Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-02T21:22:18.723Z Has data issue: false hasContentIssue false
  • English
  • Français

Amygdala and anterior cingulate resting-state functional connectivity in borderline personality disorder patients with a history of interpersonal trauma

Published online by Cambridge University Press:  26 February 2014

A. Krause-Utz ,
I. M. Veer ,
S. A. R. B. Rombouts ,
M. Bohus ,
C. Schmahl  and
B. M. Elzinga
A. Krause-Utz
Affiliation:
Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
I. M. Veer*
Affiliation:
Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany Leiden Institute for Brain and Cognition (LIBC), Leiden, The Netherlands
S. A. R. B. Rombouts
Affiliation:
Leiden Institute for Brain and Cognition (LIBC), Leiden, The Netherlands Leiden University Medical Center, Department of Radiology, Leiden, The Netherlands Leiden University – Institute of Psychology, Leiden, The Netherlands
M. Bohus
Affiliation:
Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
C. Schmahl
Affiliation:
Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
B. M. Elzinga
Affiliation:
Leiden Institute for Brain and Cognition (LIBC), Leiden, The Netherlands Leiden University – Institute of Psychology, Leiden, The Netherlands
*
*Address for correspondence: I. M. Veer, M.Sc., Charité Universitätsmedizin, Department of Psychiatry and Psychotherapy, Division of Mind and Brain Research, Charitéplatz 1, D-10117 Berlin, Germany. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Studies in borderline personality disorder (BPD) have consistently revealed abnormalities in fronto-limbic brain regions during emotional, somatosensory and cognitive challenges. Here we investigated changes in resting-state functional connectivity (RSFC) of three fronto-limbic core regions of specific importance to BPD.

Method

Functional magnetic resonance imaging data were acquired in 20 unmedicated female BPD patients and 17 healthy controls (HC, matched for age, sex and education) during rest. The amygdala, and the dorsal and ventral anterior cingulate cortex (ACC) were defined as seeds to investigate RSFC patterns of a medial temporal lobe network, the salience network and default mode network. The Dissociation Experience Scale (DES), a measure of trait dissociation, was additionally used as a predictor of RSFC with these seed regions.

Results

Compared with HC, BPD patients showed a trend towards increased RSFC between the amygdala and the insula, orbitofrontal cortex and putamen. Compared with controls, patients furthermore exhibited diminished negative RSFC between the dorsal ACC and posterior cingulate cortex, a core region of the default mode network, and regions of the dorsomedial prefrontal cortex. Last, increased negative RSFC between the ventral ACC and medial occipital regions was observed in BPD patients. DES scores were correlated with amygdala connectivity with the dorsolateral prefrontal cortex and fusiform gyrus.

Conclusions

Our findings suggest alterations in resting-state networks associated with processing of negative emotions, encoding of salient events, and self-referential processing in individuals with BPD compared with HC. These results shed more light on the role of abnormal brain connectivity in BPD.

Keywords

Amygdalaanterior cingulate cortexborderline personality disorderdissociationfunctional connectivityresting-state functional MRI
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 13 , October 2014 , pp. 2889 - 2901
Copyright
Copyright © Cambridge University Press 2014 

