Abstract
Depressive disorders contribute heavily to global disease burden; This is possibly because patients are often treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. A novel treatment that can directly influence the neural circuit relevant to an individual patient’s subset of symptoms might more precisely and thus effectively aid in the alleviation of their specific symptoms. We tested this hypothesis in a proof-of-concept study using fMRI functional connectivity neurofeedback. We targeted connectivity between the left dorsolateral prefrontal cortex/middle frontal gyrus and the left precuneus/posterior cingulate cortex, because this connection has been well-established as relating to a specific subset of depressive symptoms. Specifically, this connectivity has been shown in a data-driven manner to be less anticorrelated in patients with melancholic depression than in healthy controls. Furthermore, a posterior cingulate dominant state—which results in a loss of this anticorrelation—is expected to specifically relate to an increase in rumination symptoms such as brooding. In line with predictions, we found that, with neurofeedback training, the more a participant normalized this connectivity (restored the anticorrelation), the more related (depressive and brooding symptoms), but not unrelated (trait anxiety), symptoms were reduced. Because these results look promising, this paradigm next needs to be examined with a greater sample size and with better controls. Nonetheless, here we provide preliminary evidence for a correlation between the normalization of a neural network and a reduction in related symptoms. Showing their reproducibility, these results were found in two experiments that took place several years apart by different experimenters. Indicative of its potential clinical utility, effects of this treatment remained one-two months later.Clinical trial registration: Both experiments reported here were registered clinical trials (UMIN000015249, jRCTs052180169).
Highlights
Depressive disorders contribute heavily to global disease burden; This is possibly because patients are often treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms
If a paradigm targeting one functional connectivity (FC) related to one particular subset of symptoms can efficiently and safely cause these symptoms to decrease, in the future it would be worthwhile establishing paradigms for other subsets of symptoms as well. If this is achieved one day functional connectivity neurofeedback (FCNef) might truly be of use for precision medicine, with individual patients having the specific FCs related to their own specific symptoms normalized
Because we found overall results that look promising for our FCNef paradigm, this technique of using a data-driven biomarker to determine the general region and using a functional localizer to determine participant-specific regions might be useful for determining target regions of interest (ROIs) for other neurofeedback paradigms in the future
Summary
Depressive disorders contribute heavily to global disease burden; This is possibly because patients are often treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. For each individual patient—the specific neural mechanism(s) related to the subset of symptoms that they present with could be directly targeted with the goal of “normalizing” this (making it more like that of healthy controls) This could be achieved via neurofeedback, where participants are trained to modulate their own neural activity in order to influence their behavior and patterns of thinking. If this is achieved one day FCNef might truly be of use for precision medicine, with individual patients having the specific FCs related to their own specific symptoms normalized In this initial study, out of the different subsets of depressive symptoms, we decided to focus on rumination. It occurs when people repeatedly think about their feelings of sadness and the potential causes, without actively trying to resolve or fix the underlying p roblem[40]
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