Challenging control over emotions in borderline personality disorder - a tDCS study
Introduction
Borderline personality disorder (BPD) is characterized by affective instability associated with intense feelings of dysphoric mood, anxiety and anger (American Psychiatric Association, 2013). This marked mood reactivity is considered to be due to emotion regulation difficulties (Carpenter and Trull, 2013; Crowell et al., 2009; Linehan, 1993; Sebastian et al., 2013), which in turn are considered to be a result of enhanced affective arousal and impaired cognitive control (CC) (Soloff et al., 2015). CC is necessary to maintain goal-directed behavior in the presence of competing, goal-irrelevant sources of information or irrelevant response tendencies. Besides inhibition of goal-irrelevant responses and resistance to proactive interference, CC comprises resistance to distractor interference (Friedman and Miyake, 2004; Miyake et al., 2000). Commonly used tasks to assess resistance to distractor interference are the Delayed Response Working Memory Task (DWM; e.g. Krause-Utz et al., 2014a) and the Stroop Colour Word Task (Stroop, 1935). In the DWM BPD patients are more distracted by emotional pictures compared to healthy control participants (HCs) (Krause-Utz et al., 2012, 2014b; Prehn et al., 2013). While studies using the classical Stroop Coulour Word Task revealed rather small to no interference increases in BPD as compared to HCs (Jacob et al., 2010; LeGris et al., 2012) BPD patients respond slower to emotional than to neutral words in the Emotional Stroop Task (Arntz et al., 2000, see Kaiser et al., 2016 for a review, Sieswerda et al., 2006). Moreover, stroop performance in BPD improves following successful psychotherapeutic treatment (Sieswerda and Arntz, 2007) as well as following a treatment with quetiapine (Van den Eynde et al., 2008). Hence, emotional interference may be a core component in the pathogenesis and maintenance of BPD (Kaiser et al., 2016).
Recent reviews and meta-analyses on functional neuroimaging findings in BPD highlight that the emotion dysregulation in BPD is a result of increased limbic and reduced prefrontal activity (Schulze et al., 2015; van Zutphen et al., 2015). Therefore, an impaired fronto-limbic inhibitory network is assumed to play a critical role in BPD symptomatology. Accordingly, patients with BPD show significantly higher activation in the amygdala and insula (Krause-Utz et al., 2012; Prehn et al., 2013) and significantly lower activation in the dlPFC (Wingenfeld et al., 2009) during emotional distraction compared to HCs. Moreover, it has been shown that reductions in self-harm with psychotherapeutic treatment are associated with increases in the activity of the dlPFC (Ruocco et al., 2016).
It can be assumed that an enhancement of dlPFC activity may improve control over emotional distraction in BPD. An activation increase of the dlPFC can be achieved by neuromodulation, as for example transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) (Nitsche and Paulus, 2000; 2001; O'Shea and Walsh, 2007). Beneficial effects of activity enhancing tDCS and rTMS on executive functions and particularly CC and working memory have already been demonstrated (Fregni et al., 2005; Lantrip et al., 2017; Metuki et al., 2012; Strobach and Antonenko, 2017), for example, anodal tDCS over the dlPFC enhances Stroop performance in healthy participants (Gbadeyan et al., 2016). Moreover, symptoms in several psychopathologic domains in BPD patients can be alleviated by repeated sessions of rTMS applied over the left dlPFC (Reyes-López et al., 2018).
However, only few studies thus far investigated whether it is possible to enhance CC in patients suffering from BPD with tDCS. Two recent studies investigated the effects of repeated bilateral tDCS on different constructs associated with cognitive control: In a randomized, double-blind, sham-controlled study Lisoni et al. (2020) examined whether 15 sessions of tDCS (2 mA, 20 min, anode right – cathode left dlPFC) can modulate self-reported symptoms, impulsivity, aggression, affective dysregulation, and substance craving as well as decision-making process (as assessed with the Iowa Gambling task). While affective dysregulation as well as depressive and anxious symptoms improved in both groups, impulsivity and aggression as well as craving were reduced only in the active-tDCS group. Further promising findings are reported by Molavi et al. (2020). In this randomized, sham-controlled study participants received 10 sessions of either active bilateral tDCS (2 mA, 20 min, anode left – cathode right dlPFC) or sham tDCS. The active stimulation group in this study showed a significant improvement not only in self-reported executive skills (e.g., working memory, emotional control, stress tolerance) but also in three domains of self-reported emotional processing (emotional intrusion, uncontrolled emotion and discordant emotion) and in the self-reported use of cognitive reappraisal as emotion regulation strategy. The authors conclude that repeated tDCS improves CC over negative emotions in BPD. Interestingly, the electrode placement was the exact opposite in these two studies. Nevertheless, both studies are promising with respect to the need of new therapeutic approaches for the treatment of BPD. However, they are based on self-reports and not on more basal and objective measures assessing resistance to emotional distractor interference which is in the focus of the current study. Furthermore, due to the bilateral stimulation that was applied in both studies it remains unclear whether the findings are due to the activation increase/decrease of the left/right dlPFC or vice versa or whether the combination of both caused the changes in the active groups.
