OBJECTIVE: Orbitofrontal cortex lesions produce disinhibited or socially inappropriate behavior and emotional irregularities. Characteristics of borderline personality disorder include impulsivity and affective instability. The authors investigated whether aspects of borderline personality disorder, in particular impulsivity, are associated with orbitofrontal cortex dysfunction.

METHOD: Measures of personality, emotion, impulsivity, time perception, sensitivity to reinforcers, and spatial working memory were administered to patients with borderline personality disorder (N=19), patients with orbitofrontal cortex lesions (N=23), patients with lesions in the prefrontal cortex but not in the orbitofrontal cortex (N=20), and healthy comparison subjects (N=39).

RESULTS: The patients with orbitofrontal cortex lesions and the patients with borderline personality disorder performed similarly on several measures. Both groups were more impulsive and reported more inappropriate behaviors, borderline personality disorder characteristics, and anger and less happiness than the two comparison groups, and both groups were less open to experience and had a faster perception of time (underproduced time) than the healthy comparison subjects. The patients with orbitofrontal cortex lesions and the borderline personality disorder patients performed differently on other measures. The borderline personality disorder patients were less extraverted and conscientious and more neurotic and emotional than all other groups. Patients with orbitofrontal cortex lesions had deficits in reversing stimulus-reinforcer associations and a faster perception of time (overestimated time) than the healthy comparison subjects.

CONCLUSIONS: Orbitofrontal cortex dysfunction may contribute to some core characteristics of borderline personality disorder, in particular impulsivity. Other characteristics of borderline personality disorder, such as high levels of emotionality and personality irregularities, do not appear to be related to the type of dysfunction produced by orbitofrontal cortex damage. The similarities and differences found between the borderline personality disorder patients and the patients with orbitofrontal cortex lesions may lead to a better understanding of the etiology of borderline personality disorder and the functions of the orbitofrontal cortex.

Introduction

Damage to the orbitofrontal cortex has been associated with disinhibited or socially inappropriate behavior and emotional irregularities. Prominent characteristics of several personality disorders, in particular DSM-IV borderline personality disorder, include impulsivity and affective instability. Despite the abundance of evidence linking impulsivity to frontal lobe dysfunction, evidence for underlying frontal lobe deficits in personality disorder patients with a history of impulsivity is limited, and there is even less evidence linking borderline personality disorder specifically to frontal lobe deficits. Neuroimaging studies show differences in the prefrontal cortex in people with borderline personality disorder, compared to healthy subjects, at baseline and in response to aversive stimuli ₍₁₀₎ and neuropharmacological probes associated with impulsivity. Some evidence from brain imaging studies suggests orbitofrontal cortex dysfunction in borderline personality disorder, specifically hypometabolism _{(7, 8, 11)} and smaller volume _{(9, 13)} of the orbitofrontal cortex.

In this study, our aim was to determine if certain aspects of borderline personality disorder, in particular impulsivity, are associated with orbitofrontal cortex dysfunction. We used questionnaires on personality, emotion, and impulsivity together with a number of computer-based tasks that are sensitive to frontal lobe dysfunction to assess possible underlying factors related to impulsivity in patients with orbitofrontal cortex lesions, patients with lesions in the prefrontal cortex but not in the orbitofrontal cortex, patients with borderline personality disorder and a history of self-harm, and healthy comparison subjects. This combination of tests allows for new comparisons of cognitive and behavioral traits and for identification of patterns and dissociations between different types of dysfunctions within borderline personality disorder. A unique feature of this study is the comparison of the clinical population of borderline personality disorder patients to patients with lesions in the prefrontal cortex. This study design provides an excellent opportunity to increase understanding of the biological etiology of borderline personality disorder as well as of the functions of the brain.

On the basis of previous research, we hypothesized that frontolimbic circuit dysfunction, involving both the orbitofrontal cortex and amygdala regions, may be involved in borderline personality disorder and that some aspects of borderline personality disorder may be related to dysfunction of the orbitofrontal cortex. Our goal is to provide evidence of these relationships by comparing the performance of patients with borderline personality disorder and patients with orbitofrontal cortex lesions on a number of tests. In the absence of uniquely defined and identifiable neurological damage in patients with borderline personality disorder, this study is intended to provide information about the neurobiological correlates of certain behaviors in borderline personality disorder.

Method

Participants
Ethics approval was obtained from the University of Oxford, the Institute of Psychiatry (King’s College, London), and the Oxfordshire Psychiatric Research Ethics Committee. After complete description of the study to the subjects, written informed consent was obtained.