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

APA (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association: Washington, DC.Google Scholar
Banks, SJ, Eddy, KT, Angstadt, M, Nathan, PJ, Phan, KL (2007). Amygdala–frontal connectivity during emotion regulation. Social Cognitive and Affective Neuroscience 2, 303–312.CrossRefGoogle ScholarPubMed
Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561–571.Google Scholar
Bernstein, DP, Stein, JA, Newcomb, MD, Walker, E, Pogge, D, Ahluvalia, T, Stokes, J, Handelsman, L, Medrano, M, Desmond, D, Zule, W (2003). Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse and Neglect 27, 169–190.Google Scholar
Bernstein, EM, Putnam, FW (1986). Development, reliability, and validity of a dissociation scale. Journal of Nervous and Mental Disease 174, 727–735.Google Scholar
Bohus, M, Limberger, MF, Frank, U, Chapman, AL, Kuehler, T, Stieglitz, RD (2007). Psychometric properties of the Borderline Symptom List (BSL). Psychopathology 40, 126–132.CrossRefGoogle ScholarPubMed
Buckner, RL, Vincent, JL (2007). Unrest at rest: default activity and spontaneous network correlations. NeuroImage 37, 1091–1099.CrossRefGoogle ScholarPubMed
Chapman, A, Gratz, KL, Brown, MZ (2006). Solving the puzzle of deliberate self-harm: the experiential avoidance model. Behavior Research and Therapy 44, 371–394.CrossRefGoogle ScholarPubMed
Critchley, HD, Mathias, CJ, Dolan, RJ (2001). Neural activity in the human brain relating to uncertainty and arousal during anticipation. Neuron 29, 537–545.Google Scholar
Daniels, JK, McFarlane, AC, Bluhm, RL, Moores, KA, Clark, CR, Shaw, ME, Williamson, PC, Densmore, M, Lanius, RA (2010). Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity. Journal of Psychiatry and Neuroscience 35, 258–266.Google Scholar
Davis, M, Whalen, PJ (2001). The amygdala: vigilance and emotion. Molecular Psychiatry 6, 13–34.CrossRefGoogle ScholarPubMed
Doll, A, Sorg, C, Manoliu, A, Wöller, A, Meng, C, Förstl, H, Zimmer, C, Wohlschläger, AM, Riedl, V (2013). Shifted intrinsic connectivity of central executive and salience network in borderline personality disorder. Frontiers in Human Neuroscience 7, 727.Google Scholar
Donegan, NH, Sanislow, CA, Blumenberg, HP, Fulbright, RK, Lacadie, C, Skudlarski, P, Gore, JC, Olson, IR, McGlashan, TH, Wexler, BE (2003). Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation. Biological Psychiatry 54, 1284–1293.Google Scholar
Dosenbach, NU, Visscher, KM, Palmer, ED, Miezin, FM, Wenger, KK, Kang, HC, Burgund, ED, Grimes, AL, Schlaggar, BL, Petersen, SE (2006). A core system for the implementation of task sets. Neuron 50, 799–812.Google Scholar
Etkin, A, Egner, T, Kalisch, R (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences 15, 85–93.Google Scholar
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1997). Structured Clinical Interview for DSM-V Axis I Disorders – Clinical Version (SCID-CV). American Psychiatric Press: Washington, DC.Google Scholar
Foa, E (1995). Posttraumatic Stress Diagnostic Scale Manual. National Computer Systems Inc.: Minneapolis.Google Scholar
Fox, MD, Raichle, ME (2007). Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews. Neuroscience 8, 700–711.Google Scholar
Fox, MD, Snyder, AZ, Vincent, JL, Corbetta, M, van Essen, DC, Raichle, ME (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences USA 102, 9673–9678.Google Scholar
Gratz, KL, Roemer, L (2004). Multidimensional assessment of emotion regulation: development, factor structure, and initial validation of the Emotion Regulation Scale. Journal of Psychopathology and Behavioral Assessment 26, 41–45.Google Scholar
Greicius, M (2008). Resting-state functional connectivity in neuropsychiatric disorders. Current Opinion in Neurology 21, 424–430.Google Scholar
Greicius, MD, Krasnow, B, Reiss, AL, Menon, V (2003). Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences USA 100, 253–258.Google Scholar
