Abstract of poster presentation shown at the 2nd Biennial Schizophrenia International Research Conference on Alterations in functional brain network structure induced by subchronic phencyclidine (PCP) treatment parallel those seen in schizophrenia

Dawson, Neil

Higham, Des

Morris, Brian

Pratt, Judith

English

University of Strathclyde Institutional Repository

Strathprints Institutional RepositoryDawson, Neil and Higham, Des and Pratt, Judith and Morris, Brian (2010) Alterations in functionalbrain network structure induced by subchronic phencyclidine (PCP) treatment parallel those seenin schizophrenia. [Proceedings Paper]Strathprints is designed to allow users to access the research output of the University of Strathclyde.Copyright c© and Moral Rights for the papers on this site are retained by the individual authorsand/or other copyright owners. You may not engage in further distribution of the material for anyprofitmaking activities or any commercial gain. You may freely distribute both the url (http://strathprints.strath.ac.uk/) and the content of this paper for research or study, educational, ornot-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to Strathprints administrator:mailto:strathprints@strath.ac.ukhttp://strathprints.strath.ac.uk/demonstrated high levels of schizophrenia spectrum pathology inKlinefelter (van Rijn et al., 2006a). Difficulties in social adaptation andabnormal brain asymmetries suggest that a genetic mechanism(involving genes on theX chromosome)might affect the developmentof social cognition in XXY men. Language and emotion are importantaspects of social cognition. Reduced or abnormal lateralization oflanguage has been found in Klinefelter's syndrome (Geschwind,1998;van Rijn et al., 2008). Additionally, impairments in emotional prosodyperceptionhavebeen reported (vanRijn et al., 2007).Weexpected thatlateralization of emotional prosody differed in Klinefelter's syndrome.Therefore, we used fMRI-guided transcranial magnetic stimulation(TMS) to study lateralization effects.Methods: Sevenmenwith Klinefelter's syndrome and seven controls(matched on age, gender and education) performed an emotionalprosody task during fMRI-scanning. In this task, subjects attended tothe affective (happy, sad, angry or anxious) intonation and had toignore the neutral semantic content of the sentences. We used fMRI-guided TMS (with BrainVoyager neuronavigation) to reduce excit-ability of areas thatwere active during emotional prosody processingin the MR scanner (left and right superior temporal gyrus). TMS wasperformed for 20 minutes on 1 Hz. After stimulation, the subjectsperformed the emotional prosody task again. In addition, a baselinemeasurement without TMS was included. Results were analyzedwith repeated measures analysis of variance (ANOVA).Results: Klinefelter patients showed a trend to react slower thancontrols (p=0.12). They also showed longer reaction times on theangry condition after stimulation of the right superior gyrus(p=0.05), whereas controls reacted faster. No other effects ofTMS reached significance.Discussion: Menwith Klinefelter's syndrome respondedmore slowlyto sentences with an angry intonation in the emotional prosody taskafter right STG stimulation, whereas controls responded faster. Theemotion angry is hypothesized to be primarily processed by the lefthemisphere. Thus, the involvement of the right STG in anger prosodyprocessing in Klinefelter patients suggests a switch in lateralization.The faster responses in the healthy group for this emotion might bedue to callosal disinhibition of the left hemishere by the righthemisphere TMS. As fMRI studies have suggested similar patterns ofaberrant lateralization in Klinefelter syndrome and schizophrenia, ourresults may have implications for understanding schizophrenia.doi:10.1016/j.schres.2010.02.347Poster 120CORTICAL DYSFUNCTION IN ADOLESCENTS WITHSCHIZOPHRENIA DURING WORKING MEMORY COMPONENTPROCESSES - A FUNCTIONAL MAGNETIC RESONANCEIMAGING STUDYRobert A. Bittner1,3, Corinna