Deficits in emotion regulation are a core feature of borderline personality disorder (BPD)(1
). Patients with BPD have suicide rates 50 times the general population (5
), utilize more mental health resources than individuals with other psychiatric disorders (6
) and because BPD is present in approximately 2–5.9% of the general population, it is at least as prevalent as schizophrenia and bipolar I disorder (8
). Affective instability in BPD is characterized as an inability to regulate emotional responses (11
) with a high sensitivity to emotional stimuli and unusually strong and long-lasting reactions (2
). This phenomenological description suggests that BPD patients may have an abnormality in their decrement of response to repeatedly presented emotional stimuli. Habituation is defined as the decrease in physiological responsivity that occurs to a repeated presentation of the same stimulus (14
). Understanding the neutral substrates of emotion-processing deficits in BPD may ultimately help target biological or psychological treatments and predict which individuals with BPD respond best to a specific type of treatment. This strategy has shown promise in predicting response to cognitive behavioral therapy in depressed patients, e.g.,(16
The amygdala plays an important role in modulating attention/vigilance particularly in potentially threatening social situations and perceiving the valence of events/objects and emotional expressions of others (17
). Translational neuroscience animal models indicate the amygdala plays a central role in learning about unpleasant- and pleasantly-valenced stimuli (20
). Given BPD patients exhibit emotion dysregulation, it is not surprising that the amygdala is the most investigated brain structure in fMRI studies of this disorder and the majority employed standardized-photographic images from the International Affective Picture Show (IAPS)(21
). Yet, regardless of whether pictures, faces, or scripts were used, studies primarily show amygdala overactivity in BPD during the processing of unpleasant stimuli (13
One possible mechanism accounting for amygdala overactivity in BPD is impaired habituation. Habituation is one of the most documented and fundamental forms of nervous system plasticity (28
). The initial response to a novel stimulus involves a rapid shift of attentional processes (i.e. an orienting response), but with one or more repeated presentations without meaningful consequences, response amplitude is reduced. Prior studies in healthy adults document strong evidence of a decrement in the amygdala BOLD response to repeatedly presented emotional stimuli, e.g.,(18
). Animal models (30
) and human work (32
) also pinpoint the amygdala as an important component of the system involved in the acquisition and memory storage of unpleasant stimuli. The present study is the first to examine whether BPD patients show abnormal amygdala habituation and/or differences in the shape, amplitude, and habituation of the BOLD response to repeated-emotional stimuli.
) and others (35
) have shown that BPD patients exhibit exaggerated affective startle to borderline-salient stimuli compared with HCs which may be mediated by symptom severity (e.g., 37
). Animal models indicate whole-body startle is modulated by the amygdala in the context of fear-conditioning (20
) and we examined startle-eyeblink amplitude, a component of whole-body startle during the processing of borderline-salient (e.g., suicidal) and neutral (e.g., coin) words. Compared with HCs, BPD patients showed exaggerated startle amplitude during unpleasant but not neutral words (34
). In contrast, on self-report, the BPD patients showed a blunted response by rating the unpleasant words as less unpleasant but did not differ from the HCs for the neutral-word condition. This mismatch between the physiological and subjective response to emotional stimuli is consistent with a psychophysiological ambulatory monitoring study which also reported an inability to label emotions (35
) and fMRI studies reporting a mismatch between amygdala activation and self-report ratings in BPD (22
). The present study further examines the concept that BPD is characterized by a mismatch between physiological and self-report responses to emotional stimuli.
This fMRI study addresses several key issues unresolved by prior BPD work. First, given unpleasant pictures are highly arousing compared with neutral pictures or a resting state, we controlled for both valence and
arousal levels in our study by including three picture conditions (unpleasant/high arousal-vs.-neutral/low arousal-vs.-pleasant/high arousal) using the standardized-IAPS library (21
). Second, as a reliability check, subjective emotion was measured using self-report ratings of the pictures both in the magnet and following the session. Third, the diagnostic specificity of amygdala dysfunction in BPD was addressed by including BPD patients with no schizotypal personality disorder (SPD) traits and a psychiatric-control group of SPD patients without BPD traits. Fourth, the shape of the amygdala BOLD-response curve and its change over time was examined during novel and repeated presentations of the emotional and neutral pictures.
To examine the hypothesis that BPD patients exhibit high sensitivity to emotional stimuli and unusually strong and long-lasting reactions as measured by amygdala activation, we presented each of the pictures twice within
their respective trial block/run. This allowed an examination of changes in the BOLD response from the novel- to the repeated-picture presentation. Additionally, we examined the time-course of the amygdala BOLD response curves. Compared with both control groups, we hypothesized that BPD patients would show a (a) protracted amygdala BOLD response (i.e. slower return to baseline), particularly following emotional pictures; (b) pattern of greater amygdala activation to repeated compared with novel emotional but not neutral pictures; and (c) mismatch between their amygdala and self-report response to emotional pictures. Exploratory
correlations between amygdala activation to the repeated-unpleasant pictures and self-reported symptom severity scales were conducted separately for the patient groups. We used the strict criteria of Vul et al (38
) to conduct our correlational analysis which involved the mean BOLD response (AUC) for all voxels within our amygdala region-of-interest (i.e. aggregated data) which was traced on structural-MRI for each participant blind to their diagnosis and functional-imaging data. A standard whole-brain analysis using FSL(4.1)(39
) was also conducted to confirm our amygdala region-of-interest results and explore other regions.