rumination
Research Papers
Application of functional connectivity neurofeedback in patients with treatment-resistant depression: A preliminary report
Functional connectivity neurofeedback (FCNef) is a technique that modulates synchronous neural activity through training and is being investigated as a potential novel treatment for patients suffering from treatment-resistant depression (TRD). An FCNef protocol, based on the analysis of resting-state functional imaging data from a large cohort of depressed individuals, has been proposed to promote negative functional connectivity between the dorsolateral prefrontal cortex and the posterior cingulate cortex (DLPFC-PCC FC). This study aimed to assess the therapeutic efficacy and practicality of the protocol in a small sample of TRD patients. Of the six patients recruited, five completed the FCNef sessions. Depression and rumination scores significantly improved post-treatment, however, there were no significant changes in DLPFC-PCC FC. The study demonstrated efficacy of FCNef in ameliorating depressive symptoms, yet, it also indicated that the training itself may be burdensome for depressed patients, as evidenced by participants reporting fatigue (one of whom dropped out). Thus, a more efficient and less burdensome protocol is needed for future investigations and applications.
View Full Paper →Real-Time fMRI Functional Connectivity Neurofeedback Reducing Repetitive Negative Thinking in Depression: A Double-Blind, Randomized, Sham-Controlled Proof-of-Concept Trial
INTRODUCTION: Repetitive negative thinking (RNT) is a cognitive process focusing on self-relevant and negative experiences, leading to a poor prognosis of major depressive disorder (MDD). We previously identified that connectivity between the precuneus/posterior cingulate cortex (PCC) and right temporoparietal junction (rTPJ) was positively correlated with levels of RNT. OBJECTIVE: In this double-blind, randomized, sham-controlled, proof-of-concept trial, we employed real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) to delineate the neural processes that may be causally linked to RNT and could potentially become treatment targets for MDD. METHODS: MDD-affected individuals were assigned to either active (n = 20) or sham feedback group (n = 19). RNT was measured by the Ruminative Response Scale-brooding subscale (RRS-B) before and 1 week after the intervention. RESULTS: Individuals in the active but not in the sham group showed a significant reduction in the RRS-B; however, a greater reduction in the PCC-rTPJ connectivity was unrelated to a greater reduction in the RRS-B. Exploratory analyses revealed that a greater reduction in the retrosplenial cortex (RSC)-rTPJ connectivity yielded a more pronounced reduction in the RRS-B in the active but not in the sham group. CONCLUSIONS: RtfMRI-nf was effective in reducing RNT. Considering the underlying mechanism of rtfMIR-nf, the RSC and rTPJ could be part of a network (i.e., default mode network) that might collectively affect the intensity of RNT. Understanding the relationship between the functional organization of targeted neural changes and clinical metrics, such as RNT, has the potential to guide the development of mechanism-based treatment of MDD.
View Full Paper →Connectome-wide search for functional connectivity locus associated with pathological rumination as a target for real-time fMRI neurofeedback intervention
Real-time fMRI neurofeedback (rtfMRI-nf) enables noninvasive targeted intervention in brain activation with high spatial specificity. To achieve this promise of rtfMRI-nf, we introduced and demonstrated a data-driven framework to design a rtfMRI-nf intervention through the discovery of precise target location associated with clinical symptoms and neurofeedback signal optimization. Specifically, we identified the functional connectivity locus associated with rumination symptoms, utilizing a connectome-wide search in resting-state fMRI data from a large cohort of mood and anxiety disorder individuals (N = 223) and healthy controls (N = 45). Then, we performed a rtfMRI simulation analysis to optimize the online functional connectivity neurofeedback signal for the identified functional connectivity. The connectome-wide search was performed in the medial prefrontal cortex and the posterior cingulate cortex/precuneus brain regions to identify the precise location of the functional connectivity associated with rumination severity as measured by the ruminative response style (RRS) scale. The analysis found that the functional connectivity between the loci in the precuneus (-6, −54, 48 mm in MNI) and the right temporo-parietal junction (RTPJ; 49, −49, 23 mm) was positively correlated with RRS scores (depressive, p < 0.001; brooding, p < 0.001; reflective, p = 0.002) in the mood and anxiety disorder group. We then performed a rtfMRI processing simulation to optimize the online computation of the precuneus-RTPJ connectivity. We determined that the two-point method without a control region was appropriate as a functional connectivity neurofeedback signal with less dependence on signal history and its accommodation of head motion. The present study offers a discovery framework for the precise location of functional connectivity targets for rtfMRI-nf intervention, which could help directly translate neuroimaging findings into clinical rtfMRI-nf interventions.
View Full Paper →Autobiographical Memory Disturbances in Depression: A Novel Therapeutic Target?
Major depressive disorder (MDD) is characterized by a dysfunctional processing of autobiographical memories. We review the following core domains of deficit: systematic biases favoring materials of negative emotional valence; diminished access and response to positive memories; a recollection of overgeneral memories in detriment of specific autobiographical memories; and the role of ruminative processes and avoidance when dealing with autobiographical memories. Furthermore, we review evidence from functional neuroimaging studies of neural circuits activated by the recollection of autobiographical memories in both healthy and depressive individuals. Disruptions in autobiographical memories predispose and portend onset and maintenance of depression. Thus, we discuss emerging therapeutics that target memory difficulties in those with depression. We review strategies for this clinical domain, including memory specificity training, method-of-loci, memory rescripting, and real-time fMRI neurofeedback training of amygdala activity in depression. We propose that the manipulation of the reconsolidation of autobiographical memories in depression might represent a novel yet largely unexplored, domain-specific, therapeutic opportunity for depression treatment.
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