Haenschel1,3,5, Alard Roebroek4,Fabian Haertling2, Anna Rotarska-Jagiela3, Konrad Maurer1,Rainer Goebel4, Wolf Singer3, David E.J. Linden51Laboratory for Neurophysiology and Neuroimaging, Department ofPsychiatry, Goethe-University Frankfurt amMain Germany; 2Departmentof Child and Adolescent Psychiatry, Goethe-University Frankfurt amMainGermany; 3Department of Neurophysiology, Max-Planck-Institute forBrain Research Frankfurt am Main Germany; 4Department of CognitiveNeuroscience, Faculty of Psychology, Maastricht University MaastrichtNetherlands; 5Wolfson Centre of Clinical and Cognitive Neuroscience,School of Psychology, University of Wales, Bangor Bangor WalesBackground: Working memory (WM) impairment in schizophre-nia (SCZ) is caused by deficits of both encoding and maintenanceprocesses. Prefrontal cortical dysfunction has also consistentlybeen implicated. Yet, results from functional magnetic resonanceimaging (fMRI) studies have been contradictory with reports ofboth decreased and increased prefrontal cortical activation. Thisdiscrepancy has been explained by models of a dynamic WM loaddependent dysfunction of prefrontal cortex. Abnormal functionalconnectivity also seems to contribute to WM deficits. However, theuse of blocked experimental designs – often in conjunction withthe n-back task – has prevented the isolation of WM componentprocesses in the majority of fMRI studies. Therefore, the relation-ship between impairments in specific WM component processeswith abnormal with abnormal cortical activation, connectivity andWM load sensitivity in SCZ is still poorly understood.Methods: We used event-related fMRI to examine differences inbrain activation and functional connectivity during the encoding,maintenance and retrieval stages of a visual WM task in 17adolescents with early-onset SCZ (age 15 to 20 years) and 17matched controls. Up to three abstract visual shapes had to bemaintained for 12 seconds before comparing them to a test stimulus.Results: Patients had reduced WM capacity, which was related tolower activation in left ventrolateral prefrontal cortex (VLPFC) andextrastriate visual cortex during encoding. During early maintenancepatients showed a switch from hyper- to hypoactivation withincreasing WM load in a fronto-parietal network which included leftdorsolateral prefrontal cortex (DLPFC). Furthermore, abnormallyincreased suppression of defaultmode areas by patientswas correlatedwith WM capacity during late maintenance. During retrieval rightinferior VLPFC hyperactivation was correlated with encoding-relatedhypoactivationof left VLPFC inpatients. Cortical dysfunction inpatientsduring encoding and retrieval was accompanied by abnormalfunctional connectivity between fronto-parietal and visual areas.Discussion: Patients showed a primary encoding deficit independentofWM loadduet to a dysfunctionof VLPFC and visual areas. Prefrontalhyperactivation during retrieval seems to be a secondary conse-quence of this deficit. In contrast,WM load dependent fronto-parietaldysfunction and dysregulation of default mode areas seem tocontribute to impaired WMmaintenance. These results indicate thatWMdysfunction in SCZ is the result of a combination of disturbancesin distinct cortical networks which support the individual WMcomponent processes. In contrast,WM loaddependent abnormalitiesseem to be confined primarily to early maintenance. A separateanalysis of WM component processes and parametric manipulationofWM loadmay help to developmore valid and reliable intermediatephenotypes for genetic studies. Focusing on impairments of specificcomponent processes could also lead to more targeted and effectivepsychological and pharmacological cognitive remediation strategies.doi:10.1016/j.schres.2010.02.348Poster 121ALTERATIONS IN FUNCTIONAL BRAIN NETWORK STRUCTUREINDUCED BY SUBCHRONIC PHENCYCLIDINE (PCP) TREATMENTPARALLEL THOSE SEEN IN SCHIZOPHRENIANeil Dawson1, Des Higham2, Judith Pratt1, Brian Morris11PsyRING, Universities of Glasgow and Strathclyde Glasgow, Lanarkshire,United Kingdom; 