Haber, SN, Knutson, B (2010). The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35, 4–26.Google Scholar
Jenkinson, M, Bannister, P, Brady, M, Smith, S (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage 17, 825–841.Google Scholar
Jenkinson, M, Smith, S (2001). A global optimisation method for robust affine registration of brain images. Medical Image Analysis 5, 143–156.Google Scholar
Kleindienst, N, Bohus, M, Ludaescher, P, Limberger, MF, Kuenkele, K, Ebner-Priemer, UW, Chapman, AL, Reicherzer, M, Stieglitz, RD, Schmahl, C (2008). Motives for nonsuicidal self-injury among women with borderline personality disorder. Journal of Nervous and Mental Disease 196, 230–236.Google Scholar
Kluetsch, RC, Schmahl, C, Niedtfeld, I, Densmore, M, Calhoun, VD, Daniels, J, Kraus, A, Ludaescher, P, Bohus, M, Lanius, RA (2012). Alterations in default mode network connectivity during pain processing in borderline personality disorder. Archives of General Psychiatry 69, 993–1002.Google Scholar
Koenigsberg, HW, Fan, J, Ochsner, KN, Liu, X, Guise, KG, Pizzarello, S, Dorantes, C, Guerreri, S, Tecuta, L, Goodman, M, New, A, Siever, LJ (2009 a). Neural correlates of the use of psychological distancing to regulate responses to negative social cues: a study of patients with borderline personality disorder. Biological Psychiatry 66, 854–863.Google Scholar
Koenigsberg, HW, Siever, LJ, Lee, H, Pizzarello, S, New, AS, Goodman, M, Cheng, H, Flory, J, Prohovnik, I (2009 b). Neural correlates of emotion processing in borderline personality disorder. Psychiatry Research 172, 192–199.Google Scholar
Krause-Utz, A, Oei, NY, Niedtfeld, I, Bohus, M, Spinhoven, P, Schmahl, C, Elzinga, BM (2012). Influence of emotional distraction on working memory performance in borderline personality disorder. Psychological Medicine 42, 2181–2192.Google Scholar
Kringelbach, ML, Rolls, ET (2004). The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Progress in Neurobiology 72, 341–372.Google Scholar
Lang, S, Kotchoubey, B, Frick, C, Spitzer, C, Grabe, HJ, Barnow, S (2012). Cognitive reappraisal in trauma-exposed women with borderline personality disorder. NeuroImage 59, 1727–1734.CrossRefGoogle ScholarPubMed
Lanius, RA, Bluhm, RL, Coupland, NJ, Hegadoren, KM, Rowe, B, Théberge, J, Neufeld, RW, Williamson, PC, Brimson, M (2010 a). Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects. Acta Psychiatrica Scandinavica 21, 33–40.Google Scholar
Lanius, RA, Vermetten, E, Loewenstein, RJ, Brand, B, Schmahl, C, Bremner, JD, Spiegel, D (2010 b). Emotion modulation in PTSD: clinical and neurobiological evidence for a dissociative subtype. American Journal of Psychiatry 167, 640–647.CrossRefGoogle ScholarPubMed
Lanius, RA, Williamson, PC, Bluhm, RL, Densmore, M, Boksman, K, Neufeld, RW, Gati, JS, Menon, RS (2005). Functional connectivity of dissociative responses in posttraumatic stress disorder: a functional magnetic resonance imaging investigation. Biological Psychiatry 57, 873–884.Google Scholar
Larsen, RJ (1984). Theory and measurement of affect intensity as an individual difference characteristic. Dissertation Abstracts International 85, 2297B. (University Microfilms No. 84-22112.)Google Scholar
Leichsenring, F, Leibing, E, Kruse, J, New, AS, Leweke, F (2011). Borderline personality disorder. Lancet 377, 74–84.Google Scholar
Linehan, MM (1993). Cognitive-Behavioural Treatment of Borderline Personality Disorder. Guilford Press: New York.Google Scholar
Lis, S, Bohus, M (2013). Social interaction in borderline personality disorder. Current Psychiatry Reports 15, 338.CrossRefGoogle ScholarPubMed
Loranger, AW (1999). International Personality Disorder Examination (IPDE): DSM-IV and ICD-10 Modules. Psychological Assessment Resources: Odessa, FL.Google Scholar
Margulies, DS, Kelly, AM, Uddin, LQ, Biswal, BB, Castellanos, FX, Milham, MP (2007). Mapping the functional connectivity of anterior cingulate cortex. NeuroImage 37, 579–588.Google Scholar
