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The Neural Correlates of Anomalous Habituation to Negative Emotional Pictures in Borderline and Avoidant Personality Disorder Patients
Harold W. Koenigsberg, M.D.; Bryan T. Denny, Ph.D.; Jin Fan, Ph.D.; Xun Liu, Ph.D.; Stephanie Guerreri; Sarah Jo Mayson; Liza Rimsky; Antonia S. New, M.D.; Marianne Goodman, M.D.; Larry J. Siever, M.D.
Am J Psychiatry 2014;171:82-90. doi:10.1176/appi.ajp.2013.13070852
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The authors report no financial relationships with commercial interests.

From the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; the James J. Peters VA Medical Center, Bronx, New York; the Department of Psychology, Queens College, City University of New York, New York; and the Institute of Psychology, Chinese Academy of Sciences, Beijing.

Address correspondence to Dr. Koenigsberg (hwarrenk@nyc.rr.com).

Copyright © 2014 by the American Psychiatric Association

Received July 03, 2013; Revised August 05, 2013; Accepted August 15, 2013.


Objective  Extreme emotional reactivity is a defining feature of borderline personality disorder, yet the neural-behavioral mechanisms underlying this affective instability are poorly understood. One possible contributor is diminished ability to engage the mechanism of emotional habituation. The authors tested this hypothesis by examining behavioral and neural correlates of habituation in borderline patients, healthy comparison subjects, and a psychopathological comparison group of patients with avoidant personality disorder.

Method  During fMRI scanning, borderline patients, healthy subjects, and avoidant personality disorder patients viewed novel and repeated pictures, providing valence ratings at each presentation. Statistical parametric maps of the contrasts of activation during repeated versus novel negative picture viewing were compared between groups. Psychophysiological interaction analysis was employed to examine functional connectivity differences between groups.

Results  Unlike healthy subjects, neither borderline nor avoidant personality disorder patients exhibited increased activity in the dorsal anterior cingulate cortex when viewing repeated versus novel pictures. This lack of an increase in dorsal anterior cingulate activity was associated with greater affective instability in borderline patients. In addition, borderline and avoidant patients exhibited smaller increases in insula-amygdala functional connectivity than healthy subjects and, unlike healthy subjects, did not show habituation in ratings of the emotional intensity of the images. Borderline patients differed from avoidant patients in insula-ventral anterior cingulate functional connectivity during habituation.

Conclusions  Unlike healthy subjects, borderline patients fail to habituate to negative pictures, and they differ from both healthy subjects and avoidant patients in neural activity during habituation. A failure to effectively engage emotional habituation processes may contribute to affective instability in borderline patients.

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FIGURE 1. Schematic Depiction of Picture Presentation Designa

a Each picture is presented for 4 seconds and is followed by a 3-second rating interval when the subject rates the picture on a scale from 1 (most negative) to 5 (most positive) using a response button box. This is followed by a 3-second interstimulus interval. Pictures are shown in five consecutive blocks of 16 negative and 16 neutral pictures. Two-thirds of the pictures are shown a second time. A repeated picture is always shown 5.3 minutes after the first showing of that picture, and pictures and their repeats are distributed uniformly throughout the 27 minutes of the task. Novel and repeated pictures are counterbalanced across participants.

FIGURE 2. Behavioral Ratings of Picture Valence During the Scan in Patients With Avoidant and Borderline Personality Disorders and in Healthy Subjectsa

a Affect is rated on a scale from 1 (most negative) to 5 (most positive).

b Significant difference in emotional valence between novel and repeated negative pictures for the healthy group (p<0.01, one-tailed).

FIGURE 3. Engagement of the Dorsal Anterior Cingulate in Patients With Avoidant and Borderline Personality Disorders and in Healthy Subjects When Viewing Repeated Versus Novel Negative Picturesa

a In panel A, the map shows a 156-voxel dorsal anterior cingulate cluster indicating a significant difference between the healthy and borderline groups for RepeatedNeg versus NovelNeg activity (p<0.05, k=150, family-wise error corrected). Panel B shows extracted beta weights for each group during viewing of novel and repeated negative pictures. In panel C, the map shows a 162-voxel dorsal anterior cingulate cluster indicating a significant difference between the healthy and avoidant groups for RepeatedNeg versus NovelNeg activity (p<0.05, k=150, family-wise error corrected). Panel D shows extracted beta weights for each group during viewing of novel and repeated negative pictures. In panel E, the map shows an unbiased 65-voxel dorsal anterior cingulate region of interest derived from the conjunction of voxels showing significant between-group differences for repeated versus novel negative picture viewing for the contrasts between the borderline and healthy groups and between the avoidant and healthy groups (p<0.05). Panel F shows the correlation of repeated versus novel activation differences in the independently defined dorsal anterior cingulate region of interest (shown in panel E) with affective instability for each group.

b Significant within-group difference, p<0.05, two-tailed.

FIGURE 4. Insula-Amygdala Functional Connectivity in Borderline Patients and Healthy Subjectsa

a Left and right amygdala regions showing significant group differences in functional connectivity to left insula seed region (healthy group > borderline group).

b Significant difference between groups, p<0.05, two-tailed.

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TABLE 1.Demographic and Clinical Characteristics of Participants in a Study of the Functional Connectivity of Habituation
Table Footer Note

a Significant difference between borderline and avoidant groups (p<0.05).

Table Footer Note

b Significant difference between borderline and avoidant groups (p<0.05), borderline and healthy groups (p<0.001), and avoidant and healthy groups (p<0.001).



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During habituation to repeated aversive pictures, borderline patients show smaller increases in functional connectivity between the amygdala and which of the following brain regions, when compared to healthy subjects?
When exposed to repeated viewing of negative images, borderline patients differ from avoidant personality disorder patients in showing greater increases in functional connectivity between the insula and which of the following regions?
Affective instability in patients with borderline personality disorder is associated with decreased activation of which brain region when habituating to aversive pictures?
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