2University of Strathclyde Glasgow, Lanarkshire,United KingdomBackground: Quantitative analysis of complex network structure,based on graph theory, has recently been applied to elucidate theorganisation of structural and functional brain networks (Bullmoreand Sporns, 2009) in both healthy humans and in disease states,including schizophrenia (Bassett et al., 2008; Liu et al., 2008). Thesemethods are yet to be applied to brain imaging data from preclinicalmodels relevant to mental health. Here we investigate networkAbstracts234structure in functional brain networks in a preclinical modelrelevant to schizophrenia (Pratt et al., 2008).Methods: Cerebral metabolism in 64 brain regions was determinedin control rats (saline, male, Long-Evans, n=7) and rats treatedsubchronically with PCP (2.58 mg.kg−1, i.p, 1x daily for 5 days, n=9)by semi-quantitative 2-deoxyglucose (2-DG) autoradiography (Daw-son et al., 2009). Overt alterations in metabolism between groupswere analysed by t-test. For graph theoretical analysis binaryadjacency matrices, over a range of correlation thresholds (Pearson'sco-efficient 0.4 to 0.5), were generated from the brain region partialcorrelation matrix of each experimental group. Global networkarchitecture was characterised in terms of the mean degree, averagepath length, mean clustering coefficient and small-worldness at eachthreshold. In addition, centrality analysis (degree, betweeness andcloseness) was used to identify hub regions in these networks. Small-world properties and hub region identification were determined bystatistically comparing real with calibrated random (Erdös-Rényi)graphs. Statistical differences in network architecture betweengroups was analysed using repeated measures ANOVA. Alterationsin centrality measures between groups were analysed by comparingregional z-scores, generated relative to random networks, using t-testwith Bonferoni correction. Significance was set at p<0.05.Results: Subchronic PCP-treatment induced overt hypometabolism inselect prefrontal and thalamic regions in accordance with previousreports (Pratt et al., 2008). The functional brain network in PCP-treatedanimals had a significantly reducedmean degree, increased average pathlength and reduced mean clustering in comparison to that in controls.The network in PCP-treated animals also displayed a significantly highersmall-worldness than that in controls. In control animals themediodorsaland reticular (dorsal and ventral) thalamus and locus coeruleus wereidentified as important hubs, across all centrality measures. Of theseregions the reticular thalamus (ventral and dorsal) and locus coeruleuslost their hub status in PCP-treated animals. Several additional thalamicregions (anteromedial, centrolateral, centromedial and the nucleusreuniens) also showed reduced centrality in PCP-treated animals.Discussion: This study is the first to apply the quantitative analysis ofnetwork structure to functional brain imaging data from a preclinicalmodel relevant to schizophrenia. The global architecture of thisnetwork in control animals, including a small-world topography, isconsistent with reports from human studies. In addition, PCP-induced alterations in network structure parallel functional networkalterations seen in schizophrenia (Liu et al., 2008). Furthermore,these results provide new insight into alterations in functional brainnetworks which may contribute to the overt alterations in cerebralmetabolism seen in schizophrenia. Bassett et al, 2008. J.Neurosci.28:9239 Bullmore and Sporns, 2008. Nat.Rev. Neurosci. 10:186Dawson et al, 2009 J.Neuro.Res. 87:2375 Liu et al, 2008 Brain131:945 Pratt et al, 2008 Br.J.Pharmacol. 