This study compared the neural activation patterns of patients with BPD and healthy controls in response to the script-driven imagery of SIB. In contrast to controls, patients with BPD showed a decrease of activation in the orbitofrontal cortex (OFC) while imagining the emotional and cognitive reactions to a stressful situation. Furthermore, only patients with BPD displayed an increase of activation in the dorsolateral prefrontal cortex (DLPFC) during this section. Imagining the self-injurious act itself elicited a significant decrease of activation in the mid-cingulate of patients with BPD, which was not found in control subjects. Patients reported increased stress levels throughout the script.
So far, SIB has been studied with psychometric instruments or psychophysiological measures only (3
). To our knowledge, this study is among the first to investigate neural correlates of this key aspect of BPD psychopathology.
The most interesting finding of this study is the activation difference in OFC between patients with BPD and control subjects during the section describing the emotional and cognitive reactions to a situation triggering an act of SIB, which seems to be due to a stronger deactivation of the OFC in the patients with BPD. This deactivation may relate to a failure to inhibit or modulate their emotional or cognitive reactivity, which, in turn, may increase the urge for SIB as an alternative way to reduce their tension. However, this interpretation has to be taken with caution, since healthy controls do not show SIB and most probably do not feel an urge for it. Functional imaging studies in healthy humans, but also in psychiatric populations have linked deficits in response inhibition to anomalies of frontal lobe areas, especially the OFC (13
). These findings are of special importance considering the link between SIB, impulsivity and affective instability in BPD (6
). In patients with impulsive–aggressive personality disorders, an abnormal function of the OFC was found in serotonergic challenge studies (42
) as well as an fMRI study by Coccaro et al. (44
). In patients with BPD, an fMRI study by Vollm et al. (45
) could demonstrate orbitofrontal dysfunction in connection with response inhibition. Considering these findings together with the observation of increased state- as well as trait-impulsivity in patients with BPD (8
), the attenuated OFC activity in the patients with BPD, observed in our study could indicate a dysfunction in impulse control in these patients. Failure of inhibition may directly lead to SIB, and SIB in this context, particularly in patients with BPD has been discussed as an impulsive form of self-injury (46
Our findings of a dysfunction in the OFC are in accordance with the results of the study by Schmahl et al. (31
), who found blunted orbitofrontal activation in response to trauma scripts in traumatized patients with BPD, compared to traumatized subjects without BPD. Similarities between this study and our own investigation include the use of script-driven imagery and the description of a situation triggering aversive feelings, which might explain the analogue results. In contrast to this, Beblo et al. (29
) found an increase in OFC activity during script-driven imagination of unresolved life-events in patients with BPD. This discrepancy may be due to methodological differences. We employed scripts, whereas Beblo et al. (29
) applied cue-driven imagery. As these authors also explicate, memory recall by cues might be determined primarily by internal processes and, thus, may enable subjects to exert control over induced emotions. By contrast, script-driven imagery provides primarily external cues, possibly rendering internal control more difficult. Attenuated orbitofrontal activity may indicate impairment in patients with BPD to initiate internal control processes when external stimulation predominates.
Furthermore, only patients with BPD but not control subjects displayed activation changes in the DLPFC. In response to the trigger situation, activation decreased in the middle frontal gyrus, including parts of BA 9, 10 and 46, whereas in response to the succeeding section describing the emotional and cognitive reactions activation increased in the frontopolar cortex. Response selection has been described as one of the primary functions of the DLPFC (47
). The activation pattern in this area observed in our patients with BPD may be related to such executive processes. Whereas in the trigger situation sensory and cognitive processes might dominate, thus rendering response selection rather unimportant, the evaluation and selection of behavioral responses becomes relevant during the following section describing the emotional and cognitive responses to the stressful situation.
It should be taken into consideration that subjects are listening to a script and, thus, do not necessarily experience a situation triggering a personal urge to injure themselves. However, due to their personal experiences patients with BPD have more difficulties to distance themselves from the situation. This might initiate early processes of response evaluation and selection. Increased DLPFC activation in patients with BPD has also been reported in response to abuse scripts and scripts of abandonment (30
). Both studies confronted patients with BPD with the description of stressful situations, which would usually prompt response selection and, thus, can be compared with the DLPFC increase found in our study. Taken together, the pattern of DLPFC activation and OFC deactivation in our sample of patients with BPD could indicate early response selection and dysfunctional emotional control. The group difference may be related to the fact that the controls do not feel personally involved in the situation despite their vivid imagination and might not experience any emotional conflicts which would require impulse control or to the fact that the healthy controls are better at modulating their emotions.
