Real-Time fMRI Neurofeedback: Methods and Application to Chronic Tinnitus

In the last twenty years, advances in real-time functional magnetic resonance imaging (rt-fMRI) have offered exciting new tools to study the human brain. One of them, termed rt-fMRI neurofeedback (NF), has turned the MRI scanner environment into an interactive brain-computer interface (BCI), allowing to position brain activity as the independent variable in the relationship ranging from brain function to observed behavior. This paradigm immediately gained considerable interest in the fMRI research community, as the idea of grasping volitional control over a precisely targeted brain area suddenly became feasible. Since then, a multitude of studies have used this technique in drastic efforts to normalize pathological brain activity (or connectivity) in a wide range of neurological disorders, ultimately seeking clinical and behavioral improvement.Among these, chronic tinnitus, commonly referred to as "ringing in the ears", has been considered a promising condition for NF interventions. Tinnitus has been linked to wide disruptions in brain functions involving attention, cognition, emotional distress, and auditory and sensory processing, among others. It has also been associated with hyperactivity in the primary auditory cortex after acoustic trauma. Currently, no cure exists for a complete relief of symptoms. A previous proof-of-concept study suggested that learned down-regulation of the auditory cortex slightly improved short-term subjective reports of tinnitus severity in a small group of participants. Here, we present the longest NF clinical trial to date in chronic tinnitus (NeuroTin), in which 60 patients are enrolled across 3 different interventions: electroencephalography NF (EEG NF), fMRI NF, and cognitive behavioral therapy (CBT), nowadays considered as standard care for tinnitus. The aim is to assess whether any of the two NF approaches can outperform standard CBT training for alleviation of tinnitus distress. In this dissertation, we present clinical outcomes and neuroimaging findings for the fMRI NF group.Twenty-one participants learned to down-regulate the activity of their primary auditory cortex over 15 weeks of fMRI NF training. While only a few participants managed to learn down-regulation, we found a significant clinical relief in tinnitus distress lasting up to one year in the fMRI NF group, as opposed to the CBT group. We demonstrate the superiority of fMRI NF training over standard care CBT and show, for the first time, resulting long-term benefits in quality of life. Furthermore, we bring additional evidence regarding the implication of a highly modulated small brain region in tinnitus, bilaterally located in the parietal operculum (OP3). We describe its effective connectivity with regions pertaining to the auditory pathway and discuss its implication in a possibly altered multisensory integration mechanism in tinnitus. Then, using a co-activation patterns analysis, we unveil 4 functional brain networks co-occurring with the deactivation of OP3. We identify them as (1) an auditory-visual network comprising an important node of the auditory pathway (the medial geniculate body), (2) a part of the NF control network, (3) the default mode network, and (4) a somatosensory network likely linked to other sensory integration modalities. Lastly, we characterize the average dynamics of these 4 functional networks and discuss new avenues for fMRI NF interventions and treatments in chronic tinnitus.