To our knowledge, the only study that tried to manipulate CC in terms of resistance to emotional distractor interference (as assessed by a DWM) in patients suffering from BPD with tDCS and that used only one cephalic electrode is the one by Schulze et al. (2019). In the respective study one session of anodal stimulation of the right dlPFC (1 mA, 20 min maximum, cathode over left deltoid muscle) did not ameliorate CC of negative stimuli in BPD. So far, there is, however, no study that investigated whether anodal stimulation of the left instead of the right dlPFC can ameliorate resistance to emotional distractor interference in patients with BPD. Of note, the involvement of the dlPFC in CC is not restricted to one hemisphere (Gbadeyan et al., 2016). Accordingly, there are neuromodulation studies supporting an involvement of the left dlPFC (Frings et al., 2018) as well as the right dlPFC (Zmigrod et al., 2014) in CC. Expanding the focus to studies investigating not specifically interference control but rather broader concepts as executive functioning and working memory there is further evidence supporting the involvement of the left dlPFC (Baudewyn et al., 2019; Baumert et al., 2020; Dubreuil-Vall et al., 2019; Wolf et al., 2010). Thus, the goal of this study was to examine the effects of left-sided dlPFC stimulation on the resistance to distractor interference in BPD patients and HCs. Thereby we used a stimulation protocol that was successfully applied to manipulate resistance to emotional distractor interference before (Wolkenstein and Plewnia, 2013; Wolkenstein et al., 2014) and that abstains from using two cephalic electrodes. This enables us to trace all potential effects back to the anodal stimulation of the left dlPFC.
In a sham-controlled, double-blind, cross-over study, anodal tDCS was applied during the performance of a DWM with emotional distractors. Our hypotheses were: (I) patients with BPD show distractor interference when confronted with negative distractors (as compared to neutral and positive distractors), (II) patients with BPD show deficient CC as compared to HCs, and (III) it is possible to ameliorate CC via anodal tDCS over the left dlPFC. Since tDCS effects are baseline dependent (Habich et al., 2017; Ruf et al., 2017; Vanderhasselt et al., 2017), we tested if more pronounced CC impairment predicts a better response to anodal tDCS (IV).
Section snippets
Methods and materials
The study was approved by the local ethics committee and was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent. The trial was conducted at the Department of Psychology at the University of Tübingen, Germany.
Assessment of symptoms and neurocognitive functioning
We used the 21-item Hamilton Rating Scale for Depression (HAM-D; Hamilton, 1960) and the Beck Depression Inventory (BDI; Beck et al., 1961) to assess depressive symptoms. In order to control for the level of pre-morbid intelligence and neurocognitive functioning, we conducted the Multiple Choice Word Fluency Test (MWT-B; Lehrl, 2005), the Trail Making Test (TMT-A/B; Reitan, 1992) as well as the digit span subtest of the Wechsler Adult Intelligence Scale (DST; Wechsler, 2008).
Transcranial direct current stimulation
The anode was
Sample characteristics
Of the 20 BPD patients, four patients had one comorbid axis-I disorder, five had two comorbid axis-I disorders and eight had three or more comorbid axis-II disorders. Comorbid anxiety disorders were most prevalent in this sample, followed by affective disorders. Furthermore, eight patients had one comorbid axis-II disorder, five had two comorbid axis-II disorders and one patient had four comorbid axis-II disorders. Fig. 2 displays the distribution of comorbid mental illnesses. Detailed
Discussion
This study is the first to examine whether anodal tDCS applied to the left dlPFC can increase CC in patients with BPD and whether the extent of improvement induced by tDCS is associated with the extent of impairment that is present.
First of all, this study adds evidence that BPD patients’ ability to inhibit specifically distracting negative stimuli is actually impaired (Kaiser et al., 2016; Krause-Utz et al., 2012, 2014b; Winter et al., 2015). BPD patients showed significantly longer response
Credit author statement
Larissa Wolkenstein, Conceptualization, Methodology, Software, Formal analysis, Data curation, Supervision, Project administration, Writing – original draft. Felicitas Rombold-Bruehl, Investigation, Data curation, Writing-reviewing and editing. Tiffany Bingmann, Investigation, Data curation, Writing-reviewing and editing. Anja Sommer, Investigation, Data curation, Writing-reviewing and editing. Philipp Kanske, Software, Validation, Writing – review & editing. Christian Plewnia,
Declaration of competing interest
None.
Acknowledgements
We thank Julia Zwick for assistance with participant recruitment.
References (70)
- et al.
tDCS to the left DLPFC modulates cognitive and physiological correlates of executive function in a state-dependent manner
Brain Stimulation
(2019) - et al.
Transcranial direct current stimulation and cognitive-behavioral therapy: evidence of a synergistic effect in treatment-resistant depression
Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation
(2013) - et al.
Single session tDCS over the left DLPFC disrupts interference processing
Brain Cognit.
(2018) - et al.
Executive function and suicidal risk in women with borderline personality disorder
Psychiatr. Res.
(2012) - et al.
Change in core symptoms of borderline personality disorder by tDCS: a pilotstudy
Psychiatr. Res.
(2020) - et al.
Enhancing cognitive control components of insight problems solving by anodal tDCS of the left dorsolateral prefrontal cortex
Brain Stimulation
(2012) - et al.
The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: a latent variable analysis
Cognit. Psychol.
(2000) - et al.
Repeated transcranial direct current stimulation of dorsolateral-prefrontal cortex improves executive functions, cognitive reappraisal emotion regulation, and control over emotional processing in borderline personality disorder: a randomized, sham-controlled, parallel-group study
J. Affect. Disord.
(2020) - et al.
Serotonin affects transcranial direct current–induced neuroplasticity in humans
Biol. Psychiatr.
(2009) - et al.
Transcranial magnetic stimulation
Curr. Biol.
(2007)