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Poster #32 NEURAL MECHANISMS SUPPORTING THE COGNITIVE CONTROL OF EMOTIONAL INFORMATION IN SCHIZOPHRENIA
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Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
gyrus. We investigated whether altered functional connectivity related to these DMN regions is a marker of genetic risk for psychotic disorder. Methods: Anatomical and resting-state functional MRI scans were obtained from 59 patients with psychotic disorder (highest genetic risk), 63 nonpsychotic siblings of these patients (higher than average genetic risk) and 62 healthy controls (average genetic risk). Groups were matched on age, gender and handedness. We used dual regression analysis to estimate the functional connectivity of the DMN in Matlab. First, we regressed restingstate spatial templates obtained from a different study (Rotarska-Jagiela et al., 2010) onto the 4D time series, obtaining temporal network profiles (NPs). Second, NPs were again regressed onto the data, corrected for nuisance parameters (Fox et al., 2005), which resulted in template-based seed-regression spatial maps for each participant. Finally, we investigated group differences of DMN connectivity on a regional level (one-sample t-test, q=0.05, minimum region size = 10 voxels) using ANCOVA. Results: Compared to controls, patients with psychotic disorder displayed significant decreased connectivity between the ACC, left and right parahippocampal gyrus on the one hand and the other regions of the DMN on the other hand β=-0.11, p=0.00; β=-0.09, p=0.00; β=-0.068, p=0.035, respectively). The functional connectivity between the PCC and the other regions of the DMN (β=-0.04, p=0.271) was not significantly different from controls. Siblings showed increased connectivity between the PCC and other regions of the DMN compared to controls β=-0.0, p=0.010), with no differences in connectivity between the ACC, left and right parahippocampal gyrus and other regions of the DMN (β=0.03, p=0.411, β=-0.05,p=0.109, β=0.05, p=0.111, respectively). Patients also showed significantly decreased connectivity in the ACC, PCC and right parahippocampal gyrus with other regions of the DMN, compared to siblings β=-0.14, p=0.000, β=-0.13,p=0.000, β=0.12,p=0.000, respectively), with no difference for the left parahippocampal gyrus β=-0.04, p=0.167). Discussion: Patients with schizophrenia may have a decreased functional connectivity, related to altered connectivity patterns in the ACC and parahippocampal gyrus. These alterations may be associated with the illness phenotype and contribute to the pathophysiology of psychotic symptoms. There was no evidence for a functional connectivity endophenotype.
Poster #32 NEURAL MECHANISMS SUPPORTING THE COGNITIVE CONTROL OF EMOTIONAL INFORMATION IN SCHIZOPHRENIA Laura M. Tully, Sarah Hope Lincoln, Todd Wright, Christine I. Hooker Harvard University, Cambridge, MA, USA Background: Social impairments are characteristic of schizophrenia, yet the neural mechanisms that contribute to these impairments remain unknown. Successful social interactions require the ability to attend to relevant emotional information and inhibit the irrelevant. Neuroimaging studies in healthy individuals indicate that this cognitive control of emotional information requires an intact lateral prefrontal cortex (LPFC). While LPFC deficits are well documented in schizophrenia, it is unclear how these deficits might specifically impact cognitive control of emotional information. We hypothesize: 1) there is dysfunctional activity in the LPFC during cognitive control of emotional information in schizophrenia; 2) lower LPFC activity during emotion control predicts poorer social functioning. Methods: Twenty-two individuals with schizophrenia and 22 age and education matched healthy participants completed two cognitive control tasks whilst undergoing fMRI: the multisource interference task (MSIT), and the MSIT-Emotion, our newly developed measure that presents MSIT stimuli over a background of negative and neutral affective pictures. Social functioning was assessed with both self-report (Social Adjustment Scale) and clinician-rated (social and role scales) instruments. Results: Behavioral results for the MSIT show a main effect of interference but no effect of group; across both groups participants took longer to respond to interference trials compared to control trials. Similarly, on the MSIT-Emotion, results show a main effect of interference but no effect of group or picture type. fMRI results indicate no group differences in brain activation during the MSIT. However, compared to healthy participants, schizophrenia participants have reduced activity in the LPFC during negative interference trials of the MSIT-Emotion. Activity in the LPFC during negative interference trials did not predict social impairments, but there was nonsignificant correlation in the expected direction in the schizophrenia group.
