Human Brain
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A neurofeedback study published in the journal Neuroimage: Clinical has found that patients in recovery from depressive disorder symptoms are able to strengthen some of their brain connections while evoking guilt-related memories, which leads to increased self-esteem. Research has shown that certain brain regions - which commonly have poor connectivity in people with depression - could be strengthened in a single neurofeedback session, a result that was proven by comparing functional magnetic resonance imaging. The study was conducted by the D'Or Institute for Research and Teaching (IDOR), the Federal University of Rio de Janeiro (UFRJ) and the Federal University of ABC, in collaboration with King's College in London.

Major Depressive Disorder (MDD), also known as depression, is a disorder caused by a set of social, psychological and biological factors. Its symptoms are characterized by the continuous loss of interest or pleasure in daily life and the prevalence of negative feelings such as deep sadness, guilt and low self-esteem. According to data from the World Health Organization (WHO), last year depression affected more than 300 million people worldwide. Considering the seriousness of the problem in world public health, the medical and scientific communities are increasingly seeking to understand depressive disorder, aiming at the development of new treatments and the improvement of patients' quality of life.

The researchers studied MDD through functional magnetic resonance imaging - a noninvasive technique that allows the analysis of brain structure and function. The research developed from the earlier finding that people with depression who still feel guilty or indignant after recovery from symptoms have less connectivity between two specific brain areas: the right anterior superior temporal lobe and the subgenual cortex. By connectivity, the study refers to the exchange of information between these two structures, which are directly linked to the interpretation of social interactions.

Based on this "neural signature" of patients, the research tested the possibility of strengthening these connections through neurofeedback, a program that allows patients to observe and modify their brain activities in real time. Although at a preliminary stage, the result was striking: in just one training session, participants demonstrated greater connection between the mentioned areas, and reported an increase in self-esteem after interaction with neurofeedback.

How was the study done?

The study's first author and researcher at King's College, Dr. Roland Zahn, explains why patient selection was limited to those who had already recovered from depressive symptoms. "The over-guilt neural signature was found in depressive patients whose symptoms had already been controlled, suggesting that this feature may precede the symptoms of depression, making people more susceptible to the disease. Other than that, for safety reasons, we wanted to ensure that cases of depression would not get worse after the study, and patients already treated for MDD are much less likely to worsen their clinical condition," he says.

To conduct the research, the 28 participants with controlled depressive condition were divided into two groups. The first served as a control, being exposed to neurofeedback exercise with an instruction to maintain the intensity of their brain connections, while the other group was instructed to try to stimulate these connections during training. The procedure was performed through visual feedback, which was displayed on a screen that pointed out if people were performing the brain exercise correctly. "Participants had to imagine a specific memory of their past that made them feel guilty or outrage related to other people. On the screen, they had to change the way they thought and felt about it, so that the colored dial that reflected their brain connections also changed.

Although neurofeedback exposure time was the same in both groups, participants who were instructed to increase the activity of their brain connections showed in magnetic resonance imaging a structural strengthening of the areas exercised in their brains. At the same time, an increase in their self-esteem patterns was observed that was not found in the group that kept their connections at the same initial level.

For the study, it was also necessary to develop specific neurofeedback software, the Functional Real Time Interactive Endogenous Neuromodulation and Decoding, or simply FRIEND. Dr. Jorge Moll, neuroscientist at the D'Or Institute for Research and Teaching (IDOR) and corresponding author of the study, led the program's design group. "FRIEND is a tool developed for any neurofeedback study using functional magnetic resonance imaging. The current implementation has highlighted aspects of the pathophysiology of MDD, but several other applications, emotions or target populations may be addressed in future studies," he says.

At IDOR, Dr. Moll has participated in several studies involving the induction of brain changes through neurofeedback training. For him, functional magnetic resonance imaging is one of the most powerful tools for noninvasively analyzing brain functions, but clinical applications related to the use of neurofeedback are still at an early stage. "There is a way ahead; We still need to establish the pathophysiology, side effects and therapies, ideal target population and also the cost-effectiveness of the process. Although resonance time is expensive, it is not much more expensive than other treatments, and this can be an option, especially for those who do not respond well to conventional therapies. Still, a lot of research needs to be done, but the clinical potential of these applications is already beginning."

To encourage further research in the field, Dr. Moll reports that the neurofeedback software, FRIEND, is available online for free for use by other interested researchers. Its use is not limited to the current scope of study and can be used in several other analyzes through functional magnetic resonance imaging. The authors report that this research is the first step towards the creation of new treatments related to recurrent cases of depression, but it is not intended to prove the effectiveness of their procedures, a topic that should be investigated in future in more comprehensive studies.

Reference: Zahn, R., Weingartner, J. H., Basilio, R., Bado, P., Mattos, P., Sato, J. R., ... Moll, J. (2019). Blame-rebalance fMRI neurofeedback in major depressive disorder: A randomised proof-of-concept trial. NeuroImage: Clinical, 24, 101992. https://doi.org/10.1016/j.nicl.2019.101992

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