ارتباطات عصبی استروپ عاطفی فرد در اختلال شخصیت مرزی

Objective Emotional dysregulation is a key feature of borderline personality disorder (BPD) with altered inhibitory functions having suggested as being crucial. The anterior cingulate cortex and further prefrontal brain regions are crucial for response inhibition. The regulation of emotions is ensured via inhibitory control over the amygdala. The present study aimed to investigate neural correlates of response inhibition in BPD by using an emotional Stroop paradigm extending the task to word stimuli which were related to stressful life events. Methods Twenty BPD patients and 20 healthy controls underwent functional magnetic resonance imaging (fMRI) while performing the individual emotional Stroop task. A block design was used with the following word type conditions: neutral words, general negative words, and individual negative words. The individual negative words were recruited from a prior interview conducted with each participant. Results While BPD patients had overall slower reaction times in the Stroop task compared to healthy controls, there was no increased slowing with emotional interference. Controls exhibited significant fMRI blood oxygenation level-dependent signal increases in the anterior cingulate cortex as well as in frontal cortex contrasting generally negative vs. neutral and individual negative vs. neutral conditions, respectively. BPD patients did not show equivalent signal changes. Conclusions These results provide further evidence for a dysfunctional network of brain areas in BPD, including the ACC and frontal brain regions. These areas are crucial for the regulation of stress and emotions, the core problems of BPD patients.

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability of interpersonal relationships, self-image, affects and marked impulsivity. Affective dysregulation has been emphasized as a core difficulty in patients with a diagnosis of BPD and is evident in interpersonal relationships and stressful situations (Posner et al., 2003 and Lieb et al., 2004). Indeed, stressful life events, daily hassles and (early) trauma are frequent in BPD and seem to have an important impact on onset and course of illness (Pagano et al., 2004, Jovev and Jackson, 2006 and Zanarini et al., 2006). Moreover, enhanced endocrine responses to psychosocial stress have been reported, especially for BPD patients with high dissociation scores, further reflecting problems of these patients handling stressful situations successfully (Simeon et al., 2007). It has been shown that patients with high impulsivity are characterized by a strong intensity of affective responses (Herpertz et al., 1997) and that negative emotions as anger are not only stronger, but also more prolonged (Jacob et al., 2008). On the other hand there is also evidence that these observations are not specific for BPD, but are also seen in other personality disorders or depression (Koenigsberg et al., 2002 and Renneberg et al., 2005). Several studies investigating physiological correlates of affective responses to emotional stimuli measured the startle response. Some (Ebner-Priemer et al., 2005), but not all (Herpertz et al., 1999, Herpertz et al., 2000 and Herpertz et al., 2001b) psychophysiological investigations in BPD demonstrated an exaggerated startle reflex. This finding was interpreted in the context of an amygdala hyperresponsivity. Different methods may account for the conflicting results: while Ebner-Priemer et al. used an acoustic startle paradigm, Herpertz et al. used emotional pictures. Interestingly, only BPD patients with low dissociation were characterized by an enhanced startle reaction (Ebner-Priemer et al., 2005), which is in line with the study of Simeon et al. (2003). These data suggest subgroups of BPD patients with different psychophysiological reactions. Other studies investigating hypothalamic-pituitary adrenal functioning in BPD confirm these findings (Rinne et al., 2002, Wingenfeld et al., 2007a and Wingenfeld et al., 2007b). Neuroimaging studies found an increased responsiveness of the amygdala in response to negatively valenced pictures or to facial expressions of emotion (Herpertz et al., 2001a and Donegan et al., 2003). Beside the amygdala itself, a fronto-limbic dysfunction has been emphasized to be crucial emotional dysregulation in BPD (Schmahl and Bremner, 2006). Most brain imaging studies in BPD focused on major negative autobiographical memories. Two positron emission tomography (PET) studies analyzed memories of abandonment and traumatic events, respectively (Schmahl et al., 2003 and Schmahl et al., 2004b). Relative to a psychiatric