10b
Inga Niedtfeld, Christian Paret, and Christian Schmahl
The chapter by Chapman and colleagues (this volume) gives an excellent overview of the current state of knowledge on all aspects of borderline personality disorder (BPD). We would like to take the opportunity to extend the scope of the chapter by adding our view regarding a particularly important issue, namely the interaction between neuroscientific and psychotherapy research. We are convinced that integration of both research methodologies (which have traditionally been separated), may significantly help to improve the basic understanding of mechanisms behind the disorder as well as the treatment of BPD.
As mentioned in this chapter, emotion dysregulation is one of the core features of BPD and the main target of dialectical behavior therapy (DBT). Neuroimaging studies investigating alterations after treatment found normalization of limbic hyper-reactivity (Goodman et al., 2014; Niedtfeld et al., 2017; Schmitt, Winter, Niedtfeld, Schmahl, & Herpertz, 2016; Schnell & Herpertz, 2007; Winter et al., 2017). After successful therapy, patients exhibited changes in brain activity, pointing to reduced hypersensitivity of limbic brain regions and increased prefrontal brain activity during emotional challenge. An early study investigated six BPD patients before and after a 12-week residential DBT treatment. In response to negative pictures, patients showed reduced activity of insula and ACC after successful psychotherapy (Schnell & Herpertz, 2007). Investigating habituation processes, negative pictures were repeatedly presented to patients before and after standard DBT. The amygdala was activated to a lesser extent after 12 months of DBT, pointing to improved habituation (Goodman et al., 2014). A recent study observed reduced neural activity in eight patients with BPD in brain areas supporting emotion processing and theory of mind after brief psychiatric treatment of ten sessions (Kramer et al., 2018). Notably, these studies did not include a control group of patients without DBT, and so they cannot differentiate between DBT-specific effects and unspecific therapy, or time, effects.
Three studies were conducted in a large project investigating different emotion regulation strategies (reappraisal, distraction, and pain) before and after a 12-week residential DBT treatment (Niedtfeld et al., 2017; Schmitt et al., 2016; Winter et al., 2017), as compared to treatment as usual and HC subjects. When engaging in reappraisal of negative pictures, those with BPD showed decreased anterior insula and dorsal anterior cingulate cortex (ACC) activity during and after DBT. Therapy responders also showed reduced activation in amygdala, ACC, orbitofrontal, and DLPFC, together with increased limbic-prefrontal coupling (Schmitt et al., 2016). In the second study, DBT treatment responders also showed reduced ACC activity when viewing negative (as compared to neutral) pictures. During cognitive distraction from negative pictures, decreased activity in the right inferior parietal lobe was found in BPD patients after DBT (Winter et al., 2017). The third study examined the effect of pain on emotional reactions and found that pain-mediated affect regulation (i.e., amygdala deactivation in response to painful stimulation, a mechanism assumed to underlie non-suicidal self-injury) was reduced after DBT treatment (Niedtfeld et al., 2017).
Taken together, there is strong evidence for limbic hyper-reactivity in BPD, leading to intense and long-lasting emotional reactions. Additionally, down-regulation of emotional arousal appears to be deficient in BPD, as demonstrated by decreased recruitment of prefrontal regulation networks. These two aspects might result in affective instability in BPD. However, it is important to note that most of these effects might be not specific to BPD patients. A study in healthy subjects with childhood maltreatment demonstrated functional alterations that were strikingly similar to the findings described here for BPD (Dannlowski et al., 2012). It is possible that adverse childhood experiences lead to alterations in limbic brain regions, which in turn increase the risk for the development of psychiatric disorders in general (Gilbert et al., 2009). With regard to BPD, it has been argued that the co-occurrence of adverse childhood experiences and dysfunctional emotion regulation, together with increased impulsivity and interpersonal problems, might be more specific for the development of BPD (Crowell, Beauchaine, & Linehan, 2009).
