Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-10T13:47:49.630Z Has data issue: false hasContentIssue false
  • English
  • Français

Abnormal cortico-limbic connectivity during emotional processing correlates with symptom severity in schizophrenia

Published online by Cambridge University Press:  15 April 2020

B. Vai ,
G. Sferrazza Papa ,
S. Poletti ,
D. Radaelli ,
E. Donnici ,
I. Bollettini ,
A. Falini ,
R. Cavallaro ,
E. Smeraldi  and
F. Benedetti
B. Vai*
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), Università Vita-Salute San Raffaele, Milano, Italy PhD in Evolutionary Psychopathology, Libera Università Maria Ss. Assunta, Roma, Italy
G. Sferrazza Papa
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy
S. Poletti
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), Università Vita-Salute San Raffaele, Milano, Italy
D. Radaelli
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), Università Vita-Salute San Raffaele, Milano, Italy
E. Donnici
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy
I. Bollettini
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), Università Vita-Salute San Raffaele, Milano, Italy PhD program in Philosophy and Sciences of Mind, University Vita-Salute San Raffaele, Milano, Italy
A. Falini
Affiliation:
Department of Neuroradiology, Scientific Institute Ospedale San Raffaele, Milan, Italy CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), Università Vita-Salute San Raffaele, Milano, Italy
R. Cavallaro
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy
E. Smeraldi
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), Università Vita-Salute San Raffaele, Milano, Italy
F. Benedetti
Affiliation:
Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), Università Vita-Salute San Raffaele, Milano, Italy
*
⁎Corresponding author. Istituto Scientifico Ospedale San Raffaele, Department of Clinical Neurosciences, San Raffaele Turro, Via Stamira d'Ancona 20, Milano, Italy. Tel.: +39 02 26433156; fax: +39 02 26433265. E-mail address:b.vai@hotmail.it (B. Vai).
Get access

Abstract

Background

Impaired emotional processing is a core feature of schizophrenia (SZ). Consistent findings suggested that abnormal emotional processing in SZ could be paralleled by a disrupted functional and structural integrity within the fronto-limbic circuitry. The effective connectivity of emotional circuitry in SZ has never been explored in terms of causal relationship between brain regions. We used functional magnetic resonance imaging and Dynamic Causal Modeling (DCM) to characterize effective connectivity during implicit processing of affective stimuli in SZ.

Methods

We performed DCM to model connectivity between amygdala (Amy), dorsolateral prefrontal cortex (DLPFC), ventral prefrontal cortex (VPFC), fusiform gyrus (FG) and visual cortex (VC) in 25 patients with SZ and 29 HC. Bayesian Model Selection and average were performed to determine the optimal structural model and its parameters.

Results

Analyses revealed that patients with SZ are characterized by a significant reduced top-down endogenous connectivity from DLPFC to Amy, an increased connectivity from Amy to VPFC and a decreased driving input to Amy of affective stimuli compared to HC. Furthermore, DLPFC to Amy connection in patients significantly influenced the severity of psychopathology as rated on Positive and Negative Syndrome Scale.

Conclusions

Results suggest a functional disconnection in brain network that contributes to the symptomatic outcome of the disorder. Our findings support the study of effective connectivity within cortico-limbic structures as a marker of severity and treatment efficacy in SZ.

Keywords

Dynamic causal modelingBOLD fMRISchizophreniaEmotion
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 5 , July 2015 , pp. 590 - 597
Copyright
Copyright © Elsevier Masson SAS 2015

