Summer is coming to an end, but imagine if your fun summer vacation experiences could later help you in addressing neuropsychological conditions. That’s a concept that inspires and motivates David Mehler, an MD/PhD student and cognitive neuroscientist at Cardiff University.
“Imagine seeing a thermometer gauge that shows how strongly a specific part of your brain activated while you think about your last fantastic holiday. Using only your imagination, you could learn to control the filling of the thermometer,” Mehler says. What he is describing is a technique called neurofeedback, in which people learn to identify thoughts that work best for them to control feedback from targeted brain areas while they are in an fMRI scanner.
In a new study, Mehler and colleagues applied this technique for depression patients, to see if they could train people to influence activity in the brain regions involved in both emotional and visual processing. Their findings, published in Neuropsychopharmacology this summer, suggest that if moderately to severely depressed patients engage in successful neurofeedback training, focused on either emotional or visual processing, they can reduce their depression.
CNS spoke with Mehler about this study, past work in the field, and the general promise of clinical applications for fMRI neurofeedback training.
CNS: How did you become personally interested in this research area? Why is it important to you?
Mehler: I was always fascinated by new technologies and how these can be used to improve the treatment of neurological or psychiatric conditions. During my medical studies, I became particularly interested in noninvasive rehabilitation and worked with a robotic arm to study motor-learning principles that could one day help improving the recovery of patients. This work got me more interested in neuroimaging that can help understanding the neural mechanisms of learning. In clinical fMRI neurofeedback, neuroimaging becomes a potentially therapeutic tool itself. And so, it seemed the perfect topic for my Ph.D. with Prof. David Linden in Cardiff. I was immediately hooked when I read about its potential to help restoring motor function and support treatment of psychiatric conditions like depression. My interest in depression grew when I learned more about its impact on mental health, the limitations of current treatment that may not be sufficient for up to one-third of patients, and the fascinating, neuroscience-inspired treatments that are currently being explored by the field.
CNS: What have we known previously about fMRI neurofeedback and depression?
Mehler: Previous work by our group and others found that depressed patients can activate certain brain areas using neurofeedback, and that they showed improvements in mood. These findings encouraged a recent larger, randomized controlled trial (RCT) that was conducted by an American group and published in April 2017. In this trial, patients were instructed to remember positive events in their life and received feedback from the amygdala, a structure that is involved in processing emotions. For the clinical outcome, data showed that the depression severity of patients in the experimental group improved substantially, while patients in the control group did not. Importantly, the trial was double-blinded, so that neither the patients nor the researchers who assessed the patients knew whether they were in the experimental, or in the control group.
One interesting question that arises from these results is: What drives these clinical effects? It could be that the choice of the target region is critical, or that the experience of successful self-regulation is key. In other words, would successful fMRI neurofeedback training from a region that is not involved in emotion processing yield comparable clinical effects as reported for the experimental group of this trial?
CNS: How did you address this question?
Mehler: Our goal was to see if neurofeedback training could be successful for depression patients even if not targeted to emotional processing. We assigned patients to one of two groups that either received fMRI neurofeedback training from brain areas involved in emotion processing (NFE-group) or from areas involved in processing visual scenes (NFS-group). To ensure both groups were able to learn to self-regulate their brain activity, they were instructed to use mental strategies that allow activating their target regions: Patients in the NFE-group were asked to imagine visual images of situations they perceived as positive, and patients in the NFS-group were asked to imagine relaxing visual scenes. A clinician who was blinded to the group assignment of patients assessed the depression severity of patients before and after the treatment, using a standardized questionnaire for depression. We expected to find that the NFE-group would show larger clinical improvements than the NFS-group.
CNS: Was there anything novel about your approach?
Mehler: One novelty was that we chose to compare two groups with instructions that would allow them to learn to self-regulate the activity, and hence complete successful fMRI neurofeedback training.
Also, patients in our study completed more training sessions (five) over a longer period (12 weeks) than in previous studies. Most patients also completed a follow-up 6 weeks after the last fMRI neurofeedback training session. This design allowed us to test whether clinical effects lasted also after the trial.
Lastly, patients who took part in our study were receiving medication and many had been diagnosed with depression for many years. Our study could therefore test how the training worked for patients who were mostly chronically depressed.
CNS: What were your most excited findings?
Mehler: We found that both groups showed remarkable clinical improvements, but not the expected group difference. Rather both groups showed reductions of about 40%, which was similar to those reported for the experimental group in the above-mentioned earlier trial. Moreover, about 40% of patients were considered to no longer be depressed by the end of the study. Data from the follow-up visit showed that these improvements were largely maintained until about six weeks later.
It is possible that successful self-regulation training of brain areas can help promoting a mindset that allows patients feel more empowered in coping with challenges.
CNS: How do you explain these results – could it be a placebo?
Mehler: Our trial included a psychological scale that allows measuring people’s perception of being in control and able to cope with challenges in life, a concept called self-efficacy. We found that patients’ self-efficacy scores improved after training, and that this improvement was related to their clinical improvement. It is possible that successful self-regulation training of brain areas can help promoting a mindset that allows patients feel more empowered in coping with challenges. These results remain limited because of the relatively small size of our sample and because the relationship could also be explained by other factors that we did not measure. Yet, we believe that it is worth exploring this idea in future work.
Because both groups received fMRI neurofeedback training, we cannot rule out unspecific effects like a placebo. We also know from the literature that the placebo definitely plays a large role in the treatment of depression in general; for instance, up to 80% of the effect documented for medication treatment group is also present in the placebo groups. As treatment and placebo effects are fairly well documented in depression, we checked with the literature how much clinical improvement one would expect if patients who took part in our trial had received standard treatment instead. Data suggested that patients’ depression scores had improved at least as much as if they had received either new, or different medication instead. These findings are encouraging, but they remain limited by the relatively small sample of our trial as we discuss in the paper, together with a few other explanations why patients in the NFS-group improved to a similar extent as patients in the NFE-group.
CNS: What’s next for this line of work?
Mehler: The currently available evidence for fMRI neurofeedback is encouraging, but replication studies with larger samples and additional control conditions, such as for placebo effects, are needed. Also, longer follow-up periods, up to one or two years, would be ideal; for many patients, depression occurs in episodes and it will be important to know how many patients remain depression free after a longer period. Our understanding of the neural and psychological mechanisms underlying the therapeutic effects that have been reported for fMRI neurofeedback training are still very limited. These need to be further explored and tested to allow explaining how fMRI neurofeedback works and to refine training protocols. We are just at the beginning, but with consortia such as BRAINTRAIN researchers have the resources to address these questions and we will hopefully learn faster in the years to come.
-Lisa M.P. Munoz
You can follow Mehler on Twitter.