Healthy comparison subjects
The healthy comparison group consisted of 39 participants (10 male participants) ranging in age from 18 to 71 years (mean=40.3 years, SD=20.5). The healthy comparison subjects were recruited through the subject panel at the Department of Experimental Psychology, University of Oxford. Potential participants were excluded if they had disturbed vision (despite corrective devices) or a history of current neurological illness, a current major psychiatric illness, or current substance or alcohol abuse.

Prefrontal lesion patients
The 43 prefrontal lesion patients in this study were recruited from the Department of Neurosurgery, King’s College Hospital, London (N=19); the International Subarachnoid Aneurysm Trial at the Radcliffe Infirmary, Oxford, England (N=16); and the Oxford Centre for Enablement, Oxford, England (N=8). The time since the patients sustained their lesion varied considerably, from 6 months to 20 years (mean=5.0 years, SD=4.8). Clinical information for each lesion patient and the basis for division into orbitofrontal cortex and dorsolateral prefrontal cortex lesion groups are summarized in Table 1 of our earlier publication ₍₅₎.

Twenty patients (eight male patients) constituted the comparison patients with prefrontal cortex lesions outside the orbitofrontal cortex. The patients ranged in age from 19 to 71 years (mean=46.0 years, SD=15.1). The dorsolateral prefrontal cortex (with or without the medial prefrontal cortex) was the main site of damage in the patients included in this group.

The patients with orbitofrontal cortex lesions consisted of 23 patients (15 male patients) ranging in age from 30 to 63 years (mean=48.7 years, SD=10.0) with damage including or restricted to the orbitofrontal cortex (either bilaterally or unilaterally).

Patients with borderline personality disorder
Nineteen self-harming inpatients with DSM-IV borderline personality disorder (18 female patients) ranging in age from 19 to 49 years (mean=32.37 years, SD=8.4) were tested at the Bethlem Royal Hospital Crisis Recovery Unit, London. (About 75% of borderline personality disorder diagnoses are made in female patients.) The unit provides a rehabilitation program in which the patients are taught to seek alternatives to and gain a better understanding of self-harm and to tolerate distressing feelings. Cutting and burning were among the most common forms of self-harm in the patients who participated in the study. Self-harm provided an objective indication of impulsive behavior and was an important factor in obtaining a homogeneous patient group. Descriptive and systematic data reveal that repetitive self-mutilation is typically an impulsive act ₍₁₇₎. Potential participants were excluded if they had current substance or alcohol abuse. Because all of the patients were in a 6-month inpatient rehabilitation program, we knew that for at least the time they were in the program they were not dependent on substances or alcohol. (Although most patients with borderline personality disorder were taking medications intended to improve their borderline personality disorder symptoms, they still performed poorly on tasks related to impulsivity, emotion, and personality and did not perform poorly on other tasks such as spatial working memory tasks.)

Materials and Procedures

Questionnaires
The self-report impulsivity measure was the Barratt Impulsiveness Scale, version 11 ₍₁₈₎. This 30-item, 4-point Likert-type questionnaire was used as a trait measure of impulsivity. Long-term patterns of behavior were assessed with three subscales: nonplanning, motor, and cognitive impulsivity.

The personality questionnaire was the Big Five Inventory ₍₁₉₎, a 44-item, 5-point Likert-type questionnaire designed to measure the five scales/domains of the Five-Factor Model of Personality ₍₂₀₎: extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience ₍₂₁₎.

The frontal behavior questionnaire is a self-report 20-item, 5-point Likert-type questionnaire ₍₅₎ designed to measure types of behavioral problems believed to result from frontal brain damage ₍₂₂₎, e.g., disinhibition, social inappropriateness, perseveration, and cooperativeness.

The borderline personality disorder questionnaire ₍₂₃₎, which consists of 18 yes/no questions modeled on the DSM-III criteria for borderline personality disorder, was used for assessment of borderline personality disorder characteristics.

The subjective emotion questionnaire measures how often participants experience sadness, anger, fear, happiness, and disgust in their current daily life. Ratings are made on a 4-point Likert-type scale. The emotional change questionnaire was given only to the patients with lesions and the patients with borderline personality disorder. This questionnaire assesses change (increase, decrease, or no change) since brain injury or onset of personality disorder in the capacity to feel sadness, anger, fear, happiness, and disgust. Both questionnaires were adapted from a previously developed subjective emotion questionnaire _{(1, 24)}.

Tests
The Probabilistic Reversal Test includes an “acquisition” task in which participants learn to touch one of two patterns on the computer screen and to avoid touching the other and a “reversal” task in which they then learn to reverse or extinguish that choice based on monetary rewards and punishers ₍₅₎. Measures of performance include 1) punishment insensitivity (the total number of consecutive touches to a stimulus after having lost a minimum of £250), which measures the extent to which participants fail to switch immediately from a stimulus on the next trial following a large loss, and 2) reward insensitivity (the total number of times a participant touched a stimulus and won a minimum of £80 but did not touch the same stimulus again on the next trial), which measures the extent to which participants fail to select the same stimulus again after a large gain was associated with that stimulus.