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adolphs, R.. What does the amygdala contribute to social cognition?. Ann N Y Acad Sci 2010;1191:42–61.CrossRefGoogle ScholarPubMed
Allen, P., Laroi, F., McGuire, P.K., Aleman, A.. The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations. Neurosci Biobehav Rev 2008;32:175–191.CrossRefGoogle ScholarPubMed
Barrett, L.F., Mesquita, B., Ochsner, K.N., Gross, J.J.. The experience of emotion. Annu Rev Psychol 2007;58:373–403.CrossRefGoogle ScholarPubMed
Beauregard, M., Levesque, J., Bourgouin, P.. Neural correlates of conscious self-regulation of emotion. J Neurosci 2001;21:RC165.CrossRefGoogle ScholarPubMed
Benedetti, F., Radaelli, D., Poletti, S., Falini, A., Cavallaro, R., Dallaspezia, S., et al.Emotional reactivity in chronic schizophrenia: structural and functional brain correlates and the influence of adverse childhood experiences. Psychol Med 2011;41:509–519.CrossRefGoogle ScholarPubMed
Benedetti, F., Yeh, P.H., Bellani, M., Radaelli, D., Nicoletti, M.A., Poletti, S., et al.Disruption of white matter integrity in bipolar depression as a possible structural marker of illness. Biol Psychiatry 2011;69:309–317.CrossRefGoogle Scholar
Das, P., Kemp, A.H., Flynn, G., Harris, A.W., Liddell, B.J., Whitford, T.J., et al.Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia. Schizophr Res 2007;90:284–294.CrossRefGoogle Scholar
Davidson, R.J.. Anxiety and affective style: role of prefrontal cortex and amygdala. Biol Psychiatry 2002;51:68–80.CrossRefGoogle ScholarPubMed
Davidson, L.L., Heinrichs, R.W.. Quantification of frontal and temporal lobe brain-imaging findings in schizophrenia: a meta-analysis. Psychiatry Res 2003;122:69–87.CrossRefGoogle ScholarPubMed
Dima, D., Stephan, K.E., Roiser, J.P., Friston, K.J., Frangou, S.. Effective connectivity during processing of facial affect: evidence for multiple parallel pathways. J Neurosci 2011;31:14378–14385.CrossRefGoogle ScholarPubMed
Diwadkar, V.A., Wadehra, S., Pruitt, P., Keshavan, M.S., Rajan, U., Zajac-Benitez, C., et al.Disordered corticolimbic interactions during affective processing in children and adolescents at risk for schizophrenia revealed by functional magnetic resonance imaging and dynamic causal modeling. Arch Gen Psychiatry 2012;69:231–242.CrossRefGoogle ScholarPubMed
Ellison-Wright, I., Bullmore, E.. Meta-analysis of diffusion tensor imaging studies in schizophrenia. Schizophr Res 2009;108:3–10.CrossRefGoogle Scholar
Fairhall, S.L., Ishai, A.. Effective connectivity within the distributed cortical network for face perception. Cereb Cortex 2007;17:2400–2406.CrossRefGoogle ScholarPubMed
Fakra, E., Salgado-Pineda, P., Delaveau, P., Hariri, A.R., Blin, O.. Neural bases of different cognitive strategies for facial affect processing in schizophrenia. Schizophr Res 2008;100:191–205.CrossRefGoogle Scholar
Fan, F.M., Tan, S.P., Yang, F.D., Tan, Y.L., Zhao, Y.L., Chen, N., et al.Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: a pilot study. Neurosci Bull 2013;29:59–74.CrossRefGoogle ScholarPubMed
Friston, K.J.. The disconnection hypothesis. Schizophr Res 1998;30:115–125.CrossRefGoogle ScholarPubMed
Friston, K.J., Buechel, C., Fink, G.R., Morris, J., Rolls, E., Dolan, R.J.. Psychophysiological and modulatory interactions in neuroimaging. Neuroimage 1997;6:218–229.CrossRefGoogle ScholarPubMed
Friston, K.J., Harrison, L., Penny, W.. Dynamic causal modelling. Neuroimage 2003;19:1273–1302.CrossRefGoogle ScholarPubMed
Fusar-Poli, P., Placentino, A., Carletti, F., Landi, P., Allen, P., Surguladze, S., et al.Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci 2009;34:418–432.Google ScholarPubMed
Hare, T.A., Tottenham, N., Galvan, A., Voss, H.U., Glover, G.H., Casey, B.J.. Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task. Biol Psychiatry 2008;63:927–934.CrossRefGoogle ScholarPubMed
