METHODS cont. Functional MRI: Emotional Face Matching Task: • Participants are presented with a target face and two probe faces • They are instructed to match the probe to the face with same emotional expression • In sensorimotor control condition, participants are instructed to match the shape of the probe. • Duration: 8:33 minutes SCANNING PARAMETERS • Images were collected using a 3T GE Scanner • High-resolution Structural Scan : Flip angle = 8, Band Width =31.25, FOV = 240, Slice thickness = 3mm, in- plane resolution 1.875x1.875 mm, 170 slices, 1.00 NEX • The Emotion Face Matching Task: TR = 2000, TE = 32ms, flip angle = 90, FOV = 23, slice thickness =2.6mm, 1.4mm gap, 30 slices, matrix = 64 X 64, Bandwidth = 250 (ramped) with 290 brain images collected IMAGE ANALYSIS • Analysis of Functional NeuroImages (AFNI) software used Individual Subject Processing included: • Correction of possible motion artifacts and slice timing • Registration of functional data to anatomical images • For each participant, the general linear model was used to examine task- related brain response Group Level Analysis: • Mean activation for the contrast between emotion matching and the sensorimotor control condition was computed across all the voxels in the ROI in each individual • AFNI was used to obtain region of interests (ROIs) of the left and right amygdala in each individual • In the ROI we compared the magnitude of brain activation across the three different groups (HC > P/AR > FE) • ANOVA was used to look for main effects of Group and Condition and Group x Condition interaction Automatic Sensory Discrimination and Emotion Processing in Prodromal and First-Episode Schizophrenia Heline Mirzakhanian, Ph.D*., Carol Jahshan, Ph.D*., Lisa T. Eyler, Ph.D., Gregory Light, Ph.D., & Kristin S. Cadenhead, M.D. * Both authors have equally contributed to this project UCSD Department of Psychiatry, La Jolla, CA 92093 N (Total )=32 HC (N=12) P/AR (N=10) FE (N=12) Mean (SD) / Ratio Mean (SD) / Ratio Mean (SD) / Ratio Age (years) 23.0 (4.6) 20.0 (2.5) 23.0 (6.0) Sex (M:W) 6:6 ∞ † 7:3 11:1 Education (years) 16.4 (4.4) 13.3 (2.2) 13.1 (2.1) Handedness (R:L) 10:2 9:1 12:1 Marital Status (single : married) 12:0 10:0 11:1 ∞ = HC ≠ P/AR, (p<.05); † = HC ≠ FE, (p<.05); * = HC < P, (p<.05); # = HC < FE, (p<.05); + = P/AR < FE, (p<.05); ++ = P/AR < FE, (p<.01) BACKGROUND • Efforts to prevent or lessen he functional impact of the onset of schizophrenia can be informed by a better understanding of brain systems involved in cognitive and emotional processing at the earliest stages of the disorder. • A large body of evidence has accumulated demonstrating that patients with schizophrenia have deficits in basic cognitive and emotional processes (Cannon et al, 2005 ; Phillips et al., 1999). • Neuroimaging studies of schizophrenia are conclusive about the presence of structural and functional brain abnormalities underlying these basic cognitive and emotional processing deficits even in the earliest stages of the disorder or during the prodrome (Fusar-Poli et al., 2007). • Deficits in automatic sensory discrimination as indexed by P3a are also well documented in schizophrenia patients and could underlie deficits in more complex cognitive operations, such as emotion processing. • Although there is ample evidence to suggest that P3a is impaired in chronic schizophrenia, its reduction has not been as robust in the early stages of the disease. • Moreover, the relationship between P3a and brain functioning during a cognitive task has not been sufficiently researched in subjects at risk for schizophrenia. • A fuller understanding of disruptions in the neural systems underlying cognitive and emotional processing at the early stages of psychosis using multimodal techniques will lead to more targeted efforts to prevent or minimize functional limitations among patients with psychosis. AIMS Aim 1: To compare amygdalar activation during an emotional face matching task