Training of Neural Responding in BPD

Patients with BPD show increased emotional reactivity, slow return to baseline, and severe emotion dysregulation symptoms. On the neural level, BPD patients hyper-activate the amygdala and hypo-activate the prefrontal cortex in response to emotional stimuli. The prefrontal cortex and the amygdala are crucial nodes of the brain's emotion regulation network and thus it is assumed, that dysregulation within this network is key to BPD symptoms. Psychotherapy treatments specialized for BPD teach patients to monitor emotional arousal and to develop emotion regulation skills. However in the long run and despite of important therapeutic advances, the majority of BPD patients keep reporting significant impairments in functioning after psychotherapy.

To explore new types of therapy in BPD, the investigators have applied real-time fMRI neurofeedback, where patients are provided with their brain activation via a visual display. In previous work they found that BPD patients and healthy participants can down-regulate amygdala activation with real-time fMRI neurofeedback, and increase connectivity between the amygdala and the prefrontal cortex. Yet, we do not yet fully understand the potential effects of amygdala neurofeedback on emotion.

BPD patients (n=25) participate in a three-session fMRI neurofeedback training with 2-7 days between sessions (within 2 weeks). The effect of the training will be measured before and after training. Primarily, the investigators expect an improvement in emotion regulation, secondarily, reductions in BPD symptoms are expected.

Hypotheses:

With fMRI neurofeedback, BPD patients improve significantly in self-report and psychophysiological measures of emotion regulation with fMRI neurofeedback training. BPD patients show significantly reduced symptom severity in self-report measures with neurofeedback training.

• Neurofeedback (Behavioral), also known as real-time fMRI Neurofeedback: The Blood Oxygenation Level Dependent (BOLD) signal from the amygdala, recorded with functional magnetic resonance imaging, is utilized as a feedback signal to patients.
• MRI (Device), also known as Magnetic Resonance Imaging: Echo-planar Imaging of brain BOLD signal

Primary outcomes

• Change in self-assessment of emotion regulation capability after training [T0: max 7 days before first training session (depends on patient's availability), T1: max 7 days after third training session, T2 (Follow up): 6 weeks after T1]: Questionnaire: Difficulties in Emotion Regulation Scale (DERS)
• Change in emotion regulation after training, assessed by fear-potentiated startle response [T0: max 7 days before first training session (depends on patient's availability), T1: max 7 days after third training session, T2 (Follow up): 6 weeks after T1]: Fear-potentiated startle with instructed emotion regulation vs. natural responding to emotional pictures
• Change in heart rate variability after training [T0: max 7 days before first training session (depends on patient's availability), T1: max 7 days after third training session, T2 (Follow up): 6 weeks after T1]: Peripheral physiologic measure: resting heart rate variability (relation of high vs. low frequencies in spectrum)
• Change in amygdala response to masked faces after training [T0: max 7 days before first training session (depends on patient's availability), T1: max 7 days after third training session, T2 (Follow up): 6 weeks after T1]: Central nervous system measures: amygdala BOLD response to masked affective facial expressions
• Change in amygdala response in emotional working memory task after training [T0: max 7 days before first training session (depends on patient's availability), T1: max 7 days after third training session, T2 (Follow up): 6 weeks after T1]: Central nervous system measures: amygdala BOLD response in Sternberg-Working Memory test with emotional vs. neutral distractor images

Secondary outcomes

• Change in BPD symptom severity after training [T0: max 7 days before first training session (depends on patient's availability), T1: max 7 days after third training session, T2 (Follow up): 6 weeks after T1]: ZAN-BPD structured interview (acquisition in T0 and T2), BSL-23 self-report questionnaire (acquisition in T0, T1, T2; time lag matched to treatment group).

Sex: Female, ages: 18 Years to 45 Years

Inclusion Criteria:

* Current BPD (≥ 5 DSM-V criteria), female, informed consent for study participation

Exclusion Criteria:

* Psychotropic medication 2 weeks before start (SSRIs excluded)
* Lifetime diagnosis of schizophrenia or bipolar I
* Substance dependence in the preceding year
* Current substance use
* Pregnancy
* Epilepsy
* Antecedent cranial or brain injuries
* Organic brain diseases
* Severe medical or neurological condition
* BMI<16.5
* Metallic non-removable items in or on the body which are not MR compatible,
* Permanent make-up
* Claustrophobia, left-handedness

• Paret C, Kluetsch R, Zaehringer J, Ruf M, Demirakca T, Bohus M, Ende G, Schmahl C. Alterations of amygdala-prefrontal connectivity with real-time fMRI neurofeedback in BPD patients. Soc Cogn Affect Neurosci. 2016 Jun;11(6):952-60. doi: 10.1093/scan/nsw016. Epub 2016 Feb 1. PMID 26833918
• Paret C, Ruf M, Gerchen MF, Kluetsch R, Demirakca T, Jungkunz M, Bertsch K, Schmahl C, Ende G. fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity. Neuroimage. 2016 Jan 15;125:182-188. doi: 10.1016/j.neuroimage.2015.10.027. Epub 2015 Oct 16. PMID 26481674
• Paret C, Kluetsch R, Ruf M, Demirakca T, Hoesterey S, Ende G, Schmahl C. Down-regulation of amygdala activation with real-time fMRI neurofeedback in a healthy female sample. Front Behav Neurosci. 2014 Sep 18;8:299. doi: 10.3389/fnbeh.2014.00299. eCollection 2014. PMID 25278851

• Gabriele Ende, Professor, Principal investigator, Central Institute of Mental Health