Discussion: Results indicate no group differences on a non-affective cognitive control task, the MSIT. However, compared to healthy controls, individuals with schizophrenia have reduced activity in the LPFC during negative interference trials of the MSIT-Emotion. These findings suggest that individuals with schizophrenia fail to effectively engage the LPFC to inhibit irrelevant emotional information. Although reduced LPFC activity did not predict poorer social functioning, initial data analysis shows a nonsignificant correlation in the expected direction. It’s possible that the social impairment instruments used here was not sensitive enough to assess interpersonal difficulties that would be influenced by deficient emotional control. Future work will investigate this relationship with more specific measures.
Poster #33 SCHIZOPHRENIA, SOCIAL COGNITION, EMOTIONAL PROCESSING AND THE ROLE OF THE LEFT VENTROLATERAL PREFRONTAL CORTEX Lisette Van der Meer 1,2 , Marieke Pijnenborg 3,4 , Willem A. Nolen 5 , André Aleman 1,3 1 Department of neurosciences, University Medical Center Groningen, Groningen, Netherlands; 2 Department of longterm rehabilitation, Lentis Mental Health Care, Zuidlaren, Netherlands; 3 Dept. of Psychology, University of Groningen, Groningen, Netherlands; 4 Dept. of Psychotic Disorders, GGZ-Drenthe, Assen, Netherlands; 5 Department of Psychiatry, University Medical Center Groningen, Groningen, Netherlands Background: An extensive body of research points towards social cognitive and emotional processing difficulties in patients with schizophrenia. These processes encompass the ability to take the perspective of others (or Theory of Mind;ToM), the regulation of emotions and the processing of self-related information. The current study focussed upon the overlapping neural substrates of these processes. Methods: The results of three studies were combined. (1) an fMRI study investigating the role of the inhibition of the self-perspective in perspective taking (van der Meer et al., 2011), (2) a meta-analysis of fMRI data on self-reflective processing (van der Meer et al. 2010), (3) an fMRI study investigating emotion regulation processes, more specifically cognitive reappraisal (van der Velde et al., 2011). Study 1 tested, by means of fMRI, the hypothesis that ToM consists of two processes: (1) self-perspective inhibition and (2) other-perspective taking. This study was conducted in healthy control (HC) subjects. In study 2 a meta-analysis was conducted of published fMRI and PET studies on self-reflection in HC subjects by means of parametric voxel-based meta-analysis. Study 3 investigated the differential activation in brain regions involved in cognitive reappraisal between HC subjects and schizophrenia patients. Activation patterns of self-perspective inhibition, self-reflective processing and cognitive reappraisal were visualized in one template. Subsequently the differential activation pattern between HC subjects and patients on cognitive reappraisal was added to the template and compared with the region of overlap. Results: Overlaying the activation of the processes of self-perspective inhibition, self-reflective processing and reappraisal demonstrated a common region of activation in the left ventrolateral prefrontal cortex (vLPFC). Adding the differential activation pattern of HC subjects and patients on reappraisal revealed decreased activation in the same region within the vLPFC. Discussion: The vLPFC has been implicated in processes of both cognitive and affective control and has a distinct role in the selection, comparison and judgments of stimuli in both cognitive and emotional processes. The overlapping activation in the left vLPFC suggests a common functional role for this region in these processes. The decreased activation in patients on cognitive reappraisal in the left vLPFC may reflect a more general functional impairment in this region. This is supported by the literature in which a decrease of activation in the vLPFC in patients has also been described in discriminating self generated from externally generated stimuli, self-face recognition, self-body perception, integration of subcortical somatic and cortical information and short-term emotional memory.