153:S465.doi:10.1016/j.schres.2010.02.349Poster 122BRAIN ACTIVITY DURING SOCIAL COGNITION TASKS ININDIVIDUALS WITH SCHIZOPHRENIA, THEIR UNAFFECTEDSIBLINGS, AND HEALTHY CONTROLSSalvador M. Guinjoan1,2, Delfina de Achaval1,2, Mirta Villarreal1,2,Elsa Y. Costanzo1, Rocio Berhongaray1, Jazmin Douer1, Julieta Lopez1,Martina C. Mora1, Rodolfo Fahrer1, Ramon C. Leiguarda1, Salvador M.Guinjoan1,21Fundación para la Lucha contra las Enfermedades Neurológicas de laInfancia (FLENI) Capital Federal, Buenos Aires, Argentina; 2ConsejoNacional de Investigaciones Científicas y Técnicas (CONICET) CapitalFederal, Buenos Aires, ArgentinaBackground: Several studies have shown that patients with schizo-phrenia have impaired performance in various aspects of socialcognition including emotion processing, theory of mind, and moraljudgment. Most of the neuroimaging studies have compared patientsand healthy controls during such mental activity because the under-standing of the neural basis of social cognition might help to explainsomedeficits in social functioning in this groupofpatients. The presentstudy examined brain activation patterns during social cognition tasksin patients with schizophrenia, and try to determine whetheralterations in social cognition reflect a trait that can be detected innon-psychotic relatives of patients with schizophrenia.Methods: Eight patients with schizophrenia (age 33.9±13, 2 fe-males), ten non-psychotic relatives (age 32±3.7, 4 females) and tenmatched comparison subjects (age 27.5±7, 4 females) underwentBOLD (blood-oxygen-level-dependent) functional magnetic reso-nance imaging during visual presentation of different social cognitionparadigms. Emotion processing was measured by the Ekman FacesTest using a target (basic emotions) and a control (gender) condition.Theory of Mind (ToM) paradigms were focused on the ability todiscriminate complex mental states in Faces and Reading the Mind inthe Eyes task, with a target (complex mental states) and a control(gender) condition as well. Moral judgment task consisted in 40 shortpassages, half of themwith moral content, inwhich the subject has tojudge the characters actions. Random effects analysis was done foreach taskwithin groups, measuring signal changes between the targetand control conditions of each paradigm.Results: The Reading the Mind in the Eyes (ToM task) brought aboutactivation in the left inferior frontal gyrus, nearBrodmann's areas 44and45, in all groups. Both patients and their siblings showed activation inthe same area of the right hemisphere althoughwith less intensity, andin the left striatum. Patient's siblings showed bilateral activation of themiddle occipital gyrus. During a moral judgement task, right inferiorfrontal gyruswas activated inbothpatients and their relatives (butmoreintense in the former), and relatives activated right ventromedialprefrontal cortex as well. In this task, healthy persons activatedpreferentially bilateral postcentral gyri. Both facial tests evoked muchlesser activation in patients than in the other two groups. Healthysubjects activated preferentially bilateral middle frontal gyri. Patients'siblings displayed the most intense activation of all groups includingbilateral middle and inferior frontal gyri, parahippocampi, bilateraloccipital structures and bilateral cerebellar structures.Discussion: Reading the Mind in the Eyes and moral judgement testsevoked partially overlapping cerebral activation patterns in patientsand their siblings but not in comparable healthy individuals.Emotion processing as assessed by social cognitive tasks involvingfaces evoked strong cerebral activation in unaffected siblings ofschizophrenia patients. The present results suggest that socialcognitive and moral tasks are associated with activation of brainareas partially similar in patients with schizophrenia and theirunaffected siblings, and distinct from those in healthy individuals.doi:10.1016/j.schres.2010.02.350Poster 123SIMILAR LANGUAGE ACTIVATION IN NON-PSYCHOTICINDIVIDUALS WITH AUDITORY VERBAL HALLUCINATIONSAND CONTROL SUBJECTSKelly M. Diederen, Antoin D. De Weijer, Kirstin Daalman,Bas F. Neggers, Rene S. Kahn, Iris E. SommerUniversity Medical Center Utrecht & Rudolf Magnus Institute forNeuroscience Utrecht, Utrecht, NetherlandsBackground: Psychosis is a debilitating syndrome, characterised byhallucinations, delusions and disorganisation. A well-replicated find-Abstracts 235