Menon, V, Uddin, LQ (2010). Saliency, switching, attention and control: a network model of insula function. Brain Structure and Function 214, 655–667.Google Scholar
Minzenberg, MJ, Fan, J, New, AS, Tang, CY, Siever, LJ (2007). Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study. Psychiatry Research 155, 231–243.Google Scholar
Murphy, K, Birn, RM, Handwerker, DA, Jones, TB, Bandettini, PA (2009). The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? NeuroImage 44, 893–905.Google Scholar
Neumann, J, Fox, PT, Turner, R, Lohmann, G (2010). Learning partially directed functional networks from meta-analysis imaging data. NeuroImage 49, 1372–1384.Google Scholar
Niedtfeld, I, Schulze, L, Kirsch, P, Herpertz, SC, Bohus, M, Schmahl, C (2010). Affect regulation and pain in borderline personality disorder: a possible link to the understanding of self-injury. Biological Psychiatry 68, 383–391.Google Scholar
Ochsner, KN, Gross, JJ (2007). The neural architecture of emotion regulation. In The Handbook of Emotion Regulation (ed. Gross, J. J. and Buck, R.), pp. 87–109. Guilford Press: New York.Google Scholar
O'Neill, A, Frodl, T (2012). Brain structure and function in borderline personality disorder. Brain Structure and Function 217, 767–782.Google Scholar
Packard, MG, Knowlton, BJ (2002). Learning and memory functions of the basal ganglia. Annual Review of Neuroscience 25, 563–593.Google Scholar
Patton, J, Stanford, M, Barratt, E (1995). Factor structure of the Barratt Impulsiveness Scale. Journal of Clinical Psychology 51, 768–774.Google Scholar
Pessoa, L, Padmala, S, Kenzer, A, Bauer, A (2012). Interactions between cognition and emotion during response inhibition. Emotion 12, 192–197.Google Scholar
Phan, KL, Wager, TD, Taylor, SF, Liberzon, I (2004). Functional neuroimaging studies of human emotions. CNS Spectrums 9, 258–266.Google Scholar
Phillips, ML, Drevets, WC, Rauch, SL, Lane, R (2003). Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biological Psychiatry 54, 504–514.Google Scholar
Rabinak, CA, Angstadt, M, Welsh, RC, Kenndy, AE, Lyubkin, M, Martis, B, Phan, KL (2011). Altered amygdala resting-state functional connectivity in post-traumatic stress disorder. Frontiers in Psychiatry 2, 62.Google Scholar
Raichle, ME, MacLeod, AM, Snyder, AZ, Powers, WJ, Gusnard, DA, Shulman, GL (2001). A default mode of brain function. Proceedings of the National Academy of Sciences USA 98, 676–682.Google Scholar
Roy, AK, Shehzad, Z, Margulies, DS, Kelly, AM, Uddin, LQ, Gotimer, K, Biswal, BB, Castellanos, FX, Milham, MP (2009). Functional connectivity of the human amygdala using resting state fMRI. NeuroImage 45, 614–626.Google Scholar
Ruocco, AC, Amirthavasagam, S, Choi-Kain, LW, McMain, SF (2013). Neural correlates of negative emotionality in borderline personality disorder: an activation-likelihood-estimation meta-analysis. Biological Psychiatry 73, 153–160.Google Scholar
Saad, ZS, Gotts, SJ, Murphy, K, Chen, G, Jo, HJ, Martin, A, Cox, RW (2012). Trouble at rest: how correlation patterns and group differences become distorted after global signal regression. Brain Connectivity 2, 25–32.Google Scholar
Schmahl, CG, Elzinga, BM, Vermetten, E, Sanislow, C, McGlashan, TH, Bremner, JD (2003). Neural correlates of memories of abandonment in women with and without borderline personality disorder. Biological Psychiatry 54, 142–151.Google Scholar
Schmahl, CG, Vermetten, E, Elzinga, BM, Bremner, JD (2004). A positron emission tomography study of memories of childhood abuse in borderline personality disorder. Biological Psychiatry 55, 759–765.Google Scholar
Schulze, L, Domes, G, Krüger, A, Berger, C, Fleischer, M, Prehn, K, Schmahl, C, Grossmann, A, Hauenstein, K, Herpertz, SC (2011). Neuronal correlates of cognitive reappraisal in borderline patients with affective instability. Biological Psychiatry 69, 564–573.Google Scholar
