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Mindfulness training (MT) reduces self-referential processing and promotes interoception, the perception of sensations from inside the body, by increasing one’s awareness of and regulating responses to them. The posterior cingulate cortex (PCC) and the insular cortex (INS) are considered hubs for self-referential processing and interoception, respectively. Although MT has been consistently found to decrease PCC, little is known about how MT relates to INS activity. Understanding links between mindfulness and interoception may be particularly important for informing mental health in adolescence, when neuroplasticity and emergence of psychopathology are heightened. We examined INS activity during real-time functional magnetic resonance imaging neurofeedback-augmented mindfulness training (NAMT) targeting the PCC. Healthy adolescents (N = 37; 16 female) completed the NAMT task, including Focus-on-Breath (MT), Describe (self-referential processing), and Rest conditions, across three neurofeedback runs and two non-neurofeedback runs (Observe, Transfer). Regression coefficients estimated from the generalized linear model were extracted from three INS subregions: anterior (aINS), mid (mINS), and posterior (pINS). Mixed model analyses revealed the main effect of run for Focus-on-Breath vs. Describe contrast in aINS [R2 = 0.39] and pINS [R2 = 0.33], but not mINS [R2 = 0.34]. Post hoc analyses revealed greater aINS activity and reduced pINS activity during neurofeedback runs, and such activities were related to lower self-reported life satisfaction and less pain behavior, respectively. These findings revealed the specific involvement of insula subregions in rtfMRI-nf MT. more...

Introduction: Individual real-time functional magnetic resonance imaging neurofeedback (rtfMRI NF) might be a promising adjuvant in treating depressive symptoms. Further studies showed functional variations and connectivity-related changes in the dorsolateral prefrontal cortex (dlPFC) and the insular cortex. Objectives: The aim of this pilot study was to investigate whether individualized connectivity-based rtfMRI NF training can improve symptoms in depressed patients as an adjunct to a psychotherapeutic programme. The novel strategy chosen for this was to increase connectivity between individualized regions of interest, namely the insula and the dlPFC. Methods: Sixteen patients diagnosed with major depressive disorder (MDD, ICD-10) and 19 matched healthy controls (HC) participated in a rtfMRI NF training consisting of two sessions with three runs each, within an interval of one week. RtfMRI NF was applied during a sequence of negative emotional pictures to modulate the connectivity between the dlPFC and the insula. The MDD REAL group was divided into a Responder and a Non-Responder group. Patients with an increased connectivity during the second NF session or during both the first and the second NF session were identified as “MDD REAL Responder” (N = 6). Patients that did not show any increase in connectivity and/or a decreased connectivity were identified as “MDD REAL Non-Responder” (N = 7). Results: Before the rtfMRI sessions, patients with MDD showed higher neural activation levels in ventromedial PFC and the insula than HC; by contrast, HC revealed increased hemodynamic activity in visual processing areas (primary visual cortex and visual association cortex) compared to patients with MDD. The comparison of hemodynamic responses during the first compared to during the last NF session demonstrated significantly increased BOLD-activation in the medial orbitofrontal cortex (mOFC) in patients and HC, and additionally in the lateral OFC in patients with MDD. These findings were particularly due to the MDD Responder group, as the MDD Non-Responder group showed no increase in this region during the last NF run. There was a decrease of neural activation in emotional processing brain regions in both groups in the last NF run compared to the first: HC showed differences in the insula, parahippocampal gyrus, basal ganglia, and cingulate gyrus. Patients with MDD demonstrated deceased responses in the parahippocampal gyrus. There was no significant reduction of BDI scores after NF training in patients. Conclusions: Increased neural activation in the insula and vmPFC in MDD suggests an increased emotional reaction in patients with MDD. The activation of the mOFC could be associated with improved control-strategies and association-learning processes. The increased lOFC activation could indicate a stronger sensitivity to failed NF attempts in MDD. A stronger involvement of visual processing areas in HC may indicate better adaptation to negative emotional stimuli after repeated presentation. Overall, the rtfMRI NF had an impact on neurobiological mechanisms, but not on psychometric measures in patients with MDD. more...

