANTIC VERBAL FLUENCY TASK IN PATIENTS WITH SCHIZOPHRENIA Axel Krug, Heidelore Backes, Bruno Dietsche, Arne Nagels, Justus Marquetand, Mirjam Stratmann, Tilo Kircher Department of Psychiatry, Philipps-University Marburg, Marburg, Germany Background: Impaired performance in verbal fluency tasks is an often replicated finding in patients with schizophrenia. A new overt verbal fluency task was developed to investigate the neural correlates of word production. Methods: Brain activation was measured with functional magnetic resonance imaging (fMRI) during an overt semantic verbal fluency task in 13 patients with schizophrenia and 13 healthy controls, matched for age and verbal IQ. Subjects were cued with a word that represented a category and had to name as many members of that category as possible within 12 seconds. Resting blocks served as baseline condition. There were ten blocks of each condition. Results: Patients with schizophrenia produced significantly fewer words. When adjusted for performance, patients with schizophrenia displayed lower activations of the left middle frontal gyrus (MFG), the right cerebellum and the right hippocampus. Functional connectivity analyses revealed a verbal IQ-dependant correlation of the left middle frontal cluster and the left inferior frontal gyrus in healthy subjects compared to patients. Number of words produced by healthy subjects positively influenced the functional connectivity of the left MFG and the left superior frontal gyrus as well as the right hippocampus in comparison to patients. Discussion: This newly developed task is suitable for detecting performance deficits in patients with schizophrenia. When controlling for performance, patients show lower activations in frontal and medial temporal areas and a disturbances in fronto-frontal and fronto - medial temporal coupling which can further explain impaired performance in verbal fluency tasks.
Poster #27 NEURAL CORRELATES OF REALITY JUDGMENT ABNORMALITY IN PATIENTS WITH SCHIZOPHRENIA Jung Suk Lee 1,3 , Ji Won Chun 1 , Sang-hoon Lee 1 , Dong-Il Kang 1 , Hae-Jeong Park 1 , Jae-Jin Kim 1,2 1 Institute of Behavioral Science in Medicine, Yonsei University College of Medicine Seoul, Seoul, South Korea; 2 Department of Psychiatry, Gangnam Severance Hospital Seoul, Seoul, South Korea; 3 Department of Psychiatry, Bundang Jesaeng Hospital Seongnam, Gyeonggi-do, South Korea Background: Patients with schizophrenia are known to have reasoning biases such as “jumping to conclusion bias”. Reasoning biases may disrupt reality judgment processes, which can be the basis for delusion and hallucination. However, reality judgment process in patients with schizophrenia has not yet been investigated. This study aimed to investigate the reality judgment process in patients with schizophrenia and its neural correlate using functional magnetic resonance imaging. Methods: Twenty-six patients with schizophrenia and 25 healthy controls completed reality judgment task while viewing hand drawn real or unreal pictures (Experiment 1). Real pictures were composed of objects (e.g. human, animal, house or furniture) with appropriate backgrounds, while unreal pictures were composed of distorted objects in corresponding real pictures with appropriate backgrounds or composed of objects in corresponding real pictures with inappropriate backgrounds. Auditory hallucination and delusion in the patient group were assessed using the Psychotic Symptom Rating Scales (PSYRATS). Functional magnetic resonance imaging was conducted on fifteen patients with schizophrenia and 15 healthy controls while doing reality judgment task (Experiment 2). Results: The patient group showed significantly lower reality judgment accuracy for the unreal pictures than the control group. The PSYRATS au-
ditory hallucination frequency and duration items correlated significantly negatively with the reality judgment accuracy for the unreal condition in the patient group. In the unreal object condition compared with the real object condition, the patient group showed significantly less activation in the both frontopolar cortex, right dorsolateral prefrontal cortex, left inferior frontal gyrus and right middle temporal gyrus as compared with the control group. Discussion: These findings suggest that reality judgment process in patients with schizophrenia is impaired and this impairment may contribute to the formation or maintenance of auditory hallucination. Neuroimaging findings suggest that attenuated executive function and sensory processing during reality judgment in patients with schizophrenia may be related to the reality distortion syndrome.
