Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-26T09:47:11.390Z Has data issue: false hasContentIssue false

Defining the neurocircuitry of borderline personality disorder: Functional neuroimaging approaches

Published online by Cambridge University Press:  12 December 2005

GARY R. BRENDEL
Affiliation:
Weill Medical College of Cornell University
EMILY STERN
Affiliation:
Weill Medical College of Cornell University
DAVID A. SILBERSWEIG
Affiliation:
Weill Medical College of Cornell University

Abstract

Functional neuroimaging recently has been used to localize brain dysfunction in borderline personality disorder (BPD). Initial studies have examined baseline activity or emotional reactivity, and our group has investigated what we consider to be a crucial interaction between negative emotion and behavioral (dys)control. This research is beginning to identify abnormal frontolimbic circuitry likely underlying core clinical features of this condition. We review the evidence for dysfunction in specific frontolimbic regions, leading to a mechanistic model of symptom formation in BPD. In addition, we offer an integration of these neuroimaging findings with developmental perspectives on the emergence of borderline psychopathology, focusing on the ways in which early psychosocial experience may interact with developing brain systems. We also consider possible mechanisms of psychotherapeutic change at the neural systems level in BPD. Finally, we propose that future neuroimaging studies of BPD should integrate multiple levels of observation (structural, functional, neurochemical, genetic, and clinical) in a model-driven fashion to further understand the dynamic relationship between biological and psychological factors in the development and treatment of this difficult condition.