Seeley, WW, Menon, V, Schatzberg, AF, Keller, J, Glover, GH, Kenna, H, Reiss, AL, Greicius, MD (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. Journal of Neuroscience 27, 2349–2356.Google Scholar
Sierra, M, Berrios, GE (1998). Depersonalization: neurobiological perspectives. Biological Psychiatry 44, 898–908.Google Scholar
Silbersweig, D, Clarkin, JF, Goldstein, M, Kernberg, OF, Tuescher, O, Levy, KN, Brendel, G, Pan, H, Beutel, M, Pavony, MT, Epstein, J, Lenzenweger, MF, Thomas, KM, Posner, MI, Stern, E (2007). Failure of frontolimbic inhibitory function in the context of negative emotion in borderline personality disorder. American Journal of Psychiatry 164, 1832–1841.CrossRefGoogle ScholarPubMed
Skodol, AE, Gunderson, JG, Pfohl, B, Widiger, TA, Livesley, WJ, Siever, LJ (2002). The borderline diagnosis I: Psychopathology comorbidity, and personality structure. Biological Psychiatry 51, 936–950.Google Scholar
Smith, SM, Jenkinson, M, Woolrich, MW, Beckmann, CF, Behrens, TE, Johansen-Berg, H, Bannister, PR, De Luca, M, Drobnjak, I, Flitney, DE, Niazy, RK, Saunders, J, Vickers, J, Zhang, Y, De Stefano, N, Brady, JM, Matthews, PM (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23 (Suppl. 1), 208–219.Google Scholar
Sridharan, D, Levitin, DJ, Menon, V (2008). A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proceedings of the National Academy of Sciences USA 105, 12569–12574.Google Scholar
Sripada, RK, King, AP, Garfinkel, SN, Wang, X, Sripada, CS, Welsh, RC, Liberzon, I (2012). Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder. Journal of Psychiatry and Neuroscience 37, 241–249.Google Scholar
Stein, JL, Wiedholz, LM, Bassett, DS, Weinberger, DR, Zink, CF, Mattay, VS, Meyer-Lindenberg, A (2007). A validated network of effective amygdala connectivity. NeuroImage 36, 736–745.CrossRefGoogle ScholarPubMed
Stiglmayr, CE, Ebner-Priemer, UW, Bretz, J, Behm, R, Mohse, M, Lammers, CH, Anghelescu, IG, Schmahl, C, Schlotz, W, Kleindienst, N, Bohus, M (2008). Dissociative symptoms are positively related to stress in borderline personality disorder. Acta Psychiatrica Scandinavica 117, 139–147.Google Scholar
Stiglmayr, CE, Shapiro, DA, Stieglitz, RD, Limberger, MF, Bohus, M (2001). Experience of aversive tension and dissociation in female patients with borderline personality disorder – a controlled study. Journal of Psychiatric Research 35, 111–118.Google Scholar
van der Werff, SJA, Pannekoek, JN, Veer, IM, van Tol, MJ, Aleman, A, Veltman, DJ, Zitman, FG, Rombouts, SARB, Elzinga, BM, van der Wee, NJA (2013). Resting-state functional connectivity in adults with childhood emotional maltreatment. Psychological Medicine 43, 1825–1836.Google Scholar
Veer, IM, Oei, NY, Spinhoven, P, van Buchem, MA, Elzinga, BM, Rombouts, SA (2011). Beyond acute social stress: increased functional connectivity between amygdala and cortical midline structures. NeuroImage 57, 1534–1541.Google Scholar
Wolf, RC, Sambataro, F, Vasic, N, Schmid, M, Thomann, PA, Bienentreu, SD, Wolf, ND (2011). Aberrant connectivity of resting-state networks in borderline personality disorder. Journal of Psychiatry and Neuroscience 36, 402–411.Google Scholar
Worsley, KJ (2001). Statistical analysis of activation images. In Functional MRI: An Introduction to Methods (ed. Jezzard, P., Matthews, P. M. and Smith, S.), pp. 251–270. Oxford University Press Inc.: New York.Google Scholar
Zeki, S, Romaya, JP (2008). Neural correlates of hate. PLoS One 3, e3556.Google Scholar
Supplementary material: File

Krause-Utz Supplementary Material

Figures

Download Krause-Utz Supplementary Material(File)
File 2.7 MB
Supplementary material: File

Krause-Utz Supplementary Material

Supplementary Material

Download Krause-Utz Supplementary Material(File)
File 27.6 KB
Supplementary material: File

Krause-Utz Supplementary Material

Tables

Download Krause-Utz Supplementary Material(File)
File 79.4 KB