Depressive symptoms reduce when dorsolateral prefrontal cortex-precuneus connectivity normalizes after functional connectivity neurofeedback

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).

Frontostriatal circuitry as a target for fMRI-based neurofeedback interventions: A systematic review

“…The improvement of clinical and behavioral parameters was reported in almost all studies (Zhang et al, 2013 ; Karch et al, 2015 ; Sherwood et al, 2016 ; Kohl et al, 2019 ; Morgenroth et al, 2020 ; Takamura et al, 2020 ; Taylor et al, 2022 ). As for the long-term effects, considerable responsiveness and clinical improvement were observed 4 weeks (Kohl et al, 2019 ) and 3 months (Zilverstand et al, 2015 ; Karch et al, 2021 ) after NF training, which suggest a promising potential for NF in treatment of clinical conditions.…”

“…As shown in Figure 3 , various clinical populations have been addressed in the reviewed NF studies. According to our review, patients with depression were successful in modulating self-esteem, brooding rumination, and depressive symptoms in general (Zahn et al, 2019 ; Takamura et al, 2020 ; Jaeckle et al, 2021 ; Keller et al, 2021 ; Taylor et al, 2022 ). Additionally, studies of patients suffering from anxiety reported clinical improvements in self-report of the anxiety level or control over contamination anxiety (Scheinost et al, 2013 ; Zilverstand et al, 2015 ; Zhao et al, 2019 ; Morgenroth et al, 2020 ).…”

Targeting default mode network connectivity with mindfulness-based fMRI neurofeedback: A pilot study among adolescents with affective disorder history

“…This is also one reason that we believe circuitry-based real-time fMRI neurofeedback may outperform focally targeted methods such as TMS and ultrasound. Indeed, another recent real-time fMRI study targeting dorsolateral prefrontal cortex-precuneus circuitry led to reduced depressive symptoms in patients (77).…”

Low intensity repetitive transcranial magnetic stimulation modulates brain-wide functional connectivity to promote anti-correlated activity

“…The ability to modulate anticorrelated activity has numerous clinical implications, particularly through the lens of parvalbumin interneuron modulation. The magnitude of anticorrelated functional connectivity is dampened in several conditions, including depression [53,54], Parkinson's disease [55], stroke [56], and anxiety [57]. These same conditions have also been demonstrated to have altered parvalbumin interneuron activity [58][59][60][61].…”