Alterations in functional brain network structure induced by subchronic phencyclidine (PCP) treatment parallel those seen in schizophrenia

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     Edinburgh Research Explorer                                      Alterations in functional brain network structure induced bysubchronic phencyclidine (PCP) treatment parallel those seen inschizophreniaCitation for published version:Dawson, N, Higham, D, Pratt, J & Morris, B 2010, 'Alterations in functional brain network structure inducedby subchronic phencyclidine (PCP) treatment parallel those seen in schizophrenia' SchizophreniaResearch, vol. 117, no. 2-3, pp. 234-235. DOI: 10.1016/j.schres.2010.02.349Digital Object Identifier (DOI):10.1016/j.schres.2010.02.349Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Peer reviewed versionPublished In:Schizophrenia ResearchGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 09. May. 2019demonstrated high levels of schizophrenia spectrum pathology inKlinefelter (van Rijn et al., 2006a). Difficulties in social adaptation andabnormal brain asymmetries suggest that a genetic mechanism(involving genes on theX chromosome)might affect the developmentof social cognition in XXY men. Language and emotion are importantaspects of social cognition. Reduced or abnormal lateralization oflanguage has been found in Klinefelter's syndrome (Geschwind,1998;van Rijn et al., 2008). Additionally, impairments in emotional prosodyperceptionhavebeen reported (vanRijn et al., 2007).Weexpected thatlateralization of emotional prosody differed in Klinefelter's syndrome.Therefore, we used fMRI-guided transcranial magnetic stimulation(TMS) to study lateralization effects.Methods: Sevenmenwith Klinefelter's syndrome and seven controls(matched on age, gender and education) performed an emotionalprosody task during fMRI-scanning. In this task, subjects attended tothe affective (happy, sad, angry or anxious) intonation and had toignore the neutral semantic content of the sentences. We used fMRI-guided TMS (with BrainVoyager neuronavigation) to reduce excit-ability of areas thatwere active during emotional prosody processingin the MR scanner (left and right superior temporal gyrus). TMS wasperformed for 20 minutes on 1 Hz. After stimulation, the subjectsperformed the emotional prosody task again. In addition, a baselinemeasurement without TMS was included. Results were analyzedwith repeated measures analysis of variance (ANOVA).Results: Klinefelter patients showed a trend to react slower thancontrols (p=0.12). They also showed longer reaction times on theangry condition after stimulation of the right superior gyrus(p=0.05), whereas controls reacted faster. No other effects ofTMS reached significance.Discussion: Menwith Klinefelter's syndrome respondedmore slowlyto sentences with an angry intonation in the emotional prosody taskafter right STG stimulation, whereas controls responded faster. Theemotion angry is hypothesized to be primarily processed by the lefthemisphere. Thus, the involvement of the right STG in anger prosodyprocessing in Klinefelter patients suggests a switch in lateralization.The faster responses in the healthy group for this emotion might bedue to callosal disinhibition of the left hemishere by the righthemisphere TMS. As fMRI studies have suggested similar patterns ofaberrant lateralization in Klinefelter syndrome and schizophrenia, ourresults may have implications for understanding schizophrenia.doi:10.1016/j.schres.2010.02.347Poster 120CORTICAL DYSFUNCTION IN ADOLESCENTS WITHSCHIZOPHRENIA DURING WORKING MEMORY COMPONENTPROCESSES - A FUNCTIONAL MAGNETIC RESONANCEIMAGING STUDYRobert A. Bittner1,3, Corinna Haenschel1,3,5, Alard Roebroek4,Fabian Haertling2, Anna Rotarska-Jagiela3, Konrad Maurer1,Rainer Goebel4, Wolf Singer3, David E.J. Linden51Laboratory for Neurophysiology and Neuroimaging, Department ofPsychiatry, Goethe-University Frankfurt amMain Germany; 2Departmentof Child and Adolescent