Idea Transcript
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Hospital Clinic de Barcelona, Child and Adolescent Psychiatry, Barcelona, Spain 5 CIBERSAM, Mental Health, Barcelona, Spain 6 IDIBAPS, Child and Adolescent Psychiatry and Psychology, Barcelona, Spain 7 IDIBAPS, Multimodal neuroimaging in high risk and early psychosis, Barcelona, Spain
characterize EOP at different stages of the disease. Nevertheless, this finding needs to be interpreted taking into account that the present results correspond to ROI analyses and that the current study design does not allow to examine longitudinal change. Further research should focus on assessing longitudinal differences in resting-state networks in EOP.
Introduction: Intrinsic functional connectivity (iFC) of resting-state networks has been reported to be altered in schizophrenia, especially in fronto-temporal networks [1]. Our team have recently observed reduced connectivity in the right middle/inferior frontal gyrus (rIFG) within a network functionally related to language, in adolescents suffering a first episode of psychosis in comparison to healthy controls (HC) [2]. The aim of this study is to test whether these changes persist two year after clinical onset and to examine whether there are any structural correlates. Methods: A case-control cross-sectional study was performed evaluating iFC and grey matter structure in adolescents twoyears-after their first psychotic episode compared to HC, in sample with a partial overlap (33%) with regards to our previous report. Twenty-nine adolescents with Early Onset Psychosis (EOP) participated in this two-year follow-up assessment and were compared cross-sectionally to 36 HC. After excluding 3 cases due to excess movement, final sample (n=62) did not present significant differences in age (EOP=17.6 7 0.3 years; HC= 18.3 7 0.3 years) or sex (EOP=58% female; HC=50% female). Diagnoses were: schizophrenia (8), schizoaffective disorder (5), bipolar disorder (4), major depression (2) and psychosis not-otherwise specified (7). A DARTEL algorithm was applied to the segmented T1structural volumes to generate a sample-specific template. Functional resting-state images were pre-processed using SPM12 and co-registered to this template. Three components obtained with independent component analysis (toolbox GIFT) corresponding to the salience, language and DMN were identified from visual inspection. Whole brain analysis t-tests were covaried by sex and age using an inclusive grey-matter mask. No differences were observed in total intracraneal, grey matter or white matter volumes amongst groups. Voxel Based Morphometry (VBM) analysis was covaried for age, sex and total intracranial volume. Secondarily, we performed a region of interest (ROI) analysis using the marsbar toolbox: data of iFC and grey matter volume was extracted, using a 10-mmradius sphere centred at MNIx,y,z [42, 39, -3] [2] (rIFG) and performed a group comparison in Stata13. Results: There were no differences between groups in iFC in either of the resting state networks. The ROI analysis corresponding to the rIFG in the language network revealed an effect of group, consisting of reduced iFC in EOP participants relative to HC, survived when controlled by age and sex (p = 0.026). There were no group-effects in grey matter volumes for this region of interest. It was found an inverse correlation between grey matter and iFC at rIFG, only significant in HC group (p = 0.02). Discussion: Our results support persistence of reduced iFC in the language network in adolescents with EOP, 2 years after the first episode, in a mostly independent sample with regards our baseline study [2]. This provides further support to the notion that abnormal fronto-temporal connectivity may
References [1] Khadka, S., Meda, S. A., Stevens, M. C., Glahn, D. C., Calhoun, V. D., Sweeney, J. A., Pearlson, G. D., 2013. Is aberrant functional connectivity a psychosis endophenotype? A resting state functional magnetic resonance imaging study. Biological Psychiatry, 74, 458–466. [2] Solé-Padullés, C., Castro-Fornieles, J., de la Serna, E., Sánchez-Gistau, V., Romero, S., Puig, O., Sugranyes, G. 2017. Intrinsic functional connectivity of fronto-temporal networks in adolescents with early psychosis. European Child & Adolescent Psychiatry, 26, 669–679. http://dx.doi.org/10.1016/j.euroneuro.2017.12.116
P.3.027 Pubertal testosterone shifts neural social emotional action control during adolescence A. Tyborowskan,1, I. Volman2, H. Niermann3,4, S. Smeekens5, I. Toni4, K. Roelofs3,4 1
Donders Centre for Cognitive Neuroimaging, Donders Institute, Nijmegen, The Netherlands 2 UCL Institute of Neurology- University College London, Sobell Department of Motor Neuroscience and Movement Disorders, London, United Kingdom 3 Radboud University, Behavioural Science Institute, Nijmegen, The Netherlands 4 Donders Institute for Brain- Cognition- and Behaviour, Donders Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands 5 Open University of the Netherlands, Faculty of Psychology and Educational Sciences, Heerlen, The Netherlands
