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BACKGROUND: Mindfulness training has been shown to promote positive mental health outcomes and related changes in neural networks such as the default mode network, which has a central node in the posterior cingulate cortex (PCC). Previous work from our group reported on the impact of a novel, neurofeedback augmented mindfulness training (NAMT) task on regulation of PCC hemodynamic activity in typically developing adolescents. The present pilot study aimed to expand on this finding by examining the pre-post changes of the NAMT task on resting-state functional connectivity of the PCC. METHODS: Thirty-one typically developing adolescents (14.77 ± 1.23 years; 45% female) underwent a resting-state functional magnetic resonance imaging scan both before and after completing the NAMT task. A linear mixed effects model was used to assess for changes in functional connectivity of the PCC across the two resting-state runs. RESULTS: Data did not support the hypothesized decrease in connectivity between the PCC seed and other DMN regions from pre- to post-NAMT task. However, we observed a significant increase in functional connectivity between the PCC and a cluster encompassing the left hippocampus and amygdala following completion of the NAMT task (run 1 Fishers Z = 0.16; run 2 Fishers Z = 0.26). CONCLUSION: Although preliminary, this finding suggests NAMT has the potential to strengthen connectivity between default mode and salience regions. We speculate that such changed connectivity may facilitate enhanced self-referential and emotional processing in adolescents. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT04053582.

BackgroundMindfulness training has been shown to promote positive mental health outcomes and related changes in neural networks such as the default mode network, which has a central node in the posterior cingulate cortex (PCC). Previous work from our group reported on the impact of a novel, neurofeedback augmented mindfulness training (NAMT) task on regulation of PCC hemodynamic activity in typically developing adolescents. The present pilot study aimed to expand on this finding by examining the pre-post changes of the NAMT task on resting-state functional connectivity of the PCC.MethodsThirty-one typically developing adolescents (14.77 ± 1.23 years; 45% female) underwent a resting-state functional magnetic resonance imaging scan both before and after completing the NAMT task. A linear mixed effects model was used to assess for changes in functional connectivity of the PCC across the two resting-state runs.ResultsData did not support the hypothesized decrease in connectivity between the PCC seed and other DMN regions from pre- to post-NAMT task. However, we observed a significant increase in functional connectivity between the PCC and a cluster encompassing the left hippocampus and amygdala following completion of the NAMT task (run 1 Fisher’s Z = 0.16; run 2 Fisher’s Z = 0.26).ConclusionAlthough preliminary, this finding suggests NAMT has the potential to strengthen connectivity between default mode and salience regions. We speculate that such changed connectivity may facilitate enhanced self-referential and emotional processing in adolescents.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04053582.

Mindfulness training (MT) promotes the development of ones ability to observe and attend to internal and external experiences with objectivity and nonjudgment with evidence to improve psychological well-being. Real-time functional MRI neurofeedback (rtfMRI-nf) is a noninvasive method of modulating activity of a brain region or circuit. The posterior cingulate cortex (PCC) has been hypothesized to be an important hub instantiating a mindful state. This nonrandomized, single-arm study examined the feasibility and tolerability of training typically developing adolescents to self-regulate the posterior cingulate cortex (PCC) using rtfMRI-nf during MT. Thirty-four adolescents (mean age: 15 years; 14 females) completed the neurofeedback augmented mindfulness training task, including Focus-on-Breath (MT), Describe (self-referential thinking), and Rest conditions, across three neurofeedback and two non-neurofeedback runs (Observe, Transfer). Self-report assessments demonstrated the feasibility and tolerability of the task. Neurofeedback runs differed significantly from non-neurofeedback runs for the Focus-on-Breath versus Describe contrast, characterized by decreased activity in the PCC during the Focus-on-Breath condition (z = -2.38 to -6.27). MT neurofeedback neural representation further involved the medial prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, posterior insula, hippocampus, and amygdala. State awareness of physical sensations increased following rtfMRI-nf and was maintained at 1-week follow-up (Cohens d = 0.69). Findings demonstrate feasibility and tolerability of rtfMRI-nf in healthy adolescents, replicates the role of PCC in MT, and demonstrate a potential neuromodulatory mechanism to leverage and streamline the learning of mindfulness practice. ( ClinicalTrials.gov identifier #NCT04053582; August 12, 2019).