Psychiatry, Goethe-University Frankfurt amMainGermany; 3Department of Neurophysiology, Max-Planck-Institute forBrain Research Frankfurt am Main Germany; 4Department of CognitiveNeuroscience, Faculty of Psychology, Maastricht University MaastrichtNetherlands; 5Wolfson Centre of Clinical and Cognitive Neuroscience,School of Psychology, University of Wales, Bangor Bangor WalesBackground: Working memory (WM) impairment in schizophre-nia (SCZ) is caused by deficits of both encoding and maintenanceprocesses. Prefrontal cortical dysfunction has also consistentlybeen implicated. Yet, results from functional magnetic resonanceimaging (fMRI) studies have been contradictory with reports ofboth decreased and increased prefrontal cortical activation. Thisdiscrepancy has been explained by models of a dynamic WM loaddependent dysfunction of prefrontal cortex. Abnormal functionalconnectivity also seems to contribute to WM deficits. However, theuse of blocked experimental designs – often in conjunction withthe n-back task – has prevented the isolation of WM componentprocesses in the majority of fMRI studies. Therefore, the relation-ship between impairments in specific WM component processeswith abnormal with abnormal cortical activation, connectivity andWM load sensitivity in SCZ is still poorly understood.Methods: We used event-related fMRI to examine differences inbrain activation and functional connectivity during the encoding,maintenance and retrieval stages of a visual WM task in 17adolescents with early-onset SCZ (age 15 to 20 years) and 17matched controls. Up to three abstract visual shapes had to bemaintained for 12 seconds before comparing them to a test stimulus.Results: Patients had reduced WM capacity, which was related tolower activation in left ventrolateral prefrontal cortex (VLPFC) andextrastriate visual cortex during encoding. During early maintenancepatients showed a switch from hyper- to hypoactivation withincreasing WM load in a fronto-parietal network which included leftdorsolateral prefrontal cortex (DLPFC). Furthermore, abnormallyincreased suppression of defaultmode areas by patientswas correlatedwith WM capacity during late maintenance. During retrieval rightinferior VLPFC hyperactivation was correlated with encoding-relatedhypoactivationof left VLPFC inpatients. Cortical dysfunction inpatientsduring encoding and retrieval was accompanied by abnormalfunctional connectivity between fronto-parietal and visual areas.Discussion: Patients showed a primary encoding deficit independentofWM loadduet to a dysfunctionof VLPFC and visual areas. Prefrontalhyperactivation during retrieval seems to be a secondary conse-quence of this deficit. In contrast,WM load dependent fronto-parietaldysfunction and dysregulation of default mode areas seem tocontribute to impaired WMmaintenance. These results indicate thatWMdysfunction in SCZ is the result of a combination of disturbancesin distinct cortical networks which support the individual WMcomponent processes. In contrast,WM loaddependent abnormalitiesseem to be confined primarily to early maintenance. A separateanalysis of WM component processes and parametric manipulationofWM loadmay help to developmore valid and reliable intermediatephenotypes for genetic studies. Focusing on impairments of specificcomponent processes could also lead to more targeted and effectivepsychological and pharmacological cognitive remediation strategies.doi:10.1016/j.schres.2010.02.348Poster 121ALTERATIONS IN FUNCTIONAL BRAIN NETWORK STRUCTUREINDUCED BY SUBCHRONIC PHENCYCLIDINE (PCP) TREATMENTPARALLEL THOSE SEEN IN SCHIZOPHRENIANeil Dawson1, Des Higham2, Judith Pratt1, Brian Morris11PsyRING, Universities of Glasgow and Strathclyde Glasgow, Lanarkshire,United Kingdom; 2University of Strathclyde Glasgow, Lanarkshire,United KingdomBackground: Quantitative analysis of complex network structure,based on graph theory, has recently been applied to elucidate theorganisation of structural and functional brain networks (Bullmoreand Sporns, 2009) in both