A further interesting finding of this study is a deactivation in the posterior ACC during the description of SIB itself, which was only found in patients with BPD. Lack of significant between-group differences may be due to the limited sample size. The ACC is a large area that can be divided into the perigenual ACC, anterior midcingulate, and posterior midcingulate (50
), which is considered to be part of the cognition division of the cingulate cortex. It is primarily involved in monitoring ongoing processing as well as evaluating the need for cognitive control (e.g. 51
). A study by Ochsner et al. (52
) investigated the neural bases of reappraisal, the authors found a positive correlation between ACC activation and successful reappraisal. The authors argued that successful reappraisal would depend upon monitoring for conflicts between initial emotional appraisals and cognitively restructured appraisals. Based on this assumption, the activation decrease in the ACC in our patients with BPD may indicate enhanced emotional involvement due to possible deficits in active monitoring, which may impede changing the emotional valence of the described situation. Besides, the ACC also plays a major role in pain responsiveness (for review, see 53
). In the context of a description of self-injury one might also speculate about ACC-mediated processes connected to pain perception in this group of patients with BPD with decreased activity possibly indicating changes in pain sensitivity. However, this interpretation can only be made with caution, as we could not assess pain perception for methodological reasons. Both factors, increased conflict monitoring and reduced pain sensitivity, could explain the change in ACC activation in these patients with BPD, but not in the sample of controls, since the latter have never experienced SIB. Although control subjects can imagine the situation vividly, they would probably neither develop an urge to react nor show any changes in pain processing. In agreement with these findings, a study by Schmahl et al. (30
) has also reported decreased ACC activation in response to scripts of abandonment. An overlap between this study and our own investigation can be seen in the description of an extremely aversive situation, a condition also present in the different sections of our SIB-script.
There are several limitations to this study that should be considered. Most importantly, healthy controls do not experience SIB. Therefore activation differences may be due to differences in autobiographical memories or to differences in the urge to use SIB as a means to regulate their emotions. Second, we used fixed-effects analyses and thus the ability to generalize from the study sample to the larger population of patients with BPD is limited. However, in patient studies with relatively low sample size such as ours, fixed-effects analyses are generally accepted as a valid statistical approach, allowing to study new aspects in patient groups, where it is difficult to investigate large sample sizes. So far, conclusions can only be made for this sample and not for the whole population of borderline patients or they have to be drawn with caution. Third, we cannot determine whether our findings are related to SIB per se
or to BPD features. This is also due to the fact that we used no control condition, e.g. a script of an accident or some other event as has been used in prior studies (e.g. 27
). Fourth, it might have been helpful to include a low-level baseline condition like listening to a neutral story as a secondary comparison condition. This would have enabled us to analyze neutral and experimental conditions separately, thereby further clarifying the group-specific activation patterns associated with the different sections of the script. Fifth, due to the nature of the script, a single section could not be repeatedly presented, thus possibly diminishing the effect size of our results. The use of a standardized script necessarily neglects several individual triggers and methods of SIB, but it was a trade-off between individual responsivity and methodological limitations of the study. As it would have been extremely complicated to tailor individual scripts with exactly the same length for all patients, we decided to use a most prototypical event of SIB. Finally, it has to be mentioned that we only assessed white women with BPD of a narrow age range and that several co-occurrent disorders were excluded. This may also diminish the ability to generalize to a larger population. On the other hand, almost half of the patients fulfilled criteria for social phobia and PTSD. Due to limited sample size, subgroup analyses of patients with and without these two disorders were not possible. Despite these limitations, we believe that neural alterations in relation to disturbed impulse control and conflict monitoring in the context of SIB are of clinical importance in our understanding of BPD. Therefore, future studies will try to extend these findings to other groups of BPD patients. Also, we are currently conducting fMRI studies with designs which mirror SIB more closely than this script design.