Hariri, A.R., Mattay, V.S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., et al.Serotonin transporter genetic variation and the response of the human amygdala. Science 2002;297:400–403.CrossRefGoogle ScholarPubMed
Hempel, A., Hempel, E., Schonknecht, P., Stippich, C., Schroder, J.. Impairment in basal limbic function in schizophrenia during affect recognition. Psychiatry Res 2003;122:115–124.CrossRefGoogle ScholarPubMed
Hill, T., Lewicki, P.Statistics: methods and applications. A comprehensive reference for science, industry and data mining. General Linear Models, StatSoft, Tulsa (OK); 2006 [Chapter 18, p. 245–76].Google Scholar
Holm, S.. Holm's sequential bonferroni procedure. Scand J Stat 1979;6:65–70.Google Scholar
Holt, D.J., Kunkel, L., Weiss, A.P., Goff, D.C., Wright, C.I., Shin, L.M., et al.Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia. Schizophr Res 2006;82:153–162.CrossRefGoogle Scholar
Hooker, C., Park, S.. Emotion processing and its relationship to social functioning in schizophrenia patients. Psychiatry Res 2002;112:41–50.CrossRefGoogle ScholarPubMed
Hoschel, K., Irle, E.. Emotional priming of facial affect identification in schizophrenia. Schizophr Bull 2001;27:317–327.CrossRefGoogle Scholar
Hughett, P.Accurate computation of the F-to-z and t-to-z transforms for large arguments. J Stat Softw 2007;23.Google Scholar
Iidaka, T., Sadato, N., Yamada, H., Murata, T., Omori, M., Yonekura, Y.. An fMRI study of the functional neuroanatomy of picture encoding in younger and older adults. Brain Res Cogn Brain Res 2001;11:1–11.CrossRefGoogle ScholarPubMed
Iidaka, T., Omori, M., Murata, T., Kosaka, H., Yonekura, Y., Okada, T., et al.Neural interaction of the amygdala with the prefrontal and temporal cortices in the processing of facial expressions as revealed by fMRI. J Cogn Neurosci 2001;13:1035–1047.CrossRefGoogle ScholarPubMed
Iritani, S.. [Neuropathology of scizophrenia--from a new perspective]. Brain Nerve 2007;59:605–616.Google Scholar
Kay, S.R., Fiszbein, A., Opler, L.A.. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.CrossRefGoogle Scholar
Kring, A.M., Kerr, S.L., Smith, D.A., Neale, J.M.. Flat affect in schizophrenia does not reflect diminished subjective experience of emotion. J Abnorm Psychol 1993;102:507–517.CrossRefGoogle Scholar
LeDoux, J.E.. Emotion circuits in the brain. Annu Rev Neurosci 2000;23:155–184.CrossRefGoogle Scholar
LeDoux, J.. The emotional brain, fear, and the amygdala. Cell Mol Neurobiol 2003;23:727–738.CrossRefGoogle ScholarPubMed
Leitman, D.I., Loughead, J., Wolf, D.H., Ruparel, K., Kohler, C.G., Elliott, M.A., et al.Abnormal superior temporal connectivity during fear perception in schizophrenia. Schizophr Bull 2008;34:673–678.CrossRefGoogle Scholar
Lepage, M., Sergerie, K., Benoit, A., Czechowska, Y., Dickie, E., Armony, J.L.. Emotional face processing and flat affect in schizophrenia: functional and structural neural correlates. Psychol Med 2011;41:1833–1844.CrossRefGoogle ScholarPubMed
Liberzon, I., Taylor, S.F., Fig, L.M., Decker, L.R., Koeppe, R.A., Minoshima, S.. Limbic activation and psychophysiologic responses to aversive visual stimuli. Interaction with cognitive task. Neuropsychopharmacology 2000;23:508–516.CrossRefGoogle ScholarPubMed
Liu, H., Tang, Y., Womer, F., Fan, G., Lu, T., Driesen, N., et al.Differentiating patterns of amygdala-frontal functional connectivity in schizophrenia and bipolar disorder. Schizophr Bull 2014;40:469–477.CrossRefGoogle ScholarPubMed
Maxwell, S., Delaney, H.Designing experiments and analyzing data. A model comparison perspective, 2nd ed, New York: Taylor & Francis; 2004.Google Scholar