Background: Mindfulness training has been shown to promote positive mental health outcomes and related changes in neural networks such as the default mode network, which has a central node in the posterior cingulate cortex (PCC). Previous work from our group reported on the impact of a novel, neurofeedback augmented mindfulness training (NAMT) task on regulation of PCC hemodynamic activity in typically developing adolescents. The present pilot study aimed to expand on this finding by examining the pre-post changes of the NAMT task on resting-state functional connectivity of the PCC. Methods: Thirty-one typically developing adolescents (14.77 ± 1.23 years; 45% female) underwent a resting-state functional magnetic resonance imaging scan both before and after completing the NAMT task. A linear mixed effects model was used to assess for changes in functional connectivity of the PCC across the two resting-state runs. Results: Data did not support the hypothesized decrease in connectivity between the PCC seed and other DMN regions from pre- to post-NAMT task. However, we observed a significant increase in functional connectivity between the PCC and a cluster encompassing the left hippocampus and amygdala following completion of the NAMT task (run 1 Fisher's Z = 0.16; run 2 Fisher's Z = 0.26). Conclusion: Although preliminary, this finding suggests NAMT has the potential to strengthen connectivity between default mode and salience regions. We speculate that such changed connectivity may facilitate enhanced self-referential and emotional processing in adolescents. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04053582. [ABSTRACT FROM AUTHOR]

Repetitive negative thinking (RNT), often referred to as rumination in the mood disorders literature, is a symptom dimension associated with poor prognosis and suicide in major depressive disorder (MDD). Given the transdiagnostic nature of RNT, this study aimed to evaluate the hypothesis that neurobiological substrates of RNT in MDD may share the brain mechanisms underlying obsessions, particularly those involving cortico-striatal-thalamic-cortical (CSTC) circuits. Thirty-nine individuals with MDD underwent RNT induction during fMRI. Trait-RNT was measured by the Ruminative Response Scale (RRS) and state-RNT was measured by a visual analogue scale. We employed a connectome-wide association analysis examining the association between RNT intensity with striatal and thalamic connectivity. A greater RRS score was associated with hyperconnectivity of the right mediodorsal thalamus with prefrontal cortex, including lateral orbitofrontal cortex, along with Wernicke's area and posterior default mode network nodes (t = 4.66–6.70). A greater state-RNT score was associated with hyperconnectivity of the right laterodorsal thalamus with bilateral primary sensory and motor cortices, supplementary motor area, and Broca's area (t = 4.51–6.57). Unexpectedly, there were no significant findings related to the striatum. The present results suggest RNT in MDD is subserved by abnormal connectivity between right thalamic nuclei and cortical regions involved in both visceral and higher order cognitive processing. Emerging deep-brain neuromodulation methods may be useful to establish causal relationships between dysfunction of right thalamic-cortical circuits and RNT in MDD. • Right thalamic connectivity was associated with repetitive negative thinking (RNT). • Increased connectivity in perception, cognition, and lexical-semantic regions. • Right thalamo-cortical connectivity may refine RNT-specific therapeutic strategies. [ABSTRACT FROM AUTHOR]

Resting-state functional connectivity (RSFC) has been proposed as a potential indicator of repetitive negative thinking (RNT) in depression. However, identifying the specific functional process associated with RSFC alterations is challenging, and it remains unclear whether alterations in RSFC for depressed individuals are directly related to the RNT process or to individual characteristics distinct from the negative thinking process per se. To investigate the relationship between RSFC alterations and the RNT process in individuals with major depressive disorder (MDD), we compared RSFC with functional connectivity during an induced negative-thinking state (NTFC) in terms of their predictability of RNT traits and associated whole-brain connectivity patterns using connectome-based predictive modeling (CPM) and connectome-wide association (CWA) analyses. Thirty-six MDD participants and twenty-six healthy control participants underwent both resting state and induced negative thinking state fMRI scans. Both RSFC and NTFC distinguished between healthy and depressed individuals with CPM. However, trait RNT in depressed individuals, as measured by the Ruminative Responses Scale-Brooding subscale, was only predictable from NTFC, not from RSFC. CWA analysis revealed that negative thinking in depression was associated with higher functional connectivity between the default mode and executive control regions, which was not observed in RSFC. These findings suggest that RNT in depression involves an active mental process encompassing multiple brain regions across functional networks, which is not represented in the resting state. Although RSFC indicates brain functional alterations in MDD, they may not directly reflect the negative thinking process. • Resting-state functional connectivity (RSFC) did not predict rumination in MDD. • Negative-thinking-state functional connectivity (NTFC) predicted rumination in MDD. • Both RSFC and NTFC distinguished between healthy and depressed individuals. • Rumination in depression involves active mental process across functional networks. • NTFC associated with higher FC between default mode and executive control regions. [ABSTRACT FROM AUTHOR]