healthy humans and in disease states,including schizophrenia (Bassett et al., 2008; Liu et al., 2008). Thesemethods are yet to be applied to brain imaging data from preclinicalmodels relevant to mental health. Here we investigate networkAbstracts234structure in functional brain networks in a preclinical modelrelevant to schizophrenia (Pratt et al., 2008).Methods: Cerebral metabolism in 64 brain regions was determinedin control rats (saline, male, Long-Evans, n=7) and rats treatedsubchronically with PCP (2.58 mg.kg−1, i.p, 1x daily for 5 days, n=9)by semi-quantitative 2-deoxyglucose (2-DG) autoradiography (Daw-son et al., 2009). Overt alterations in metabolism between groupswere analysed by t-test. For graph theoretical analysis binaryadjacency matrices, over a range of correlation thresholds (Pearson'sco-efficient 0.4 to 0.5), were generated from the brain region partialcorrelation matrix of each experimental group. Global networkarchitecture was characterised in terms of the mean degree, averagepath length, mean clustering coefficient and small-worldness at eachthreshold. In addition, centrality analysis (degree, betweeness andcloseness) was used to identify hub regions in these networks. Small-world properties and hub region identification were determined bystatistically comparing real with calibrated random (Erdös-Rényi)graphs. Statistical differences in network architecture betweengroups was analysed using repeated measures ANOVA. Alterationsin centrality measures between groups were analysed by comparingregional z-scores, generated relative to random networks, using t-testwith Bonferoni correction. Significance was set at p<0.05.Results: Subchronic PCP-treatment induced overt hypometabolism inselect prefrontal and thalamic regions in accordance with previousreports (Pratt et al., 2008). The functional brain network in PCP-treatedanimals had a significantly reducedmean degree, increased average pathlength and reduced mean clustering in comparison to that in controls.The network in PCP-treated animals also displayed a significantly highersmall-worldness than that in controls. In control animals themediodorsaland reticular (dorsal and ventral) thalamus and locus coeruleus wereidentified as important hubs, across all centrality measures. Of theseregions the reticular thalamus (ventral and dorsal) and locus coeruleuslost their hub status in PCP-treated animals. Several additional thalamicregions (anteromedial, centrolateral, centromedial and the nucleusreuniens) also showed reduced centrality in PCP-treated animals.Discussion: This study is the first to apply the quantitative analysis ofnetwork structure to functional brain imaging data from a preclinicalmodel relevant to schizophrenia. The global architecture of thisnetwork in control animals, including a small-world topography, isconsistent with reports from human studies. In addition, PCP-induced alterations in network structure parallel functional networkalterations seen in schizophrenia (Liu et al., 2008). Furthermore,these results provide new insight into alterations in functional brainnetworks which may contribute to the overt alterations in cerebralmetabolism seen in schizophrenia. Bassett et al, 2008. J.Neurosci.28:9239 Bullmore and Sporns, 2008. Nat.Rev. Neurosci. 10:186Dawson et al, 2009 J.Neuro.Res. 87:2375 Liu et al, 2008 Brain131:945 Pratt et al, 2008 Br.J.Pharmacol. 153:S465.doi:10.1016/j.schres.2010.02.349Poster 122BRAIN ACTIVITY DURING SOCIAL COGNITION TASKS ININDIVIDUALS WITH SCHIZOPHRENIA, THEIR UNAFFECTEDSIBLINGS, AND HEALTHY CONTROLSSalvador M. Guinjoan1,2, Delfina de Achaval1,2, Mirta Villarreal1,2,Elsa Y. Costanzo1, Rocio Berhongaray1, Jazmin Douer1, Julieta Lopez1,Martina C. Mora1, Rodolfo Fahrer1, Ramon C. Leiguarda1, Salvador M.Guinjoan1,21Fundación para la Lucha contra las Enfermedades Neurológicas de laInfancia (FLENI) Capital Federal, Buenos Aires, Argentina; 2ConsejoNacional de Investigaciones Científicas y Técnicas (CONICET) CapitalFederal, Buenos Aires, ArgentinaBackground: Several