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Page 1: NEURAL CORRELATES OF KETAMINE-INDUCED PSYCHOPATHOLOGICAL SYMPTOMS

acquisition delay 2 s., TE 30 ms, FoV 12 cm, 64x64x32 voxel, slicethickness 3.3 mm,distance factor 10%, flip angel 90°). Data and statisticalanalyseswere conductedwith SPM8. Activationswere detected byusingt-tests for the following contrasts: shift > non-shift, non-shift > shift;shift > reading, non-shift > reading. Additional between subjectanalyses were conducted using independent 2sample t-tests.Results:Between subject analyses (controls vs. patients, p<.001 unc.)in the shift > non-shift contrast revealed increased BOLD activationin the anterior right STG (BA38) in patients. Furthermore, we foundincreased activation in controls in the left MTG in the non-shift >reading contrast. Inpatients,within subject comparisons for the shift>non-shift contrast revealed increased activation in the left anteriorMTG (BA21) (p<.001 unc.) whereas in the non-shift > shift contrastwe found activation in the right MTG (BA21) (p<.001 unc.). Bothbaseline contrasts (shift > reading, non-shift > reading) in controlsrevealed robust BOLD effects (p<.05 FWE) with peak activations inthe left STG (BA22). In patients we found activation (p<.001 unc.) inthe left precentral gyrus (BA6) for shift > reading and in the STG(BA22) for non-shift > reading contrasts.Discussion: In our study, we found robust speech versus readingcontrasts which were largely comparable between shift and non-shift conditions in patients and controls. Direct comparisons of shiftversus non-shift conditions in patients vs. controls showedincreased right anterior STG activation in Patients. In patients, theshift-condition was associated with left anterior MTG activation.Overall, our results are not fully compatible with the theory ofauditory information processing on prediction deficits in patientswith schizophrenia but may also include aspects of match andmismatch processing. Our results will have to be replicated in alarger sample and with increased within-condition power.

doi:10.1016/j.schres.2010.02.626

Poster 132NEURAL CORRELATES OF KETAMINE-INDUCEDPSYCHOPATHOLOGICAL SYMPTOMS

Arne Nagels1, Sören Krach1, Andre Kirner-Veselinovic2, Tilo Kircher11Philipps-University Marburg, Department of Psychiatry andPsychotherapy, Marburg, Germany; 2RWTH Aachen University,Department of Psychiatry and Psychotherapy, Aachen, Germany

Background: The N-methyl-D-aspartate receptor (NMDAR) hasbeen implicated in the pathophysiology of schizophrenia. In healthyindividuals, a subanaesthetic dose of the non-competitive NMDARantagonist s-ketamine reproduces positive, negative and disorga-nized symptoms of schizophrenia.Methods: 15 healthy, right-handed, native German-speaking maleindividuals performed an overt verbal fluency task (phonological,lexical, semantic) while brain activation was measured withfunctional magnetic resonance imaging (fMRI). A within-subject,placebo controlled, counterbalanced design was applied to allsubjects. Psychopathological effects were assessed with the Positiveand Negative Syndrome Scale (PANSS).Results: The administration of s-ketamine led to an overalldecrement in task performance. Psychopathological symptomsevident during s-ketamine administration encompassed heigh-tened levels of disorganization and stereotypical thinking as wellas hallucinations. Multiple regression analyses revealed enhancedbilateral activations of the superior frontal gyri along withsymptoms of disorganization, thalamic activations for hallucina-tions and activations in a widespread network including the rightparahippocampus, the precuneus, the posterior cingulate and themiddle temporal gyrus for stereotypical thinking.

Discussion: Similar patterns of cortical activation were previouslyfound in patients with schizophrenia. These results together withthe diminished verbal fluency performance under s-ketamineadministration support the role of glutamatergic dysfunction inthe symptoms of schizophrenia.

doi:10.1016/j.schres.2010.02.627

Poster 133AN OPTIMIZED FMRI PULSE SEQUENCE FOR MEASURING BOLDSIGNAL CHANGE IN SUBCORTICAL BRAIN AREAS

Sebastiaan F.W. Neggers, Iris E.C. Sommer, Rene S. KahnRudolf Magnus Institute for Neuroscience, dept of Psychiatry, UMCUtrecht Utrecht, Utrecht, Netherlands

Background: Many mental health problems probably includediseases of subcortical areas such as the basal ganglia and theirdopaminergic neuronal projections. Increasingly, functional mag-netic resonance imaging revealing Blood Oxygenation LevelDependent (BOLD) signal changes revealing sites of increasedneuronal activation is used to investigate the neurobiologicalorigins of such disabling diseases. Nevertheless, only a limitednumber of studies report alterations of neuronal signaling insubcortical areas in schizophrenia. This is probably not due to thefact that subcortical areas are unaffected, as deep brain structuresare difficult to investigate using standard fMRI measurements.Rather, the widely used echo planar imaging (EPI) pulse sequenceat relatively low spatial resolutions (∼4x4x4 mm3) covering thewhole brain at once is known to be biased to cortical signal changedetection. It is not optimal to detect BOLD signal changes in thebasal ganglia for several reasons. First, due to the large distancefrom the send and receive coils, signal to noise is poor. Second, asEPI scanning was originally designed mainly for cortical signalchange detection long echo times are often used, further reducingsignal to noise in subcortical areas. Third, higher acquisitionresolutions known to be superior when using scanners with higherfield strengths might reveal the detailed functional representationsin the small basal ganglia nuclei as they are known from animalresearch. This could demonstrate essential aspects of basal gangliadysfunction that remain obscure to standard EPI fMRI studies.Finally, high cardiac and respiratory noise rhythms in the BOLDsignal in subcortical areas are known to cause further reduction insignal to noise.Methods: Here we present a functional MRI pulse sequence at 3 Tthat deals with most of the above problems, and demonstrate that itis possible to detect basal ganglia signal changes. High-resolution(2x2x2 mm3) EPI and parallel imaging (SENSE) was used to keepbandwidth relatively low (and thus SNR high). This was combinedwith physiological rhythm correction (RETROICOR) during postprocessing, and optimized registration techniques.Results: Using an eye movement countermanding task, we couldpick up signal changes in the striatum, putamen, superior colliculusand other subcortical and cortical brain areas at a detail previouslynot achievable using standard EPI sequences.Discussion: This technique might enable further investigations intomechanisms underlying the development of schizophrenia andother mental health problems in subcortical areas, and remove themethodological bias towards cortical signal change detection as isoften observed in fMRI studies of psychiatric illnesses.

doi:10.1016/j.schres.2010.02.628

Abstracts 357

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