The Matching Familiar Figures Test ₍₂₅₎, a standard cognitive behavioral measure of impulsivity, measures reflection-impulsivity, a composite of two dimensions: 1) latency to first response and 2) accuracy of choice or total errors. Participants observe a standard picture and select from a set of highly similar pictures the one that is the same as the standard picture. Twelve target objects with eight variants each were administered. The mean time of the latency of participants’ first response across all trials and the number of errors made before choosing the correct item were recorded.

The Spatial Working Memory Task from the Cambridge Neuropsychological Test Automated Battery (CeNeS Ltd., Cambridge, U.K.), a standard test _{(5, 26)}, was used as a comparison condition. The measures were 1) between errors (number of times the subject revisits a box where a token has already been found), 2) within errors (number of times a subject revisits a box already found to be empty during the same search), and 3) strategy (the number of times the subject begins a new search with the same box) ₍₂₆₎. A high score denotes poor use of the strategy, and a low score denotes effective use.

The time perception task ₍₅₎ has two elements: time estimation and time production. For time estimation, participants were asked to estimate time intervals (10, 30, 60, and 90 seconds; each presented twice in a random sequence) during which they were distracted by being required to read aloud from a computer screen a series of randomly generated numbers from 1 to 9 that ranged in presentation time from 100 to 2900 milliseconds in order to prevent subvocal counting. The number of seconds estimated after each interval, averaged across two runs, and the total time estimated (the sum of the average times estimated at each interval divided by 190, which was the total number of seconds that actually passed) were recorded. The procedure for time production was the same as that for time estimation (reading aloud randomized numbers) except that participants were asked to press a computer key when they thought a set number of seconds had passed. For each time interval, the time produced was compared to the actual time participants were asked to produce. The number of seconds produced at each interval, averaged across two runs, and the total time produced (sum of the average times produced at each interval divided by 190, which was the total number of seconds participants were asked to produce) were recorded.

Statistical Analyses
A one-way analysis of variance (ANOVA) was performed for each of the variables to determine if the mean scores differed significantly by group. If an ANOVA yielded a significant F value, a Fisher’s least significant difference post hoc test was performed to identify the specific source of the difference. An alpha level of 0.05 was used for all statistical tests. Kruskal-Wallis nonparametric tests were performed for variables for which normality was not present. If the Kruskal-Wallis test yielded nonsignificant results, no results are reported for that variable.

Because ANOVAs revealed between-group differences in terms of age (F=4.36, df=3, 97, p=0.006) and gender (F=7.30, df=3, 97, p<0.001), analyses of covariance were performed across all variables, and these analyses discounted any confounding effects of age or gender on the results. No significant difference in the number of years since their lesion was found between the patients with orbitofrontal cortex lesions (mean=4.94, SD=4.22) and those with lesions in the prefrontal cortex but not in the orbitofrontal cortex (mean=4.95, SD=5.40), and years since lesion did not correlate significantly with any of the test variables, with Bonferroni correction.

The patients recruited from King’s College completed most questionnaires, but they did not complete the behavioral tests because of time constraints and did not complete the borderline personality disorder questionnaire because of sensitivity issues. A few other participants did not complete all of the tasks because of testing time constraints.

Full text

Heather A. Berlin, D.Phil., M.P.H., Edmund T. Rolls, D.Phil., D.Sc., and Susan D. Iversen, Ph.D., Sc.D.