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
gyrus. We investigated whether altered functional connectivity related to these DMN regions is a marker of genetic risk for psychotic disorder. Methods: Anatomical and resting-state functional MRI scans were obtained from 59 patients with psychotic disorder (highest genetic risk), 63 nonpsychotic siblings of these patients (higher than average genetic risk) and 62 healthy controls (average genetic risk). Groups were matched on age, gender and handedness. We used dual regression analysis to estimate the functional connectivity of the DMN in Matlab. First, we regressed restingstate spatial templates obtained from a different study (Rotarska-Jagiela et al., 2010) onto the 4D time series, obtaining temporal network profiles (NPs). Second, NPs were again regressed onto the data, corrected for nuisance parameters (Fox et al., 2005), which resulted in template-based seed-regression spatial maps for each participant. Finally, we investigated group differences of DMN connectivity on a regional level (one-sample t-test, q=0.05, minimum region size = 10 voxels) using ANCOVA. Results: Compared to controls, patients with psychotic disorder displayed significant decreased connectivity between the ACC, left and right parahippocampal gyrus on the one hand and the other regions of the DMN on the other hand β=-0.11, p=0.00; β=-0.09, p=0.00; β=-0.068, p=0.035, respectively). The functional connectivity between the PCC and the other regions of the DMN (β=-0.04, p=0.271) was not significantly different from controls. Siblings showed increased connectivity between the PCC and other regions of the DMN compared to controls β=-0.0, p=0.010), with no differences in connectivity between the ACC, left and right parahippocampal gyrus and other regions of the DMN (β=0.03, p=0.411, β=-0.05,p=0.109, β=0.05, p=0.111, respectively). Patients also showed significantly decreased connectivity in the ACC, PCC and right parahippocampal gyrus with other regions of the DMN, compared to siblings β=-0.14, p=0.000, β=-0.13,p=0.000, β=0.12,p=0.000, respectively), with no difference for the left parahippocampal gyrus β=-0.04, p=0.167). Discussion: Patients with schizophrenia may have a decreased functional connectivity, related to altered connectivity patterns in the ACC and parahippocampal gyrus. These alterations may be associated with the illness phenotype and contribute to the pathophysiology of psychotic symptoms. There was no evidence for a functional connectivity endophenotype.
Poster #32 NEURAL MECHANISMS SUPPORTING THE COGNITIVE CONTROL OF EMOTIONAL INFORMATION IN SCHIZOPHRENIA Laura M. Tully, Sarah Hope Lincoln, Todd Wright, Christine I. Hooker Harvard University, Cambridge, MA, USA Background: Social impairments are characteristic of schizophrenia, yet the neural mechanisms that contribute to these impairments remain unknown. Successful social interactions require the ability to attend to relevant emotional information and inhibit the irrelevant. Neuroimaging studies in healthy individuals indicate that this cognitive control of emotional information requires an intact lateral prefrontal cortex (LPFC). While LPFC deficits are well documented in schizophrenia, it is unclear how these deficits might specifically impact cognitive control of emotional information. We hypothesize: 1) there is dysfunctional activity in the LPFC during cognitive control of emotional information in schizophrenia; 2) lower LPFC activity during emotion control predicts poorer social functioning. Methods: Twenty-two individuals with schizophrenia and 22 age and education matched healthy participants completed two cognitive control tasks whilst undergoing fMRI: the multisource interference task (MSIT), and the MSIT-Emotion, our newly developed measure that presents MSIT stimuli over a background of negative and neutral affective pictures. Social functioning was assessed with both self-report (Social Adjustment Scale) and clinician-rated (social and role scales) instruments. Results: Behavioral results for the MSIT show a main effect of interference but no effect of group; across both groups participants took longer to respond to interference trials compared to control trials. Similarly, on the MSIT-Emotion, results show a main effect of interference but no effect of group or picture type. fMRI results indicate no group differences in brain activation during the MSIT. However, compared to healthy participants, schizophrenia participants have reduced activity in the LPFC during negative interference trials of the MSIT-Emotion. Activity in the LPFC during negative interference trials did not predict social impairments, but there was nonsignificant correlation in the expected direction in the schizophrenia group.