McCulloch, C.E., Searle, S.R., Neuhaus, J.M.Generalized, linear and mixed models. 2nd ed, New York: John Wiley & Sons; 2008.Google Scholar
Minzenberg, M.J., Laird, A.R., Thelen, S., Carter, C.S., Glahn, D.C.. Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Arch Gen Psychiatry 2009;66:811–822.CrossRefGoogle Scholar
Modinos, G., Ormel, J., Aleman, A.. Altered activation and functional connectivity of neural systems supporting cognitive control of emotion in psychosis proneness. Schizophr Res 2010;118:88–97.CrossRefGoogle ScholarPubMed
Ochsner, K.N., Gross, J.J.. The cognitive control of emotion. Trends Cogn Sci 2005;9:242–249.CrossRefGoogle ScholarPubMed
Ochsner, K.N., Ray, R.D., Cooper, J.C., Robertson, E.R., Chopra, S., Gabrieli, J.D., et al.For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. Neuroimage 2004;23:483–499.CrossRefGoogle ScholarPubMed
Pankow, A., Friedel, E., Sterzer, P., Seiferth, N., Walter, H., Heinz, A., et al.Altered amygdala activation in schizophrenia patients during emotion processing. Schizophr Res 2013;150:101–106.CrossRefGoogle ScholarPubMed
Penny, W.D., Stephan, K.E., Daunizeau, J., Rosa, M.J., Friston, K.J., Schofield, T.M., et al.Comparing families of dynamic causal models. PLoS Comput Biol 2010;6:e1000709.CrossRefGoogle ScholarPubMed
Pettersson-Yeo, W., Allen, P., Benetti, S., McGuire, P., Mechelli, A.. Dysconnectivity in schizophrenia: where are we now?. Neurosci Biobehav Rev 2011;35:1110–1124.CrossRefGoogle ScholarPubMed
Pezawas, L., Meyer-Lindenberg, A., Drabant, E.M., Verchinski, B.A., Munoz, K.E., Kolachana, B.S., et al.5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 2005;8:828–834.CrossRefGoogle ScholarPubMed
Phan, K.L., Fitzgerald, D.A., Nathan, P.J., Moore, G.J., Uhde, T.W., Tancer, M.E.. Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study. Biol Psychiatry 2005;57:210–219.CrossRefGoogle ScholarPubMed
Phelps, E.A., LeDoux, J.E.. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 2005;48:175–187.CrossRefGoogle ScholarPubMed
Phillips, M.L., Drevets, W.C., Rauch, S.L., Lane, R.. Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol Psychiatry 2003;54:515–528.CrossRefGoogle ScholarPubMed
Phillips, M.L., Drevets, W.C., Rauch, S.L., Lane, R.. Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry 2003;54:504–514.CrossRefGoogle ScholarPubMed
Quirk, G.J., Beer, J.S.. Prefrontal involvement in the regulation of emotion: convergence of rat and human studies. Curr Opin Neurobiol 2006;16:723–727.CrossRefGoogle ScholarPubMed
Rasetti, R., Mattay, V.S., Wiedholz, L.M., Kolachana, B.S., Hariri, A.R., Callicott, J.H., et al.Evidence that altered amygdala activity in schizophrenia is related to clinical state and not genetic risk. Am J Psychiatry 2009;166:216–225.CrossRefGoogle Scholar
Ray, R.D., Zald, D.H.. Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex. Neurosci Biobehav Rev 2012;36:479–501.CrossRefGoogle ScholarPubMed
Salvador, R., Sarro, S., Gomar, J.J., Ortiz-Gil, J., Vila, F., Capdevila, A., et al.Overall brain connectivity maps show cortico-subcortical abnormalities in schizophrenia. Hum Brain Mapp 2010;31:2003–2014.CrossRefGoogle Scholar
Satterthwaite, T.D., Wolf, D.H., Loughead, J., Ruparel, K., Valdez, J.N., Siegel, S.J., et al.Association of enhanced limbic response to threat with decreased cortical facial recognition memory response in schizophrenia. Am J Psychiatry 2010;167:418–426.CrossRefGoogle Scholar
Schaefer, S.M., Jackson, D.C., Davidson, R.J., Aguirre, G.K., Kimberg, D.Y., Thompson-Schill, S.L.. Modulation of amygdalar activity by the conscious regulation of negative emotion. J Cogn Neurosci 2002;14:913–921.CrossRefGoogle ScholarPubMed
Scheel, M., Prokscha, T., Bayerl, M., Gallinat, J., Montag, C.. Myelination deficits in schizophrenia: evidence from diffusion tensor imaging. Brain Struct Funct 2013;218:151–156.CrossRefGoogle ScholarPubMed