in individuals at risk for psychosis and in first episode psychosis patients using fMRI. Aim 2: To investigate the association between preattentional processing and brain functioning during emotion processing in individuals at risk for psychosis or early in the course of their illness. HYPOTHESES 1) Healthy individuals will show greater amygdalar activation when compared to at risk individuals. At risk individuals in turn will show greater amygdalar activation when compared to the first episode individuals. Amygdala Activation: HC>P/AR > FE 2) Individual automatic sensory discrimination as measured by P3A will be associated with brain activation in the amygdala in at–risk and FE patients during the emotion matching task. • Our preliminary fMRI results show amygdalar hyperactivation in first episode patients but no differential activation in individuals at risk for psychosis. • Hyperactivation during emotional tasks in temporal brain regions including the hippocampus and amygdala have been reported previously (Hempel et al., 2003; Holt et al., 2006a; Kosaka et al.,2002; Russell et al., 2007) and our results are consistent with these previous studies. • Hyperactivation in the amygdala in FE patients possibly suggests a compensatory mechanisms in particular in light of comparable behavioral performance. • The present results also show an association between preattentional processing as measured by P3a and amygdalar brain activation. • Smaller P3a amplitudes at frontocentral electrodes were correlated with lower bilateral amygdala activation and slower performance in the at risk group. • Our preliminary findings suggest that emotional systems are disrupted in the earliest stages of psychosis and that basic preattentional processes could underlie more complex emotion recognition abilities. • Studies using multi modal research techniques can be helpful to shed some light at the mechanism involved in psychosis. Functional MRI: Hypothesis 1: Behavioral Performance: • No main effect of Group (F (6,124)= .54, p=.78) or Group x Condition interactions F(6,124)= .13, p=.99) were significant Amygdalar Brain Activation During Emotional Face Matching Challenge: RESULTS DISCUSSION METHODS PARTICIPANTS • A total of 32 participants were included in the study • 10 prodromal/individuals at risk for schizophrenia (P/AR) • 12 individuals with first episode of psychosis (FE) • 12 healthy individuals Demographic Information ** ** Hypothesis 1 In contrast to our hypothesis, the FE group showed greater activation in both hemispheres, followed by the P/AR group and healthy individuals. There were no significant differences in magnitude of activation between HC and P/AR individuals in the left or right hemisphere. REFERENCES: 1) Bowie, C.R., Reichenberg, A., Patterson, T.L., Heaton, R.K. & Harvey, P.D. (2006). Determinants of real-world functional performance in schizophrenia subjects: Correlations with cognition, functional capacity, and symptoms. American Journal of Psychiatry, 163, 418-425. 2) Cannon, T.D., Glahn, D.C., Kim, J., Van Erp, T., Karlsgodt, K., Cohen, M.S., Nuechterlein, K.H., Bava, S. & Shirinyan, D. (2005). Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia. Archives of General Psychiatry, 62, 1071-1080. 3) Fusar-Poli, P., Perez, J., Broome, M., Borgwardt, S., Placentino, A., Caverzasi, E., Cortesi, M., Veggiotti, P., Politi, P., Barale, F. & McGuire, P. (2007). Neurofunctional correlates of vulnerability to psychosis: A systematic review and meta-analysis. Neuroscience and Behavioral Reviews, 31, 465-484. 4) Hempel, A., Hempel, E., Schönknecht, P., Stippich, C. & Schröder, J. (2003). Impairment in basal limbic function in schizophrenia during affect recognition. Psychiatry Research, 122, 115–124. 5) Holt, D.J., Kunkel, L., Weiss, A.P., Goff, D.C., Wright, C.I., Shin, L.M., Rauch, S.L., Hootnick, J.& Heckers, S.( 2006a). Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia. Schizophrenia Research, 82, 153–162. 