Type
Research Article
Copyright
© 2005 Cambridge University Press

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

REFERENCES

Arntz, A., Appels, C., & Sieswerda, S. (2000). Hypervigilance in borderline personality disorder: A test with the emotional Stroop paradigm. Journal of Personality Disorders 14, 366373.CrossRefGoogle Scholar
Baxter, M. G., Parker, A., Lindner, C. C., Izquierdo, A. D., & Murray, E. A. (2000). Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex. Journal of Neuroscience 20, 43114319.Google Scholar
Bechara, A., Damasio, H., & Damasio, A. R. (2000). Emotion, decision making and the orbitofrontal cortex. Cerebral Cortex 10, 295307.CrossRefGoogle Scholar
Bohus, M., Limberger, M., Ebner, U., Glocker, F. X., Schwarz, B., Wernz, M., et al. (2000). Pain perception during self-reported distress and calmness in patients with borderline personality disorder and self-mutilating behavior. Psychiatry Research 95, 251260.Google Scholar
Brambilla, P., Soloff, P. H., Sala, M., Nicoletti, M. A., Keshavan, M. S., & Soares, J. C. (2004). Anatomical MRI study of borderline personality disorder patients. Psychiatry Research: Neuroimaging 131, 125133.CrossRefGoogle Scholar
Breiter, H. C., Etcoff, N. L., Whalen, P. J., Kennedy, W. A., Rauch, S. L., Buckner, R. L., et al. (1996). Response and habituation of the human amygdale during visual processing of facial expression. Neuron 17, 875887.CrossRefGoogle Scholar
Breiter, H. C., Rauch, S. L., Kwong, K. K., Baker, J. R., Weisskoff, R. M., Kennedy, D. N., et al. (1996). Functional magnetic resonance imaging of symptom provocation in obsessive–compulsive disorder. Archives of General Psychiatry 53, 595606.CrossRefGoogle Scholar
Bremner, J. D., Narayan, M., Staib, L. H., Southwick, S. M., McGlashan, T., & Charney, D. S. (1999). Neural correlates of childhood sexual abuse in women with and without posttraumatic stress disorder. American Journal of Psychiatry 156, 17871795.Google Scholar
Carmichael, S. T., & Price, J. L. (1995). Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. Journal of Comparative Neurology 363, 615641.CrossRefGoogle Scholar
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science 301, 386389.CrossRefGoogle Scholar
Clarkin, J. F., Yeomans, F. E., & Kernberg, D. F. (1999). Psychotherapy for borderline personality. New York: Wiley.
Damasio, H., Grabowski, T., Frank, R., Galaburda, A. M., & Damasio, A. R. (1994). The return of Phineas Gage: Clues about the brain from the skull of a famous patient. Science, 264, 11021105.CrossRefGoogle Scholar
Davidson, R. J. (2002). Anxiety and affective style: Role of prefrontal cortex and amygdala. Biological Psychiatry 51, 6880.CrossRefGoogle Scholar
Davidson, R. J., Jackson, D. C., & Kalin, N. H. (2000). Emotion, plasticity, context, and regulation: Perspectives from affective neuroscience. Psychological Bulletin 126, 890909.CrossRefGoogle Scholar
Davis, M., & Whalen, P. J. (2001). The amygdala: Vigilance and emotion. Molecular Psychiatry 6, 1334.CrossRefGoogle Scholar
De la Fuente, J. M., Goldman, S., Stanus, E., Vizuete, C., Morlán, I., Bobes, J., et al. (1997). Brain glucose metabolism in borderline personality disorder. Journal of Psychiatric Research 31, 531541.CrossRefGoogle Scholar
Debiec, J., & LeDoux, J. E. (2004). Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala. Neuroscience 129, 267272.CrossRefGoogle Scholar
Devinsky, O., Morrell, M. J., & Vogt, B. A.. (1995). Contributions of anterior cingulate to behavior. Brain 118, 279306.CrossRefGoogle Scholar
Dolan, R. J. (1999). On the neurology of morals. Nature Neuroscience 2, 927929.CrossRefGoogle Scholar
Dolan, R. J. (2002). Emotion, cognition, and behavior. Science 298, 11911194.CrossRefGoogle Scholar
Donegan, N. H., Sanislow, C. A., Blumberg, H. P., Fulbright, R. K., Lacadie, C., Skudlarski, P., et al. (2003). Amygdala hyperreactivity in borderline personality disorder: Implications for emotional dysregulation. Biological Psychiatry 54, 12841293.CrossRefGoogle Scholar
Dougherty, D. D., & Rauch, S. L. (2001). Psychiatric neuroimaging research: Contemporary strategies. Washington, DC: American Psychiatric Press
Dougherty, D. D., Shin, L. M., Alpert, N. M., Pitman, R. K., Orr, S. P., Lasko, M., et al. (1999). Anger in healthy men: A PET study using script-driven imagery. Biological Psychiatry 46, 466472.CrossRefGoogle Scholar
Drevets, W. C. (1999). Prefrontal cortical–amygdalar metabolism in major depression. Annals of the New York Academy of Sciences 877, 614637.CrossRefGoogle Scholar
Drevets, W. C. (2001). Neuroimaging and neuropathological studies of depression: Implications for the cognitive–emotional features of mood disorders. Current Opinion in Neurobiology 11, 240249.CrossRefGoogle Scholar
Drewe, E. A. (1975). Go–no go learning after frontal lobe lesions in humans. Cortex 11, 816.CrossRefGoogle Scholar