Sladky, R., Hoflich, A., Kublbock, M., Kraus, C., Baldinger, P., Moser, E., et al.Disrupted effective connectivity between the amygdala and orbitofrontal cortex in social anxiety disorder during emotion discrimination revealed by dynamic causal modeling for fMRI. Cereb Cortex 2013.Google ScholarPubMed
Stein, J.L., Wiedholz, L.M., Bassett, D.S., Weinberger, D.R., Zink, C.F., Mattay, V.S., et al.A validated network of effective amygdala connectivity. Neuroimage 2007;36:736–745.CrossRefGoogle ScholarPubMed
Stephan, K.E., Harrison, L.M., Kiebel, S.J., David, O., Penny, W.D., Friston, K.J.. Dynamic causal models of neural system dynamics: current state and future extensions. J Biosci 2007;32:129–144.CrossRefGoogle ScholarPubMed
Stephan, K.E., Friston, K.J., Frith, C.D.. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 2009;35:509–527.CrossRefGoogle ScholarPubMed
Stephan, K.E., Penny, W.D., Daunizeau, J., Moran, R.J., Friston, K.J.. Bayesian model selection for group studies. Neuroimage 2009;46:1004–1017.CrossRefGoogle ScholarPubMed
Stephan, K.E., Penny, W.D., Moran, R.J., den Ouden, H.E., Daunizeau, J., Friston, K.J.. Ten simple rules for dynamic causal modeling. Neuroimage 2010;49:3099–3109.CrossRefGoogle ScholarPubMed
Takahashi, H., Koeda, M., Oda, K., Matsuda, T., Matsushima, E., Matsuura, M., et al.An fMRI study of differential neural response to affective pictures in schizophrenia. Neuroimage 2004;22:1247–1254.CrossRefGoogle Scholar
Taylor, S.F., Phan, K.L., Decker, L.R., Liberzon, I.. Subjective rating of emotionally salient stimuli modulates neural activity. Neuroimage 2003;18:650–659.CrossRefGoogle ScholarPubMed
Timm, N., Kim, K.Univariate and multivariate general linear models: theory and applications with SAS, 2nd ed, Berlin/Heidelberg: Springer; 2006.Google Scholar
Urry, H.L., van Reekum, C.M., Johnstone, T., Kalin, N.H., Thurow, M.E., Schaefer, H.S., et al.Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults. J Neurosci 2006;26:4415–4425.CrossRefGoogle ScholarPubMed
Vai, B., Bollettini, I., Benedetti, F.Corticolimbic connectivity as a possible biomarker for bipolar disorder. Expert Rev Neurother 2014;14:631–650.CrossRefGoogle ScholarPubMed
Vauth, R., Rusch, N., Wirtz, M., Corrigan, P.W.Does social cognition influence the relation between neurocognitive deficits and vocational functioning in schizophrenia?. Psychiatry Res 2004;128:155–165.CrossRefGoogle Scholar
Walther, S., Federspiel, A., Horn, H., Razavi, N., Wiest, R., Dierks, T., et al.Alterations of white matter integrity related to motor activity in schizophrenia. Neurobiol Dis 2011;42:276–283.CrossRefGoogle Scholar
Weierich, M.R., Wright, C.I., Negreira, A., Dickerson, B.C., Barrett, L.F.Novelty as a dimension in the affective brain. Neuroimage 2010;49:2871–2878.CrossRefGoogle ScholarPubMed
Whalley, H.C., Steele, J.D., Mukherjee, P., Romaniuk, L., McIntosh, A.M., Hall, J., et al.Connecting the brain and new drug targets for schizophrenia. Curr Pharm Des 2009;15:2615–2631.CrossRefGoogle Scholar
Williams, L.M., Das, P., Harris, A.W., Liddell, B.B., Brammer, M.J., Olivieri, G., et al.Dysregulation of arousal and amygdala-prefrontal systems in paranoid schizophrenia. Am J Psychiatry 2004;161:480–489.CrossRefGoogle ScholarPubMed
Wolf, C., Wenda, N., Richter, A., Kyriakopoulos, A.Alteration of biological samples in speciation analysis of metalloproteins. Anal Bioanal Chem 2007;389:799–810.CrossRefGoogle ScholarPubMed
Supplementary material: File

Vai et al. supplementary material

Supplementary materials

Download Vai et al. supplementary material(File)
File 654.8 KB
Submit a response

Comments

No Comments have been published for this article.