5) Karlsgodt, K.H., Glahn, D.C., van Erp, T.G.M., Therman, S., Huttunen, M., Manninen, M., Kaprio, J., Cohen, M.S., Lönnqvist, J. & Cannon, T.D. (2007). The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects. Schizophrenia Research, 89, 191–197. 6) Kosaka, H., Omori, M., Murata, T., Iidaka, T., Yamada, H., Okada, T., Takahashi, T., Sadato, N., Itoh, H., Yonekura, Y., Wada, Y. (2002). Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study. Schizophrenia Research, 57, 87–95. 7) Pantelis, C., Velakoulis, D., Wood, S.J., Yucel, M., Yung, A.R., Phillips, L.J., Sun, D.Q. & McGorry, P.D. (2007). Neuroimaging and emerging psychotic disorders: Melbourne ultra-high risk studies. International Review of Pyschiatry, 19, 373-381. 8) Phillips, M.L., Williams, L., Senior, C., Bullmore, E.T., Brammer, M.J., Andrew, C. & David, A.S. (1999). A differential neural response to threatening and non-threatening negative facial expressions in paranoid and non-paranoid schizophrenics. Psychiatry Research, 92, 11–31. 9) Seiferth, N.Y., Pauly, K., Habel, U., Kellermann, T., Shah, N.J., Ruhrmann, S., Klosterkötter, J., Schneider, F.& Kircher, T. (2008). Increased neural response related to neutral faces in individuals at risk for psychosis. NeuroImage, 40, 289–297. P3a Paradigm ERP Recording •EEG recordings were acquired with a Neuroscan NuAmp system. •34 electrodes with 1 reference electrode at nose tip, 1 ground electrode at Fpz, and 4 electrodes above and below the left eye and at the outer canthi of both eyes. EEG was digitally referenced off-line to linked mastoids (TP9/TP10). Stimuli •Binaural stimulation (1-kHz 85-dB sound pressure level with 1ms increase/decrease) with a fixed stimulus onset-to-onset asynchrony of 500ms. •Standard (P=.90; 50ms duration) and deviant (P=.10; 100ms duration) tones were presented in pseudorandom order while subjects watched a silent cartoon videotape. Acquisition •All impedances were kept below 4 kΩ. Signals were digitized at a rate of 1kHz with system filter settings at 0.5-100 Hz. •Recording was terminated when a minimum of 225 artifact-free deviant trials were collected. Processing •Continuous recordings were mathematically corrected for eye movement artifact. •Continuous data were divided into epochs relative to the onset of stimuli (-100 to 500 ms) and centered at the mean of the prestimulus baseline. •Following blink correction, epochs containing more than + 50 µV in frontal recording sites were automatically rejected Auditory Stimuli P3a ERP Responses to “Oddball” (10%) Stimuli Difference Waveform s Clinical Information + = P/AR < FE, (p<.05); ++ = P/AR < FE, (p<.01) P/AR (N=10) FE (N=12) Mean (SD) Mean (SD) Global SAPS Positive Symptoms 3.7 (3.9) 6.2 (5.4) Global SANS Negative Symptoms 6.5 (5.3) + 10.7 (4.6) BPRS Total 13.5 (11.4) 14.7 (10.1) GAF 53.1 (13.1) 46.3 (7.6) ERP & Functional MRI: Hypothesis 2: • Significant correlations were found between P3a, brain activation, and reaction time on the facial emotion matching task in the AR group only. More specifically, smaller P3a amplitudes at frontocentral electrodes were correlated with lower bilateral amygdalar activation (r=.67 to .81, p <.05) and slower performance (r=-.67 to -.70, p <.05). Association between Right and Left Amygdala Brain Activation and P3a: ** ** ** ht protected. F1000 Posters. sters. Copyright protected. F1000 Posters. Copyright pro ed. F1000 Posters. Copyright protected. F1000 Posters. Copyright protected. F1000 yright protected. F1000 Posters. Copyright protected. F1000 Posters. Copyright protected. F1000 Posters. Cop Posters. Copyright protected. F1000 Posters. Copyright protected. F1000 Posters. Copyright protected. F1000 Posters. Cop Copyright protected. F1000 Posters. Copyright protected. F1000 Posters. Copyright protected. F1000 ected. F1000 Posters. Copyright protected. F1000 Posters. Copyright pro Posters. Copyright protected. F1000 Posters. yright protected. F1 View publication stats View publication stats