Driessen, M., Herrmann, J., Stahl, K., Zwaan, M., Meier, S., Hill, A., et al. (2000). Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Archives of General Psychiatry 57, 11151122.CrossRefGoogle Scholar
Elliott, R., Rubinsztein, J. S., Sahakian, B. J., & Dolan, R. J. (2002). The neural basis of mood-congruent processing biases in depression. Archives of General Psychiatry 59, 597604.CrossRefGoogle Scholar
Fonagy, P., Gergely, G., Jurist, E. L., & Target, M. (2002). Affect regulation, mentalization, and the development of the self. New York: Other Press.
George, M. S., Ketter, T. A., Gill, D. S., Haxby, J. V., Ungerleider, L. G., Herscovitch, P., et al. (1993). Brain regions involved in recognizing facial emotion or identity: An oxygen-15 PET study. Journal of Neuropsychology 5, 384394.Google Scholar
Goyer, P. F., Andreason, P. J., Semple, W. E., Clayton, A. H., King, A. C., Compton–Toth, B. A., et al. (1994). Positron-emission tomography and personality disorders. Neuropsychopharmacology 10, 2128.CrossRefGoogle Scholar
Hazlett, E. A., New, A. S., Newmark, R., Haznedar, M. M., Lo, J. N., Speiser, L. J., et al. (in press). Reduced anterior and posterior cingulate gray matter in borderline personality disorder. Biological Psychiatry.
Herpertz, S. C., Dietrich, T. M., Wenning, B., Krings, T., Erberich, S. G., Wilmes, K., et al. (2001). Evidence of abnormal amygdale functioning in borderline personality disorder: A functional MRI study. Biological Psychiatry 50, 292298.CrossRefGoogle Scholar
Hofbauer, R. K., Rainville, P., Duncan, G. H., & Bushnell, M. C. (2001). Cortical representation of the sensory dimension of pain. Journal of Neurophysiology 86, 402411.Google Scholar
Irle, E., Lange, C., & Sachsse, U. (2005). Reduced size and abnormal asymmetry of parietal cortex in women with borderline personality disorder. Biological Psychiatry 57, 173182.CrossRefGoogle Scholar
Isenberg, N., Silbersweig, D., Engelien, A., Emmerich, S., Malavade, K., Beattie, B., et al. (1999). Linguistic threat activates the human amygdala. Proceedings of the National Academy of Sciences of the United States of America 96, 1045610459.CrossRefGoogle Scholar
Juengling, F. D., Schmahl, C., Hesslinger, B., Ebert, D., Bremner, J. D., Gostomzyk, J., et al. (2003). Positron emission tomography in female patients with borderline personality disorder. Journal of Psychiatric Research 37, 109115.CrossRefGoogle Scholar
Kimbrell, T. A., George, M. S., Parekh, P. I., Ketter, T. A., Podell, D. M., Danielson, A. L., et al. (1999). Regional brain activity during transient self-induced anxiety and anger in healthy adults. Biological Psychiatry 46, 454465.CrossRefGoogle Scholar
LaBar, K. S., Gatenby, J. C., Gore, J. C., LeDoux, J. E., & Phelps, E. A. (1998). Human amygdala activation during conditioned fear acquisition and extinction: A mixed-trial fMRI study. Neuron 20, 937945.CrossRefGoogle Scholar
Lange, C., Kracht, L., Herholz, K., Sachsse, U., & Irle, E. (2005). Reduced glucose metabolism in temporo-parietal cortices of women with borderline personality disorder. Psychiatry Research 139, 115126.Google Scholar
LeDoux, J. (1996). The emotional brain: The mysterious underpinnings of emotional life. New York: Touchstone.
Leyton, M., Okazawa, H., Diksic, M., Paris, J., Rosa, P., Mzengeza, S., et al. (2001). Brain regional alpha-[11C]methyl-l-tryptophan trapping in impulsive subjects with borderline personality disorder. American Journal of Psychiatry 158, 775782.CrossRefGoogle Scholar
Liotti, M., & Mayberg, H. S. (2001). The role of functional neuroimaging in the neuropsychology of depression. Journal of Clinical and Experimental Neuropsychology 23, 121136.CrossRefGoogle Scholar
Magariños, A. M., McEwen, B. S., Flugge, G., & Fuchs, E. (1996). Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. Journal of Neuroscience 16, 35343540.Google Scholar
McEwen, B. S. (2004). Protection and damage from acute and chronic stress: Allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Annals of the New York Academy of Sciences 1032, 17.CrossRefGoogle Scholar
McEwen, B. S., & Magariños, A. M. (2001). Stress and hippocampal plasticity: implications for the pathophysiology of affective disorders. Human Psychopharmacology: Clinical and Experimental 16, S7S19.Google Scholar
McGlashan, T. H., Grilo, C. M., Skodol, A. E., Gunderson, J. G., Shea, M. T., Morey, L. C., et al. (2000). The collaborative longitudinal personality disorders study: Baseline Axis I/II and II/II diagnostic co-occurrence. Acta Psychiatrica Scandinavica 102, 256264.CrossRefGoogle Scholar
Mega, M. S., & Cummings, J. L. (1994). Frontal–subcortical circuits and neuropsychiatric disorders. Journal of Neuropsychiatry and Clinical Neuroscience 6, 358370.Google Scholar
Olausson, H., Ha, B., Duncan, G. H., Morin, C., Ptito, A.., Ptito, M., et al. (2001). Cortical activation by tactile and painful stimuli in hemispherectomized patients. Brain 124, 916927.CrossRefGoogle Scholar