The increased occurrence of reward- and sensation-seeking behaviors often observed during adolescence [1] is attributed to the relative imbalance in the maturation of prefrontal areas compared with already well-developed limbic and striatal regions [2]. This general developmental pattern applies also to the control of social emotional actions, a fundamental adult skill. In adults, the anterior prefrontal cortex (aPFC) plays a crucial role in emotional action control by down-regulating amygdala activity [3]. However, during mid adolescence the involvement of the aPFC during executive control of emotions is linked to pubertal maturation. When controlling emotion action tendencies, 14-year-old individuals with more advanced pubertal maturation (indexed by testosterone levels) show greater aPFC activity. However, same-age adolescents with less advanced pubertal maturation show greater pulvinar and amygdala activity [4]. The present study builds on these
Abstracts of the ENCP Workshop for Junior Scientists in Europe, 2018 findings in order to assess the neuro-developmental trajectories of emotional control and how they relate to the changing role of pubertal hormones during late adolescence. Specifically, we address the largely unexplored issue of how and when executive control of emotions transitions to the lateral aPFC. Using a prospective longitudinal design, we investigated the transition of social emotional control from mid to late adolescence using an fMRI-adapted social approach-avoidance (AA) task [5]. Adolescents (n=41) completed the AA task at age 14 and again at age 17. During the task, they had to evaluate the emotional expression (happy, angry) of faces and respond by either pulling a joystick toward (approach) or away (avoidance) from themselves. Affect–congruent conditions involved intuitive stimulus-response mappings (i.e. approach–happy and avoid-angry faces). In contrast, affect-incongruent conditions required participants to override these emotional action tendencies in order to meet task demands (i.e. approach–angry and avoid–happy faces). A multiple regression analysis (including testosterone levels at age 14 and 17) was used to test how emotional control (affect incongruent vs. affect congruent responses) changed over time. Results showed that the role of pubertal testosterone in modulating aPFC activity during emotional control was stronger at age 14 than at age 17 (MNI coordinates: -36, 46, -6, SVCpFWE = .052). The emergence of mature neural control was further supported by a decrease in amygdala activity at age 17 compared to age 14 (MNI coordinates: -26, 0, -24, SVEpFWE= .003), thus replicating previously found adult-like patterns of activation. Lastly, there was a change in connectivity between the aPFC (seed region) and amygdala as a function of testosterone and gender (MNI coordinates: 32, -2, -26, SVCpFWE = .029). Namely, positive aPFCamygdala connectivity in more mature 14-year-old girls flipped to negative connectivity at age 17. This transition did not occur yet in boys, who are known to mature later.
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Taken together, these findings tentatively suggest the maturation of prefrontal down-regulation over emotiondriven amygdala activity. Our findings are relevant for current neurobiological models of pubertal development by qualifying the circuits implicated in the maturation of emotional action control and the timing of these changes. As such, they are important for understanding neurobiological indicators of emotion control alterations, given that the onset of affective disorders peaks during adolescence.
References [1] Harden, K.P., Tucker-Drob, E.M., 2011. Individual differences in the development of sensation seeking and impulsivity during adolescence: further evidence for a dual systems model. Dev. Psychol. 47, 739–746. [2] Braams, B.R., van Duijvenvoorde, A.C.K., Peper, J.S., Crone, E.A., 2015. Longitudinal changes in adolescent risktaking: A comprehensive study of neural responses to rewards, pubertal development, and risk-taking behavior. J. Neurosci. 35, 7226–7238. [3] Volman, I., Roelofs, K., Koch, S., Verhagen, L., Toni, I., 2011. Anterior prefrontal cortex inhibition impairs control over social emotional actions. Curr. Biol. 21, 1766–1770. [4] Tyborowska, A., Volman, I., Smeekens, S., Toni, I., Roelofs, K., 2016. Testosterone during puberty shifts emotional control from pulvinar to anterior prefrontal cortex. J. Neurosci. 36, 6156–6164. [5] Roelofs, K., Minelli, A., Mars, R.B., van Peer, J., Toni, I., 2009. On the neural control of social emotional behavior. Soc. Cogn. Affect. Neurosci. 4, 50–58. http://dx.doi.org/10.1016/j.euroneuro.2017.12.116