Bipolar Disorder (BD) is a severe mood disorder affecting between 1% and 3% of the general population. It is characterized by the succession of depressive and manic episodes, with periods of stabilization during which patients may present "residual" depressive or anxious symptoms, which are characterized by sadness and emotional hyper-reactivity. Although subthreshold, these residual symptoms are very disabling for their daily lives and are associated with the risk of recurrence and poor global functioning. The effect of pharmacological and psychotherapeutic treatments is demonstrated in the management of acute episodes but remains insufficient on residual symptoms. Therefore, there are so far few therapeutic options to target the inter-episode residual symptoms in BD. One novel approach is the real-time functional magnetic resonance imaging (fMRI) neurofeedback (NFB), which has already been shown to be an efficient method for self-regulating brain function, behavior and treating depression.

Hypothesis/Objective :

This study aims at assessing the efficacy of 3-weeks neurofeedback training with real-time fMRI on the treatment of residual mood symptoms in patients with BD. The investigators will specifically target depressive symptoms by training the patients to regulate the emotional network hemodynamic response to emotional stimuli.

Method :

The investigators will include 64 stabilized patients with BD. The investigators will recruit them in three French expert centers for BD and will randomly assign them to the experimental group, receiving feedback from the emotional brain network hemodynamic activity, or to the control group, receiving the signal from control brain areas not involved in emotion processing. Both groups will be trained to regulate their brain activity while they are presented with negatively valenced emotional pictures, based on the neurofeedback shown immediately after the trial. They will continue their usual treatment (as prescribed) throughout the duration of the study. Clinical scales and cognitive tests will enable us to evaluate the symptomatic, emotional, and cognitive changes after NFB training. The investigators will also measure resting-state functional connectivity and brain morphology before and after NFB to assess brain plasticity and to explore the neural mechanisms associated with successful regulation.

Inclusion Criteria:

• Patients diagnosed with bipolar disorder I or II (DSM-5 criteria);
• Aged between ≥ 18 and ≤ 65;
• Absence of major mood episode for at least 3 months before inclusion (MADRS scores < 12; YMRS score < 10);
• Presence of residual depressive symptoms, as assessed by the MADRS (score > 5);
• Stabilized dose of mood stabilizer medication for at least 3 months before inclusion.
• Written consent
• Affiliation to a social security system
• Effective contraception for women of childbearing age

Exclusion Criteria:

• Severe physical disorders that may be life-threatening;
• Major psychiatric (Axis 1) comorbidities except for anxiety disorders;
• Any current substance abuse except for tobacco or cannabis. Substance abuse will be defined by the DSM V criteria;
• Exclusion criteria applicable to MRI Panic disorder, claustrophobia, epilepsy Pace maker or neuronal stimulator, intraocular or intracerebral metallic foreign body, cochlear implant, cardiac valve or metallic surgical arterial material, non removable removable magnetizable metallic material
• Somatic disorder that may affect cognitive abilities and brain structures (e.g., HIV infection, MS, lupus, Parkinson's disease, epilepsy, dementia...);
• Ongoing non-pharmacological treatment: structured psychotherapeutic interventions (Cognitive Behavioral Therapy - CBT, Interpersonal and Social Rhythm Therapy - IPSRT) as well as brain stimulation techniques (Electroconvulsive Therapy - ECT, Transcranial Magnetic Stimulation - TMS, Deep Brain Stimulation - DBS);
• Subject included in clinical and / or therapeutic experimentation in progress.
• Patients under legal protection
• Prisoners
• Pregnancy
• Breastfeeding

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