control groups, BPD patients showed altered brain activation mainly in the orbitofrontal and in the anterior cingulate cortex. A fMRI study of our group compared autobiographical memories of unresolved vs. resolved life events in BPD relative to controls (Beblo et al., 2006). Patients showed increased bilateral activation of the frontal cortex including parts of the insula and of the orbitofrontal cortex as well as temporal activation including the amygdala. These findings suggest altered brain functioning during the retrieval of negative autobiographical events in BPD. In sum, most (but not all) studies suggest a decreased activation and responsiveness of the ACC (Donegan et al., 2003, Schmahl et al., 2003 and Schmahl et al., 2004b), the hippocampus (Juengling et al., 2003), the medial and orbitofrontal cortex (Soloff et al., 2003 and Schmahl et al., 2004b) and the dorsolateral prefrontal cortex (Schmahl et al., 2003 and Schmahl et al., 2004b). On the other hand the amygdala seems to be characterized by increased activity (Herpertz et al., 2001a and Donegan et al., 2003). Accordingly, one hypothesis to explain emotional dysregulation in BPS is a failure of the ACC and of prefrontral brain areas to inhibit the amygdala. Inhibition has been suggested to be one principal mechanism of emotional regulation and inhibitory dysfunctions have been hypothesized to play an important role in BPD patients (Domes et al., 2006 and Fertuck et al., 2006). A widely used method for investigating inhibition of interference is the emotional Stroop task. In this test subjects have to name the colors in which words are printed. Cohen et al. (1990) generally proposed that this “Stroop effect” or “Stroop interference” might be due to an inherent property of parallel distributed processing systems, e.g. neural circuits for reading and color-naming. The strength of an interfering neural circuit, or pathway, depends on an individual's prior practice and learning, on emotional impact, and on personal relevance. Thus, interference grows in proportion to the strength of these parallel stimulated processing routines. Summarizing neuroimaging results on the Stroop task, most studies found activation in the following brain regions: the ACC (Carter et al., 1995, Bush et al., 1998, Whalen et al., 1998 and Peterson et al., 1999;), parietal lobe (Carter et al., 1995, Taylor et al., 1997 and Peterson et al., 1999) and lateral prefrontal cortex (Carter et al., 1995 and Taylor et al., 1997). Further, activation of the middle frontal gyrus and the inferior frontal gyrus has been reported (Taylor et al., 1997). The ACC is an important component of parallel distributed attentional networks and is involved in several emotional and cognitive processes, as integrating input from various sources (Bush et al., 2000). In our context, the inhibitory role of medial prefrontal structures with respect to regions involved in emotional responses, e.g. fear, as the amygdala has to be emphasized (Morgan et al., 1993 and Morgan and LeDoux, 1995). In sum, the Stroop task seems to be a reliable tool to investigate neural correlates of the inhibitory control of emotional stimuli. Reduced inhibition has been shown in several clinical populations, especially when emotional stimuli are specifically related to the core psychopathology (Williams et al., 1996). For example, when presenting trauma-related words in the Stroop test, patients with posttraumatic stress disorder (PTSD) showed remarkably slower reaction times and more interference to these words, interpreted as an attentional bias to trauma-related stimuli (Foa et al., 1991, Cassiday et al., 1992, McNally et al., 1993 and Kaspi et al., 1995). Noteworthy, these stimuli are not only related to psychopathology but also to highly stressful events. Interestingly, research has shown that enhanced interference could also be evoked in a non-clinical sample, but predominantly to words which were related to stressful life events, and, thus are characterized by personally relevance (Wingenfeld et al., 2006). Attentional bias to personally relevant information has been shown in several other studies, too (Mogg and Marden, 1990 and Riemann and McNally, 1995). Due to the fact that BPD is characterized by disturbances of emotion regulation, one may expect an enhanced interference of emotional stimuli in the Stroop test. However, several studies investigating the emotional Stroop effect in BPD could not confirm this hypothesis (Sprock et al., 2000 and Domes et al., 2006). Another study found an altered interference, but the effect was not specific for BPD patients (Arntz et al., 2000). In two other studies the authors also