Training of Neural Responding in BPD

Study Overview
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Brief Summary
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Emotion-related brain activation is made visible for patients via neurofeedback with the aim to improve discriminability of emotional arousal and emotion regulation. With functional magnetic resonance imaging (fMRI), information of current brain activation is imaged and fed back to the patient via a visual display. Patients with borderline personality disorder (BPD) usually hyper-activate brain regions associated with emotion. In this study, BPD patients will be provided with neurofeedback from the amygdala, which is crucial for the processing of emotions. The aim of the study is to observe, whether amygdala-neurofeedback would help BPD patients to improve emotion regulation. Compared to a control condition, improved brain self-regulation and emotion regulation is expected with three neurofeedback training sessions.

Detailed Description
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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.

Official Title
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Training of Neural Responding With fMRI Neurofeedback in Borderline Personality Disorder

Conditions
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Borderline Personality Disorder

Intervention / Treatment
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* Behavioral: Neurofeedback
* Device: MRI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>25 patients with BPD. In a diagnostic session, diagnostics of psychiatric disorders are conducted. For BPD diagnosis, the International Personality Disorder Examination (IPDE) is used and symptom severity is assessed with the Borderline Symptom List. The Treatment group will receive fMRI amygdala neurofeedback training (3 sessions within 2 weeks). Patients in regular psychotherapeutic treatment (treatment-as-usual) will not be excluded. | Behavioral: Neurofeedback<br>* The Blood Oxygenation Level Dependent (BOLD) signal from the amygdala, recorded with functional magnetic resonance imaging, is utilized as a feedback signal to patients.<br>* Other names: real-time fMRI Neurofeedback;Device: MRI<br>* Echo-planar Imaging of brain BOLD signal<br>* Other names: Magnetic Resonance Imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in self-assessment of emotion regulation capability after training | Questionnaire: Difficulties in Emotion Regulation Scale (DERS) | 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 | 
| Change in emotion regulation after training, assessed by fear-potentiated startle response | Fear-potentiated startle with instructed emotion regulation vs. natural responding to emotional pictures | 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 | 
| Change in heart rate variability after training | Peripheral physiologic measure: resting heart rate variability (relation of high vs. low frequencies in spectrum) | 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 | 
| Change in amygdala response to masked faces after training | Central nervous system measures: amygdala BOLD response to masked affective facial expressions | 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 | 
| Change in amygdala response in emotional working memory task after training | Central nervous system measures: amygdala BOLD response in Sternberg-Working Memory test with emotional vs. neutral distractor images | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BPD symptom severity after training | 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). | 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 |