Discussion: Results indicate no group differences on a non-affective cognitive control task, the MSIT. However, compared to healthy controls, individuals with schizophrenia have reduced activity in the LPFC during negative interference trials of the MSIT-Emotion. These findings suggest that individuals with schizophrenia fail to effectively engage the LPFC to inhibit irrelevant emotional information. Although reduced LPFC activity did not predict poorer social functioning, initial data analysis shows a nonsignificant correlation in the expected direction. It’s possible that the social impairment instruments used here was not sensitive enough to assess interpersonal difficulties that would be influenced by deficient emotional control. Future work will investigate this relationship with more specific measures.
Poster #33 SCHIZOPHRENIA, SOCIAL COGNITION, EMOTIONAL PROCESSING AND THE ROLE OF THE LEFT VENTROLATERAL PREFRONTAL CORTEX Lisette Van der Meer 1,2 , Marieke Pijnenborg 3,4 , Willem A. Nolen 5 , André Aleman 1,3 1 Department of neurosciences, University Medical Center Groningen, Groningen, Netherlands; 2 Department of longterm rehabilitation, Lentis Mental Health Care, Zuidlaren, Netherlands; 3 Dept. of Psychology, University of Groningen, Groningen, Netherlands; 4 Dept. of Psychotic Disorders, GGZ-Drenthe, Assen, Netherlands; 5 Department of Psychiatry, University Medical Center Groningen, Groningen, Netherlands Background: An extensive body of research points towards social cognitive and emotional processing difficulties in patients with schizophrenia. These processes encompass the ability to take the perspective of others (or Theory of Mind;ToM), the regulation of emotions and the processing of self-related information. The current study focussed upon the overlapping neural substrates of these processes. Methods: The results of three studies were combined. (1) an fMRI study investigating the role of the inhibition of the self-perspective in perspective taking (van der Meer et al., 2011), (2) a meta-analysis of fMRI data on self-reflective processing (van der Meer et al. 2010), (3) an fMRI study investigating emotion regulation processes, more specifically cognitive reappraisal (van der Velde et al., 2011). Study 1 tested, by means of fMRI, the hypothesis that ToM consists of two processes: (1) self-perspective inhibition and (2) other-perspective taking. This study was conducted in healthy control (HC) subjects. In study 2 a meta-analysis was conducted of published fMRI and PET studies on self-reflection in HC subjects by means of parametric voxel-based meta-analysis. Study 3 investigated the differential activation in brain regions involved in cognitive reappraisal between HC subjects and schizophrenia patients. Activation patterns of self-perspective inhibition, self-reflective processing and cognitive reappraisal were visualized in one template. Subsequently the differential activation pattern between HC subjects and patients on cognitive reappraisal was added to the template and compared with the region of overlap. Results: Overlaying the activation of the processes of self-perspective inhibition, self-reflective processing and reappraisal demonstrated a common region of activation in the left ventrolateral prefrontal cortex (vLPFC). Adding the differential activation pattern of HC subjects and patients on reappraisal revealed decreased activation in the same region within the vLPFC. Discussion: The vLPFC has been implicated in processes of both cognitive and affective control and has a distinct role in the selection, comparison and judgments of stimuli in both cognitive and emotional processes. The overlapping activation in the left vLPFC suggests a common functional role for this region in these processes. The decreased activation in patients on cognitive reappraisal in the left vLPFC may reflect a more general functional impairment in this region. This is supported by the literature in which a decrease of activation in the vLPFC in patients has also been described in discriminating self generated from externally generated stimuli, self-face recognition, self-body perception, integration of subcortical somatic and cortical information and short-term emotional memory.