showed an enhanced interference in BPD patients using specific schema-related negative cues (Sieswerda et al., 2007a, 2007b). Thus, difficulties in inhibitory function seem to occur predominantly when personally relevant stimuli or concerns come into the focus of attention. Further, it has been shown that recovering from BPD was associated with normalization of interference in the Stroop task (Sieswerda et al., 2007a). Using the attention network test, Posner et al. (2002) also found difficulties in BPS patients’ ability to conflict resolution, i.e. cognitive control, suggesting a dysfunction of fronto-limbic circuits (Posner et al., 2002). Most studies in BPD investigate brain functioning during resting condition or during the recollection and imaging of personal events. To our knowledge, research is missing examining the neural correlates of inhibitory function associated with the Stroop task in BPD. While imaging studies on autobiographical memory and results from the emotional Stroop task suggest altered inhibitory function in BPD, fMRI or PET have not been used in Stroop studies. In PTSD, the link between these two lines of research, namely (neural correlates of) autobiographic memory and inhibition processes have been realized. Two studies focused on this topic, both suggesting dysfunctions of brain networks including the anterior cingulate cortex when processing emotional relevant stimuli. In one study combat veterans with and without PTSD were studied with the emotional counting Stroop including combat-related, generally negative and generally neutral words (Shin et al., 2001). Only the non-PTSD group exhibited BOLD increases in the anterior cingulate cortex whereas the PTSD group failed to activate this region. Activation of the anterior cingulate cortex is a robust finding in brain imaging studies using the Stroop test (Peterson et al., 1999 and Whalen et al., 1998) and prefrontal and parietal regions are involved, too (Bush et al., 1998, Milham et al., 2001 and Milham et al., 2003; van Veen and Carter, 2005). Another study investigated women with early childhood sexual abuse with and without PTSD (Bremner et al., 2004). Again, in women with PTSD reduced activity in the anterior cingulate cortex has been found in the emotional Stroop test, as well as greater increase in blood flow in visual and parietal cortex in women without PTSD. However, the numbers of participants in the studies by Shin et al., and Bremner et al., were small and healthy controls were not included (Shin et al., 2001 and Bremner et al., 2004). Furthermore, stimuli strictly related to traumatic events had been used, thus information about inhibitory function to less serious autobiographical stimuli was missing, e.g. critical life events or daily hassles. However, there is a high comorbidity between PTSD and borderline personality disorder, and traumatic experiences are frequent in BPD. Interestingly, when using autobiographical scripts findings in BPD were quite similar to those studies in PTSD presenting trauma-related stimuli as pictures, sounds or word pairs (Bremner et al., 1999b and Bremner et al., 2003), including failure to activate anterior cingulate cortex (Schmahl et al., 2003 and Schmahl et al., 2004b). PTSD and BPD are both characterized by stressful life events and it has been argued that “both disorders are thought to be related to neurobiological alterations brought about by traumatic experiences” (Schmahl and Bremner, 2006). Thus, we agree with the conclusion of Schmahl and Bremner that methods which have been successfully used in PTSD should be transferred to BPD research. Here we investigate the neural correlates of response inhibition in BPD using an emotional Stroop task extending the paradigm to word stimuli which were related to stressful life events as reported by patients and controls. Given the results of prior imaging studies in PTSD using the emotional Stroop test and neuropsychological data on attentional and inhibitory dysfunction (Posner et al., 2002 and Domes et al., 2006), BPD patients compared with controls were expected to exhibit difficulties in activating the ACC (Shin et al., 2001 and Bremner et al., 2004), as well as medial prefrontal brain regions (Shin et al., 2001 and Shin et al., 2006).

In conclusion, the results reported here are consistent with former imaging studies suggesting altered functioning of the ACC in BPD patients. Thus, altered inhibitory functions and emotional dysregulation might be related to a dysfunctional brain network, including the ACC and frontal brain regions, which are important for the regulation of stress and emotions, the core problems of BPD patients.