fMRI neurofeedback

Research Papers

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Real-Time fMRI Functional Connectivity Neurofeedback Reducing Repetitive Negative Thinking in Depression: A Double-Blind, Randomized, Sham-Controlled Proof-of-Concept Trial

Tsuchiyagaito, Aki, Misaki, Masaya, Kirlic, Namik, Yu, Xiaoqian, Sánchez, Stella M., Cochran, Gabe, Stewart, Jennifer L., Smith, Ryan, Fitzgerald, Kate D., Rohan, Michael L., Paulus, Martin P., Guinjoan, Salvador M. (2023) · Psychotherapy and Psychosomatics

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.

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Efficacy of bio- and neurofeedback for depression: a meta-analysis

Fernández-Alvarez, J., Grassi, M., Colombo, D., Botella, C., Cipresso, P., Perna, G., Riva, G. (2022) · Psychological Medicine

BACKGROUND: For many years, biofeedback and neurofeedback have been implemented in the treatment of depression. However, the effectiveness of these techniques on depressive symptomatology is still controversial. Hence, we conducted a meta-analysis of studies extracted from PubMed, Scopus, Web of Science and Embase. METHODS: Two different strings were considered for each of the two objectives of the study: A first group comprising studies patients with major depressive disorder (MDD) and a second group including studies targeting depressive symptomatology reduction in other mental or medical conditions. RESULTS: In the first group of studies including patients with MDD, the within-group analyses yielded an effect size of Hedges' g = 0.717, while the between-group analysis an effect size of Hedges' g = 1.050. Moderator analyses indicate that treatment efficacy is only significant when accounting for experimental design, in favor of randomized controlled trials (RCTs) in comparison to non RCTs, whereas the type of neurofeedback, trial design, year of publication, number of sessions, age, sex and quality of study did not influence treatment efficacy. In the second group of studies, a small but significant effect between groups was found (Hedges' g = 0.303) in favor of bio- and neurofeedback against control groups. Moderator analyses revealed that treatment efficacy was not moderated by any of the sociodemographic and clinical variables. CONCLUSIONS: Heart rate variability (HRV) biofeedback and neurofeedback are associated with a reduction in self-reported depression. Despite the fact that the field has still a large room for improvement in terms of research quality, the results presented in this study suggests that both modalities may become relevant complementary strategies for the treatment of MDD and depressive symptomatology in the coming years.

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Neurotherapeutics for Attention Deficit/Hyperactivity Disorder (ADHD): A Review

Rubia, Katya, Westwood, Samuel, Aggensteiner, Pascal-M., Brandeis, Daniel (2021) · Cells

This review focuses on the evidence for neurotherapeutics for attention deficit/hyperactivity disorder (ADHD). EEG-neurofeedback has been tested for about 45 years, with the latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly the dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has been shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.

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Just a very expensive breathing training? Risk of respiratory artefacts in functional connectivity-based real-time fMRI neurofeedback

Weiss, Franziska, Zamoscik, Vera, Schmidt, Stephanie N. L., Halli, Patrick, Kirsch, Peter, Gerchen, Martin Fungisai (2020) · NeuroImage

Real-time functional magnetic resonance imaging neurofeedback (rtfMRI NFB) is a promising method for targeted regulation of pathological brain processes in mental disorders. But most NFB approaches so far have used relatively restricted regional activation as a target, which might not address the complexity of the underlying network changes. Aiming towards advancing novel treatment tools for disorders like schizophrenia, we developed a large-scale network functional connectivity-based rtfMRI NFB approach targeting dorsolateral prefrontal cortex and anterior cingulate cortex connectivity with the striatum. In a double-blind randomized yoke-controlled single-session feasibility study with N ​= ​38 healthy controls, we identified strong associations between our connectivity estimates and physiological parameters reflecting the rate and regularity of breathing. These undesired artefacts are especially detrimental in rtfMRI NFB, where the same data serves as an online feedback signal and offline analysis target. To evaluate ways to control for the identified respiratory artefacts, we compared model-based physiological nuisance regression and global signal regression (GSR) and found that GSR was the most effective method in our data. Our results strongly emphasize the need to control for physiological artefacts in connectivity-based rtfMRI NFB approaches and suggest that GSR might be a useful method for online data correction for respiratory artefacts.

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Functional connectivity changes associated with fMRI neurofeedback of right inferior frontal cortex in adolescents with ADHD

Rubia, K., Criaud, M., Wulff, M., Alegria, A., Brinson, H., Barker, G., Stahl, D., Giampietro, V. (2019) · NeuroImage

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. We showed previously that 18 ADHD adolescents over 11 runs of 8.5 min of real-time functional magnetic resonance neurofeedback of the right inferior frontal cortex (rIFC) progressively increased activation in 2 regions of the rIFC which was associated with clinical symptom improvement. In this study, we used functional connectivity analyses to investigate whether fMRI-Neurofeedback of rIFC resulted in dynamic functional connectivity changes in underlying neural networks. Whole-brain seed-based functional connectivity analyses were conducted using the two clusters showing progressively increased activation in rIFC as seed regions to test for changes in functional connectivity before and after 11 fMRI-Neurofeedback runs. Furthermore, we tested whether the resulting functional connectivity changes were associated with clinical symptom improvements and whether they were specific to fMRI-Neurofeedback of rIFC when compared to a control group who had to self-regulate another region. rIFC showed increased positive functional connectivity after relative to before fMRI-Neurofeedback with dorsal caudate and anterior cingulate and increased negative functional connectivity with regions of the default mode network (DMN) such as posterior cingulate and precuneus. Furthermore, the functional connectivity changes were correlated with clinical improvements and the functional connectivity and correlation findings were specific to the rIFC-Neurofeedback group. The findings show for the first time that fMRI-Neurofeedback of a typically dysfunctional frontal region in ADHD adolescents leads to strengthening within fronto-cingulo-striatal networks and to weakening of functional connectivity with posterior DMN regions and that this may be underlying clinical improvement.

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Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis

Nicholson, Andrew A., Rabellino, Daniela, Densmore, Maria, Frewen, Paul A., Paret, Christian, Kluetsch, Rosemarie, Schmahl, Christian, Théberge, Jean, Ros, Tomas, Neufeld, Richard W. J., McKinnon, Margaret C., Reiss, Jeffrey P., Jetly, Rakesh, Lanius, Ruth A. (2018) · Human Brain Mapping

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

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