Poster #28 GENDER-DEPENDENT DIFFERENCES IN THE NEURAL RESPONSES TO FEAR ACQUISITION: A VOXEL-BASED DIFFUSION TENSOR IMAGING (DTI) STUDY Qi Li 1,2 , Abby Y. Ding 3,4 , Ran Wei 1 , Wendy Kong 1 , Sylvia Lam 1 , Xiao F. Zhang 1 , Siew E. Chua 1,2,5 , Ed X. Wu 3,4 , Grainne M. McAlonan 6 1 Department of Psychiatry, HKU Hong Kong, SAR, China; 2 Centre for Reproduction Growth and Development, HKU Hong Kong, SAR, China; 3 Laboratory of Biomedical Imaging and Signal Processing, HKU Hong Kong, SAR, China; 4 Department of Electrical and Electronic Engineering, HKU Hong Kong, SAR, China; 5 State Key Laboratory for Brain and Cognitive Sciences, HKU Hong Kong, SAR, China; 6 Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King’s College London, London, United Kingdom Background: It is well established that men and women learn and remember differently on some types of learning task, including classical eye blink conditioning, fear-conditioning, active avoidance and conditioned taste aversion. Gender differences have been reported during acquisition, retention and extinction in most of these paradigms. The importance of the amygdale, as a key component of a distributed neural system for effective perception and regulation of fear, has been well documented. Although the role of amygdale in fear acquisition has been studied well, the gender effects on the function of amygdale in fear learning or molecular mechanism involved in it are not clear. DTI is widely used to characterize tissue micro-architecture and brain connectivity. Therefore, it is interesting to explore gender effects on the fear acquisition using DTI. In addition, we conducted a preliminary immunohistochemical exploration of the expression of phosphorylated extracellular signal-regulated kinase (pErk) to investigate the molecular mechanism of fear acquisition. The pErk acts as a central mediator of fear learning and extinction. Methods: DTI: Eleven C57BL/6N mice (12-week) were scanned using a 7T Bruker scanner 1 day before, and 1 hr after fear conditioning (FC) training. DW images were acquired using a SE 8-shot EPI sequence with 15 diffusion gradient directions. Five additional images with b-value=0 (B0 images) were also acquired. The imaging parameters were: TR/TE=3000/28.6ms, δ=5/17ms, NEX=4, FOV=2.×2.8cm2 , acq matrix= 128×128 (zero-filled to 256×256), slice thickness=0.48mm (0.07mm gap), b-value =1000 s/mm2. Fear Conditioning Protocol: Mice were placed individually into a conditioning chamber (25×25×25 cm3) for 6-min habituation, followed by 3 paired presentations of a clicker as the conditioned stimulus (CS, 30 sec, 4Hz, 80 dB) and footshock as the unconditioned stimulus (US, 2 sec, 0.5 mA). The inter-trial interval was 2 min and an additional 2-min rest was allowed after the final clicker/shock pairing in the chamber. Video monitoring was performed throughout the training and was used for behavioral analysis. Data Analysis: Each mouse brain volume was normalized to a custom B0 template generated from a representative animal using SPM5. Voxel-wised paired t-test was first performed between pre- and 1 hr post- FC FA maps (N=11). And gender effects (male=5, female=6) were analyzed by using two-sample t-test between the differences FA maps in the each gender. Histology: Mice trained used the same FC protocol, except for neither CS nor US presentation was selected as a control group. 1hr after fear training, the brain tissues were collected and IHC was performed. Results: Significant fractional anisotropy (FA) increase was found in the right amygdale (FA increased 22.9±18.4% (Mean±SD), p<0.005), caudate putamen (FA increased 15.3±10.4%, p<0.005), and cingulated cortex (FA increased 17.9±13%, p<0.005). However, the responses pattern of FC in
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
to search for compromise alternatives. Also, as patients with schizophrenia experience high emotional arousal when positivity and negativity was co-activated, patients seem to activate emotional regulation function over-excessively.