Frontiers in psychiatry 12, 715898 (2021). doi:10.3389/fpsyt.2021.715898, Published by Frontiers Research Foundation, Lausanne

Posttraumatic stress disorder (PTSD) is widely associated with deficits in implicit emotion regulation. Recently, adaptive fMRI neurofeedback (A-NF) has been developed as a methodology that offers a unique probe of brain networks that mediate implicit emotion regulation and their impairment in PTSD. We designed an A-NF paradigm in which difficulty of an emotional conflict task (i.e., embedding trauma distractors onto a neutral target stimulus) was controlled by a whole-brain classifier trained to differentiate attention to the trauma distractor vs. target. We exploited this methodology to test whether PTSD was associated with: (1) an altered brain state that differentiates attention towards vs. away from trauma cues; and (2) an altered ability to use concurrent feedback about brain states during an implicit emotion regulation task. Adult women with a current diagnosis of PTSD (n = 10) and healthy control (n = 9) women participated in this task during 3T fMRI. During two initial non-feedback runs used to train a whole-brain classifier, we observed: (1) poorer attention performance in PTSD; and (2) a linear relationship between brain state discrimination and attention performance, which was significantly attenuated among the PTSD group when the task contained trauma cues. During the A-NF phase, the PTSD group demonstrated poorer ability to regulate brain states as per attention instructions, and this poorer ability was related to PTSD symptom severity. Further, PTSD was associated with the heightened encoding of feedback in the insula and hippocampus. These results suggest a novel understanding of whole-brain states and their regulation that underlie emotion regulation deficits in PTSD. more...

Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) is a prospective tool to enhance the emotion regulation capability of participants and to alleviate their emotional disorders. The hippocampus is a key brain region in the emotional brain network and plays a significant role in social cognition and emotion processing in the brain. However, few studies have focused on the emotion NF of the hippocampus. This study investigated the feasibility of NF training of healthy participants to self-regulate the activation of the hippocampus and assessed the effect of rtfMRI-NF on the hippocampus before and after training. Twenty-six right-handed healthy volunteers were randomly assigned to the experimental group receiving hippocampal rtfMRI-NF (n = 13) and the control group (CG) receiving rtfMRI-NF from the intraparietal sulcus rtfMRI-NF (n = 13) and completed a total of four NF runs. The hippocampus and the intraparietal sulcus were defined based on the Montreal Neurological Institute (MNI) standard template, and NF signal was measured as a percent signal change relative to the baseline obtained by averaging the fMRI signal for the preceding 20 s long rest block. NF signal (percent signal change) was updated every 2 s and was displayed on the screen. The amplitude of low-frequency fluctuation and regional homogeneity values was calculated to evaluate the effects of NF on spontaneous neural activity in resting-state fMRI. A standard general linear model (GLM) analysis was separately conducted for each fMRI NF run. Results showed that the activation of hippocampus increased after four NF training runs. The hippocampal activity of the experiment group participants was higher than that of the CG. They also showed elevated hippocampal activity and the greater amygdala-hippocampus connectivity. The anterior temporal lobe, parahippocampal gyrus, hippocampus, and amygdala of brain regions associated with emotional processing were activated during training. We presented a proof-of-concept study using rtfMRI-NF for hippocampus up-regulation in the recall of positive autobiographical memories. The current study may provide a new method to regulate our emotions and can potentially be applied to the clinical treatment of emotional disorders. more...

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self‐control, underpinned by inferior fronto‐striatal deficits. Real‐time functional magnetic resonance neurofeedback (rtfMRI‐NF) allows participants to gain self‐control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological‐NF on ADHD symptoms, no study has applied the spatially superior rtfMRI‐NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI‐NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region‐specificity, an active control group received rtfMRI‐NF of the left parahippocampal gyrus (lPHG). Thirty‐one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI‐NF runs over 2 weeks. Feedback was provided through a video‐clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11‐month follow‐up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof‐of‐concept study demonstrates for the first time feasibility, safety, and shorter‐ and longer‐term efficacy of rtfMRI‐NF of rIFG in adolescents with ADHD. Hum Brain Mapp 38:3190–3209, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. more...

© 2014 Emmert Breimhorst Bauermann Birklein Van De Ville and Haller. Real time functional magnetic resonance imaging (rt fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt fMRI neurofeedback on pain we directly compared two different target regions of the pain network notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age matched groups of 14 participants each (7 females per group) for AIC and ACC feedback. First a functional localizer using block design heat pain stimulation was performed to define the pain sensitive target region within the AIC or ACC. Second subjects were asked to down regulate the BOLD activation in four neurofeedback runs during identical pain stimulation. Data analysis included task related and functional connectivity analysis. At the behavioral level pain ratings significantly decreased during feedback vs. localizer runs but there was no difference between AIC and ACC groups. Concerning neuroimaging ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down regulation (17/28) in both task related and functional connectivity analysis. The functional connectivity toward the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex. Consequently the ACC and AIC are suitable targets for real time fMRI neurofeedback during pain perception as they both affect the caudate nucleus although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally the caudate an important area involved in pain perception and suppression could be a good rt fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt fMRI neurofeedback on pain perception. more...