Another example supporting an integrated neuroscientific-psychotherapeutic as well as mechanism-based approach for understanding BPD is real-time fMRI neurofeedback (rtfMRI-NF). RtfMRI-NF has recently become a focus of clinical psychiatry and psychotherapy research (deCharms et al., 2005; Linden, 2014; Linden et al., 2012; Ruiz, Birbaumer, & Sitaram, 2013; Ruiz, Lee, et al., 2013; Young et al., 2014; Zilverstand, Sorger, Sarkheil, & Goebel, 2014), with pioneering studies providing initial evidence that it might play a promising role in future therapies for chronic pain, and mental disorders such as depression, schizophrenia, and phobias. Several studies conducted in healthy participants have demonstrated improvement in control over key areas of emotional responding, such as the amygdala or the insula (Brühl et al., 2014; Caria, Sitaram, Veit, Begliomini, & Birbaumer, 2010; Hamilton, Glover, Hsu, Johnson, & Gotlib, 2011; Johnston, Boehm, Healy, Goebel, & Linden, 2010; Lawrence et al., 2013; Paret et al., 2014; Scheinost et al., 2013; Sulzer et al., 2013; Veit et al., 2012; Zotev et al., 2011). This literature supports the feasibility of using neurofeedback to target brain regions of the affective system, such as the amygdala, as an alternative or at least an add-on to psychotherapy for mental disorders that are associated with emotion dysregulation.
Extending this important body of work on real-time fMRI NF, our research team has conducted three studies to test the feasibility of this approach in BPD. First, we investigated whether participants would be able to down-regulate their amygdala response to aversive pictures when they were provided with continuous feedback from this region. The first study was conducted in healthy persons (Paret et al., 2014). Thirty-two female participants completed one session of training that comprised four runs, with each run presenting aversive pictures under three different conditions. In the REGULATE condition, participants were provided with continuous visual feedback on brain activation via a thermometer display, and were instructed to use this feedback to try to consciously down-regulate the thermometer. One-half of the participants received feedback on activation in the amygdala, while the other half received it from a control region located in the basal ganglia. In the VIEW condition, they were instructed to respond naturally to the aversive pictures; i.e., to not make any attempt to regulate the thermometer. In the fourth run, they were given the same instructions about down-regulation that they had been given in the REGULATE condition, but this time they did not receive feedback on brain activation, in order to assess the transfer of the regulation training. RtfMRI-NF was associated with successful down-regulation of the amygdala response in both groups. During transfer, we found evidence for a differential influence of Group on brain self-regulation and of down-regulation of the right amygdala response in the experimental group.
In a second study (Paret, Kluetsch, et al., 2016), we applied the same protocol to eight BPD patients to investigate if down-regulation of amygdala activation could be achieved in this population as well. Participants underwent four training sessions over two weeks. We found a reduced amygdala response in the REGULATE condition as contrasted with the VIEW condition, with reduction already seen in the first session. BPD patients also demonstrated an increase of amygdala-prefrontal connectivity over the course of training, a pattern which was also observed in healthy subjects during one session of rtfMRI-NF (Paret, Ruf, et al., 2016).
Finally, in a recently completed study (Zaehringer et al., 2019), we were interested in which aspects of emotion dysregulation would be amenable to change with NF. Twenty-five female BPD patients (mean age = 33.36, SD = 10.65) participated in three rtfmri-NF sessions and were tested again six weeks later. Patients were on constant medication or outpatient treatment throughout the study period. Emotion regulation was assessed on physiological, behavioral, and self-report levels. Results show significant down-regulation of amygdala activation. After training, patients indicated less aversive arousal and negative emotions, as well as lower hour-to-hour variability in these measures. BPD symptoms decreased in results from the Zanarini Scale for BPD. In the psychophysiology lab, patients improved emotion regulation skills after training, indicated by decreased startle response to negative pictures. However, repeated measures analysis of variance showed that this effect did not persist until the follow-up test. Taken together, this one-arm clinical study revealed significant improvement in emotion regulation and reductions in affective instability in daily life after fMRI-NF in BPD. The treatment affected emotion processing on several systems levels, including psychophysiology, behavior, and subjective experience. In order to control for psychosocial effects, future studies need to compare the treatment with a control group.
The examples depicted here may help to illustrate how state-of-the art neuroscientific methodology and psychotherapy work hand in hand to understand mechanisms of change in BPD treatment as well as develop innovative, yet experimental therapy approaches. This integrated approach not only broadens our view on this complex disorder but also gives hope to a better understanding and treatment of disturbed emotion regulation in and beyond BPD.
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