Poster #26 ATTENUATED FRONTAL ACTIVATIONS AND REDUCED FUNCTIONAL CONNECTIVITY ELICITED BY AN OVERT SEMANTIC VERBAL FLUENCY TASK IN PATIENTS WITH SCHIZOPHRENIA Axel Krug, Heidelore Backes, Bruno Dietsche, Arne Nagels, Justus Marquetand, Mirjam Stratmann, Tilo Kircher Department of Psychiatry, Philipps-University Marburg, Marburg, Germany Background: Impaired performance in verbal fluency tasks is an often replicated finding in patients with schizophrenia. A new overt verbal fluency task was developed to investigate the neural correlates of word production. Methods: Brain activation was measured with functional magnetic resonance imaging (fMRI) during an overt semantic verbal fluency task in 13 patients with schizophrenia and 13 healthy controls, matched for age and verbal IQ. Subjects were cued with a word that represented a category and had to name as many members of that category as possible within 12 seconds. Resting blocks served as baseline condition. There were ten blocks of each condition. Results: Patients with schizophrenia produced significantly fewer words. When adjusted for performance, patients with schizophrenia displayed lower activations of the left middle frontal gyrus (MFG), the right cerebellum and the right hippocampus. Functional connectivity analyses revealed a verbal IQ-dependant correlation of the left middle frontal cluster and the left inferior frontal gyrus in healthy subjects compared to patients. Number of words produced by healthy subjects positively influenced the functional connectivity of the left MFG and the left superior frontal gyrus as well as the right hippocampus in comparison to patients. Discussion: This newly developed task is suitable for detecting performance deficits in patients with schizophrenia. When controlling for performance, patients show lower activations in frontal and medial temporal areas and a disturbances in fronto-frontal and fronto - medial temporal coupling which can further explain impaired performance in verbal fluency tasks.
Poster #27 NEURAL CORRELATES OF REALITY JUDGMENT ABNORMALITY IN PATIENTS WITH SCHIZOPHRENIA Jung Suk Lee 1,3 , Ji Won Chun 1 , Sang-hoon Lee 1 , Dong-Il Kang 1 , Hae-Jeong Park 1 , Jae-Jin Kim 1,2 1 Institute of Behavioral Science in Medicine, Yonsei University College of Medicine Seoul, Seoul, South Korea; 2 Department of Psychiatry, Gangnam Severance Hospital Seoul, Seoul, South Korea; 3 Department of Psychiatry, Bundang Jesaeng Hospital Seongnam, Gyeonggi-do, South Korea Background: Patients with schizophrenia are known to have reasoning biases such as “jumping to conclusion bias”. Reasoning biases may disrupt reality judgment processes, which can be the basis for delusion and hallucination. However, reality judgment process in patients with schizophrenia has not yet been investigated. This study aimed to investigate the reality judgment process in patients with schizophrenia and its neural correlate using functional magnetic resonance imaging. Methods: Twenty-six patients with schizophrenia and 25 healthy controls completed reality judgment task while viewing hand drawn real or unreal pictures (Experiment 1). Real pictures were composed of objects (e.g. human, animal, house or furniture) with appropriate backgrounds, while unreal pictures were composed of distorted objects in corresponding real pictures with appropriate backgrounds or composed of objects in corresponding real pictures with inappropriate backgrounds. Auditory hallucination and delusion in the patient group were assessed using the Psychotic Symptom Rating Scales (PSYRATS). Functional magnetic resonance imaging was conducted on fifteen patients with schizophrenia and 15 healthy controls while doing reality judgment task (Experiment 2). Results: The patient group showed significantly lower reality judgment accuracy for the unreal pictures than the control group. The PSYRATS au-
ditory hallucination frequency and duration items correlated significantly negatively with the reality judgment accuracy for the unreal condition in the patient group. In the unreal object condition compared with the real object condition, the patient group showed significantly less activation in the both frontopolar cortex, right dorsolateral prefrontal cortex, left inferior frontal gyrus and right middle temporal gyrus as compared with the control group. Discussion: These findings suggest that reality judgment process in patients with schizophrenia is impaired and this impairment may contribute to the formation or maintenance of auditory hallucination. Neuroimaging findings suggest that attenuated executive function and sensory processing during reality judgment in patients with schizophrenia may be related to the reality distortion syndrome.