Phillips, M. L., Drevets, W. C., Rauch, S. L., & Lane, R. (2003). Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biological Psychiatry 54, 504514.CrossRefGoogle Scholar
Phillips, R. G., & LeDoux, J. E. (1992). Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behavioral Neuroscience 106, 274285.CrossRefGoogle Scholar
Posner, M. I., Rothbart, M. K., Vizueta, N., Thomas, K. M., Levy, K. N., Fossella, J., et al. (2003). An approach to the psychobiology of personality disorders. Development and Psychopathology, 15, 10931106.CrossRefGoogle Scholar
Radley, J. J., Sisti, H. M., Hao, J., Rocher, A. B., McCall, T., Hof, P. R., et al. (2004). Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125, 16.Google Scholar
Rolls, E. T. (2000). The orbitofrontal cortex and reward. Cerebral Cortex 10, 284294.CrossRefGoogle Scholar
Ross, J. M. (2003). Preconscious defence analysis, memory and structural change. International Journal of Psychoanalysis 84, 5976.CrossRefGoogle Scholar
Rusch, N., van Elst, L. T., Ludaescher, P., Wilke, M., Huppertz, H. J., Thiel, T., et al. (2003). A voxel-based morphometric MRI study in female patients with borderline personality disorder. Neuroimage 20, 385392.CrossRefGoogle Scholar
Schmahl, C. G., Elzinga, B. M., Vermetten, E., Sanislow, C., McGlashan, T. H., & Bremner, J. D. (2003). Neural correlates of memories of abandonment in women with and without borderline personality disorder. Biological Psychiatry 54, 142151.CrossRefGoogle Scholar
Schmahl, C. G., Vermetten, E., Elzinga, B. M., & Bremner, J. D. (2003). Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder. Psychiatry Research: Neuroimaging 122, 193198.CrossRefGoogle Scholar
Sergerie, K., Lepage, M., & Armony, J. L. (2005). A face to remember: Emotional expression modulates prefrontal activity during memory formation. Neuroimage 24, 580585.CrossRefGoogle Scholar
Shin, L. M., McNally, R. J., Kosslyn, S. M., Thompson, W. L., Rauch, S. L., Alpert, N. M., et al. (1999). Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation. American Journal of Psychiatry 156, 575584.Google Scholar
Shin, L. M., Orr, S. P., Carson, M. A., Rauch, S. L., Macklin, M. L., Lasko, N. B., et al. (2004). Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Archives of General Psychiatry 61, 168176.CrossRefGoogle Scholar
Siever, L. J., Buchsbaum, M. S., New, A. S., Spiegel–Cohen, J., Tsechung, W., Hazlett, E. A., et al. (1999). d,l-Fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography. Neuropsychopharmacology 20, 413423.CrossRefGoogle Scholar
Soloff, P. H., Meltzer, C. C., Becker, C., Greer, P. J., Kelly, T. M., & Constantine, D. (2003). Impulsivity and prefrontal hypometabolism in borderline personality disorder. Psychiatry Research: Neuroimaging 123, 153163.CrossRefGoogle Scholar
Soloff, P. H., Meltzer, C. C., Greer, P. J., Constantine, D., & Kelly, T. M. (2000). A fenfluramine-activated FDG-PET study of borderline personality disorder. Biological Psychiatry 47, 540547.CrossRefGoogle Scholar
Stern, E., & Silbersweig, D. A. (2001). Advances in functional neuroimaging methodology for the study of brain systems underlying human neuropsychological function and dysfunction. Journal of Clinical and Experimental Neuropsychology 23, 318.CrossRefGoogle Scholar
Tebartz van Elst, L., Hesslinger, B., Thiel, T., Geiger, E., Haegele, K., Lemieux, L., et al. (2003). Frontolimbic brain abnormalities in patients with borderline personality disorder: A volumetric magnetic resonance imaging study. Biological Psychiatry 54, 163171.CrossRefGoogle Scholar
Tebartz van Elst, L., Thiel, T., Hesslinger, B., Lieb, K., Bohus, M., Hennig, J., et al. (2001). Subtle prefrontal neuropathology in a pilot magnetic resonance spectroscopy study in patients with borderline personality disorder. Journal of Neuropsychiatry and Clinical Neuroscience 13, 511514.CrossRefGoogle Scholar
Treyer, V., Buck, A., & Schnider, A. (2003). Subcortical loop activation during selection of currently relevant memories. Journal of Cognitive Neuroscience 15, 610618.CrossRefGoogle Scholar
Tulving, E., Kapur, S., Craik, F. I. M., Moscovitch, M., & Houle, S. (1994). Hemispheric encoding/retrieval asymmetry in episodic memory: Positron emission tomography findings. Proceedings of the National Academy of Sciences of the United States of America 91, 20162020.CrossRefGoogle Scholar
Vollm, B., Richardson, P., Stirling, J., Elliott, R., Dolan, M., Chaudhry, I., et al. (2004). Neurobiological substrates of antisocial and borderline personality disorder: Preliminary results of a functional fMRI study. Criminal Behavior and Mental Health 14, 3954.CrossRefGoogle Scholar
Zanarini, M. C. (2000). Childhood experiences associated with the development of borderline personality disorder. Psychiatric Clinics of North America 23, 89101.CrossRefGoogle Scholar