studies have shown that patients with schizo-phrenia have impaired performance in various aspects of socialcognition including emotion processing, theory of mind, and moraljudgment. Most of the neuroimaging studies have compared patientsand healthy controls during such mental activity because the under-standing of the neural basis of social cognition might help to explainsomedeficits in social functioning in this groupofpatients. The presentstudy examined brain activation patterns during social cognition tasksin patients with schizophrenia, and try to determine whetheralterations in social cognition reflect a trait that can be detected innon-psychotic relatives of patients with schizophrenia.Methods: Eight patients with schizophrenia (age 33.9±13, 2 fe-males), ten non-psychotic relatives (age 32±3.7, 4 females) and tenmatched comparison subjects (age 27.5±7, 4 females) underwentBOLD (blood-oxygen-level-dependent) functional magnetic reso-nance imaging during visual presentation of different social cognitionparadigms. Emotion processing was measured by the Ekman FacesTest using a target (basic emotions) and a control (gender) condition.Theory of Mind (ToM) paradigms were focused on the ability todiscriminate complex mental states in Faces and Reading the Mind inthe Eyes task, with a target (complex mental states) and a control(gender) condition as well. Moral judgment task consisted in 40 shortpassages, half of themwith moral content, inwhich the subject has tojudge the characters actions. Random effects analysis was done foreach taskwithin groups, measuring signal changes between the targetand control conditions of each paradigm.Results: The Reading the Mind in the Eyes (ToM task) brought aboutactivation in the left inferior frontal gyrus, nearBrodmann's areas 44and45, in all groups. Both patients and their siblings showed activation inthe same area of the right hemisphere althoughwith less intensity, andin the left striatum. Patient's siblings showed bilateral activation of themiddle occipital gyrus. During a moral judgement task, right inferiorfrontal gyruswas activated inbothpatients and their relatives (butmoreintense in the former), and relatives activated right ventromedialprefrontal cortex as well. In this task, healthy persons activatedpreferentially bilateral postcentral gyri. Both facial tests evoked muchlesser activation in patients than in the other two groups. Healthysubjects activated preferentially bilateral middle frontal gyri. Patients'siblings displayed the most intense activation of all groups includingbilateral middle and inferior frontal gyri, parahippocampi, bilateraloccipital structures and bilateral cerebellar structures.Discussion: Reading the Mind in the Eyes and moral judgement testsevoked partially overlapping cerebral activation patterns in patientsand their siblings but not in comparable healthy individuals.Emotion processing as assessed by social cognitive tasks involvingfaces evoked strong cerebral activation in unaffected siblings ofschizophrenia patients. The present results suggest that socialcognitive and moral tasks are associated with activation of brainareas partially similar in patients with schizophrenia and theirunaffected siblings, and distinct from those in healthy individuals.doi:10.1016/j.schres.2010.02.350Poster 123SIMILAR LANGUAGE ACTIVATION IN NON-PSYCHOTICINDIVIDUALS WITH AUDITORY VERBAL HALLUCINATIONSAND CONTROL SUBJECTSKelly M. Diederen, Antoin D. De Weijer, Kirstin Daalman,Bas F. Neggers, Rene S. Kahn, Iris E. SommerUniversity Medical Center Utrecht & Rudolf Magnus Institute forNeuroscience Utrecht, Utrecht, NetherlandsBackground: Psychosis is a debilitating syndrome, characterised byhallucinations, delusions and disorganisation. A well-replicated find-Abstracts 235

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Alterations in functional brain network structure induced by subchronic phencyclidine (PCP) treatment parallel those seen in schizophrenia

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