Poster #28 GENDER-DEPENDENT DIFFERENCES IN THE NEURAL RESPONSES TO FEAR ACQUISITION: A VOXEL-BASED DIFFUSION TENSOR IMAGING (DTI) STUDY Qi Li 1,2 , Abby Y. Ding 3,4 , Ran Wei 1 , Wendy Kong 1 , Sylvia Lam 1 , Xiao F. Zhang 1 , Siew E. Chua 1,2,5 , Ed X. Wu 3,4 , Grainne M. McAlonan 6 1 Department of Psychiatry, HKU Hong Kong, SAR, China; 2 Centre for Reproduction Growth and Development, HKU Hong Kong, SAR, China; 3 Laboratory of Biomedical Imaging and Signal Processing, HKU Hong Kong, SAR, China; 4 Department of Electrical and Electronic Engineering, HKU Hong Kong, SAR, China; 5 State Key Laboratory for Brain and Cognitive Sciences, HKU Hong Kong, SAR, China; 6 Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King’s College London, London, United Kingdom Background: It is well established that men and women learn and remember differently on some types of learning task, including classical eye blink conditioning, fear-conditioning, active avoidance and conditioned taste aversion. Gender differences have been reported during acquisition, retention and extinction in most of these paradigms. The importance of the amygdale, as a key component of a distributed neural system for effective perception and regulation of fear, has been well documented. Although the role of amygdale in fear acquisition has been studied well, the gender effects on the function of amygdale in fear learning or molecular mechanism involved in it are not clear. DTI is widely used to characterize tissue micro-architecture and brain connectivity. Therefore, it is interesting to explore gender effects on the fear acquisition using DTI. In addition, we conducted a preliminary immunohistochemical exploration of the expression of phosphorylated extracellular signal-regulated kinase (pErk) to investigate the molecular mechanism of fear acquisition. The pErk acts as a central mediator of fear learning and extinction. Methods: DTI: Eleven C57BL/6N mice (12-week) were scanned using a 7T Bruker scanner 1 day before, and 1 hr after fear conditioning (FC) training. DW images were acquired using a SE 8-shot EPI sequence with 15 diffusion gradient directions. Five additional images with b-value=0 (B0 images) were also acquired. The imaging parameters were: TR/TE=3000/28.6ms, δ=5/17ms, NEX=4, FOV=2.×2.8cm2 , acq matrix= 128×128 (zero-filled to 256×256), slice thickness=0.48mm (0.07mm gap), b-value =1000 s/mm2. Fear Conditioning Protocol: Mice were placed individually into a conditioning chamber (25×25×25 cm3) for 6-min habituation, followed by 3 paired presentations of a clicker as the conditioned stimulus (CS, 30 sec, 4Hz, 80 dB) and footshock as the unconditioned stimulus (US, 2 sec, 0.5 mA). The inter-trial interval was 2 min and an additional 2-min rest was allowed after the final clicker/shock pairing in the chamber. Video monitoring was performed throughout the training and was used for behavioral analysis. Data Analysis: Each mouse brain volume was normalized to a custom B0 template generated from a representative animal using SPM5. Voxel-wised paired t-test was first performed between pre- and 1 hr post- FC FA maps (N=11). And gender effects (male=5, female=6) were analyzed by using two-sample t-test between the differences FA maps in the each gender. Histology: Mice trained used the same FC protocol, except for neither CS nor US presentation was selected as a control group. 1hr after fear training, the brain tissues were collected and IHC was performed. Results: Significant fractional anisotropy (FA) increase was found in the right amygdale (FA increased 22.9±18.4% (Mean±SD), p<0.005), caudate putamen (FA increased 15.3±10.4%, p<0.005), and cingulated cortex (FA increased 17.9±13%, p<0.005). However, the responses pattern of FC in