References

  _{1. Rolls ET, Hornak J, Wade D, McGrath J: Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. J Neurol Neurosurg Psychiatry 1994; 57:1518–1524
  2. Rolls ET: Emotion Explained. Oxford, UK, Oxford University Press, 2005
  3. Hornak J, Bramham J, Rolls ET, Morris RG, O’Doherty J, Bullock PR, Polkey CE: Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices. Brain 2003; 126:1691–1712
  4. Hornak J, O’Doherty J, Bramham J, Rolls ET, Morris RG, Bullock PR, Polkey CE: Reward-related reversal learning after surgical excisions in orbitofrontal and dorsolateral prefrontal cortex in humans. J Cogn Neurosci 2004; 16:463–478
  5. Berlin HA, Rolls ET, Kischka U: Impulsivity, time perception, emotion, and reinforcement sensitivity in patients with orbitofrontal cortex lesions. Brain 2004; 127:1108–1126
  6. Lieb K, Zanarini MC, Schmahl C, Linehan MM, Bohus M: Borderline personality disorder. Lancet 2004; 364:453–461
  7. Goyer PF, Andreason PJ, Semple WE, Clayton AH, King AC, Compton-Toth BA, Schulz SC, Cohen RM: Positron-emission tomography and personality disorders. Neuropsychopharmacology 1994; 10:21–28
  8. De La Fuente JM, Goldman S, Stanus E, Vizuete C, Morlan I, Bobes J, Mendlewicz J: Brain glucose metabolism in borderline personality disorder. J Psychiatr Res 1997; 31:531–541
  9. Lyoo IK, Han MH, Cho DY: A brain MRI study in subjects with borderline personality disorder. J Affect Disord 1998; 50:235–243
  10. Herpertz SC, Dietrich TM, Wenning B, Krings T, Erberich SG, Willmes K, Thron A, Sass H: Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study. Biol Psychiatry 2001; 50:292–298
  11. Soloff PH, Meltzer CC, Greer PJ, Constantine D, Kelly TM: A fenfluramine-activated FDG-PET study of borderline personality disorder. Biol Psychiatry 2000; 47:540–547
  12. Leyton M, Okazawa H, Diksic M, Paris J, Rosa P, Mzengeza S, Young SN, Blier P, Benkelfat C: Brain regional {alpha}-[11C]methyl-L–tryptophan trapping in impulsive subjects with borderline personality disorder. Am J Psychiatry 2001; 158:775–782
  13. Tebartz van Elst L, Hesslinger B, Thiel T, Geiger E, Haegele K, Lemieux L, Lieb K, Bohus M, Hennig J, Ebert D: Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study. Biol Psychiatry 2003; 54:163–171
  14. Schmahl CG, Vermetten E, Elzinga BM, Bremner JD: A positron emission tomography study of memories of childhood abuse in borderline personality disorder. Biol Psychiatry 2004; 55:759–765
  15. Driessen M, Beblo T, Mertens M, Piefke M, Rullkoetter N, Silva-Saavedra A, Reddemann L, Rau H, Markowitsch HJ, Wulff H, Lange W, Woermann FG: Posttraumatic stress disorder and fMRI activation patterns of traumatic memory in patients with borderline personality disorder. Biol Psychiatry 2004; 55:603–611
  16. Vollm B, Richardson P, Stirling J, Elliott R, Dolan M, Chaudhry I, Del Ben C, McKie S, Anderson I, Deakin B: Neurobiological substrates of antisocial and borderline personality disorder: preliminary results of a functional fMRI study. Crim Behav Ment Health 2004; 14:39–54
  17. Herpertz S, Sass H, Favazza A: Impulsivity in self-mutilative behavior: psychometric and biological findings. J Psychiatr Res 1997; 31:451–465
  18. Patton JH, Stanford MS, Barratt ES: Factor structure of the Barratt Impulsiveness Scale. J Clin Psychol 1995; 51:768–774
  19. John OP, Donahue EM, Kentle RL: The Big Five Inventory Versions 4a and 54. Berkeley, University of California, Berkeley, Institute of Personality and Social Research, 1991
  20. McCrae RR, Costa PT: Toward a new generation of personality theories: theoretical contexts for the Five-Factor Model, in The Five-Factor Model of Personality: Theoretical Perspectives. Edited by Wiggens JS. New York, Guilford Press, 1996, pp 51–78
  21. Berlin HA, Rolls ET: Time perception, impulsivity, emotionality, and personality in self-harming borderline personality disorder patients. J Personal Disord 2004; 18:358–378
  22. Levin HS, Goldstein FC, Williams DH, Eisenberg HM: The contribution of frontal lobe lesions to the neurobehavioral outcome of closed Head injury, in Frontal Lobe Function and Dysfunction. Edited by Levin HS, Eisenberg HM, Benton LB. Oxford, UK, Oxford University Press, 1991
  23. Claridge G, Broks P: Schizotypy and hemispheric function, I: theoretical considerations and the measurement of schizotypy. Pers Individ Dif 1984; 5:633–648
  24. Hornak J, Rolls ET, Wade D: Face and voice expression identification in patients with emotional and behavioural changes following ventral frontal lobe damage. Neuropsychologia 1996; 34:247–261
  25. Kagan J: Reflection-impulsivity: the generality of dynamics of conceptual tempo. J Abnorm Psychol 1966; 1:17–24
  26. Owen AM, Downes JJ, Sahakian BJ, Polkey CE, Robbins T: Planning and spatial working memory following frontal lobe lesions in man. Neuropsychologia 1990; 28:1021–1034
  27. Barratt ES: Time perception, cortical evoked potentials, and impulsiveness among three groups of adolescents, in Violence and the Violent Individual. Edited by Hays JR, Solway KS. New York, Spectrum, 1981, pp 87–96}