Reduction of brooding and more general depressive symptoms after fMRI neurofeedback targeting a melancholic functional-connectivity biomarker

Abstract

Depressive disorders contribute heavily to global disease burden; This is possibly because patients are usually treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. On the contrary, treatment that directly influences 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, using fMRI functional connectivity neurofeedback to target a neural biomarker that objectively relates to a specific subset (melancholic) of depressive symptoms and that is generalizable across independent cohorts of patients. The targeted biomarker was the functional connectivity between the left dorsolateral prefrontal cortex and left precuneus, which has been shown in a data-driven manner to be less anticorrelated in patients with melancholic depression than in healthy controls. We found that the more a participant normalized this biomarker, the more related (brooding and more general depressive), but not unrelated (trait anxiety), symptoms were reduced. Thus, one-to-one correspondence between a normalized neural network and decreased depressive symptoms was demonstrated. These results were found in two experiments that took place several years apart by different experimenters, indicating their reproducibility. Indicative of their potential clinical utility, effects remained one-two months later.

Common Brain Networks Between Major Depressive-Disorder Diagnosis and Symptoms of Depression That Are Validated for Independent Cohorts

“…The 16 FCs discovered in this study are promising candidates as theranostic biomarkers for depression symptoms. Future work should investigate whether modulation of FCs could be an effective treatment for depression symptoms by using an intervention method with regard to FCs, such as functional connectivity neurofeedback training (53)(54)(55)(56)(57)(58)(59).…”

EEG-based neurofeedback with network components extraction: a data-driven approach by multilayer ICA extension and simultaneous EEG-fMRI measurements

“…Brooding factor is specifically thought to be associated with depression and mistake concern (Treynor et al, 2003;Hasegawa 2013), which is considered a specific trait of melancholic depression. The EEG network feature estimated from SPLICE was not directly calculated from the target FC like FCNef (Yamada et al, 2017;Taylor et al, 2021). However, we confirmed the statistical equivalence between EEG network features and fMRI data in the selection process of SPLICE module.…”

“…It is The copyright holder for this preprint this version posted June 21, 2021. ; https://doi.org/10.1101/2021.06.20.449196 doi: bioRxiv preprint then found large effect size on RRS (total, brooding and reflection) compared the NF group with the sham group, but not on BDI. The FCNef protocol of Taylor et al (2021) for four days' training with fMRI showed significant reduction of BDI and brooding in RRS.…”

“…CC-BY-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is The copyright holder for this preprint this version posted June 21, 2021. ; https://doi.org/10.1101/2021.06.20.449196 doi: bioRxiv preprint 7 neurofeedback paradigm for three days targeting regions (DLPFC/mFC or precuneus/PCC) in a single-blind design while referring a FCNef paradigm (Yamada et al, 2017;Taylor et al, 2021). For training of the SPLICE model, we conducted two-days EEG-fMRI experiments for each participant to simultaneously acquire EEG-fMRI data at resting and during N-back task.…”

“…To consider a practical application, there is a problem of scheduling and long-term treatment to achieve this NF training. For example, a case ofTaylor et al (2021) is four-days training, Tsuchiyagaito et al (2021) and Zotev et al (2020) are just one-day training. In making a NF protocol, balance of training intensity and efficacy is a crucial issue, but critical point in the realistic treatment, therefore, we have to carefully design the NF experiment.…”