Background: Repetitive negative thinking (RNT), a cognitive process that encompasses past (rumination) and future (worry) directed thoughts focusing on negative experiences and the self, is a transdiagnostic construct that is especially relevant for major depressive disorder (MDD). Severe RNT often occurs in individuals with severe levels of MDD, which makes it challenging to disambiguate the neural circuitry underlying RNT from depression severity. Methods: We used a propensity score, i.e., a conditional probability of having high RNT given observed covariates to match high and low RNT individuals who are similar in the severity of depression, anxiety, and demographic characteristics. Of 148 MDD individuals, we matched high and low RNT groups (n = 50/group) and used a data-driven whole-brain voxel-to-voxel connectivity pattern analysis to investigate the resting-state functional connectivity differences between the groups. Results: There was an association between RNT and connectivity in the bilateral superior temporal sulcus (STS), an important region for speech processing including inner speech. High relative to low RNT individuals showed greater connectivity between right STS and bilateral anterior insular cortex (AI), and between bilateral STS and left dorsolateral prefrontal cortex (DLPFC). Greater connectivity in those regions was specifically related to RNT but not to depression severity. Conclusions: RNT intensity is directly related to connectivity between STS and AI/DLPFC. This might be a mechanism underlying the role of RNT in perceptive, cognitive, speech, and emotional processing. Future investigations will need to determine whether modifying these connectivities could be a treatment target to reduce RNT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rumination, repetitively thinking about the causes, consequences, and one's negative affect, has been considered as an important factor of depression. The intrusion of ruminative thoughts is not easily controlled, and it may be useful to visualize one's neural activity related to rumination and to use that information to facilitate one's self‐control. Real‐time fMRI neurofeedback (rtfMRI‐nf) enables one to see and regulate the fMRI signal from their own brain. This proof‐of concept study utilized connectivity‐based rtfMRI‐nf (cnf) to normalize brain functional connectivity (FC) associated with rumination. Healthy participants were instructed to brake or decrease FC between the precuneus and the right temporoparietal junction (rTPJ), associated with high levels of rumination, while engaging in a self‐referential task. The cnf group (n = 14) showed a linear decrease in the precuneus‐rTPJ FC across neurofeedback training (trend [112] = −0.180, 95% confidence interval [CI] −0.330 to −0.031, while the sham group (n = 14) showed a linear increase in the target FC (trend [112] = 0.151, 95% CI 0.017 to 0.299). Although the cnf group showed a greater reduction in state‐rumination compared to the sham group after neurofeedback training (p <.05), decoupled precuneus‐rTPJ FC did not predict attenuated state‐rumination. We did not find any significant aversive effects of rtfMRI‐nf in all study participants. These results suggest that cnf has the capacity to influence FC among precuneus and rTPJ of a ruminative brain circuit. This approach can be applied to mood and anxiety patients to determine the clinical benefits of reduction in maladaptive rumination. [ABSTRACT FROM AUTHOR]

The ventromedial prefrontal cortex (vmPFC) is involved in regulation of negative emotion and decision‐making, emotional and behavioral control, and active resilient coping. This pilot study examined the feasibility of training healthy subjects (n = 27) to self‐regulate the vmPFC activity using a real‐time functional magnetic resonance imaging neurofeedback (rtfMRI‐nf). Participants in the experimental group (EG, n = 18) were provided with an ongoing vmPFC hemodynamic activity (rtfMRI‐nf signal represented as variable‐height bar). Individuals were instructed to raise the bar by self‐relevant value‐based thinking. Participants in the control group (CG, n = 9) performed the same task; however, they were provided with computer‐generated sham neurofeedback signal. Results demonstrate that (a) both the CG and the EG show a higher vmPFC fMRI signal at the baseline than during neurofeedback training; (b) no significant positive training effect was seen in the vmPFC across neurofeedback runs; however, the medial prefrontal cortex, middle temporal gyri, inferior frontal gyri, and precuneus showed significant decreasing trends across the training runs only for the EG; (c) the vmPFC rtfMRI‐nf signal associated with the fMRI signal across the default mode network (DMN). These findings suggest that it may be difficult to modulate a single DMN region without affecting other DMN regions. Observed decreased vmPFC activity during the neurofeedback task could be due to interference from the fMRI signal within other DMN network regions, as well as interaction with task‐positive networks. Even though participants in the EG did not show significant positive increase in the vmPFC activity among neurofeedback runs, they were able to learn to accommodate the demand of self‐regulation task to maintain the vmPFC activity with the help of a neurofeedback signal. [ABSTRACT FROM AUTHOR]